Jump to:

NYSA TI Single-Page 3

The Health Consequences of Involuntary

Date: No date
Length: 176 pages

Jump To Images
nysa_ti_s3 TI07870611-TI07870786

Fields

Named Organization
AFL-CIO (American Federation of Labor/Congress of Industrial Organiza)
Labor Union
American Academy of Pediatrics
American Cancer Society
American Chemical Society
American Health Foundation (Health Research)
Plaintiff
American Industrial Hygiene Association
American Journal of Epidemiology (scientific periodical)
American Journal of Public Health (periodical)
American Medical Association (physicians group)
Professional trade group representing American physicians.
Americans for Nonsmokers' Rights (Anti tobacco organization)
Concerned with clean indoor air.
Archives (National Archives and Records Administration)
ASH (Action on Smoking and Health)
Action on Smoking and Health
Baltimore Sun
Baptist Hospital (Miami, Florida)
Bell Telephone
Boeing (Aircraft manufacturer)
British Medical Journal (BMJ) (scientific periodical)
scientific periodical
Chamber of Commerce
Control Data Corporation
*Department of Health and Human Services
*Department of Health, Education, and Welfare (HEW) (use United States Departmen (use @hew_dept)
Environmental Protection Agency (EPA)
Federal Trade Commission (Enforcement agency for laws against deceptive advertising)
Enforces laws against false and deceptive advertising, including ads for tobacco products. Ensures proper display of health warnings in ads and on tobacco products;collects and reports to Congress information concerning cigarette and smokeless tobacco advertising, sales expenditures, and the tar, nicotine, and carbon monoxide content of cigarettes.
Federal Trade Commission (FTC)
Gallup Organization (Polling firm)
formerly known as Gallup & Robinson, Inc. (1975)
Harvard School of Public Health
Harvard University
*Health and Human Services (HHS) (use United States Department of Health and Hum (US)
Hilton Hotels
International Agency for Research on Cancer (IARC) (WHO cancer research arm)
International Agency for Research on Cancer - The cancer research arm of the WHO. Conducted a multi-center epidemiology study on ETS, initiated in 1988, data collection completed in 1994 and results were published in 1998
Information Center
Institute for the Study of Smoking Behavior and Policy
Institute of Psychiatry (London)
John F. Kennedy School of Government
Journal of Occupational Medicine (scientific periodical)
Lancet
Massachusetts Institute of Technology (MIT)
Medical College of Georgia (Did youth recognition studies of Joe Camel, Mickey Mouse)
Reported circa 1994 that almost as many 6-year-olds recognized Joe Camel as know Mickey Mouse
Medical College of Virginia
Mint (Treasury Department)
National Academy of Sciences
National Heart Lung and Blood Institute
National Institutes of Health
National Restaurant Association
New England Journal of Medicine
New York Times
Nonsmokers Rights (California anti-smoking organization created by Stanton Glan)
Oak Ridge National Laboratory
Contract research lab; does gov't work and also takes private contracts.
Office on Smoking and Health
Responsible for creating reports on the health effects of smoking. Created by the Public Health Service.
PMI (See Philip Morris Inc.)
See Philip Morris Inc.
Preventive Medicine (periodical)
Roper Organization (Consumer Research/Public Relations Org.)
Interested in finding out what drives consumer behavior; surveys consumers on their prime areas of concern; assists corporations with reputation-building and public image based on its findings.
Seventh Day Adventists (religion that prohibits smoking. runs smoking cessation prog)
Simmons Market Research Bureau (Advertising auditing company)
Singer
Texas Instruments
Tobacco Institute (Industry Trade Association)
The purpose of the Institute was to defeat legislation unfavorable to the industry, put a positive spin on the tobacco industry, bolster the industry's credibility with legislators and the public, and help maintain the controversy over "the primary issue" (the health issue).
U.S. Department of Commerce
University of Arizona
University of Athens
University of British Columbia (Located in Vancouver, British Columbia, Canada)
*University of California (use specific branch)
University of California Los Angeles (UCLA)
University of California Davis
University of California San Diego
University of Kentucky
University of Minnesota
University of New Mexico School of Medicine
University of Southern California
Veterans Administration
Xerox
Yale University
Named Person
Adams, Elvin E., M.D., M.P.H. (Internist, Ft. Worth, TX -worked on Surgeon Gen. reports)
Dr. Adams practices internal medicine in Fort Worth, Texas. Dr. Adams was a participant in the Surgeon General's tobacco reports for several years and has knowledge about morbidity related to smoking. (Source: As per Rhett Klok and Harriet Chaney.)
Adams, Erica W.
Amacher, Richard H.
Ayres, Stephen M.
Bates, David V.
Bell, Lea
Bishop, Jr., Mike A. (RJR Corp. Public Relations)
Manager Smoking
Brown, Charles A.
Brown, Clarice D.
Brubaker, Richard C.
Buist, A. Sonia
Burns, David M.
Burrows, Benjamin
David, Virginia
Devita, Vincent T., Jr.
Diamond, Louis
Doll, Richard
Dyas, B. J. (BAT)
Finnegan, Robert
Finnigan, Robert
Goodman, Danny A.
Gritz, Ellen R., Ph.D.
Plaintiff
Healy, Patricia E.
Henry, Terri L.
Hensley, Timothy K.
Hiller, Charles
Hoffmann, Dietrich, Ph.D. (Biochemist, American Health Foundation, Plaintiff's Expert)
Plaintiff
Janoff, April
Jarvis, Martin J.
Professor at University College London. Clinical psychologist interested in behavioral and psychological aspects of tobacco dependence
Jones, R.T. (BATCO GR&DC)
R. T. Jones was with BATCO-GR&DC. (Source: NM Tobacco Companies Personnel List)
June, May
Keep, C. Everett
Kon, Hang
Kong, Hang
Li, Charles
Lugton, W.G.D. (BATCo Groupt R&D Centre, Southampton, c. 1972)
Lynn, William R.
Marks, James S.
Mccarthy, John
Mcginnis, J. Michael
McGinnis, J. Michael, M.D.
Plaintiff
Morrison, B.J. (BW Brand Research Manager 1982-83)
Defense
Muir, David
Nii, June
Peek, Russell D.
Pete, Richard
Pickerel, Margaret E.
Pierce, John B.
Poole, Raymond K.
Raabe, Otto
Register, Sunday
Repine, J.E. (Webb-Waring Institute employee)
Rigotti, Nancy A., M.D. (Internist, Harvard Med. School, Anti-Tobacco Expert)
Samet, Jonathan M.
Shepard, R.J. (researcher, ETS)
Shepherd, Roy J.
Shopland, Donald R. (NCI Public Health Advisor)
Plaintiff
Stein, Jesse L.
Study, German
Traynor, Gregory W.
Warner, Kenneth E., Ph.D (Plaintiff's expert, health care costs)
Plaintiff
Weber, Annetta
Wehner, A. P. (said no carcinogenic synergy between smoking and asbestos)
"Neither a carcinogenic effect of asbestos nor a co-carcinogenic effect of cigarette smoke was observed."
Weiss, Scott T.
Wiedemann, Herbert P. (Pulmonologist, Cleaveland Clinic Foundation)
ETS Researcher
Wiley, John
Wilton, Lynda V. (BAT)
Young, Frank E.
Zuniga, Pamela
Date Loaded
18 Jul 2005
Box
1322

Document Images

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size:

Page 1: TI07870611
---
Page 2: TI07870612
THE HEALTH CONSEQUENCES OF INVOLUNTARY SMOI~NG a report of the. Surgeon General 1986 U.$. OEPARTMENT OF HEALTH AND HUMAN SERVICES Ce~zlera Im ~sease C~tr~ Center I~ Heallh Pr~ti~ a~ Ed~li~ OliVe oa 5mo~i~ ~d Health
Page 3: TI07870613
PREPUBLICATION EDITION This copy is Issued as a prepubllcatlon edition conlalnlng no sub~ecl Index. A llnal edillon wilh Index will be available approximalely elghl weeks from date el release. FOREWORD The data reviewed in 17 previous U.S. Public Health Service re~orts on the health consequences of smoking have conclusively established cigarette smoking'as the largest single preventable cause of premature death and disability in the United States. ' The quesl.ion whether tobacco smoke is harln[ol to smokers was answered more than 20 yem's ago. As a resuR, many scientists began to questio, whether the low levels of ex~sure to environmental tobacco sm~ke lETS) received by nonsmokers could.also be harmful, The cunent Report, The tlealth Consequences of Involuntary Smoking, examines the evidence that even the lower exposure to smoke recHved by the nonsmoker carries with it a health risk. Use of the term "i~=voluutary smoking" denotes that I~r man~ nonsmokers, ex~ure t~ ~FS is the result of an unavoidable consequence of being in pruximily to smokers. It is the first Re~rt in the health consequences o~ smoking series to establish a health risk due to tobacco sm,ke exposure for individuals uther than the smoker, and represents the work o~ more than ~ distinguished physicians and ~ientisls, both in this country and abroad. Afh~r careful examination of the available evidence, the following overall conclusions can be reachM: 1. Involuntary smoking is a cause of disease, including lung cane,',', in healthy nonsmokers. 2. The children of paren~ wire smoke, compared with the chflJren of nonsmoking parent, have an increased frequency of respiratory infections, increased respiratory symptoms, and sligbl.ly smaller rates of increase in lung I~nctlon as the lung tnaI.u res. 3. Simple separation of smokers and nonsmokers within ~he smn~. air space may reduce, but d~s not eliminate, exposure of n~msmokers to environmental tobacco smoke. Exposm'~, to environmental tobacco smoke occurs at, home, at, the worksite, in public, and in other places where smoking is permitted, vii
Page 4: TI07870614
The quality of lhe indoor environment must be a concern of all who control and occupy that environment. Protection of individuals exposure to environmental tobacco smoke is tllere/~re a respoasibili- ty shared by alh As parents and adults we nmst protect the health of our children by not ex~ing them to envir(mmen{al tobacco smoke. As employers and employees we must ensure that the act of smoking does not ex~se the nonsmoker to ~obacco smoke. • For smoker~, it is their resl~nsibility to assure that their behavior dues not jeopardize the health of or hers. • For nonsmokers, it i~ their res~nsibility to provide a support- ice environment for smokm~ who are attempting to ~top. Actions taken by individuals, employers, and employee m~ani~- tions reflect the growing concern for protecting nonsmokers. The number of laws and regulations enacted at the naHonal, State, l~al level governing smoking in public has increased au~tantiully over the past 10 years, and surveys conducted by numerous organizations show strong public ~up~rt for these action~ among bo~h smokers and nonsmokm~. As a Nation, we have made substantial progress in addre~ing the enormous toll inflicted by active smoking. Efforts to improve protect individual health must not only ~ continued hut strength- en~. On the basis of the evidence pre~nted in this Re~rt, it is 'clear that actions to p~'otect ncmamokers fi'om ~1~ exposure m~t only are warranted but are e~ential to pro~ect public health. Robert E. Windcm~, M.D. Assistant Secretary Ibr |lealth PREFACE This, the 1986 Report of the Surgeon General, is the U.S. Public Health Service's 18th in the health consequencei~ of smoking series and the 5th issued during my tenure as Surgeon General. Previous Reports have documented the tremendous health burden to society from smoking, particularly cigarette smoking. The evi- dence establishing cigarette smoking as the single largest prevents. hie cause of premature death and disability in the United States is overwhelmlng--totaling more than 50,000 studies from dozen~ of cultures. Smoking is now known to be causally related to a variety of cancet~ in addition to lung cancer; it is a cause of cardiovascular disease, parl.icularly coronary heart disease, and is tbe major cause of chronic.obstructive lung disease. It is estimated that smoking is responsible for well over 300,000 deaths annually in the United States, reprtmenting approximately 15 percent of all mortality, Thirty years ago, hewers, r, the scientific evidence linking smoking with early death and disability was more limited. By 1964. the year the Advisory Committee to the Surgeon Gerleral issued the first report on smoking and health, a substantial body of evidence had accumulated upon which a judgment could be made that smoking was a cause of disease in active smokers. Subs~luent reports over the last 20 years have expanded our understanding and knowledge about smoking behavior, the toxicity and =weimgenieity of tobacco smoke, and the specific disease risks resulting h'om exposure to this agent. This ltelaWt is the first issued since 19641hat identifies a chronic disease risk resulting from exposure to tobacco smoke for individuals other titan smokers. It is now clear that disease risk due to the inhalation ~f tobacco smoke is not limited to the individtml who is smoking, but can extend to those who inhale tobacco smoke emitted into the air. This Report represents a detailed review of the health effects resulting front nonsmoker exposure to environmental tobacco smoke (bJl,~). E-~I~ is the combination of smoke emitted from a burning tobacco product between puffs (sidestream smoke) and the smoke exhaled by the smoker. The 1986 Report, The Health Consequem'es of Involuntary Smoking, is a critical review of all the available sHentific evidence pertaining to the health effects of ETS exposure o*~ nonsmokers. The term "involuntary smoking" is used to viii Ix
Page 5: TI07870615
note that such exposures often occur as an utmvoidable consequence of being in close proximity to smokers. Lung Cancer and Environmental Tobacco Smoke The appropriate framework for an examination of the lung cancer risk from involuntary smoking is that of a low-dose eXlmsure I.o a known human carcinogen. Over 30 years of research have conclu- sively established .cigarette smoke as a carcinogen. This Relmrt presents evidence that the chemical c.omposition of sidestream smoke is qualitatively similar to the mainstremn smoke inhaled by, the active smoker, and that both mainstream and sldestream smoke act as carcinogens in bioassay systems. Data related to environmen- tal levels of tobacco smoke constituent~ and from measures of nicotine absorption in nonsmokers suggest that nonsmokers are exposed to levels of environmbntal tobacco smoke that would be expected to generate a lung cancer risk; epidemiological studies of populations exposed to I,~]'S hbve documented an increased risk for lung cancer in those nonsmokers with increased exposure. It is rare to huve such detailed exposure data or hunmn epide=nio- logic studies on disease nccurrence when attempting to evaluate the risk of low<lose exposure to an agent with established toxicity at higher levels of exposure. The relative abundance of data reviewed in this Report, their cohesiveness, and their biologic plausibility allow a judgment that involuntary smoking can cause lung cancer in nonsmokers. Although the number o1": lung cancers due to involun- tary smoking is smaller than that due to active smoking, it still represents a number sul'ficiently large to generate substantial public health concern. it is certain that a substantial proportion of the lung cancers that occur in nonsmokers are due to ETS exposure; however', more complete data on the dose and variability of smoke exposure in the nonsmoking U.S. populutlon will be needed before a quantitative estimate of the number of such cancers can be made. Children and Infants This Report also documents a relationship between parental smoking and the respiratory health o[ infants and children (under 2 years o[ age). ]nfant~ o1" parents who smoke have an increused risk of hospitalization for bronchitis and pneumonia when compared with infants of nonsmoking parents. There is a relationship between parental smoking and ou increased frequency of respiratory symp- toms in ~hildren. A slower rate o1" growth in lung function has been observed in children of smoking parents. ]n many studies, if both parents m=n~ke, a stronger relationship exists than iF only one parent smoke'.~. What rul.t~re respiratory burden these findings may represent for these children later in life is not known. As a former pediatric surgeon, I strongly urge paren~ to refrain from smoking in the presence o1 children as a means of protecting ~ot only their children's ct~r~'ent health s~atus but also their own. Diseases Other Than Lung Cancer Severul ~tudies have provided data on the relationship between ETS and c=mcers other than lung cancer and on ETS exposure and cardiovascular disease. However, further research in these areas will be required to determine whether an association exists between ETS exposure and an increased risk of developing these diseases, ' Policies Restricting Smoking In Public Places The growth in our understanding of the disease "risk associated with involuutary smoking has been accompanied by a change in the social acceptability of smoking and by a growing body of legislation, regulatim~, m~d voluntary action that addresses where smoking may occur in public. Forty States and the District of Columbia now have some form .f legislation controlling or restricting smoking in various public settings. Some States limit smoking to only a few designated areas; however, States are increasingly developing and implement- ing comprehensive legislation that restricts smoking in many public settings, im'luding the workplace. Nine States have restrictions that cover smokb~g not only by public employees but also by employees in the private sector. No systematic evaluation of the effects these measures may h&ve • on smokint', behavior has been conducted, but there is little doubt that strong public sentiment exists for implementing such restric- tions. A number of national surveys conducted by voluntary health organizn{ions, government agencies, and even the tobacco industry have doctn,~ented that an overwhelming majority of both smokers and nonmn~kers support restricting smoking in public, Public Health Policy and Involuntary Smoking The 1986 Surgeon General's Report on the Health Consequences of Involuntary Smoking clearly documents that nonsmokers are p.laced at increased risk for developing disease as the result of exposure to environmental tobacco smoke. Critics olten express that more research is required, that certain • studies arc flawed, or that we should delay action until more conclusive proof is produced. As both a physician and a public health '
Page 6: TI07870616
official, it is my judgmeut that the time for delay is past; measures to protect the public health are required now. The scientific case against involuntary smoking as a health risk is more than sufficient to justify appropriate remedial action, and the goal of any remedial action must be to protect the nonsmoker from environmental tobacco smoke. The data contained in this Report on the rapid diffusion of tobacco smoke throughout an enclosed environment suggest that separation of smokers and nonsmok.ers in the same room or iu different rooms that share the same ventilation system may reduce I,Yl~] exposure but will not eliminate exposure. The responsibility to protect the safety of the indoor environment is shared by all who occupy or control that enviromnent. Changes in smoking policies regarding the workplace and other environments necessitated by the data presented in this Relmrt should not be designed to punish the smoker. Successful impl~menhv tion of protection for the nonsmoker requires the support and cooperation of smokers, nonsmokers, management, and employees and should be developed through a cooperative effort of all groups affected. In addition, changes are often more effective when suplmrt aud assistance is provided for the smoker who wants to quit. Cigarette smoking is an addictive behavior, and the individual smoker must decide whether or not to continue that behavior; however, it is evident h'om the data presented in this volume that the choice to smoke cannot interfere with the nonsmokers' right to breathe air free of tobacco smoke. The right of smokers to smoke ends where their behavior affects the health and well-being of others; furthermore, it is the smokers' responsibility to ensure that they do not expose nonsmokers to the potential harmful effects of tobacco smoke. C. Everett Keep, M.D. Surgeon General ACKNOWLEDGMENTS This Rel~rt was prepared by the Department of Health and Human Services under the general editorship of the Office on Smokiog and Health, Donald R. Shopland, Acting Director. Manag- ing Editor was William R. Lynn, Acting Technical Information. Officer, Office on Smoking and Health. Senior scientific editor was David M. Burns, M,D., A~sociate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Medical Center, San Diego, San Diego, Calitbrnia. Consulting ~ientific editors were Ellen R. Gritz, Ph.D., Director, Division of Cancer Control, Jonson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles~ California; John H. Holbro~k, M.D., Associate Professor of Internal Medicine, Department of Internal Medicine, University Hospital, Salt I~ke City, Utah; and Jonathan M. Samet, M.D., Professor of Medicine, Department of Medicine, The University of New Mexico School OF Medicine, Albuquerque~ New Mexico, The following indiv|duals prepared draft chapters or portions of the Report. Neal Benowitz, M.D., San Francisco General Medical Center, San Francbco, California" A. Sonia Buist, M.D., Professor of Medicine, Department of Physiolo. g'y, Oregon Health S~iences University, Portland, Oregon Charles Hiller, M.D., Pulmonary Division, University Hospital, Little Rock, Arkansas Dietrich Hoffmann, Ph.D., A~ociate Director, Naylor Dana Institute for Dise,~se Prevention, American Health Foundation, Valhalla, New York llse lloffmann, Research Coordinator, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York John It. ll~ddal, M.D., Director of Pulmonary Medicine, University of Tenn~.,e Center for llealth Sciences, Memphis, Tennessee John McCarthy, M.P.H., Harvard School of Public Health, Boston, MaHsacht,setts xii xiii
Page 7: TI07870617
Nancy A. Rigotti, M.D., Institute for the Study of Smoking Behavior and Policy, John F. Kennedy School of Government, Harvard University, Cambridge, Massachusetts Jonathan M. Samet, M.D., Professor of Medicine, Departmel~t of Medicine, The University of New Mexico School of Medicine, Albuquerque, New Mexico Jo|m Spengler, Ph.D., Harvard School of Public Health, Boston, Massachusetts Annetta Weber, Ph.D., Federal Institute of Technology, Zurich, Switzerland Scott T. Weiss, M.D., M~.0 Associate Professor of Medicine, Chan- ning Laboratories, Harvm'd Medical School, Boston, Massachu- setts Anna II. W.u, Ph.D., Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, Califor- The editors acknowledge with gratitude the following distin- gulshed scientists, physicians, and others who lent their support in the development of this Report by coordinating manuscript prepara- tion, contributing critlc~d reviews of tl~e manuscript, or assisting in other ways. Elvin E. Adams, M.D., M.P.H., Director, Health and Temperance Department, General Conference of Seventh-Day Adventists, Washington, D.C. Stephen M. Ayres, M.D., Dean, School of Medicine, Medical College of Virginia, Richmond, Virginia David V. Bates, M.D., Professor of Medicine and Physioh~,y, Department of Medicine, Acute 'Care Hospital, University of British Columbia, Vancouver, British Columbia William J. Blot, Ph.D., Chief, Biostatistics Branch, Epldemloiogy and Blosthtistlcs Program, Division of Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Benjamin Burrows, M.D., Professor of Internal Medicine, and Director, Division of Respiratory Sciences, The University of Arizona College of Medicine, Tucson, Arizona D. M. DeMarini, Ph.D., Genetic Toxicology Division, U.S.-Environ- mental Protection Agency, Research Triangle Park, North Caro- lina Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Louis Diamond, Ph.D., College of Pharnmcy, University of Kentucky, Lexington, Kentucky • Richard Doll, Cancer Epidemiology and Clinical Trials Unit, Imperi- al Cancer Research Fund, The Radcliffe Infirmary, University of Oxford, Oxfonl, England, United Kingdom xlv Manning l",.inle~.~, M.D., Dr.P.tI., Director, National Center for Ilealth SI.atistics, Office of the Assistant Secretary for Health~ HyatLqvil h,, Maryland Edwin 1~. I,'isher, Jr., Ph.D., Associate Professor, Department of Psychology, Wastdagton University, St. Louis, Missouri William It. Foege, M.D., Executive Director, Task Force for Child Survival, ( ~arter Presidential Center, Atlanta, Georgia Joseph F. l;'ramneni, Jr., M.D., Assoc'iate Director for Epidemio|ogy and Bio.statistics, Division of Cancer Etiology, National Institutes of Itealth, Bel~hesda, Maryland Lawrence t;arfinkel, M.A., Vice President for Epidemiology and Statistics, and Director of Cancer Prevention, Amerl/mn Cancer Society, blew York, New Yo/'k R.A. Griesemer, D.V.M., Ph.D., Director, Biology Division, OakRidge National I,aboratory, Oak Ridge, Tennessee Michael It. Guerln, Ph.D., Organic Chemistry Section, Analytical Chemistry, Oak Ridge National l,aboratery, Oak Ridge, Tennessee deffery E. I larris, M.D., Ph.D., Associate Professor, Department of Econo,ni~.~, Massachusetts Institute of Technology, Cambridge, Massachusetts Millicent lliggins, M.D., Associate Director, Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Takeshi 1 lirnyama, M.D., Director, Institute of Preventive Oncology, Shinju ku-ku, Tokyo, Japan Dwight Jam:rich, D.D.S., M.P.H., Department of Epidemiology and Public H~,alth, Yale University Sehtml of Medicine, New Haven, Connecticut Martin Jarvis, M.P.H., Senior Clinical Psychologist, Addiction Research Unit, Institute of Psychiatry, London, England, United Kingdom Brian P. L~,aderer, Ph.D., M.P.H., Associate Fellow, John B. Pierce Foundation Laboratory, Associate Professor, Department of Epide. miology and Public Health, Yale University School of Medicine, New llaven, Connecticut Charles L. I,eMaistre, M.D., President, University of Tex~s Systems Cancer C~'nter, Houston, Texas Claude I,enl'ant, M.D., Director, National Heart, Lung, and Bloo~l Institute, National Institutes of Health, Bethesda, Maryland r7 Donald Inn Macdonald, M.D., Administrator, Alcohol, Drug Abuse, and Menial Health Administration, Rockville, Maryland James S. Marks, M.D., M.P.H., Assistant Director for Science, Center for llcalth Promotion and Education, Centers for Disease Control, Atlanta, (;eorgia James O. l~lason, M.D., Dr.P.H.,Director, Centers for Disease Con- trol, Atlm=ta, Georgia xv
Page 8: TI07870618
J. Michael McGinnis, M.D., Deputy Assistant Secretary for Health (Disease Prevention and Health Promotion], Office of the Assistant Secretary for Health, Washington, D.C. A. J. McMichnel, M.I)., M.B.B.S., Ph.D., Uhairman and Senior Principal Research Scientist, CSIRO Division of Iluman Nu[rRion, Adelaide, Seuth Australia D. J. Moschandreas, Ph.D., Research Director, !'1"~ Research tote, Chicago, Illinois David Muir, M.D., Director, ~cnpational Heallh Progrmn, Health ~iences ~nter, ~cMaster University, llamilten, Ontario, Cann- da Richard Pete, M.A., M.Sc., !.C.R.F., ReguJs Assessor oF Medicine, Radcliffe Infirmary, University of Oxlbrd, Oxford, England, Unit- ed Kingdom Otto Raabe, M.D., La~ratory for ~nergy Related Health R~arch, University of California, Davis, Davis, California James L. Repace, Chief' of T~hnical Services, Ind~r Air Quality Program, U.S. Environmen~l Protection Ageucy, Washing~n, M.A.II. Russell, F.R.C.P., Addiction Research Unit, ]nstRu~ of Psychiatry, University or ~ndon, ~ndon, England, Unit~ Kin~- Roy J. Shepherd, M.D., Ph.D., Director, School of PIwsieal and Health Education, UniversRy of Toronte, Toronto, Canada Frank E. Speizer, M,D., Channin8 ~borateries, Harvard Medi~l ~hool, 9os~on, Massachuset~ Jesse L. Stein[eld, M.D., President, Medical College of Georgia, Augusta, Georgia David N. Sundwall, M.D., Administrator, HeaRh Re~urcesaml Services Administration, R~kville, Maryland Gregory W. Traynor, S~ff ~ien~is~, ~wrence Berkeley l~ratary, Berkeley, California DimRrios Trieho~ulos, Dir~ter, Department of.Hygiene and Epide- miology, School of Medicine, University of Athens, A~bena, Grebe Kenneth E. Warner, Ph.D.~ PreCeder, and Chairman, ~par~men~ Public Health Policy and Administration, School ot Public Health, The Unive~ity of Michigan, Ann Arbor, Michigan Erns~ L. Wynder, M.D., PresidenL American Health Foundation, New York, New York 'James B. Wyn~aarden, M.D., Director, National Institutes of Health, Be~hesda, Maryland Frank E. Young, M.D., ~mmissioner, Food and Dru~ Adminis~ra- ~ion, Rockvillo, Maryhmd The editors also acknowledge ~he contributions of the following staff members and oth=~rs who assisted in tl~e preparation of this Report. xvi Erica W. Adams, Chief Copy Editor and Assistant Production Manager, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Marylar~d Richard H. Amacher, Director, llealth and Natural Resources Depertment, Sterling Software, Inc., Rockville, Maryland Margaret L. Anglln, Secretary, Office on Smoking and Health, Rockville, Maryland John L. llagrosky, Associate Director for Program Operations, Office . on Smoking and Health, Rockville, Maryland Charles A. Brown, Programmer, Automation and Technical Services Deportment, Sterling Software, Inc., Rockville, Maryland' Clarice D. Brown, Statistician, Office on Smoking and Iiealth, Rock ville, Maryland • Richard C. Brubaker, Information Specialist, Health and Natural Resources Department, Sterling Software, Inc,, Rockville, Mary- land Catherine E. Burckhardt, Secretary, Office on Smoking and Health, Rockville, Maryland Joanna I~. Crichton, Copy Editor, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Stephauie D. DeVoe, Programmer, Automation and Technical Services I k:partment, Sterling Software, Inc., Rockville, Maryland Danny A. Goodman, Information Specialist, llealth and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Patricia E. Healy, Technical Information Specialist, Office' on Smoking and Health, Rockville, Maryland Terri L. Henry, Clerk-Typist, Offica on Smoking and Health, Roekville, Maryland Timothy K. Hensley, Technical Publications Writer, Offic.e on Smoking nnd Health, Rockville, Maryland Shirley K. llickman, Data Entry Operator, Health and Natural Resources Department, Sterling Software, Inv., Rockville, Mary- land Robert S. llutchings, Associate Director for Information and Pro- grant Development, Office on Smoking and Health, Rockville~ Maryland Maureen lllnr, Editorial Assistant, Office on Smoking and Health, Rockville, Maryland Julie i{m~, Graphic Artist, Information Center Management De- partment, Sterling Software, Inc., Rockville, Maryland Ruth C. I'nhner, Secretary, Office on Smoking and Health, Rockville, Maryhmd Jeromv A. l'aulson, M.D., Medical Officer, Office on Smoking and Health, R~ekville, Maryland xvii
Page 9: TI07870619
Russell D. Peek, Library Acquisitions Specialist, Ileaith and Natnral Resources Department, Sterling Software, Inc., Rockville, Mary- land Margaret E. Pickerel, Public |nformation and Publications Special-ist, Office on Smoking a.nd liealth, Rockviile, Maryland Raymond K. Poole, Production Coordinator, Health aud Natural Resources Department, SLerling Software, Inc., Rockville, Mary- land Linda R, Spiegelman, AdministraLive Officer, Office on Smoking and HealLh, Rockville, Maryland l~velyn L. Swarr, AdminisLraLive Secretary, Automation and Techni- cal Services DeparLmunt, Sterling SofLware, inc., Rockviile, Mary- land Debra C. Tats, Publications Systems Specialist, Publishing Systems Division, Sterling Software, Inc., Riverdale, M.aryland" Jerry W. Vaugbn, Pregrammer, University of California, San Diego, San Diego, California Mary !. Waiz,.Computcr Systems Analyst, Office on Snmking and Health, Rockville, Maryland Louise O. Wiscman, Technical lnformaLJon Specialist, Office on • Smoking and Health, Ro~kville, Maryland Pamela Zuniga, Secretary, University of California, San Diego, San Diego, California xviii TABLE OF CONTENTS Foreword .............................................................. vii Preface .................................................................. ix Acknowledg~nents .................................................. Xll! 1. lntroduction~ Overview, and Summary and Coaclusions ........................................................ 1 2. ltealth l,~ffects of Environmental Tobacco Smoke Ex- Ix)sure ............................................................. 17 3. Enviromnental Tobacco Smoke Che=nistry and Expo- sures of Nonsmokers ........................................ 119 4. Del~mil.ion and Absorption of Tobacco Smoke Constit- uents .............................................................. 175 5. Toxicity, Acute Irritant Effects, and Carcinegenicity of Eavlronmental Tobacco Smoke ....................... 223 6. Policies Restricting Smoking in Public Places and the Workphtce ....................................................... 2159
Page 10: TI07870620
CHAPTER 1 INTRODUCTION, OVERVIEW, AND SUMMARY AND CONCLUSIONS
Page 11: TI07870621
CONTENTS Introducti.n ~Jevelopment and Organization of the 1986 Report 'Overview Enviro~mlental Tobacco Smoke Constitutents Extent of Exposure Lung (,~ancer llespir~tory Disease Cardiovascular Disease Irritation Determinan~ of Ex~sure Pelici~'s Restricting Smoking Summary and Conclusions of the 1986 Report llealth Effects of Environmental Tobacco Smoke Exp.sure F, nvironmental Tobacco Smoke Chemistry and Exls~sures of Nonsmokers Deposition and Absorption of Tobacco Smoke Constit- ttenl.~ q oxtcdy, Acute Irritant Effects, and Carcinogenicity of E,wironmental Tobacco Smoke Polici~,.~ Restricting Smoking in Public Places and the Workplace
Page 12: TI07870622
Introduction Development and Organization of the 1986 Report The 1986 Iteport was developed by the Office on Smoking and Health of the U.S. Dej~artment of llealth and iluman Services as part o1" the L~partment's responsibility, under Public Law 91-222, to report ~ew nud current information on smoking and health to the United Staten Congress. The scientific content of this Report reflects tile contributions of more than {10 scientists representing a variety of disciplines. Individual nmnuscripts were written by experts known for their understandi,lg of and work in specific content areas. These manu- scripts were ~'efined through a series or" meetings attended by the autho~, Offh:e on Smoking Health staff and consultants, and the Surgeon Gem,ral. Upon receipt of the final manuscripts from the authors, the Office and its conBnltants edited and consolidated the individual manu- scripts ini~ appropriate chapters. These draft chapters were subjec- ted to nn exlensive outside peer review (see Acknowledgments for individuals a,td their affiliations) whereby each was reviewed by up to seven eXl,;rts. Their comments were integrated and the entire volume was assembled. This revised edition of .the Report was resubjected I.o review by 17 distinguished scientists outside the Federal (]ow,rnment, both in this country sad abroad. Parallel to this review, the entire' Report was also submitted to various institut~ mtd agencies within the U.S. Public Health Service for review and c~mment. The ]986 Report contains a Foreword by the Assistant Secretary for Health, a Preface by the Surgeon General of the U.S. Publiv Health Service, and the following chapters: Chapter t.'lntroduction, Overview, and Summary and Conclu- sions Chapter 2. Health Effects of Environmental Tobacco Smoke Exposure Chapte.r 3. Environmental Tobacco Smoke Chemistry and Expo- sures of Nons~nokers Chapter 4. Deposition and Absorption of Tobacco Smoke Constit. uents Chapter 5. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke Chapter 6. Policies Restricting Smoking in Public Places and the Workplace Overview lnhalalion of tobacco smoke during active cigarette smoldng remains the largest single preventable cause of death and disability
Page 13: TI07870623
for the U.8. populatim~. The health consequences of cigaretle smoking and of the u~e of other tobacco producl8 h~we heen exlensively documented in the 17 previous Repor~ in lhe he~llh consequences of smoki,~g series issued by the U,S. Public Health Service. Cigarette smoking is a major cause of cancer; it is m~t strm~gly ~ssoci~ted with c~ncers of the hmg m~d respireto~T tract, but also causes cnncer~ at other sites, including the pancreas and urinnry bladder. It is the single greatest cause.of chronic obstructive lung diseases. It ~uses cardiovascular diseases, including coronary henri disesse, aortic aneurysm, and atber~lerotic ~ripheral v~scular disevse. Maternal cigarette smoking endangers fetal and neonatal healih; it co~tributes to perinatal mortality, low birth weight, and complications during pregnancy, More than 3~,~ premature deaths ~cnr in the United States each year that are directly attributeble to tobacco use, particularly cigarette smoking. This Report examines in detail th~ scientific evidence on involun- tary smoking as a l~tentiel cause of disease in nonsmokers. Nonsmokbrs' ex~sure to enviromnm~tal tobacco smoke is termed involm~tury smokln~ in this Report because the ex~ure generally occurs as an nnavoidable consequence of being in proximity I.o smokers, partk'ularly in encl~ed indoor environment. The term "lmssive smokit~g" is else used throughout the scientific literature I~ describe this ex~sure. The magnitude or the disease risks fur active smokers secondary to their "high dose" expos~lre to tobacco smoke sugges~ that the "lnwer dose" exposure to tobacco smoke received by involun~ry smokers nmy also have risks. Although the risks of involuntary smnking are smaller titan the risks of active smoking, the humor o[ individuals injured by involuntmT smoking is large both in ab~lute terms and in comparison with the numlmr injured by some other agen~ in the generol environment that are regulated to curtail their ~tenthd to cuuse hunmn illness. This Re~rt reviews the evidence on the chnruc~ristics of main- slreum tobacco smoke ~md of" environmental tolmcco snm~e, o~ the levels of exposure to environmental tobacco smoke that ~cur, ~nd on the health effects of involunlmT exposure to tobacco smoke. The composition of the tobacco smoke inhaled by ~ctive smokm~ and by involuntary smokers is examined for similm-il.ies and differences, and the concentrations of tobacvo smoke coml~nenLs that ~n ~ measured in ~ v~riety ol'settlngs are vxplored, ~s is smoke de~ition and absorption in the r(~pira~ry tract. The studies that descri~ the risks of environmental tobacco smoke exp~ure for humans are c~welhlly reviewed for their findings and their validity. The evidence o~t the health el'fec~ of involuntary smoking is rev{ew~ for biologic I~lausibility, and compared with extra,lotions of the risks of active stnoki=lg I,o Ihc lower dose o1' exposure to tob==cco .~mt~ke round in oonsmokcr~;. This review leads to three major conclusions: Involuntary smoking is a cause of disease, includir~ lultg cancer, in healthy ==onsmokers. 2. 'l'h~, chihlreu of ~aren~ who smoke compm'ed with thv chihlren of mmsmokiug parents have an increased frequency or respiratory infections, increased respira. tory symptoms, and slightly smaller ='ares of increase iu ' hmg fu==ction as the lung matures. 3. The. simple'separatlon of smokers and nonsmokers wi~hln the same air space may reduce, but does not eliminate, the exposure of nonsmohers to environmen. tal tobacco smoke. The sub~,.quent chapters of this volume describe in detail the evidenct, tlmt supp~r~ these conclusions; the evidence is briefly summarized here. lmporl.:~H consider~tions in ex~mining the risks of involuntary smoking ~n'~, the comlmsition of environmental tobacco smoke (BTS) and ils toxicity and carcinog~nicity relative to the tobacco smoke inhaled by ~ctive smolcers. Mainstream cigarette smoke is ghe smoke drawn I.Itr~=~h the tobacco into the smoker's mouth. SidesLreum smoke is the smoke emitted ~y the burning tobacco between puffs, Envirname~,tal tobacco smoke resul~ from the combination o~ s.idestremn smoke and the fraction of exhaled nminstream smoke not retained hy the smoker. In contrast with mainstream smoke, ETS is diluted inb, ~] larger volume of air, and it ages prior to inhalation, The c~mq~=wison or the chemical composition of the smoke inhaled by activ~ smokers with that inhaled by involuntary smokers suggests that the iConic and carcinogenic el'fec~ are qualitatively similar, a similarity that is not too surprising ~cause both mainstream qmoke and envir~mrnentul tobacco smoke resait ~rom the combustion of tobacco. Individual mainstream smoke constituent, with appropri- ate testing, hove usually been found in sidestream sfnoke as well. However, di/'l~rences between sidestream smoke and maJnstrea~ smoke Imw, heen well documented. The tem~rature of combustion during side.stream smoke formation is lower than during main. stream smolce formation. As a result, greater nmoun~ of many of the organic co~tstituen~ of smoke, including some carcinogens, are genernted when tobacco burns and forms sidestream smoke than wheo mainstream smoke is pr~uced. For example, in contrast with mainstream smoke, sidestream smoke confine greater a~o~l~ of ammenia, benzene, carbon monoxide, nicotine, and the varcinogens
Page 14: TI07870624
2-napthylamine, 4-aminobiphenyl, N-tdtrosamine, benzla]- anthracene, and benzo-pyrene per milligram o~" tobacco burned. Although only limited bioassay data comparing mainstream smoke and sidestream smoke are available, one study has suggested titat sidestrea=zi smoke may be more carcinogenic. Extent of Exposure Although sidestream smoke and mainstream smoke differ some- what qualitatively, the differing quantitative doses of smoke compo- nents inhaled by the active smoker and by the involuntary smoker are of greater importance in considering the risks of the two exposures. A number of different markers for tobacco smoke exposure and absorption have been identified for both active and involuntary smoking. No single marker quantifies, with precision, the exposure to each of the smoke i:onstituents over the wide ra)kge of environmental settings in which involuntary smoking occurs. However, in enviromnents without other significant sources of dust, respirable suspended particulate levels (RSP} can be used as a marker of smoke exposure. Levels of nicotine a~d its metabolite cotinine in body fluids provide a sensitive and specific indication o1" recent whole smoke expo.aure under most conditiok~s. Widely varying levels of environmental tobacco sn,oke can be measured in the home and other environments t=si~=g n,arkers. The time-activity patterns o~ nonsmokers, which indicate the time spent in environments containing El'S, also vary widely. Tiros, the extent of exposure to ETS is probably highly variable amo,~g individuals at a given point in time, and little is known about the variation in' exposure of the same individual at different points in time. Lung Cancer The American Cancer Society estimates that Ihere will be more than 135,000 deaths ft'om lung cancer.in the United StarLet in 19~6, and 85 percent of these hmg cancer deaths are directly attributable to active cigarette smoking. Therefore, eve~ if the ~umber of lung cancer deaths caused by involuntary smoki~g were much smaller .than the number of lung cancer deaths caused by ~ctive smok.ing, the number of lung cancer deaths attributable to invohu~tttry expost~re would still represent a problem of sufficient magnitude, to warrant substantial public health concern. Exposure to environmental tobacco smoke has b~cn ~:xnmined in numerous recent epidemio|ogical studies ~s a risk factor for lung cancer in nonsmokers. These studies have compared Ihe risks subjects exposed Lo ~'l~J nt home or at work with the risks for people not reported to be exposed in these environ,uent~. Bccatlse exposure to I~IPS is an almost universal experieuce in tl,e more developed countries, these ~tudies involve comparison u[ more exposed and exposed pool,le, rather than compurison of exposed and unexposed people. Thus, the studies are inherently conservative in assessing the • conseque,~ce, of exposure to ETS. Interpretation of these studies must consider the extent to which Populations with different ~I'S exposures hnve been identified, the gradient in ~ exposure from the lower exlmsure to the .higher exposure groups, and the magni- tude of the increased lung cancer risk that results from the gradient in BTS expoHure. To date, questionnaires have been used to classify ]b--~S exposure, Quantifiesti~m of exposure by questionnaire, particularly lifetime exposure, is difficult and has not been validated, floweret, spousal and parental smoking status identify individuals with different levels of eXl~mure to E'I~J. Therefore, investigation has focused on the children anti nonsmoking spouses of smokers, groups for whom greater i,~-~S exposure would be expected and for whom increased nicotine absorptim; has been documented relative to the children and nonmaoklng spouses of nonsmokers. Of the epidemiol.ogic studies reviewed in this Report that have examined the question of involuntary smoking's association with lung concer, most (11 of 13) have shown u positive association with exposure, a,kd in 6 the association reached statistical significance, Given the difficulty in identifying groups with differing ETS, exposure, the low-dose range of exposure examined, 'and the small numbers of subjects in some series, it is not surprising that some studies have found no assotiation and that in others the association did not reach a conventional level of statistical significance, The question is ~mt whether cigarette smoke can cause lung cancer; that question ha~ been answered unequivocally by examining the evi. dance for active smoking. The question is, rather, can tobacco smoke at a lower dt~e and through a different mode of exposure cause lung cancer in nonsmokers? The answer must be sought "in the coherence and trends of the epidemiologie evidence available on this low-dose exposure to a known human carcinogen. In general, those studies with larger population sizes, more carefully validated diagnosis of lung cnncor, and more careful assessment of ~ exposure status have shown statistically significant associations. A number of these studies have demonstrated a dose-response relationship between the level of I~I'S exposure and lung cancer risk. By using data on nicotine abserptiuu hy the nonsmoker, the nonsmoker's risk of developing lung ca~,cor observed in human epldemiologic studies can be compare~l with the level of risk expected from an extrapolation of the dose-rcslmn~e data for the active smoker. This extrapolation yields estimates, of an expected lung cancer risk that approximate the obserw:d luttg cancer risk in epidemiologic studies o1" involuntary smoking.
Page 15: TI07870625
Cigarette smoke is well established ~.s a hum:u! carcinogen. The chemical composition of l~-"rs is qualitatively similar to mainstream smoke and sidestream smoke and also acts as a carcinogen in bioassay systems. For many nonsmokers, the quantitative exposure to ETS is large enough to expect an increased risk of lung cancer to occur, and epidemiologic studies have demonstrated an increased lung cancer risk with involuntary ~moking. in examining a low-&~e exposure to a known carcinogen, it is rare to have such an abundance of evidence on which to make o judgment, and given this abundance of evidence, a clear judgment can now be made: exposure to ETS is a cause of lung cancer. The data presented in this Report establish that a substantial number of the iuug cancer deaths that occur amoag nonsmokers can be attributed to involuntary smoking, llowever, better data on rite extent and variability of E-~I'S exposure are needed to estimate the number of deaths with confidence. Respiratory Disease Acute and chronic respiratory diseases have also been linked to involuntary exposure to tobacco smoke; the evidence is strongest in infants, During the first 2 years of life, infants of parent~ who smoke are more likely than infants of nonsmoking parents to be hospi~d- lzed for bronchitis and pneumonia. Children whoc~, pareuts smoke also develop respiratory symptoms more frequently, and they show small, but measurable, differences on tests of lung function when compared with children of nonemoking parents. Respiratory infections in young children represent a direct health burden for the children and their parents; moreover, these infec- tions, and the reductions in pulmonary function found in the school- age children of smokers, may lacrosse susceptibility to develop lung disease as an adult. Several studies have reported small decrements in the average level of lung function in nonsmoking adults exp~ed to I~I'S. These differences may represent a response of the lung to chronic exposure to the irritants in ETS, but it seems unlikely that I~I~S exposure, by itself, is responsible for a sub~tsntial number of cases of clinically significant chronic obstructive lung disease. The small magnitude of the changes associated with ETS exposure suggest~ that only individuals with unusual susceptibility would be at risk of develop- ing clinically evident disease from ETS exposure alone. However, ETS exposure may be a factor that contributes to the development of clinical disease in individuals with other causes of lung injury. Cardiovascular Disease A few studies have exmnined the relationship between involun- tsry smoking and cardiow~scular disease, but no firm conclusion on lO the relationship can be ~nade owing to the limited number of deaths in the studies. Irritatinn Perhaps the: most common effect of tobacco smoke exposure is tissue irrltalion. The eyes appear to be especially sensitive to irritation by ~I'S, but the 'nose, throat, and airway may also be affected by smoke exposure. Irritation has been demonstrated to occur at levels that are similar to those found in real-life situations, The lew;I of irritation increases with an increasing concentration of smoke and dm'a~.ion of exposure, in addition, participants in surveys rapport irritation and annoyance due to smoke in the environment under real-lib" situations. Determinants of Exposure Exposure {. ETS has been documented to be .common in the United States, but additional data on the extent and determinants of exposure m'~ needed to identify individuals within the population who have the highest exposure and are at greatest risk, Studies with biologicnl nu|rkers and measurements of ETS components in indoor air confirm Ihat measurable exposure to ETS is widespread. How- ever, withi,~ ~:xposed p~pulations, levels of cotinine excretion and presunmbly I,',TS exposu re vary greatly. in a r~mm or other indoor area, the size of the space, the number of smokers, tbe ~mmunt of ventilation, and other factors determine the concentration of tobacco smoke in the air. The technology for the cost-effective liltration of tobacco smoke from the air is not currently available, and because of their small size, the smoke particles remain suspended in the air for long periods of time; thus, the only way to remove smoke from indoor air is to increase the exchange of indoor air with clem~ outdoor air. The number of air c|/anges per hour required to maintain acceptable indoor air quality is much higher when smoking is allowed than when smoking is prohibited. Environnwntal tobacco smoke originates at the lighted tip of the cigarette, and exposure t~ ETS is greatest in close proximity to the smoker. I lowcver, the smoke rapidly disseminates throughout any airspace conl.iguous with the space in which the smoking is taking place. Dissemination of smoke is not uniform, and substantial gradients in I,;TS levels have been demonstrated in different parts of the same air~pace. The time course of tobacco smoke dissemination is rapid end,ugh to ensure the spread of smol~e throughout an airspace witl,in an 8-hour workday. In the home, the presence of even oae smoker can significantly increase levels of respirable suspended p~rticulates. These dater lead to the conclusion that the simple separation, of smokers and nonsmoker~ within the same airspace will reduce, but 11
Page 16: TI07870626
not eliminate, exposure to ETS, particularly in those settings where exposure is prolonged, such as the working environment. The exposure of an individual nonsmoker to E"['S is also deter- mined by that person's time-activity pattern; that is, the mnount nf time spent in various locations. For adults, the duration of time spent in smoke-contaminated environments at work or at home is the principal determinant of ETI'S exposure, along with the levels of smoke in those enviromnents. For infants and very young children, the smoking habit of the primary caretaker, as well as that person's time-activity pattern, is likely to play a major role in determining E-~I'S exposu re.. Policies Restricting Smoking Policies regulating cigarette smoking with the objective of reduc- ing explosion or fire risk, or. of safeguarding the quality of manufac- tured products, have been in force in a number of States sinde the late 1800s. More ~cently, and with steadily increasing frequency, policies regulating smoking on the basis of the health risk or the irritation of involuntary smoking bays been promulgated. State and local governn|ents have enacted laws and regulations restricting smoking in public places. These policies have been implemented with few problems and at little cost to the respective governments. The public awareness of these policies that results from the media coverage surrounding their impleme'ntation proba- bly facilitates.their self-enlbrcoment. Public awareness may best be fostered by encouraging the establishment of these changes at the local level. Policies limiting smoking in tl~e worksite have also become increasingly widespread and more restrictive. However, changes worksite policies have evolved largely through voluntary ra~her than governmental action. In a steadily increasing number of worksites, smoking has been prohibited complelely or limited to relatively few areas within the worksite. The creation of u smoke- free workplace has proceeded successfully when the policy has been jointly developed by emph~yees, employee organizations, and man- agement; instituted in phases; and accompanied by support and assistance for the smokers to quit mnoking. This tread to protect nonsmokers from I~T['S exposure ~nny have an added public health benefit--helping those smokers who are tempting to quit to be more successful and not encouraging smoking by people enteri,~g the workforce. Summary and Conclusions of the 1986 Report The three major conclusi~ms of this report are the following: 12 1. lnwduntary smoking is a cause of disease, including hmg cancer, in healthy nonsmokers. 2. The children of parents who smoke compared with the chihlren of nonsmoking parents have an increased f=;equency of respiratory infections, increased respira- tory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. The simple separation of smokers and nonsmoke~ within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to environmen- tal tobacco smoke. Individual chapter summaries and conclusions follow. Health Effects of Environmental Tobacco Smoke Exposure I. Involunlary smoking can cause lung cancer in, nonsmokers, 2. Althoul;h a substantial number of the lung cancers that occur in nonmnokers can be attributed to involuntary smoking, more data ou the dose and distribution of EYI'S exposure in the population are needed in order to accurately estimate the magnitude of risk in the U.S. population. 3. The children of parents who mnoke have an increased frequen- cy of h¢~pitalization for bronchitis and pneumonia during the fh'st ye~,r of life when compared with lhe children of nonsmok- er,~. 4. The children of parents who smoke have an increased frequen- cy of a variety of acute respiratory illnesses and infect[one, includiz,g chest illnesses befor.e 2 years of age and physician- dingnosc~! bronchitis, tracheitis, and laryngitis, when com. pa='ed with the children of nonsmokers. 5. Chronic cough aud phlegm are more frequent in children who.~e parents smoke compared with children of nonsmokers, The imldications of chronic respiratory symptoms for respira- tory he~tlth as an adult are (mknown and deserve further study. 6. The children of parents who smoke have small differences in t~tu of pulmonary function when compared with the childretl of nonmnokers. Although this decrement is insufficient to cause symptoms, the possibility thai; it may increase suscepti- bility to chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., active smoking or occupation- al expo.~ures, needs investigation. 7. H=:althy adults exposed to'environmental tobacco smoke may bays m!,all changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmo- 13
Page 17: TI07870627
nary function as a result of exposure to environmental tobacco smoke alone. ' 8. A number of studies report that chronic middle ear effusions are more common in young children whose parents smoke Lhau in children of nonsmoking parents. 9. Validated qnesLionnaires are needed for the asse~ment of recent and remote exposure to environmen .tpl tobacco smoke in the home, workplace, and other envlronmenL~. 10. The associations between cancers, other than cancer of the lung, and involuntary smoking require further investigation before a determination can be made about the relationship of involuntary smoking to these caacers. ll. Further studies on the relationship between involuntary smoking and cardiovascular disease are needed in order to determine whether i,lvoluntary smoking increases the risk of cardiovascular disease. Environmental Tobacco Smoke Chemistry and Exposures of Nonsmolcers 1. Undiluted sidestream smoke is characterized by significantly higher concentrations of many of the toxic and carcinogenic compounds found in mainstream smoke, including ammonia, volatile amines, volatile nitrosamine~, certain nicotine decom- position products, and aromatic amines. 2. Environmental tobacco smoke can be a substantial contributor to tile level of indoor air pollution concentrations or resplrable particles, benzene, acrolein, N-nitrosamine, pyrene, and carbon monoxide. ETS is the only source of nicotine and some N- nitrosamine compounds in the general envlroament. 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to environmental tobacco smoke. Exposures to ETS occur widely in the non- smoking population. 4. The small particle size of environmental tobacco smoke places it in the diffusion-controlled regime of movement in air for deposition and removal mechanisms. Because these submicron particles will follow air streams, convective currents will dominate and tile distribution of ETS will occur rapidly through the volume of a room. As a result, the simple separation of smokers and nonsmokers within the santo airspace may reduce, but will not elimiaate, exposure to ETS. 5. it has been demonstrated that Ig]'S has resulted in elevated resp, lrable suspended particulate levels in enclosed places. 14 Deposition ~,nd Absorption of Tobacco Smoke Constituents 1. Absorpl ion of tobacco-specific mnok~ constituents (i.e., nicotine) fr~m~ e~,vironmental tobacco smoke exlu,sures bus been docu- m~mted in a number of samples of the general ~pulation of develol,'d countries, suggesting that measurable ex~sure to envirm~nental tobacc~ mnoke is coffimofl. 2. Mean h,vels of nicotine and cotinine in b~y fluids increase with sell:reported I~FS exposure. 3. Bccuusv or the s~bility of cotlnine levels measured at dlfferen~ timcs dm'ing exposure and the availability of naninvaslve sampling techniques, cotinine appears to be the short-term marker of choice in epidemiological studies. 4. Both matl~ematicai m~eling t~hniques and ex~rimental da~ suggest tlmt 10 to 20 ~rcent o[ the particulate fraction of sidestream smoke would .~ de~it~ in the airway. 5. The development of s~cific chemical a~ays for human exp~ sure t~ the componen~ or cigaret~ ~r is an im~rtan~ resear¢'h goal. Toxicity, Acute Irritant Effects, and Carcinogenlclty of Environmental Tobacco Smoke 1. The m=dn effec~ of the Jrri~n~ present in ~S ~cur in the coujum'tiva of the eyes and the mucous membranes of the nose~ thr, mt, nnd lower respiratory tract The~ irritant effec~ are a frequent cause of complain~ a~ut ~r air quality due to enviro==mental tobacco smoke. 2. Active cigaret~ smoking is ass~iated with ~romlnent changes in the nmnber, ty~, and function of r~piratory epithelial and inflammatory cells; the ~tentiai for environmen~l tobacco mnoke ~xposure to pr~uce similar changes should be investi- gated. 3. Aninml models have demonstrated the carcinogencJty of clga- felts smoke, and the limit~ da~ that exist suggest that more carcim~genic activity ~r milligram of cigarette smoke concen- trate may be con~in~ in sid~tream smoke than in main- stream cigarette smoke. Policies Restricting Smoking in Public Places and the Workplace 1. Beginning in the W7~, an increasing number of public and privah, sector institutions have adopted policies to protect individuals from environmen~l tobacco smoke exposure by rcstricling the circumstanc~ in which smoking is permitted, 2. Smoki.g in public places h=m ~en regulated primarily by government actions, which have ~curred at Federal~ State~
Page 18: TI07870628
and local levels. Ail but nine States have enacted laws regulating smoking in at least one lmblic place. Since the mid- 1970s, there has beelt an increase in the rate of enactment a~d in the comprehensiveness of State legislation. Local goverw monte have enacted smoking ordinances at a~ iacreasing rate since 1980; more thau 80 cities and counties have smoking laws in effect. 3. Smoking at the workplace is regulated by a combiuation of government action and private initiative. Legislation in 12 States regulates smuking by government employees, and 9 States and more timer 70 communities regulate smoking in the private sector workplace. Approximately 35 percent of busi- nesses have adopted smoking policies. The lacrosse in work- place smoking policies has been a trend of the 1980s. 4. Smoking policies muy have multiple effects. In ~tddition to reducing environme~tal tobacco smoke exl~osqre, tl,ey may alter smoking behavior and public attiLtzdes about tobzzcco use. Over time, this may contribute to a reductio~z in smoki,zg in the United States. To the present, there Ires beezz relatively little systematic evaluatiozz o[ policies restricting smoking in public places or at the workplace, 6. On the basis of case e'eports and a tonsil number of systematic studies, it appears thnt workplace smoking l~olicies iznprove air quality, are met with good compliance, and are well nccepted by both smokers and nonsmokers. Policibs appear to be followed by a decrease in smokers' cigarette consumption at work and an increase in enrollment in coml~any-sponsored smoking cesszttion programs. 6. Laws restricting sm~king in public places I~ve bcezz imple- mented with few problems and at little cost to State and local government. Their impact on smoking behavior aml attitudes has not yet been evaluated. 7. Public opinion polls document strong and growizzg support for restricting or banning smoking in a wide range of public places. Changes in attitudes about smoking in Imblic appe~zr to have preceded legislation, but the interrelaLionshil~ of smoking attitudes, behavior,.aetd legislation are complex. 16 CHAPTER 2 I IEALTH EFFECTS OF ENV IRONMENTAL TOBACCO SMOKE EXPOSURE
Page 19: TI07870629
CONTENTS ' Introductio~ Evaluation ~f Low-Dose Tobacco Smoke Exposures Extrapolation of Active Smoking Data to Envlron- ment~d 'robaeeo Smoke Exposure Comparison of Mainstream Smoke and Side- stream Smoke l)t'posltion of Mainstream Smoke and Side- stream Smoke and Environmental Tobacco Smoke Dose Estimates Do::e-l~esponse Relationships and Threshold for Risk Fathophysiologie Considerations Cllllcer Ltmg Disease Method,dogical Consideration~ in Epidemiologie Studi,,s M~,asurement of Exposure Atmospheric Markers Personal Monitoring t~uestionnaires Mt.asurements o1" Absorption P~d.entiaily Confounding Variables S! ntistical Issues Respiratory System Effects of Involuntary Cigarette Smok~: Exposure Infants and Children A~'ute Respiratory Illness Longitudinal Studies Cross-Sectional Studies Case-Control Studies O~ugll, Phlegm, and Wheezing Pulmonary Function B~ onchoconstriction Enr, Nose, and Throat Adults Acute Respiratory Illness C~ugh, Phlegm, and Wheezing 19
Page 20: TI07870630
Pulmonary Function Bronchocmtstriction Normal Subjects Asthmatics Ear, Nose, and Throat Lung, Cancer Observed Risk General Methodological Issues Spousal Exposure: Prospective Studies The Japanese ~hort Study The American Cancer Society Cohort Study Tile Scottish Sttldy Spousal Exposure: Case-Control Studies The Greek Study The Louisiana Study The Hong Kong Studies An Ongoing Study of Tobacco-Related Cancers The Los Angeles County Study The Four Hospitals Study A United Kingdom Study The Japanese Cus~Control Study The Swedish Study The German Study Other Sources of Tobacco Smoke Exposure Parental Smoking Coworker's Smoking Dose-Response Relationship 'Expected Lung Cancer Risk Summary Other Cancers -.drdiovaseular Diseases Conclusions Rel'erences 2O Introdu¢llon in 1964, the first Report of the Surgeon General on smoking and health (US I'HS 1964) determined tlmt cigarette smoking was a cause o1" lung cancer in men and probably a cause of lung cancer in women, 'llmt Report also noted causal relationships between smok- ing and other cancers, as well as chronic lung disease, Subsequent Reports have described a~sociations, beth causal and noncausal, between tobacco smoking and a wide range o1" acute and chronic diseases. Epidemiological investigations have documented the efl'ecta o1" tobacco s,,toking in humans; complementary laboratory investiga- tions have elucidated some of the mechanisms through which tobacco smoke causes disease. More rect, ntly, the effects of the inhalation of environmental tobacco smoke by nonsmokers have become a pressing public health concern. No=~smokers, as well as active smokers, inhale environmen- tal tobacco smoke, the mixture of sidestream smoke .and exhaled mainstream smoke. Various terms have been applied to the inhala- tion of environmental tobacco smoke by nonsmokers; the terms "invohmtary smoking" and "paSsive smoking" are the most p~:eva- lent and are often used interchangeably by researchers and the public. Many of the known toxic and carcinogenic agents found in' • mainstream cigarette smoke have also been demonstrated to be present in sidestream smoke. Furthermore, the combustion condi- tions under which sidestream smoke is produced result in the generation nf larger amounts o1" many of these toxic and carcinogenic agents per I;ram of tobacco burned than the conditions under which mainstream smoke is generated (see Chapter 3). The characteristics of environmental tobacco smoke also differ from those o/" main- stream smoke because the sidestream smoke ages before it is inhaled and the malustream smoke exhaled by the active smoker is modified during its residence in the lung. There is no evidence to suggest that environmenl.al tobacco smoke has a qualitatively lower toxicity or carcinogenicity than mainstream smoke per milligram of smoke inhaled. In fact, the available evidence suggests that airiest.ream smoke conl~dns higher concentrations of many known toxic and carcim~onic agents per milligram of smoke and is more tumorgenic than mainstream smoke in animal testing (Wynder and Hoffmann 1967). As a result, involuntary smoking should not be viewed as a qualitatively different exposure from active smoking, but rather as a low-dose exposure to a known hazardous agent--cigarette smoke. Evaluation of Low-Dose Tobacco Smoke Exposures Ass~ssmc~t of the healt)~ effecl~ of any environments] exposure poses meLh.dologica| problems, particularly when exposure levels 21
Page 21: TI07870631
are low and therefore tbe m~=gnitude of the expected effect is small. Tile evaluation of an effect due to a" low-dose exposure such ~s environmental tobacco smoke requires the investigation of popu- lations with differences in exposure large enough so that an effect could be anticipated. The population studied must also be of sufficient size to quantitate the effects in the range of interest with precision. Failure to fulfill these requirements may preduce a false- negative result in a study ofn low-dose exposure. Exposure to environmental tobacco smoke is a nearly universal experience in tile more develnped countries, so tile identification era truly unexposed population is very difficult. Epidmnioiogical studies of invol.untary smoking have attempted to identify populations with lower exposure and higher exposure to enviromne==tal tobacco smoke, most notably by examining nonsmokers expesed to tobacco smoke generated by the smokers of their family. The effects of environmental tobacco smoke have been investigated in a number of populations throughnut the world. The diversity of these populations is likely to be accompanied by a similar diversity of their exposure to environmental tobacco smoke. Thus, the gradient in exposure to environmental tobacco smoke betweeu the °'exlmsed" and '°nonex- posed" groups is likely to vary widely among the reported studies. For example, the husband's smoking status may be a strong predictor of total exposure to E'rs in traditional societies, such as Japnn and Greece, where the wife's expiate outside the home is limited, in contrast, the husband's smoking status in the United States, where substantial exposure may occur outside the home, may not be as predictive. Sample size considerations are of particular concern for the epidemiological studies of hmg cancer and ievoluntary smoking. Because the frequency of lung cancer in nonsmokers is low, many of these studies ores included small uumbers of nonsmokers and lacked the statistical Power necessary to find the modest effect expected from this low-dose exposure. Given the constraints of sample size and the varying gradients of exposure, it would be expected that some studies would find no association between involuntary smoking and lung cancer, and that other studies would find associations that lacked statistical significance. Nonuniformity of the data, however, does not imply a lack of effect; rather, it is the coherence and trends of the evidence that 'must be judged. Thus, this Report examines the entire body of evidence on the health effects of involuntary smoking, as the hosis for its conclusions. In evaluating the hazards posed by an air Pollutant such as environmental tobacco smoke, laboratory, toxicological, human exposure, and epidemiologicnl investigations provide relevant data. Each approach has limitatious, but tile insights each provides are complementary. Epidemiological investigations describe the effects 22 in Imman I.~pulati<ms, but their results must be interpreted in tile context ~1" the other types of investigations, Risk ass~,ssment techniques have also been used to characterize the potenti~d adverse health effects of human exposures to envirdh- men~l polh~tants, particularly those at low levels. The four steps of risk assessment have been described by the National Academy of Sciences as Imz~rd identi~cation, dose-response assessment, sxpo~ sure assessment, and risk characl~erization (NAS 1983). Risk assess. meat ires else been used to describe tile consequences of exposure to ETS. l Iowever, unlike many environmental exposures for which risk assessment represents tile only approach for estimating human r|sk, the health ~,flects of ETS exlmsure can be examined directly using epidemiolol;ical methods. Although this Report reviews several risk assessments d~me by individual researchers on ETS, its conclusions are based .~ the labor.story, toxicological, and epidemiological evidence. Extraimlallon of Active Smoking Data to Environmental Tobacco Smoke Exposure Coml~wis(m of Mainstream Smoke and 8idestream Smoke A dehdlcd comparison of mainstream and sidestream smoke can be found in Chapter 3. M~instream smoke (MS) is the term applied to the.complex mixture that is inhaled by the smoker from the mouthpiece, of a cigarette, cigar, or pipe with each puff, Sidestream • smoke (SS) is the aerosol that comes from the burning end of the cigarette, pipe, or cigar between puffs. Enviromnental tobacco smoke (El'S) is tlw term applied to the combination of SS and exhaled MS, which is dilated and aged in an area where smoking has taken place, Most of the: existing dat~ on mainstream and sidestrcam smoke characteristics relate to cigarette smoking and relatively little infornmtlon is available pertaining to cigar and pipe smoking. Because both MS and SS are generated from the tip of the burning tobacco pr.duct, it is not surprising that their compositions are similar. Of the thousands of compounds identified in tobacco smoke, many have been identified as present in both MS and SS. Among these nre cnrcinogens, gases such as carbon monoxide and the oxides of nitrogen, and nicotine. Since there is a wealth of .informaLi.on relating to tile toxicity and carclnogenicity of MS, it should be emphasized again that ETS cannot be treated as a new environmen- tal agent f~w the purpose o~" assessing health risks. The presence of the same agents in MS and SS leads to the conclusion that ETS ha~ a toxic and carcinogenic potential that would not be expect~'d to be qualitatively different from that of MS. Quantitative differences between the: active smoker's exposure to MS and theinvoluntary smoker's exposure to ETS are likely to be the more' important 23
Page 22: TI07870632
determinant of the differing magnitudes of risks associated with these two exposures. Differences in the composition of MS and SS primarily reflect their generation at different temperatures in different oxygen environments. Also, SS is diluted very rapidly, under most circum. stances, and has the opportunity to age before inhalation. The involuntary smoker usually inhales ETS, not SS, the aerosol that comes from the tip of a burning cigarette. In considering the characteristics of SS, it must be emphasized that much of the existing data about the composition of MS and SS is derived from studies carried out in special chambers rather than by sampling MS and SS generated by smokers, in these chamber studies, SS has been sampled by a probe located close to the burning tip. This experimen- tal situation clearly differs from that of a room with one or more smokers freely smoking. In that situation, SS is mixed with exhaled MS, diluted and aged. Nevertheless, these chamber studies provide very useful information about the compounds present in the SS. These studies have established that SS in comparison with MS has ~ higher pH, smaller particle size, and more carbon monoxide, benzene, toluene, acrolein0 acetone, pyridine, ammonia, methyl- amine, nicotine, aniline, cadmium, radon daughters, benzo[aJpyrene and benz[a]anthracene. Comparison of the relative concentrations of the various compo- nents of SS and MS smoke provides limited insights concerning the toxicological potential of ETS in comparison with active smoking. As described above, SS characteristics, as measured in a chamber, do not represent those of ETS, as inhaled by the nonsmoker under nonexporimental conditions. Further, the dose-response relation- ships between specific tobacco smoke components and specific diseases are not sufficiently established for the necessary extrapola- tions from active smoking to environmental tobacco smoke exposure for individual agents. For that reason the extrapolations in this section are confined to the doas-response relationships of wholb smoke for those diseases with established dose-response relation- ships. With regard to the potential of ETS to cause lung cancer, undiluted SS has 20 to 100 times greater concentrations of highly carcinogenic volatile N-nitrosamines than MS (Brunnemann etal. 1978) as well as higher concentrations of bonzopyrenes and benz~aJanthracenes. For nonnmlignant effects on airways and the lung parenchyma, the agents responsible for the development of acute and chronic respiratory disease have not been identified, although many tobacco smoke components have been shown to cause lung injury (US DIIHS 1984). Presumably, both vapor phase (gaseous) and partictdate phase (solid) components o~" MS are involved. Both airways disease and 24 parenchy=nal disease are probably a response to the total burden of respiratory insults, some of which, like active smoking, may be sufficient by themselves to cause physiologic impairment and ultimately, clinical disease. Others, such as ~-WS, may contribute to the total burden but be insufficient, individually, to cause clinical disease. Deposition of Mainstream Smoke and Side~tream Smoke and Eauironmenlal Tobacco Smoke Dose Estimates The dese of tobacco smoke delivered to the airways and alveoli depends, among other factors, on the volume of MS,. SS, or ETS inhaled, on the rate and depth of inhalation, and on the size, shape, and density of the individual particles or droplets. Patterns of deposition of MS in the lungs have been described, but similar information about deposition patterns for ETS is not yet available, Without such data, it is necessary to extrapolate from the informa- tion on MS. The major factors that affect the pattern of deposition and retention for particle~ are particle size distribution and breathing pattern. The particle size range and mean aerodynamic diameter for particulate~ in sidestream smoke are similar to those of mainstream smoke (particle size range of 0.01 to 0.8 Itm for sidestream smoke and 0.1 to 1.0 itm for mainstream smoke, and mean aerodynamic diameter 0.32 ~tm for sidestream smoke and 0,4 pm for mainstream smoke) (see Chapters' 3 and 4). The deposition "site is determined largely by the size of the particles, with large particles being deposited preferentially in the nasopharynx and large conducting airways. Smaller particles are deposited more peripherally~ and very small particles tend to be exhaled and to have a very low deposition fraction. The particulates of ETS, because of their size range~ are likely to be deposited peripherally. The b~eathing patterns for the inhalation of MS and ETS are al~o different; MS is inhaled intermittently by the smoker with an intense inhalation, often followed by a breathhold that results in a more equal distribution. Environmental tobacco smoke, on the other hand, is inhaled continuously with tidal breaths when the passive smoker is at rest and with deeper inhalations when the passive smoker is physically active. Breathholding does not normally occur with tidal breathing. Estimates of the equivalent exposure, in terms of cigarettes per day, resulting from ETS, as compared with MS, vary quite widely and depend on the way in which the estimates were made. Rei~ace and Lowrey ~1985) estimated that nonsmokers in the United States are exposed to from 0 to 14 mg of tobacco tar (average 1,4 mgl per day. Vutuc {1984) estimated that the exposure to environmental cigarette smoke is equivalent to 0.1 to I cigarette per day actively 25
Page 23: TI07870633
smoked. Estimates of ETS exposure, based on cotinine measure- meats, sugges~ that involuntary smokers absorb about 0.5 to 1 percent of the nicotine that active smokers absorb {Jarvls etal. 1984; Haley and Hoffmann 1985; Wold etal. 1984; Russell et al. 1986). Dose-Response Relationshil~s and Tiweshold for Risk Dose-response relationships for active smoking can provide in- sights into the expected magnitude of disease resulting from the exposure of nonsmokers to E'PS. These data are reviewed to determine whether disease can be expected in association with ETS. Data from cohort and case-control studies demonstrate dose- response relationships for lung cancer, which exte,~d to the lowest levels of reported active smoking. The dose-responss relationship of active smoking with lung cancer risk has been described by several investigators in several different data sets (Whittemore and Altshu- let 1976; Doll and Peta 1978; Pathak et al. 1986). Although the mathematical forms of these models vary, none have included a threshold li~vel of active smoking that must be passed for lung cancer to develop. The dose-response relationship for active smoking and lung cancer has been used to project the lung cancer risk for nonsmokers (Vutuc 1984). Such projections yield risk estimates of 1.03 to 1.36 for exposures, considered to be reasonable estimates of involuntary smoking exposures, i.e., 0.1 to 1.0 cigarettes per day. The reference population for these risk estimates is the risk for nonsmokers as a group, including those with higher and those with lower, exposures to environmental tobacco smoke. In contrast, the reference population • for the risk estimates in studies of involuntary smoking is the lung cancer risk in only that group of nonsmokers who have lower exposure to ETS. Comparisons of lung cancer risk estimates from active smoking studies with those from involuntary smoking studies require reference to the same exposure group for proper interpreta- tion. In general, the lung cancer experience of all nonsmokers (i.e., those with higher and lower involuntary smoking exposure com- bined) has been used to establish the reference rate of lung cancer occurrence (i.e., set as a risk of 1) in studies of active smoking. The use of all nonsmokers as the reference group averages the lower risks of nonsmokers with less ETS exposure with the higher risks those with more ~ exposure. Thus, with the relative risk for the entire group of nonsmokers set to unity, the relative risk for nonsmokers with lower exposure is below 1 and that for the group with higher exposure is above 1. As a consequence, relative risk estimates from studies of involuntary exposure cannot be directly compared with risk estimates extrapolated from active smoking, unless comparison to a single level of exposure is possible. Failure to 26 consider the differences between the reference populations explains the app~wcnt discrepancy noted by Vutuc. Consider, for example, the mortality study reported by HirByama (1981a). In this study, the relative risk of lung cancer for nonsmoking wives of smoking husbands (current and former) compared with nonsmoking wives of nonsmoking husbands (as calculated ['rom Figure I in Hirayama 1981a) was 1.78. If the relative risk for nonsmoking wives of nonsmoking husbands were expressed in relation to the combined group of nonsmoking women, then a value of 0.63 is ~btained, while with a similar calculation, that for nonsmoking wives of smoking husbands (both current and former), yields n value of 1.12. Thus, when the appropriate comparlson is made, ti~e risk estimates developed by extrapolation of the active smoking dat~ (1.03 to 1.36) closely approximate those actually found in a study of lung cancer risk due to involuntary smoking. Dose-resp~mse relationships between active smoking and the level of lung functiou, the rate of decline of lung function in adult life, and the development of chronic airflow obstruction are well established (US DItlIS 1984)~ Different measures of dose have provided the. strongest co,'relation with functional decline in different studies. '. Pack-years, n cumulative dose measure, was the strongest predictor of the level ~f forced expiratory volume in 1 second (FEVd in the Tucson epidemiologic study (Burrows, Knudson, Cline et al. 1977). Duration of smoking and the amount smoked were found to be the best predictors in male subjects in a study of three U.S. communities (Beck et al. 1981), and pack-years was the best predictor in female subjects. In both of these studies, however, the estimated dose accounted fur only about 11~ percent of the variation of age- and height-adjusted FEV, levels. The relatively low predictive capability of cigarette smoking variables in these studies most likely reflects a lack of information on the determinants of individual susceptibility to tobacco smoke. Further, exposure variables obtained by question- naire, such as the number of cigarettes smoked daily, may only roughly approximate the dose delivered to target sites in the respiratory tract. Many factors, such as puff volume, lung volume at which inhabttlon starts, and airways geometry will influence the smoke dose ~md its distribution within the lungs. Extrapolation from the results of these studies to the pulmonary effects of exposure to ETS is, therefore, likely to be inaccurate. Another approach for assessing low-dose exposures is to consider the inform:ttion available from studies involving children and teenagers who have recently taken up smoking. Even with brief smoking experience, cross-sectional studies of active cigarette smok- ing by children and adolescents have demonstrated an increased frequency of respiratory symptoms (Rawbone et al. 1978; Rush 1974; Bewley et ~d. 1973; Seely etal. 1971) and small but statistically 27
Page 24: TI07870634
significant reductions in lung function (Seeiy et al. 1971; Peters and Ferris 1967; Lira 1973; Walter et al. 1974; Backhouse 1975; Woolcock et al, 1984). Longitudinal studies involving children and adolescents have demonstrated that a physiol6gic impairment attributable to smoking may be found in same children by age 14 and may be present after only 1 year of smoking 10 or more cigarettes per week in children with previously ,tormai airways (Woolcock et al. 1984), and that relatively small amounts of cigarette use ,nay |cad to significant effects on FEV, and on the growth of lung function in adolescents (Figure 1) (Tager et al. 1985). When considering the risk of low-dose exposures for the develop- ment o~ chronic respiratory disease, the existence of a spectrum of risk and a distribution o[dosv within the population should be taken into consideration, The characteristics of the part of the population most susceptible to involuutary smoke exposure is still being clarified. Evidence is accumulating that airways hyperrespon- slvene~m, atopy, childhood respiratory illness, and occupational exposures may all influence response to ETS. Current understanding of lung injury suggests that individuals with o,ze or more of these characteristics that place them at the most sensitive end of the susceptibility curve amy be the most likely to develop symptoms or ,~unctionai changes as a result of ETS exposure. Dose d ETS also varies in the population, and the coincidence of high dose and increased susceptibility may convey a particularly high risk. Fur- thermore0 ETS exposure may damage iuugs that are also affected by other insults~ Pathophyslologlc Conslderation~ Cancer Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell with uncontrolled replication. Carcinegenesis hem been conceptualized as a multistage process involving a sequence of alterations in cellular DNA that terminate with the development era malignant cell. Agents acting early in this sequence are referred to as initiators; those acting later are referred to as promoters. Compounds with both initiating activity and promoting activity have been identified in tobacco smoke. Carcinogenesis reflects DNA damage; although some repair may take place, biological models have not suggested that there is a threshold of damage that must be exceeded. Rather, carcinogenesis has been considered to involve a series of changes, each occurring at a rate dependent on the dose of a damaging agent, lligher doses increase the probability that the entire sequence will be completed, but lower doses may also lead to malignancy. 28 I0,000 ~0,000 FIGURE l.--Relationship between levels of predicted for FEV, (A) and FEF.-~s (B) at examination 8 and cumulative number of ctgarette~i smoked during examinations 4 lhrough 8 ~ M~ .~nd w~cmrn c~.binzd iN - 44), 29
Page 25: TI07870635
Lung Disease The noncarcinogenic pathcJphyslologic effects of active smoking on the respiratory tract can be separated into (1) effects on the airways and (2) effects on the lung parenchyma. In the airways, the structural changes include inflamnmtion in the small airways and mucous gland hypertrophy acid hyperplasia. In the parencilyma, the nmin structural change is alveolar wall destruction. Both the airways and the parenchymai changes are caused by active smoking, but the interrelationships of these changes are not clear. They may be independent pathophysiologic processes, linked only by their joint association with tobacco smoking. As discussed earlier, there is evidence showing an approximately linear dose-response relationship between FEVI level and amount mnoked; however, the dase-response relationships have not been as well described for tile underlying pathophysiologic change~ in. the airways or in the lung parenchyma. Host factors and other environ- mental factors presumably interact with active smoking to affect an individual's risk for the development of disease. In this regard, present evidence would suggest that only 10 to 15 percent of smokers develop clinically significant airflow obstruction, although parenchy- real and airways changes can be demonstrated in a substantially higher percentage at autopsy (US DHHS 1984). Extrapolation from the evidence on active smoking to the likely effect of exposure to environmental tobacco smoke on the airways and parenchyma suggests that pathophyslologic effects on beth the airways and the lung parenchyma might be expected. Because the dose o1" smoke components from ETS exposure is small in comparison with the dose from active smoking, the extent of lung injury would most likely also be much smaller than that found in active smokers. Small changes in the lung may be below the threshold for detection on pulmonary function testing. If clinically significant chronic airflow obstruction occurs in nonsmokers exposed to I~,~I'S, tile risk is likely to be concentrated among those individuals highly susceptible to the airway or parenchy[nal effects of cigarette smoke. This susceptible group may include individuals with bronchial hyperre- sponsivene~s and with other, as yet unidentified, genetic and familial risk factors. Identifying the risk factors for susceptibility to the airway and parenchymsl effects of beth mainstream smoke and ETS is an important priority. The d~e of environmental t~bacco smoke received by the nonsmoker is unlikely, by itself, to be sufficient to cause a clinically significant degree of parenchymal disease (em- physema) unless an individual is at the extreme end of the susceptibility distribution. Any particulate load is likely to !ncrease the elastase burden in the lungs by causing an itlflux of neutrophils. However, only in the individual with very inadequate lung defenses, specifically severe deficiency of pretense inhibitor (PD associated 3O with the I'iZZ or ot[~er pbenotypes, are modest particulate exposures likely to il~c~ease the risk for disease to an appreciable extent. The deveb,pment of acute and chronic airway disease or symptoms of cough, pblegm production, and wheeze may require a considerably smaller exp~sure than changes in the lung parenchyma, and it is not unreasonable to hypothesi~ that these symptoms may be related to repeated and continuous exposure to ETS in the susceptible individu- al. Strong evidence that low-dose active smoking causes increased rates of respiratory symptoms and functional impairment comes from the studies of children and adolescents discussed earlier (Wcolcock ctal. 1984; Tager et ai. 1985). Because of the length of exposure, it is likely that these reflect airway rather than parenchy- real effects. Another patbophysiological mechanism by which exposure to ETS may increase an individual's risk for the development of chronic airflow obstruction is through respiratory viral infections. Mounting evidence indicates that the. very young child (under 2 years of age) exposed to I,',TS is at increased risk for lower respiratory tract viral infections (l larlap and Davies 1974; Colley 1974; Colley et al. 1974; Leader et al. 1976a; Fergusson et al. 1981; Dutau et al. 1979; Pedreira et al. 1985~. There is also increasing, though still inconclusive, epidemiologic evidence that respiratory viral infections in early life may be associated with an accelerated decline in FEV~ and, theref(~re, a,l increased risk for the development of chronic airflow obstruction in adult life in smokers (Burrows, Knudson, Lebowitz, .1977; Samet et al. 1983). By increasing the occurrence of viral infections of the lower respiratory tract in early life, exposure to ETS in childhood may have an appreciable, but indirect, effect on the risk for the development of chronic airflow obstruction in adult Ills. The structural basis for this increased susceptibility has not yet been elucidated, however. Furthermore, the child whose parents smoke is also more .likely to take up smoking than is the child of nonsmoklng parents. Thus, the child made susceptible to the effects of active smoking by prior ETS exposure is also more likely to become an active smokc:r. The possibility that exposure to constituents of tobacco smoke in utero may exert a prenatal effect must also.be considered, This exposure is clearly not the same as ETS exposure, since the lungs of the fetus are not being exposed to ETS; rather, the developing fetal lung is expnsed to compounds absorbed by the mother and delivered to the fetus transplacentally. Evidence of an in utero effect in p~:egnant retie has been reported by Collins and coworkers (1985). These investigators reported that pregnant rats exposed to smoke from day 5 to day 20 of gestation, in comparison with control rats, showed redfaced lung volume at term and saccules that were reduced in number ~md increased in size as a result of the reduced formation 31
Page 26: TI07870636
of .~accule partitions. These hypoplastic lungs showed an internal surface area that was decreased. Whether this study in rats has any relevance to humans is not yet clear, but this issue deserves further investigation. Whether continued exposure to E'I~J during childhood, while the lung is remodeling and growing, effects the process of growth and remodeling is not yet clear. In general, rapidly dividing cells and immature organs are more susceptible to the effects of environmen- tal toxins than are cells undergoing a normal rate of division and mature organs. Apart from the evidence, cited above, linking lower respiratory tract viral infections in very early life to an accelerated decline of FEV~ in adult life, there is no information yet to link the rate of growth of lung function during childhood to the rate of decline of lung function in adult life because tim necessary Iougitudi- hal studies have not been done. More information is needed to I..~cribe the relationship of exposure to ETS at various times during 'childhood to the maximal level of lung function achieved at full lung growth. Methodological Considerations in Ep|demiologic Studies Measurement of Exposure In assessing the health effects of ETS exposure, as with other environmental pollutants, accurate assessment of exposure is critical for obtaining estimates of this agent's effects. Both random end systematic misclassification of the exposures of subjects in an investigation are of concern. Random miscla~ification refers to errors that occur at random; the consequence of such random mi~cla~ification is to bias toward finding no effect. Systematic misclasslfication refers to nonrandom errors in exposure assevament; the consequence may be to bias toward a greater or lesser effect than is actually present. Biased answers in response to a questionnaire may introduce systematic misclassification. Some misclassification occurs in most observational (nonexperi- mental) epidemiological studies, and is inherent in all epidemiol'ogi- col studies of ETS. Tobacco smoking is ubiquitous in nearly all environments; few people escape being exposed to ETS.. Thus° the exposure variables for l~'l'S in epidemiological studies do not separate nonexposed subjects from exposed subjects; rather, they identify groups with more or less exposure, or with a qualitative or semiquantitative gradient of exposure. In assessing exposure to ETS, the information should, cover the biologically appropriate time period for the health effect of interest and be collected in a form that permits the construction of biologically appropriate exposure measures. However, the collection of a full lifetime history of I~['S exposure, as in a study of malignancy, may not be feasible, and the accuracy of the informs- 32 tion may be limited, in evaluating the effects of I~'I'S exposure, cumulative exposure, duration of exposure, and i~tensjty of exposure may each iufluence the magnitude of effects, as may the timing of exposure in relation to age and level of development. Because of the difficulties inherent in assessing exposures through questionnaires, increased .emphasis has been placed on measuring exposure through the use of molecular or biochemical markers, With available nmrkers, this approach is limited to providing an indica- tion of recent Iwithin 48 hours) exposure, which may not necessarily correlate with past exposure. A marker has not yet been devised for total integrated dose. Nevertheless, biological markers provide another |m:thed for classification of current exposure, and a stan- dard for validating questionnaires. The strem,,ths and weaknesses of the existing methods of measur- ing exposure are further discussed below. Atmospheric Markers A number of different markers of atmospheric contamination by tobacco combustion products cap be feasibly measured. Ideally, the atmospheric lev6is of the air contaminant or class of contaminants that are implicated in producing the adver~ health effects would be • measured. A variety of contaminants have been measured as indicators o~ ETS, but no single measure can adequately index all of its myriad components. Further, some contaminants are produced by sources of environmental contamination other than tobacco smoke. Nicotine is absorbed only from tobacco and tobacco combustion products. Some of the pollutants that have been measured include (1) carbon monoxide, 12~ respirable suspended particulates (RSP), (3) nicotine, (4) a ,~umber of aromatic hydrocarbons, such as benzene~ toluene, benzo-wre~e, and phenols, and (5) acrolein. Some of these are in the vapor phase and some in the particulate phase. Some, such as nicotine, may exist in one phase (purtlculatel in MS and in the other (gas) phase in SS. Until more is learned ubout the contaminants and their physical state in ~-~S, the results of monitoring for a particula.r ETS comlmnent will be difficult to relate to its disease-causing potential. At a practical level, the tecimology for measuring nicotine levels and I~SP levels is available and accurate. Personal Monitoring Both active and passive persomd monitors c, an be used to measure an individu~d's total exposure to an air contaminant at the breathing zone. Actiw: personal monitoring systems employ pumps to concen. irate the air contaminaqts on a collection medium for laboratory analysis o,' to deliver the air to a continuous monitor. Passive
Page 27: TI07870637
personol monitoring sysbenm use diffusion and permeation to concentrate gases on a collection medium for laboratory analysis. Persoual monitoring should provide a more accurate estimate of the dose of a contaminant than area monitoring, because the actual air in the breathing zone is sampled and the subject's tlme-aetivity pattern is inherently considered. As with area monitoring, the results for a particular component of ETS may not adequately characterize exposure to other component~ responsible for a particular disease or effect. Resplrabie suspended particulates can be measured with accuracy and give a reasonably accurate measurement of current exposure. Questionnaires The questionnaire has been the most frequently used means of estimating exposures for epidemiologieal investigations. Question- nnires typically have obtained information about the smoking habit~ of parents, spouses, .or other family members and often about exposure outside the home. Front this information, the subject is classified as exposed or not exposed to ~TI~, and the extent o[ exposure may be estimated. The questionnaire approach for exposure estimation has several potential limitations. First, the information obtained cannot exhaus- tively cover lifetime exposure to ETS; therefore, a completely accurate reconstruction of integrated dose over the years cannot be achieved. Second, in evaluati~g ETS exposure in the home, the usua| daily masking of the smokers has ores been used as a measure of exposure intensity at home. This assumption may not be correct, since mnoking does not occur only in the hmne. For example, a one-' pack-a-day smoker may smoke only five cigarettes a day in the home environment and smoke the rest at work or elsewhere outside the home. Third, quantitatlon of exposure in the workplace is inherently difficult because of changes in jobs and the varying exposure in any particular workplace. Despite these shorlcomlngs, the information obtained by question. naires does discriminate between more exposed and less exposed subjects. The evidence validating the questionnaire method is strongest for" domestic exposure. In several studies, levels of cotinine in body fluids have varied with reported exposure to tobacco smoke at home (Greenberg et al. 1984; Wald and Ritchie 1984; Matsukura etal. 1984; Jarvis et al. 1984). In fact, residence with a smoker may identify a population that is more tolerant of ETS, and therefore more likely to be exposed outside the home. Evidence in support of this speculation is provided by a study of urlnaary cotinine levels in nonsmoking men in the United Kingdom (Wald and Ritchie 1984). In this study, the men married to women who smoked reported a 34 greater dur,tioa of e~posure ouLside the home than men married to women wire did no~ ~.~i~oke. Until ~tccurnte m~d inexpensive ex~sure markers are available for cumulative ETS exposure, the. questionnaire approach will remain the simplest mean~ of ob~ining ex~sure information. It i~, there- fore, im~rl.ant to consider the misela~ifieation that can be intro duc~ by using this indir~t measure of on.sure. In studies of the effect of EI'S ex~sure, two ty~s of miscla~ifieation are of concern: miscla~ification of current or former smoke~ as never smokers and mi~la~ification of the extent of grs ex~ure. B~ause active smoking has a greater eff~t on the lungs than ex~sure tt~ ETS, the inclusion of active smokers within a larger group of nonsmokers may lead t~ the finding of a significant effect on lung function, which is actually attrlbu~ble to active smoking rather than to involuntary smoking. Miscl~ification of undeclar~ active masking is a particularly imprint source of error in studies involving teenagers. Miscla~ification of smoking s~tas is also o£ ~ncern in cas~ontrol studies of the ass~iatlon between exposure ~ ~ and lung cancer. Information a~ut smoking habi~ for these studies often comes from interviews with a surviving s~use or surr~ate, who may have ~en a cl~e family member, neigh~r, or friend, ur hom a review of m~ical r~ords. The smoking habi~ the subject may be incorrectly re~rt~. Clarification o~ individuals who are current or former smokers as never smokers would lead ~ a spurious increase in the relative risk for lung cancer in nonsmoEers ex~ed to I~I'S, because the smoking ~abi~ of s~ases tend to be ~rrelated. The extent of this bi~ in the c~ontrol studies un~r~in. The pro~rtion of ~ple re~r~ ~ never smokers, but who in fact did smoke in the past, is unknown. The proportion curreut smokers who report themselves as nonsmokers can be estimated from studies using marke~ ~ validate questionnaires. Using bi~hemlcal markers of tobacco smoke absorption, the proof- tion would appear to be a~ut 0.5 ~ 3 percent, depending on the ~puintion studied and the qu~tlonnaire used (Wald et al. 198J; ~l~jee et ul. t982). Minc]as~i Hcation of the extent of ~S ex~ure can also ~cur, and may r~uce the observed risk ira nonsmoking s~use o~ a smoker not ex~ed to smoke at home. Fri~man and co]lea~ (1983)~ re~rting una survey of 38,~ subj~, no~d that 47 percent of nonsmoking women married ~'smokers re~rt~ that they were ex~ to tobacco smoke at home. Measurements of Absorption The diflicultles inherent in estimating exposure and dose have provided the impetus for the development of biological markers for eXlmsure to both MS and ETS. The marker that at present holds the 35
Page 28: TI07870638
highest promise is cotinine, the major ~netebolite o1" nicotine. Cotinine may be measured in saliva, blood, or urine. Numerous studies have demonstrated that there is good correlation between these measures of cotinine and the estimated exposure to tobacco smoke under laboratory conditions (Russell and Feyerabeud 1976; Hoffmann et el. 1984) and under conditions of daily ilfe (Russell and Feyorabend 1976; Feyerabond et el. 1982; Foli,,rt et el. 1983; Weld et el. 1984; Weld and Ritchie 1984; Jarvis et el. 1984; Matsukura et el. 1984; Greenberg et el. 1984). Cotinine is probably the best marker for tobacco smoke intake because it is highly sensitive and specific for tobacco smoke and because it can be detected both i~t active smokers and in individuals exposed to ETS. Further details about cotinine and other markers are to be found in Chapter 4. Potentially Confounding Variables In any epidemiological study, the confounding factors must be considered and their effects controlled. Confounding refers to the biasing effect of a factor that independently influences the risk for the disease of conceru and is also associated with the exposure under evaluation. Confounding is of particular concern when the effects of the exposure of interest are expected to be small. The potential confounding variables depend on the health outcome of interest. For lung cancer, occupational exposures, diet, and exposure to other combustion pr.oducts are of concern. For acute and chronic pulmonary effects, potential confounders include airways hyperresponsivenass, other indoor air pollutants, outdoor air pollu- tion, respiratory tract infections, occupational exposure, and socio- economic status, which may potentially influence disease risk through its environmental correlates. While this list is extensive, it may not be inclusive; in any single iuvestigatlon it may not be possible to measure and control all potentially confounding vari- ables. Statistical Issues In general, the evidence m~ active smoking in combination with the dosimetry of involuntary smoking leads to the conclusion that the effects of IZI'S on a population will be substantially less than the effects of active smoking. The effects of ETS on infauts and young children are an important exception. The association of ETS with an adverse effect in an imlividual study may reflect bias, chance, or a causal relationship. St~tistical significance testing is used to quantitate the ,'ale of chance; by convention, a p (probabilit~l value less than 0.05 is d~.~mod sh~tisti- cally significant. A p value less than 0.05 means that the observed results would occur by chance less than 5 times otlt of 10L1, if there is 36 truly no a~iation between ETS and the effect, The choice of 0,05 hz arbitrary, a~d as the significance level declines, the probability that the observation could have occurred by chance lessens. For cffect~ of small magnitude, as may be anticipat.ed for some consequences of exposure to ETS, a large s~udy population may be necessary to demonstrate statistical significance. The absence 'of statistical significance for an v~ciation may reflect an inadequate sample size and is not always indicative of the absence of an a~ociation. In this regard, reports describing the absence of effects of ]gTS should provide the calculations needed to demonstrate the study's statistical power (ability to detect effects of the magnitude expectedl or a confidence interval for the estimate of effect. An addititmal statistical i~ue is the directionality of statistical significance testing. Either one-sided or two-sided tests may be used; in the first, only effects in one direction are considered a possibility, whereas two-sided tests consider the po~ibility of effects in opposing directions, i.e., increase or decrease of risk. Given the strength of the evidence on active smoking and disease risk, one-sided testing in the direction of an adverse effect seems appropriate for mo~t potential consequences of ETS. However, one-sided tests have not been performed in ell investigations of El'S; the use of two-sided te~ts make~ these studies conservative, as statistical significance will leas often be attained. Respir.atory System Effects of Involuntary Cigarette Smoke Exposure This section reviews the evidence on involuntary smoking and the adverse physiologic effects, respiratory symptoms, and respirato.ry diseases in nonsmoking adults and children. Health effects related to fetal exposure in utero from active smoking by the mother are not discussed. Lung growth and development may be influenced by in utoro exposure, and the effects of such exposures have not been separated from those of exposure after birth. More complete treatments of this issue have been published (US DHEW 1979; US DHHS 1980; Abel 1980; Weinberger and Weiss 1981). This section begins with a review of the data on infants and children who are exposed primarily through parental smoking. The health effects examined are increased respiratory illnesses, of both the upper and. the lower respiratory tracts, increased chronic respiratory symptoms and iilne~es, and alterations in lung growth and develolqnent. Studies of adult~, whose exposures .to environmen- tal tobacco smoke occtzr in a variety of settings, arc examined with regard to symptoms and changes in measures of lung function. The potential for ETS to produce bronchoconstriction in astltmatic and nonasthmatic subjects is also examined. 37
Page 29: TI07870639
6£90ZgZOll
Page 30: TI07870640
TABLE 1.--~ntinued TABLE 1.--.Continued ~p m a~m ~ ouly mammal N~x ~ T107870640
Page 31: TI07870641
of nonsmoking mothers. In addition, they demonstrated a dose- 'response relationship between the amount of maternal smoking and the number of hospital admissions for these conditions. The infauts were classified by the mothers' prenatal smoking behavior and not by the mothers' smoking behavior during the first year of the child's life. Maternal smoking habits would probably have remained relatively stable across the short observation period. British investigators (Colley etal. 1974) followed children born between 1963 and 1965 in London and also observed an increased frequency of bronchitis and pneumonia during the first year of llfe in the children of parents who smoked. This difference did not persist at 2 to 5 years of age. Tlds effect was independent of the parents' personal reports of winter morning phlegm and increa~d with the amount of smoking by parents. The annual incidence of bronchitis and pneumonia during the first year of life also increased with a I~reater number of siblings, This variable was not controlled in the original analysis; however, Leader and colleagues (1976b) subse- quently reported that, in this same cohort, a dose-response relation- ship with parental smokh|g persisted for bronchitis and pneumonia in the first year of life, after control for parental respiratory symptoms, the sex of the child, the number of siblings, and a history of respiratory illness in the siblings. Fergusson and colleagues {198D studied 1,265 New Zealand children from birth to age 3. They demonstrated an increase in bronchitis and pneumonia and in lower respiratory illness during the first 2 years of life in children whose mothers smoked compared with "children whose mothvrs did not smoke. Correction for matermd age, family size, and s~cioeconomic status did not affect the relationship between the amount of maternal smoking and the rate of respiratory il{ness. The effect o[" maternal smoking declined with increasing age of the child. In a second report (Fergusson and Horwood 1965) the followup w~m extended to include the first 6 years ofllfe. The results confirmed the initial finding.~. Maternal, but not paternal, smoking was associated with a statistically significant increase in lower respiratory illnesses during the first 2 years of llfe. However, after age 2 there was no significant effect of maternal smoking on respiratory illness occur- Fence. Rnntakallio (1978) followed more than 3,600 children during the first 6 years of lt~e; half of the'children had mothers who smoked cigarett~ during pregnancy and half did not. The children of mothers who smoked had n 70 percent greater chance of hospitaliza- tion for a respiratory illness than the children of nonsmoking mothers. Pedreirs and a~ociates ~1985) prospectively studied 1,144 infants and their families in the i;reater Washington, D.C., urea. Maternal 42 smoking was associated with an excess frequency of acute bronchitis, tracheitis, ~md laryngitis, as diagnosed by the pediatricians caring for these ramilies. Episodes of croup, pneumonia, and bronchiolitis were ,mr increased by maternal smoking. A family history of chronic respiratory symptoms was also a~iated with excess respiratory illness. Ware =rod coworkers (1984) studied more than 10,~ children in six American cities. Maternal cigarette smoking was associated with increased pm'ental re~rting era doctor-dlagnosed respiratory illness ~fore the age of 2 years and of an acute r~plratory illne~ within the past ye~tr. The prevalen~ of ~sitive questionnaire res~nses increas~l consistently with the current daily cigarette consumption of the mother; the dos~res~nse relationships were unchanged by a~justmeat for maternal symptoms and ~ucational status, Cross-Sectlo=~al Studies Schenker and coworkers (1983) studied 4,071 children between the ages of 5 aild 14 years in a cross-sectional study in Pennsylvania. Both chest illness in the past year and severe chest illness before age 2 were mot,, frequently reported in nonsmoking children of parents who smoked. These investigators found that symptom and illness rates were higher ia children of parents with respiratory symptoms, However, a significant effect of maternal smoking on these illness variables remained after adjustment for the parents' own respira- tory symptom history. In a study of 1,355 children between 6 and 12 years of age in the Iowa public schools, Ekwo and coworkers (1983) found that the presence in ti~e home of at least one parent who smoked was significantly associated with reported hospitalization of the child for a respiratory illness during the first 2 years of life. As in other studies, tlw effect was stronger for maternal smoking than for pa.ternal smoking. Case-Control Sludies In Englm=d. Sims and colleagues (1978) examined 35 children at 8 years of a~e who had been hospitalized during infancy for RSV bronchiolitis and compared them with 35 control children of similar age. Mater=ml smoking was associated with a relative risk of 2,65 for hospitalizalion due to broachiolitis. The sample size was small~ and this effect of maternal smoking was not statistically significant, Pullan m~d Hey (1982l studied children who had been hospitalized with documented RSV infection in infancy. They found significantly greater snmking by their mothers at the time of the infection, compared with children hospitalized for other illnesses, including respire=tory disease for which RSV infection was not documented. At 43
Page 32: TI07870642
TABLE 2.---Chortle respiratory symptoms in children in relation to involuntary smoke exposm'e T107870642
Page 33: TI07870643
TABLE ~.~on~nued • Sche~ st zl. 4.071 chi/d~ ~ 5-14. Chruaic coqh ~2 7.0 8.3 Cnmeic phl*s/m 4.1 4,8 4.O Per~x~t wheeze 7.2 7.7 5.4 for atym~tomar.ic hou.~hoids: no adje~m~.c for ~hild's own smokt.~ T107870643
Page 34: TI07870644
Parental smoking had no significant effects on citronic respiratory symptoms. Lebewitz and l|urrows (1976) assessed the effects of household members' smoking on respiratory symptoms in 620 Tucson children younger than 15 years of age. Children from homes with current smokers had higher symptom rates than those from homes with ex- smokers and with never smokers, tlowever, the effect of household smoking type was statistically significant only for persistent cough. In a general population study, Schilling and colleagues (1977) reported no association between wheeze and involuntary smoking. Ware and associates (1984) enrolled 10,106 children between 6 and 9 years of age from six U.S. cities in a prospective study. The prevalence of persistent cough and persistent wheeze, measured at the second examination, was higher in children whose parents smo.ked. The effect was greater for maternal smoking than for paternal smoking. Symptom prevalence rates increased linearily with the number of cigarettes smoked daily by the mother. In a multiple logistic model, the effect of maternal smoking persisted after adjustment for reported illness in the parents. Dodge (1982), studying tldrd and fourth grade children in Arizona, found that symptoms, including wheeze, were related to beth the presence of symptoms in the parents and the number of smokers in the household. in summary, children whose parents smoke had a 30 to 80 percent excess prevalence of chronic cough or phlegm compared with children of nonsmoking parents. For wheezing, the increase in risk varied from none to over sixfold among the studies reviewed. Many studies showed an exposure-related increase in the percentage of children with reported chronic symptoms as the nmnber of parental smokers in the home increased. Misclassification as nonsmokers of children who are actively smoking could bias the results of these dtudies. Adolesceut smokers may be reluctant to accurately report their smoking habits, and more objective measures of exliosure may not help to distinguish active experimentation wiLl~ cigarettes from Involuntary exposure to smoke (Tager 1986). Although misclassificn- tion of children who are actively smoking as nonsmokers must be considered, many studies showing a positive association between parental smoking and symptoms in children, including children at ages before significant experimentation with cigarettes is prevalent. In addition, many studies (Bland et el..1978; Weiss et el. 1980; Charlton 1984; Schenker et el. 1983; Dodge 1982; lturchfiel et 1986) found significant effo~ts of parental smoking ai'ter, co=,sidering active smoking by the chihlren. Chronic respiratory symptoms represent an immediate health burden for the child, llowcver, the long-term significance o1" chronic respiratory symptoms for the health of the child is unclear. Mo.~t 48 available d~tta are cross-sectional, and followup studies of chronically symptomatic children are necessary to determine the long-tarm health cons~.~luences of chronic respiratory symptoms. Pulmonary Function In recent years, the effect of parental cigarette smoking on pulmonary function in children has been examined in crops-sectional studies fFable 3) and a few longitudinal studies. The cross-sectional studies have demonstrated lower values on tests of pulmonary function (FI~Vo.~, FI/~V~, FEF~-~, and flows at low lung volumes) in children of mothers who smoked compared with children of non- smoking m~the~s. The longitudinal studies ('Fable 4) have confirmed the cross-se~:tional results and provide some insight into the implica- tions of the cross-sectional data. Dose-rosiness relationships have been found in both cross-section- al and longitudinal studies (Tager et el. 1979; Weiss et el. 1980; Ware et el. 1984; Berkey et el. 1986); the level of function decreases with an increasing number of smokers in the home. As would be anticllmted from the mother's greater contact time with the child, maternal smoking tends .to have a greater impact than paternal emokiug. Ynunger children seam to experience greater effects than older children {Tsger et el. 1979; Weiss et el, 1980), and in older children the effects of personal smoking may be additive with those of involuntary smoking (Tager et el. 1979, 198fi). As noted by Tager (1986), the effect of maternal smoking on lung function m~ly vary with the child's sex. Some studies have reported greater effects on flows at lower lung volumes in girls than in boys (Burchfiel et el. 1986; Tashkin et el. 1984; Yarnell and St, Lever 1979; Vedal et el. 1984). Flows at higher lung volumes seem more affected in Imys (Burchfiel et el. 1986; Yarnell and St, Lever 1979; Berkey et el. 1986; Tashkin et el. 1984), Whether these sex effects represent differences in exposure, differences in susceptibility to environmental cigarette smoke, or differences in growth and devel- opment is unclear. Tager aml colleagues (1983) followed 1,156 childrer~ for 7 years to determine the effect of maternal smoking on the growth of pulmo- nary functi~m in children (Figure 2). After correcting for previous level of FEV~, age, height, personal cigarette smoking, and correla- tion between mother's and child's pulmonary function level, mater- nal smoking was associated with a reduced annual increase in and FEF~, using two separate methods of analysis. If the effect maternal smoking is maintained to 20 years of age, then a 3 to/~ percent reduction of FEV~ and FgF~-~ due to maternal smoking would be projected. The validity of this projection remains to be established. Because few'mothers changed their smoking habits~ the
Page 35: TI07870645
TABLE ~.--Pulmonary function in children exposed ~o involuntary smo .]dng " Sdfil~ e~ ~L 816 chiIdre,, aged T-1T, FEV, a~ p~mr, predk-ted (L97~ Connec~m~ ~ South Ca~wHaa. Uei~d $~ No cou~'~l for ~midp ~ 9r f~ f~r ¢~Idr~ ~ho m~r smoked. V,.~a T~ e~ aL 444 choline. ~ 5-19. W~ ~~9. ~ TABLE 3.--C~ntinued T~hk~ e~ aL I.~ ~rmmoid~, V,m. V,,~ V,m.~ FEF~-n (19~4) nor~hm~r.,c ch~d~ L~ ~ U~i~d Sm~e~ V,.~.s [or boys. for girta mot]mr at 1~ No eff~-~ of pa~nud smoking S~ ~ al. &;.2~ chiI~ ~ed 6-10. FVC tea FEV, as p~e~t Na ~q'~ for F~'~ or FVC P.acent anal~ d~mens~ra~d (1980) ~ix U.S. dti~ ~ ~a df~ f~r FVC ~d FEV, Le~wil= 117 fanfilk~ Turin. FVC a~d FEV, No tqfe~ ot pa~n~l ~mokin~ ALw ~ T~P and ozone (1984) ~ Unil~l Stal~ ratm had little eff~'t Ek~ ~ el. L3~ ~ at'~d 6-12. FEV,, FVC No efl'~t ~ pa~n~l smoking Data for ~ ~:ome ~t n~3) I~ City, ~ U~i~i spe~s~tly a~iy~l; hs=e~l t1985~ Italy macern~ ,nm~ differ~ be~w~n boys ~d T107870645
Page 36: TI07870646
52 Low.s! 20'% ~ 00% High.s! 20% FIGURE 2.--Percentage of children with mothers who were current cigarette smokers at initial examination (black columns) and sixth examination (white columns), according to distribution of mean age, height, and sex- corrected FEVz over the first six examinations NOT~ I~*~*~ 2, I'X-, middle eO'~, and Id~he*! 20'& ~ to cklkl,e~ with valm in the bott~ on.fifth, middle study couhl not establish the ages at which children were mint vulnerable I~) exposure to tobacco smoke. Ware anti colleagues (1984) followed 10,106 white children for two successive a,nual examinations as part of the Harvard Air Pollution Health Study in six U.S. cities. The forced vital capacity was significantly higher for children 0f mothers who were either current smokers or ex-smokers. However, children whose mothers were curre~t smokers had a 0.6 percent lower mean FEVz at the first examination and 0.9 percent lower mean FEV~ at the second examinatio,t. Maternal smoking had a greater effect than paternal smoking, although the effects of both were significant. The changes in level of i0'EV, observed were small. For exposure to a mother who smoked one pack of cigarettes per day, the FEV~ was estimated te be decrea~d hy less than I percent, or 10 to 20 mL for a child with an FEV, betweem 1.5 and 2.5 liters. Projecting the effect cumulatively to age 20 yields an approximately 3 percent deficit. This effect is comparable to that observed by Tager and colleagues (1983), These small aver,ge effects may underestimate the effects on populations of susceptible children. 53
Page 37: TI07870647
A more extensive analysis of longitudinal daLa From the Harvard cohort was performed using a mathematical model to describe lung ~rowth (T~erkey et ai. 1986). '['his analysis included 7,834 children between 6 and "10 years or age who were evaluated from two to five times over a 6-year period. '['he model estimated that a smoke- exposed child at age 8 would have an Fl~VlO.81 percent lower than a non-smoke-exposed child, and growth of FRVI would be 0.17 percent lower per year. ]Both effects were statistically significant. For an 8- year-old child with nn FRV= of 1.62 liters, these resultst~'anslat.e into a deficit of 13 mL in FEV~ and of 3 mL in annnal Increase in FEV:. The magnitude of the maternal smoking effect is consistent with a deficit in FEV~ of 2.8 percent in naturally attained growth, if the effect is sustained throughout childhood. Burchfiel and colleagues (1986) have conducted a longitudinal study of 3,482 children observed over a 15-year period in Tecumseh, Michigan. The mean increase in FEV~ for aonemoking boys between the ages of 10 and 19 years was 82.3, 76.2, and 74.5 mL per year for subjects with zero, one, and two smoking parents, respectively. Boys with one parent who ~moked experienced 92.6 percent and boys with two parents who smoked experienced 90.~ i~ercent of the growth in FEV~ seen in male children with nonsmoking parents. Effects of parental smoking were not found in girls. The available data demonstrate that materaal Smoking reduces lung function in young children. However, the absolute magnitude of the difference in lung "function is smell on average. A small reduction of function, on the order of I to 5 percent, of predicted value, would not be expected to have functional consequences. However, some children may be affected to a greater extent, and even small differences might be important for children who become active cigarette smokers as adults. A minority of adult cigarette smokers develop chronic obstructive lung disease, and factors influencing lung growth and development during childhood might predispose to disease in adulthood (Samet et hi. 19[~3; Speizer and Tager 1979). In Figure 3 is depicted a model of grjwth and decline in pulmonary function from childhood through adulthood, as measured by the FEV~. Pulmonary function peaks in early adult llfe and declines steadily thereafter in both smokers (curve B) and nonsmokers (curve A). In people who develop chronic lung disease (curve C), a more rapid decline has occurred. Childhood factors could predispose to the development of disease by reducing the functional level at which decline begins or by increasing susceptibility to cigarette smoke and ~ncreusing the rate of decline. Thus, in this model, small decrements in the maximally attained level of pulmonary function: may be important in identifying the susceptible smoker. However, the prerequisite longitudinal studies needed to test this hypothesi.~ have nat yet been conducted. 64 xg'~ 20.-25 // II I/ II ~ 10 15 ~ ~ ~ ~ 70 FIGURE 3.~Theoretical curves representing varying.rates of change In FEV~ by age ~ (:urea A. tmrmnl d~llne In ~V= Ifo~ ex~rnt~ ~u~ in I ~k ~e 9. s~lcrat~ dwll~ In FEV, ~ith clgnre(l~ ~mnkl~ cv~e I~, !~ eff~t ~ ~1~ ~t~, arm ~n In dluM~ IndjvMuak (¢U~ £~ fl~ncimcw~ triction Nons~cific bronchial res~nsivene~ has been considered a poten- tial. risk f~ctor for the development of chronic obstructive lung di,ea~e in b.th odul~ ~nd children (US'DHHS 1984). This physiolog- ic trait tony be ~n~nenc~ by environmen~l expo~ure~ such a~ involuntary smoking by children and ~ctive smoking by adult, and by respirat~ry in~ection~ at all ages. Asthm~ is a chronic disease characterized by bronchial hyperre. s~nsivene~. Epldemlologic ~tudi~ er children have shown no ~n~i~tent relationship between the re~rt of a d~r's diagno~i~ of esthma and exposure to involuntary ~moking. Although one ~tudy showed an ~s~iation between involun~ry smoking and ~thma (Gortm~ker eL al. 1982), others have not (~henker e~ ~1. 1983; Ho~d et al. 198~). This variability may reflect differing age~ of the children ~tudied, differing ex~sures, or uncontrolled bi~. ~n ~ver~d recent studie~ (Murray m~d Morrison 1986; O'~nnor et al,
Page 38: TI07870648
1986; Weiss et al. 1985; Martinez et al. 1985; Ekwo et al. 1983h nonspecific bronchial responsiveness was examined in relationship to involuntary smoking. The results of these studies suggest that exposure to maternal cigarette smoking is associated witi, increased nonspecific airways responsiveness. Some reports suggest that the increased responsiveness is present only in childre~! known to be asthmatic (Murray and Morrisen 1986; O'Connor et al. 1986), whereas others suggest that the increased responsiveness is seen i,l all children (Ekwo et ai. 1983; Martinez et al. 1985). Tbe pathophysi- ological mechanisms underlying the increased responsiveness and the long-term consequences of the increased responsiveness remain unknown. This section reviews the studies on asthma and on bronchial hyperresponsiveness. Oortmaker and coworkers (1982) studied tire relationship betweeu parental smoking and the prevalence of asthma in children up to 17 years of age. Random community-based populations in Michigmr (3,072 children) and Massachusetts (894 children) were surveyed. Parents reported on their own smoking habits and on tile asthma histories of their children. Biased reporting by parents who smoked was assessed by examining the relationship between parental smoking and other conditions, and considered not to be present. Asthma prevalence declines with. age, and asthmatic children are unlikely to tolerate active smoking; therefore, misclassiflcation of actively smoking asthmatic children as nonsmokers seems unlikely. In comparison with children of nonsmokers, children whose parents smoked were more likely to have asthma (relative risks of 1.5 and 1.8 for Michigan and Massachusetts children, respectively) and severe asthma (relative risks of 2.0 and 2.4, respectively). The investigators estimated that between 18 and 23 percent of all childhoed asthma and 28 and 34 percent of severe childhood asthma is attributable to exposure to maternal cigarette smoke. Schenker and coworker~ (1983) studied 4,071 children between 5 and 15 years of age in western Pennsylvania. These investigators found no relationship of parental smoking to the occurrence of asthma, after adjustment far potential confounding factors. Horwood and coworkers (1985) conducted a cohort study of 1,056 children in New Zealand who were followed front birth to age 6 years. A family history of allergy and male sex were the only significant predictors of incident cases of astlzma. Neither parental smoking nor respiratory illnesses were predictive of the occurrence of asthma in this investigation. A recently reported cross-sectional study by Murray and Morrison (1986) suggests a mech.anis~n by which maternal cigarette smoking might influence the severity of childhood asthma. These investiga- tors studied 94 children, aged 7 to 17 years, with a history of asthma. The children of mothers who smoked had 47 perce,t more syrup- 4 ! 0.~ 0.0~ 0.03 ,,~ 0 O0 O0 O- 0 0 FIGURE 4.--PC.o in two groups of children with a history of wheezing toms, a 13 percent lower FEV|, and a 23 percent lower FEF~than the children of nonsmoking mothers. Forty-one children, who had been able to discontinue medication and had no recent respiratory illness, underwent a histamine challenge test. There was a fourfold greater responsiveness to histamine among the asthmatic children of mothers wh(,.smoked (Figure 4) compared with asthmatic children of nonsmokmg mothers. Dese-response relationships wore present for all outconte variables in this study: symptoms, pulmonary function, and airways responsiveness. The differences between children of smoking |nothers and children of nonsmoking mothers were greatest in the older children. The father's smoking behavior did not influence the child's asthma severity. The sample of asthmatic childre~l with mothers who smoked was small {N = 10), and only 41 of 96 children had histamine challenge tests. Given the heterogeneity of asthma, the variable nature of bronchial hyporreactivity in asthma, and the potential for biased selection, these results must be interpreted with caution. O'Co~mor nnd coworkers (1986) studied 236 children and young adults, 6 to 21 years of age, drawn from a community-based sample,
Page 39: TI07870649
nnd confirmed the. finding, of Murray and Mortises (198(;). Bronchi- al responsiveness was measured with eucapneic hyperpnea to subfreezing air. Among the 265 subjects without asthma there was no significant relationship between maternal cigarette smoking and nonspecific bronchial reelmnsiveness. However, in the 21 subjects with active asthma, maternal smoking was significantly asaociat~ with increased levels of bronchial responsiveness. In s study of 1,355 children 6 to 12 years of age, significant increases in FEV and FEF=-~ were observed following isoprotereno] administration in children whose parents smoked (Ekwo et el. 1983). Increases after isoproterenol were nat observed in children of nonsmoking pareuts. Weiss and coworkers (1985) e~aluated 194 subjects between the ages of 12 and 16 drawn from the same population as those reported by O'Connor and eoworkers (1986), with eucapneic hyperpnea to subfreezing air as a test for bronchial responsiveness and allergy skin tests as a test For atepy. Subjects defined as staple (auy skin test wlaeal greater than or equal to E; ram) had twice the frequency of lower respiratory illnesses in early childhood and were twice as likely to have a mother who smoked. However, there was no relationship between maternal smoking and increased bronchial responsiveness. Martinez and associates (1985) studied 170 g-year-old children in Italy. Nonspecific bronchial responsiveness to methachollne and allergy prick test pesitivity in these subjects was significantly associated with maternal cigarette smoking. These data suggest that maternal cigarette smoking may influence the severity of asthma; a mechanism for this effect may be through alteration of nanspeeific bronchial responsiveness. Furthbr investi- gation is needed to determine Wliether exposure to environmental cigarette smoke can induce asthma in children and whether ETS exposure increases the frequency or severity of attacks of broncho- constriction in asthmatics. The effect of involuntary smoking on Increased branchial responsiveness in asthmatics and in nonasth- rustics has only recently been addressed. These initial data are provocative, but the magnitude of the effect, the target population at risk, the underlying mechanisms, and the long-term consequences have not been described. Furthermore, ~he complex interrelation- ships among respiratory illness, atopy, parental smoking, and airways responsiveness have =tot been clarified and require further study. Ear, Pleas, and Throat Five studies (Said et el. 1978; lverson et el. 1985; Krnemer et hi. 1983; Black 1985; Pukander et el. 1985) show an excess of chronic 68 n~iddic ~,m' ~.ll',sio,;s sad diseases in chihlren exposed to parental smoke. Said and ¢~lleagues (1978) questioned 3,920 children ~tween 10 and 20 yea;=; of age about prior tonsillectomy or adenoid~tomy=~ considered an index of frequent upimr respiratory or ear inactions. The invcsLil~ators reporte~ that, in general, this sur@ry w~ ~rformed b{,lbre the children were 5 years old. The prevalence of prior surgery incre~ed with the number of currently smoking paren~ h= tim home. Ive~on and coworkers (1985) pr~tlvely studi~ 337 children enrolled in all day-care institutions in a municipality over a 3-month ~ri~ to evaluate the im~r~nce of involun~ry smoking for middle ear effusion in children. Middle ear effusion w~ a~ed with tympanometry, and the overall prevalence was found to ~ approxi- mately 23 percent. Although various ind~r environmen~l racers were assessed in this investigation, only paschal.smoking w~ significantly associated with middle ear effusion. The effect of paren~l sin.king ~rsist~ with control for the num~r of siblings, The overall age-a~usted ~ds ratio w~ 1.6 (95 ~rcent ~nfidence instal 1.~2.6~. in 5- ~ 7-year~ld children, 10 ~ 36 ~rcent of all chronic middle car effusions could thus ~ attributed ~ smoking on th$ basis of these result. Kraemer and coworke~ (1983) ~rformed a cas~ontrol study of 76 chihiren to examine the relationship of environmen~l ~bacco smoke ex~ure to the ~currence of ~is~nt middle ear effusions. Fr~uent ear in~ections, nasal congeries, environmen~l tobec~o smoke ex~ure, and atepy were all more frequent in children wJ~h ear effusions. The effect of involun~ry smoking w~ observ~ only if n~al ~ngestion was print, and w~ grea~t in children who were a~pic. Black (1985) perform~ a c~ntrol study of glue car with 1~0 ~ and 3~ controls. Paren~l smoking was ass~ia~ with a relative risk of 1.64 (95 ~rcent C.I. 1.0~2.61) for glue ear. In Finland, Pukander and coworkers (1985) conduced a c~ontrol study of 264 2- ~o 3-year~ld children with acu~ otitis media and 207 ~ntrol children and found an a~iation ~tween paren~ smoking and this scale illness. These studies are consls~nt in their demonstration of exc~ chronic middle ear effusions, a sign of chronic ear dise~e, in children exp{~sed to paren~l cigaret~ smoke. Palatial confounding fac~rs for middle ear effusions should ~ examined carefully in futu~ studk,a. The long-~rm impllc~tlons of the exc~ middle ear problems dearie further study.
Page 40: TI07870650
TABLE ~;.--Pulmonary function in adults exposed to involuntary smoking T107870650
Page 41: TI07870651
Knuffmann and colleagues (1983) suggested that the effects of exposure from a spouse who smoked =nay be manifest only after many years of exposure. These investigators a~e~d the effec~ of marriage to a smoker in 7,818 aduI~ drawn from several citi~ France. Among 1,985 nonsmoking women ag~ 25 to 59, 58 ~rcent of whom had husbaads who smoked, the level ,of MMEF was significantly redu~d ia women married to smokers ~mpared with women married to nonsmoker; this effect did not ~me apparent until age 40. The reduction was small, on average. Recently, studying another ~pulation, Kauffmunn and ~ileagu~ (J986~ suggested that the FEV~/FVC ratio may ~ a more ~nsifive test for detecting difl~rences ~tween ex~s~ and nonexl~ed subject, particularly in thee with symptoms of wheezing; however, this sugg~tion has not ~en evalua~d in other l~pulations. Brunekreef and coworke~ (1985), from the Netherlnnds, re~rted on 173 nonsmoking women who were participan~ In a larger longitudinal study of pulmonary function. The women were citi- fied by whether they were or were not ex~s~ ~ ~ba~o ~moke at study onset or at followup. Cry-sectionally, signifi~nt differen~s in pulmonary #unction were o~erv~ ~tw~n smok~x~ and nonex~sed women. However, the rate of decline of lung function . during the followup l~ri~ was not a~t~ by ~ba~o smoke ex~ure in the home. This study had a small humor ofeubj~ and inadequate s~tistical ~wer ~ de~t eff~ o~ ex~ure on rate o~ decline that were not extremely large. Jon~ and colleagues ([983) sel~d women with either h~h or low FEVs ~rom a ~pulafion-bas~ longitudinal study in T~umseh, Michigan. Ex~sure ~ cigaret~ smoke at home from husbands who ~moked was not significantly different in the two grou~ of women. Nonsmoking men who partlcipat~ in the Multiple Risk Facet Intervention Trial had signifi~ntly lower levels of pulmonary function if their wives smoked in compari~n with similar men whose wives did not smoke (Svendsen et The physiol~ic and clinical significance pulmonary function found in some studies of adul~ remains ~ be determined. The small magnitude o~ effect impli~ that a previously healthy individual would not develop chronic lung disease ~lely on the basis of involuntary ~bacco smoke ex~ure in adult life. Whether particular charac~risti~ .increa~ su~eptibility, such as vhildho~ ex~ures or illness, atopy, redu~d pulmonary function from whatever cause, and incre~ed airways r~nsivene~, remains unknown. These small changes may al~ ~ marke~ of an i~i~nt response, po~ibly transient, to the irri~n~ known envlronmen~l tobacco ~moke. 62 Bronchoconstrictitm Normal Sublecls Only li~,lited data have been published on the acut~ effects of inhalation of environmental tobacco smoke on pulmonary function in normal subjec~ (Table 6) and none on bronchial res~nslveness, The available data have ~en ob~ined in exposure cham~ers under carel'ully monitored and controlled circumstances (Pimm et el, 1978; Shepherd ct el. ~979; Dahms et el. 1981), Pimm and colleagues (1978) ex~ nonsmoking adui~ ~ smoke in an exposure chamber. Relatively constant levels of carla monuxlde (approximately 24 ppm) were achieved in the during involuntary smoking, Peak bl~ car~xyhemoglobin were always less ~han t ~rceut in thee subjec~ ~[ore smoke execute, but were significantly greater afar the study ex~sure. Lung wflumes, flow volume curv~, and heart rates were for all subject. Moasuremen~ were made at rest and exerci,e umler control and smoke-ex~ure conditions. Flow at 25 ~rconL tfl' the vital capacity was r~u~d at rest in men and with exercise in women. Although s~tistically signi~ant, the magnitude of the clmage was small: a 7 ~rcent d~rease in flow in men and 14 ~rcenL in women. Shephurd and coworkers (1979) utilized a similar ero~ver design in n chamber of exactly the same size as [ha~ used by Pimm and a~iu[e,. Their resul~ ware similar, with a small (3 [o 4 pereenD decrease in FVC, F~V=, ~=,~, and ~=,~. They concluded tha~ tbe~ changes were of the magnitude anticipated from ex~sure ~ smoke of less Umn one-half of n cigarette in 2 hours (the ex~ure ' an~iclpatcd for an involun~ry smoher). Dahms and colleagu~ (1981) usM a slightly larger chamber and an exlm~ure with an es[ima~d ~ak ~rbon monoxide level of approximately 20 par~ ~r million. They found no change in FVC, F~V~, or.F~F~ in normal subj~ after I hour of exposure. The act.ire smoker mnnifes~ aeu~ res~nsea to the inhalation of cigarette smoke; thus, high-d~e involun~ry exposure to ~bacco smoke may plausibly induce similar r~nses in nonsmokers. The magnitude of these changes is quite small, even a~ m~era~e ~ high explore level~, and if is unlikely that this change in htrflow, per resul~ in symptoms. Aslhmatics Dahms and colleagues (1981) exposed 10 patients with bronchial asthma and 10 normal subjects to cigarette smoke in an environmen. tel chamber. Pulmonary function was measured at 15.minute interval, for I hour after smoke exposure. Blood carboxyhemoglobln levels were measured before and after the l-hour exposure. Ths 63
Page 42: TI07870652
~4 carboxyhem~lobin levels in subjects with asthma increased from 0.82 to 1.20 percent. In normal subjects the increase was from 0.62 to 1.05 percent. The increases in carboxyhemog~obin in the two study g~oupe wer~ not significantly different.. Asthmatic subjects had a decrease in forced vital capacity (FVC), FEVn, and MIVIEF to a level significantly different from their preexposure values. The decreases in asthmatic subjects were present at 15 ndnutes, but worsened over the course of the hour to approximately 75 percent of the preexpo- sure values. Normal subjects had no change in pulmonary l'unction with this level of ekpcsure. In this study, subjects were not blinded as to the exposure and were selected because of complaints about snloke sensitivity. Shephard and colleagues (1979), in s very similar experime.nt, subjected 14 asthmatics to a 2-hour cigarette smoke exposure in a closed room (14.6 mS). The carbon monoxide levels (24 ppm) were similar to tiloee predicted in the study of Dahms and coworkers (1981). Blood carbexyhemoglobin levels were not measured. Subjects were randomized and blinded to sham (no smoke) and smoke exposure and tested on two separate occasions. Data were expressed as the percentage change l'rom the sham exposure. Significant changes in I0'~'C and FEVe were not observed between the sham and the smoke exposure periods, although 5 of 12 subjects did report wheesiug or tightness in the chest on the day of smok.e exposure. Wiedemann and associates (1986) examined nonspecific bronchial responsiveness to methacholine in 9 asthmatic subjects and 14 controls and the effect of acute involuntary smoking on nonspecific bronchial responsiveness. At the time of the study, all asthmatics were stable with normal or near normal pulmonary function. The subjects underwent baseline pulmonary function and methacholine challenge testing. On a separate day they were exposed to cigarette smoke for I hour at 40 to 50 ppm of ca.rbon monoxide and underwent pulmonary function and methachollne cha]lenge testing. Pulmonary function was not influenced by exposure. Nonspecific bronchial respensivem:es decreased significantly, rather than increasing, as would be a.nticipated following an irritant exposure. Acute exlmsure in a chamber may not adequately represent exposure in the general environment. Blames in observation and the in selection of subjects and the subjects' own expectations may account for the widely divergent results. Studies of large numbers of individuals with measurement of the relevant physiologic and exposure parameters will be necessary to adequately addre~ the effects of environmental tobacco smoke exposure on asthmatics. Ear, Nos~ ~md Throat There are no studies of chronic ear, no~e, and throat symptoms in adults with involuntary smoking exposure.
Page 43: TI07870653
Lung Cancer This section reviews the epidemiological evidence on iavolunbtry smoking and lung cancer in nonsmokers, which has been derived from retrospective and prospective epldemiologlc~d studies. First, common methedological Issues that apply to all these studies are cotleldered. Second, for each type of study design, individual studies are reviewed for their methodological approach (Tables 7 and 8), findings associated with tobacco smoke exposure (Table 9, Figure 5), and strengths and limitations. Third, the lung cancer risk associated with involuntary smok|||g is examined as a low-dose exp~ure to cigorette smoke by combining the dose-response relationships for active smoking with the exposure date for involuntary .smoking to predict the expected lung cancer risk due to involuntary smoking. This expected risk is then compared with the actual risks observed studies of involuntary smoking. Finally, the existing epidemiologlcal evidence is summarized and the plausibility of the association between lung cancer and ln¢~luntary smoking is evaluated on the basis of our current knowledge. Observed Risk Ge,|ernl Methodological issues For both retrospective and prospective studies, the c~mmon methodo|ogic concerns are disease misclassification and |nisclas.~ifi- cation of the subject's personal smoking status or exposure to Errs. Disease misclasslficatJon, for example, refers to the incorrect classifi- cation of the lung as the primary site of a cancer that originated elsewhere. Disease misclassificatlon is of greatest concern in studies h| which the diagnosis of lung cancer was not I|istologically confirmed. ~uch misclassification tends to be random and to bias relative risk estimates toward unity (Copeland et al. 1977). Patients with lung cancer, or any disease associated with cig~retto smoke exposure, |~/ay report exposure to ETS more frequently titan controls .because of bias in recall. ]~Jsclassiricatlon of the subject's; personal an|eking status amy occur in both retrospective and prospective studies; this miselas~ifi- cation refers to incorrectly classifying a subject as a nonsmoker when the subject is actually an ex-smoker or a current smoker~ or to incorrectly classifying the subject as a smoker when the subject is, nonsmoker. Biochemical markers such as cotinine and nicotine, which can be used to detect unadmitted active smokers, are sensitive only to a recent expvsur6 to tobacco smoke; thus, they are aot particularly useful for identifying ex-smokers who de.y their past smoking h|stories. Misclassificatioa of smokers or ex-smokers as nonsmokers may p~'oduct: the appearance of an involuntJ~ry smoking eft'act when, in fact, the true relationship is with active smoking. 66 TABLE 7.--Description of prospective studies F~tar I lira)'ame G~rfinke| Giliiz Source or suh.k.cf~ CensUS papular|on. 29 Vo|unteers. ~ States. I{eollh lurvey health distrk~. Japan Unltt~l Sl~t¢~ pertlrlpanta, two urban are~, N~s~k~r i~pu/;~ion 91.4~ (FI 176.7~ (F/ 827 ~1~ (RXl 1,917 (FI Y~ d Pmollm,'nt I~ 185~1~ 1~2-1970 ~ y~r d f~lluwup I~1. I~ 1972 Met~ d rolluwul, R~rd llnk.~ ~tw~ Monltor~ by At~ R~rd llnk~ with risk fsct~ ~ u~ ~unl~, death R~iit~r death ~HIF~ ~rti~s~ f~m fil~ ~lmrtmen~ Verl~t~m of None Ver[~ met~ ~ ~ul ~n~r hlstol~y for fi~t 6 ~' f~iowup Inf~mst~n ~d.in~ s~ drinkin~ h.~. ~n~lR: ~m,kln~ dle~ry hb~ry. ~ti~, ~i~n~. sym~oml ~upsl~, ~r ~u~t~nal , r~p[ll[o~ ~nd heslth-r¢l~t~ v~rls~ extra, ~klng ~/ov~ular z~ m~l hl~ di~ I~x ~ I~iVe Iius~'a s~kinK at H~'e smoking S~u~'s z~klnl ~1~ entry: ~s~ker. e~- at entry: ~ker. entry: curtal or smoker. ~rrent ~Rnt $~er, and never ImoEer: ~m0ker {¢i~/dayl rig/day; ¢a4~e~ i~ke~ excl~ (quit ~5 yta~ ~f0r¢ Number ,4" lung mincer 200 IF) 153 IF! 6 IMl, B IF') d,..atha (n rmn.moker~ ~SOURt 'E: I liri~y.m. ~ 19~tl n, 1963, Ig64~, b,. Oud'i.kel I I~1 l. (]111|~ ~ el, ! l~4f. Mischtssificatlon of involuntary smoking exposure refers to the incorrect categorization of exposed subjects as nonexposcd and of nonexlmsed subjects as exposed. Most studies of lung cancer to have used the number of cigarettes smoked by spouses as a measure of exl~sure to involuntary smoking, and thus have disregarded duratio~ of exposure, exposure from other sources, and factors that, influeuce exposure, such as proximity to the smokers or size and ventilation of the room where the exposure occurred. Moreover, all 67
Page 44: TI07870654
TABLE 8.~Description of case-control studies . control Trlchopouloz Greece Che~ ~.nd cancer Orthopedic et .I (1981. hmpitais: TI' NS (F1 NS; u~ mar, till Self: n~. blinded Currt.nt znd i'm'met mt:~usea t~mo~nt. Corr~ ~ ~ New Oft,runs. Ho~iml~ ~0 NS (~ ~ ~ ~ ~ ~!9~ U~*d $cs~m 2~ F) mlsu~i ~ 313 ~ 31~0 M. 133 F); ma~c~d f~ ~tr~L ll~k 97% ~4~ ~ ~ ~ H~ ~ Four hmp~a~ Orcbowdic. s~ne bmpitalz: Fun~ (1~2) 84 NS (F) I~'NS; ~. ~ K~o ~ ~L Hmn~ K~ FA~,ht hmpir~k; Popu~io~ l~ ~; (I~83. 19~4~ 5~ NS (~ ~ for ~ r~ ~ S¢4f: ~t blind~i 97% ~ Curr~nt and former o~er co~bir.mncm. and United Smmz Mcs~ from one ~ Same hmpi~l C~. ~n- Sel~: no~ blinded 100~ 54% M ~4% F of 134 NS l~t or pm~ TABLE &--Continued (1965) Uui~d S¢~e~ ~ ~9 NS iF) f~ ~ ~ ~rk4e~ (bryn-y, • I. ~19~) . o~ Uni~d 134 NS (~ ~ ~ ~ N& I~ T107870654-
Page 45: TI07870655
TABLE 8.---Continu~d ~n~rd ? ? HYumki=~ ~nd . bomb 103 NS Self f~m,. 10%: coau'oL 12%) and Nat~ ¢~mm~ o~ (css~ alma~ 99% T107870655
Page 46: TI07870656
g ! 6' S S LowlHi~ ).~Ogl÷ I.lll ~0.29 30.F I-Ig ~).t. Low I~ I-~02l t- 140 411- yea~¢ pec d~ pec day I~ day FIGURE 5.--Relative risks and 95 percent confidence Intervals in case-control studies of passive smoking and lung cancer A~l~ ~ *l, I I~ flarflnkel ~ ml. li~ I*e~ d d. fin ~k T¢~I~ el sl ( I~ ~r~ ~ d. of the published studies have based.involuntary smoking exposure measures on questionnaires without validation of I.lzesc data with b[echemicai markers or environment~zl]y m(;asured concentrations of tobacco smoke constituents. Misclas~ificatioo of involuntary smoking exposure is likely to be r~ndom and to bias the effect measures toward the null (Copelsnd etal. 1977). Misc]assificatJon of exposure to environmental tobacco smoke i~ inherent in epidemiologica] studies of involuntary smoking. Tobscco smoking has not been restricted in most indoor environments until recently, and exposure hns been almost inevitabtc i, the home, the workplace, or other local.ions. Studies with the biological markers nicotine and coLinine confirm that tobacco mnoke exposure is widespread; detectable levels of these markers are fonnd even in people without .reported recent exposure. Thus, the exposure vari- ables employed in epidemiological studies do not sepa*'ate nnnex- posed from exposed subj,.~ts; instehd, they discriminate more ex- posed grdups front less exposed groups. As a resull., the epidemiologi- 72 cal approach is conservative in estimating the effects of involuntary smoking. A truly nonexposed but otherwise equivalent comparison popular{on has not been identified. The extent of the resulting bias cannot be readily estimated and probably varies with the exposure under consideration, which may be one reason for the variability in risk estimates obtained by different studies. Information bias is an added concern in case-control studies, since neither interviewer nor respondent bias can be ruled out, It is not feasible to blind interviewers to the case or control status of respondents because o1" the ust~ally obvious manifestations of lung cancer and because of the setting in which ~ome of the interviews are conducted. Moreover, blinding of interviewers and respondents to the study hylmthesie is difficult because the majority of questions are concerned with exposure to tobacco smoke. The direction of the information bias may be dependent on the type of respondent. Self- respondents may be more apt to Interpret their disease as related to exposure to tobacco smoke and thus overreport the exposure, However, the direction of the information bias is less clear when interviews are conducted with surrogate respondents. The ability of a surrogate to provide accurate information may depend on the relatiozzship of the surrogate respondent to the subject, whether the surrogate lived with the subject during the time frame of the questions asked, the degree of detail requested, and the amount of • time elapsed since the event in question (Gordis 1982; Pickle etal. 1983; I~rchen and Samet 1986). Surrogate respondents ,may mini- mize the relmrting of their own mnoking because of guilt, or may overreport about involuntary smoking exposure in an attempt to explain their relative's illness. Thus, depending on the direction of the information bias, it may dilute or strengthen the effect being measured (S,ckett 1979). In general, however, the information on smoking status and on amount smoked provided by surrogates has been found to be fairly comparable to that provided by the individuals themselves (Blot and McLaughlin 1985). Finally, participants and nonparticip.ants in case-control studies may be inherently different with respect to their exix~ure to involuntary smoking because their awareness of the hypothesis under stady may motivate the decision to participate. However, participants in case-control studies are generally not informed of the hypothesis u,der study. Spousal Exp,sure: Prospective Studies The Japanese Cohorl Study ' Hirayanm (1981a, 1983, 1984a) has presented data from a large cohort study that included 91,540 nonsmoking married women who were residenls of 29 health districts in Japan. Subjects were 40 years 73
Page 47: TI07870657
or age or older at enrollment in 1965; information was collected on smoking and drinking habiL~, diet (e.g., green-yellow vegetables, n|cat), occupatio==, and other health-related variables. '['he initial report on involuntary smoking was based on 14 years of followup (1966-1979). The husbands' smoking histories were avail- able for 174 of 240 lung cancer cases identified among the non- smoking married women (Hirayama 1981a); this number increased to 200 with 2 additional years of followt=p (Hirayama 1983, 1984a). Results pertaining to the association or spouses' lung cancer risk with the husbands' smoking were essentially identical in the flint and second reports. On the basis of .the smoking habits oF the husbands at entry, the 200 nonsmoking women were classified as married to a nonsmoker, an ex-smoker, or a current smoker. The lung cancer mortality ratios standardized by husband's age were 1.00, 1.36, 1.42, L58, and 1.91 for women whose husbands were nonsmokers, ex-smokers, and daily smokers of I to 14, 15 to 19, and 20 or more cigarettes, respectively (one-sided p for trend, 0.002). Similarly significant dose-respouse trends were observed when the mortality ratios were standardi~l by age of the wives, by occupation of the husbands (agricultural, industrial, other), by age and occupation of the husbands, and by the time period of observatien (1966--1977 versus 1978-t981). The risk of lung cancer bmong nonsmoking wives of smokers was rc~luced to 0.7 (two-sided p=0.05) if they ate green-yellow vegetables daily com- pared with 1.0 if they ate such vegetables less arian than daily (Hirayama 1984b). No other characteristic of the wives (e.g., drinking habits, parity, occupation, nonvegetable dietary items) or of hus- bands (e.g., drinking habits) was significantly predictive of lung cancer risk. Nonsmoklng men whese wives were smokers also showed an elevated I'ung cancer risk. On the basis of 67 lung cancers in nonsmoking married men, the lung cancer mortality ratios were 1.00, 2.14, and 2.31 if their wives had never smoked or had smoked 1 to 19 cigarettes or 20 or more cigarettes per day, respectively (one- sided p for trend, 0.023)(Hirayama 1984b). This study has been critically discussed in correspondence since its initlal publication. Because a detailed breakdown of the at-risk population was not presented in the initial report, the lung cancer mortality rate was thought by some to be higher in the unmarried nonsmoklng women than in the nonsrnoking women married to smokers (Rutsch 1981; Orundmann etal. 1981). This impression wa~ clarified by the researcher (Hirayama 1981b,c,d) and shown to be the result of incorrect Interpretation of data in the original paper. Other potential problems cited were sampling bias in the study cohort, misclassification in the diagnosis of lung cancer, mlschtssificatiou of the nonsmoking status of wives, misvlassification of involuntary 74 smoking,, exp;,stlre, failure to control for potential confounders, nnd inadeq.uate ~l.atistical treatment of data. Each of these points of criticism is di:~cussed below. MacDonald (198Is,b) questioned the representativeness of the 29 health distri~:ts selected in the study cohort and suggested that industrial p~llution, such as asbestos exposure from shipbuilding industric~ Sl,:Cific to the selected health districts, may have biased • the results. ! Iowever, the levels of exposure to this factor would bare to coincide with the husbands' smoking level to explain the effect observed. Such an association seems unlikely. If the cohort were not representative, the generalizibility but not the validity of the . finding~ would be challenged (Criqui 1979). The nccur~cy of the diagnosis of primary lung cancer on the basis of death certificates and the adequacy of the data without informa- tion on the histology of the tumor were questioned (Grundmann et al. 1981; MacDonald 1981a). From n sample of 23 cases, Hirayama. (1981b) reported that the distribution by histology of lung cancer in nonsmoking women whose husbands smoked was similar to that in women who smoked. Failure to discriminate in some cases between primary and metataetic lesions to the lung may be a potential problem with disease diagnosis. Although Hirayama was unable to assess the accuracy of the diagnosis listed on the death certificate, there is nn reason to believe that error in recording the causes of death of wives was influenced by the smoking habits 01~ their husbands, m=d any misclassification is likely to be random. Inclusion of nonlm~g ca~lcer cases would tend to bias the risk ratio toward unity or no clfect (Barren 1977; Greenland 1980). The relatively high risks observed for nonsmokers whose husbands smoked led to speculation that Japanese women may report them- selves ns nonsmokers when they actually smoke (Lehnert 1984~. However, some assurance of the reliability of the smoking data provided by the Japanese women comes from an investigation in Hiroshinm =rod Nagasaki (Akiba et ai. 1986) that found strong concordauce between s=noking status reported by the women them- selves and by their next of kin. Classifying nonsmoking womi~n solely on the basis of the smoking habits of their current husbands probably does not quantify their exposure wil h precision because it accounts for only one of the many possible sources or tobacco smoke exposure. Moreover, using the number o{" cigarettes smoked per day by the husbands as a measure of exposure dose assumes that the husbands' increasing daily cigarette c, msumption is directly related to an increasing ETS exposure of the wives (Kornegay and Kastenbaum 198~[; Lee 1982b). The analyses were further criticized for not accounting for potential co,t founding factors such as socioeconomic status (SES) and exposure to indoor air pollutants (e.g., from heating and cooking
Page 48: TI07870658
sources) (Sterling 1981). liowever0 Hirayanm showed a fairly consis- tent relationship between involuntary smoking exposure and lung cancer across SF_~ categories. The role of indoor air pollutants could not be addressed directly in the study, but data from one health district in the study indicated no association between heating or cooking practices and the smoking habil~ of the husbands (Hirayama 1981b). The researcher's failure to specifically de~ribe the methods for age standardization in the initial report led to speculation that the statistical methods used were incorrect (Kornegay and Kastenbeum 1981; Mantel 1981; Tsokos 1981; Lee 1981); however, the calculations were later confirmed (Harris and DttMouchel 1981; Hammond end Selikoff 1981). The choice of stratification variables used for age standardization was also criticized be~uve the i~usbands' ages instead of the wives' ages and 10-year age groups instead of narrower ones were used (Tsokos 1981; MacDonald 1981b). L, ter publicat!ons confirmed that similar results were obtained regardless el" the method of standardization (Hirayama 1984a). The American Cancer Society Cohort Study A second prospective study (Garfinkel 1981) that examined the effects of involuntary smoking was the American Cancer Society (ACS) study of about 1 million people living in 25 States. A self. administered questionnaire on education, residence, eccupotional exposure, and smoking nnd medical history was completed by the study subjects upon enrollment. This report on involuntary smoking was based on 12 years of followup (1960-1972) and included 176,739 nonsmoking married women whose husbands' smoking habits were available and whose husbands were never smokers or current smokers, in the total cohort of nonsmoking women, 564 lung cancer deaths occurred, and data on the husbands' smoking habits were available for 153 (27.1 perceut). Wives of ex-smokers and nf cigar or pipe smokers were excluded from the analysis. A small, statistically nonsignificant increased risk for lung cancer was found (br nonsmokers married to smokers. The mortality ratios for lung cancer in nonsmoking women were 1.0, 1.27, a=~d 1.I0 when the husbands were nonsmokers, daily, smokers of fewer than 20 cigarette.s, and daily smokers of 20 or more cigarettes, respectively. The results were essentially unchanged after accounting .for the potential confounding effects of age, race, educatio==, residence, and husband's occupational exposure. The ACS study, like the Japanese study, was not designed to study the long-term effects of involuntary smoking. Ilowever, the ACS s~udy does provide an estimate of the extent of misclassification of lung cancer. On the basis of medical record verification, the death 76 certificate diagnosis of lung cancer in nonsmoklng women was incorrect for 12 percent of the cases. Although confirmation of diagnosis was sought only for the first 6 years of fo|lowup, the available d, ta suggest that some misclaesification of lung cancer occurred. Ta the extent that passive smoking is related to lung cancer in mmsmokers, inclusion of unslung cancers would tend to dilute a true. effect. • A limitation of the ACS study is the nonavailability of smoking information on the husbands of a large proportion of the nonsmoking women who died of lung cancer. Because smoking habits are correlated with various social characteristics, this. large loss of infornmtion may have created a bias in this study. The researcher stated that an index of tobacco smoke exposure based only on smoking habits of current husbands may be particularly inadequate for the United States, with its high rate of divorce and substantial proportion nf women working outside the home. This specular.ion is supported hy data from a group of 37,881 nonsmokers and smokers wire were members of a health plan in California, Friedman and c~dleagues (1983) stated that 47 percent of .the nonsmoking women and 39 percent of the nonsmoking men married to smokers reported n,~ exposure at home. Moreover, being married to a nonsmoker did not assure the absence of exposure to tobacco smoke, since 40 percent of the nonsmoking women and 49 percent of the nonsmokinf¢ men married to nonsmokers reported some exposure to tobacco sm~tke during the week. Thus, random misclassificatlon could have biased the results toward unity and led to an undersell-. mate of the effect of passive smoking, The Scoltish Study Gillie aml colleagues (1984) conducted a prospective cohort study of 16,171 Scottish men and women, aged 45 to 64 years, from two urban aras, who attended a muitipha~ic health screening clinic between 1972 and 1976. A questionnaire on smoking habits and symptoms of respiratory and cardiovascular diseases was completed at entry into the study. The preliminary analysis of involuntary smoking, representing 6 to 10 years of follewup, was based on the 2,744 nonsmokers among the 8,128 subjects who lived as couples and could be paired according to smoking habits. Subjects who lived alone or whose partner did not participate and ex-smokers who had stopped smoking for 5 years or more Were excluded. The nonsmokers were classified as nonsmokers not expesed to environmental tobacco smoke or as nonsmokers exposed to environmental tobacco smoke, according to the smoking habits of their spouses. A higher age-standardized lung cancer mortality rate was reported for nonsmoking men exposed to tobacco smoke (13 per 10,000) than
Page 49: TI07870659
(,or nonsmoking men not exposed (4 Imr 10,000); however, no statistical tests were conducted because of the small number of cancers. Lung cancer rah.e were similar for nonsmoking women regardless of the status of their exposure to tobacco smoke (4 per 10,000). The extremely small number of observed lung cancer deaths (6 men, 8 women) limit the interpretation o(, the atudy's findings. Spousal Exp,.sure: Case-Cfmtrvl Studies Table B summarizes the case-control studies that have examined the relationship between involuntary smoking exposure and lung cancer. The Greek Study Trichopoulos and colleagues (1981, 1983; Trichopoulos 1984) examined the effect of involuntary smoking on lung cancer risk in a case-control study of 51 Caucasian female lung cancer patients (excluding adenocarcinoma and terminal bronchiolar carcinomas) from three chest hospitals and 163 female controls from an orthopedic hospital in Athens, Greece. All subjects were interviewed in person by one physician who questioned them regarding their persoual smoking habits and those of t.helr current and former husbands. Thirty-five percent of the cases were diagnosed only on the basis of clinical or radiologic infornintioa; the remainder were cytologically (37 percent) or histologically (28 percent) confirmed. Nonemoking women were classified by th~ smoking habits of their current or former husbands. Husbands were nonsmokers if they had never smoked or had stopp~l smoking more than 20 years previous- ly, ex-smokers if they etoplmd 5 to 20 years previously, and current smokers if they were smoking or had stopped less than 5 years before the interview. Being never married, widowed, or divorced was equated as being married to a nonsmoker or an ex-smoker, depend- ing on the length of time in the category. The initial report was based On 40 nonsmoking cases and 149 nonsmoking controls. The odds ratios (OP, s) (,or women married to nonsmokers, ex-smokers, current smokers o[I to 20 cigarettes per day, and current amokers of 21 or more cigarettes per day were 1.0, 1.9, 2.4, and 3.4, respectively (two-aided p for trend, < 0.02). In a later report on 77 nonsmoking cases and 225 noasmoking coutrole, the ORs were somewlmt lower: 1.0, 1.9, 1.9, and 2.5, respectively (Trichopoules et el. 1983; Trichopoulos 1984). The findings of this study were questioned becaus~ the diagnosis of cancer was not pathologically copfirmed for 35 percent of the cases (Hammond and Selikoff 1981; Lee 1982b). The inclusion of cases that were not lung cancers would tend to dilute the results toward the null because they may not be related to involuntary smoking. 78 Termi=ml broncl~ial (alveolar) carcinoma and adenocarcinoma of the lung were ,,xcluded from the pathologically confirmed group; this exclusion may have been premature (Hammond and Selikoff 1981; Kabat =rod Wynder 1984), as the causal association between person" ~ smoking anti adenocarcinoma o(' ti~e lung is well established (lib. ~ 1986). I]ccat~se the controls were selected from a different hospital than were the cases, selection bias cannot be ruled out, Interviewer bias is also possible, since all subjects were interviewed'~by a single physician who knew the case or control status of each ~ubject, and also knew the hypothesis under investigation. The index of exposure to tobacco smoke used in this study included the smoking habits of former and current husbands. Since the definitiou of ex-smokers excluded those who had stopped smoking recently (within the last 5 years), it was unanticipated that the risks observed for women whose husbands were ex-smokers (i.e,, quit 5 to 20 years previously) were as high as for those whose husbands were current: smackers. Additional infornmtlon on the smoking habits of these ex-snmkers would be valuable. The Louisiaua Study The case-control study by Correa and colleagues (1983) was based on 1,338 primary lm=g cancer cases, of which 97 percent were pathologically confirmed. Controls (N 1,393) were matched to cases by race, sex, and age (±5 years) and were patients at the same hospitals as cases but without a diagnosis related to tobacco smoking. Standardized interviews were conducted with the subjects (76 percent o(' cases, 89 percent of controls) or their next of kin. Questions o~ occupation, residency, personal smoking and drinking habits, and ~moking habits (including type of tobacco smoked and amount aml duration of smoking) of the current spouse and parents were asked. Thirty nonsmoking ever-married lung cancer (excluding bron- chloalveolar ceil) patients (8 men, 22 women) and 313 ever-muffled nonsmoking controls (180 men, 133 women) were classified according to their spouse's total lifetime pack-years and current daily amount smoked at the time of interview. A(,ter adjusting for sex, ORs of 1,00, 1.48, and 3.11 were observed when spouses had smoked none, l to 40 pack-years, and _>41 pack-years, respectively (two-sided: p<O,05), The results based on current daily ~umber of cigarettes smoked by spouses were similar. The study is limited by the small number of nonsmoking cases, but the consistency of the results for men and women strengthens the findings. Misclassification of involuntary smoking is possible because only smoking habits of the current husband were assessed, ignoring the effect ~,(, divorce, remarriage, and exposure from coworkers, Exposure from parents during childhood was determined, but case 79
Page 50: TI07870660
numbers were too small for a meaningful analysis of this factor among nonsmokers. The Hong Kong Studies The high rates of lung cancer, particularly adenocarcinoma of the lung, among women of Chinese descent i~t Hong Kong.are unexpect- ed in the face of their low rates of tobacco smokiug. The role of involuntary smoking was investigated in two studies conducted in Hong Kong (Chan et al. 1979; Chan and Fung 1982; Koo et ai. 1983, 1984). Chan and colleagues (1979) examined the role of involunta,T smoking among 84 female lung cancer patients and 139 orthopedic control patients who had never smoked. Of the 84 nm~smoking cases, 69 (82 percent) were pathologically confirmed, and 38 of these 69 cases were adenocarcinoma of the lung. The controls were from the same hospitals as the cases, but were not individually matched to the cases on any characteristics. Cases and controls were questioned regarding their residence, education, occupation, cooking practices, and personal smoking habit. One question on exposure to others' tobacco smoke was included: "Are you exposed to the tobacco smoke of others at home or at work?" The researchers reported that the controls lived with smoking husbands more frequently (47.5 percent) than the cases (40.6 percent) (OR 0.77), but did not explain how this question was used to classify the habits of the spouse alone. The methed used to classify currently unmarried respondents (i.e., never married, wid- owed, divorced) with regard to exposure to their spouses' smoking was not described, and it is not known if the nonsmoking cases and controls were comparable in terms of current marital and employ- ment status. Thus, insufficient information on the measure used to assess ETS exposure, and on the comparability of tlm nonsmoklng cases and controls, limits iutsrpretation of this study's results. The study by Koo and colleagues (1983, 1984) involved 200 Chinese female~.lung cancer patients who were identified from eight hospitals in Hong Kong; almost all cases were pathologically confirmed (97 percent). Among these women, 88 had never smoked, of whom 52 {59 percent) had adenocarcinomas of the lung. An equal number ~f "healthy" population controls, individually matched to cases by age~ (±5 years), socioeconomic status, and district of residence, were interviewed. Among the controls, 137 had never smoked. Using a semistructured questionnaire, taped interviews were obtained and informatiou on resikience, occupation, fmnily and medical history, personal smoking habits, and smoking habits of all cohabitants and coworkers was obtained. ETS exposure was quanti- fied in hours and years according to who {i.e., husband, parents, in- laws, children, others) smoked in the subject's prc~ence and where 8O (i.e., at horny, at work) the exposure occurred. The analysis was based on a ctmmlative smoke exposure index (in total hours and total. years) specific to place of exposure. The investigators concluded that there was no association between involuntary smoking and lung cancer in nonsmoking Chinese women, regardless of the index of smoke exposure used. A small, but statistically nonsignificant," increased risk (RR 1.24) was associated with auy exposure to tobacco smoke. There were no significant differences between the cases and the controls in total hours or total years of eXlSmure. The results remained unchanged when exposure hours were categorized into three levels of exposure. Odds ratios of 1.00, 1.28, a~td 1.02 were associated with no, low (<35,000 hours), and high (> 35,000 hours) exposure levels, respectively, There was no apparent trend of lung cancer risk with the age when exposure to tobacco smoke began. The ORs for never exposed and first exposed at ages 0 to 19, 20 to 39~ and 40 or older ware 1.00~ 0.96, 1.53, and 0.91, respectively (Koo et al. 1984). Analysis by cell type suggested that the eflbcts of involuntary smoking may be more pronounced for Kreyberg ! tumors (squamous, small-cell, and large-cell carcinomas) (OR 1.47, 9~ percent C.I. 0.64, 3.36~ than for adenocaroinoma (OR 1.11, 95 I~rcent C.I. 0.49, 2.50) (Koo et al. 1985), but these numbers were instal|. The design of this study addressed the criticisms of other studies that an index of involuntary smoking exposure based only on spouses' smoking habits is inadequate, and broadened the exposure assessment to include all locations of tobacco smoke exposure, However, the cumulative exposure index created in this study may have limited validity. Unlike personal smoking, where there is essentially one source (personal smoking), one dose (usual or maximum amount smoked), and one duration of exposure (age at start and ag~: at stop), ETS exposure derives from diverse sources at differeltt d~mes and durations of exposure. The accuracy of the information on exposure to ETS will depend on the amount of detail requested, the age of the respondent, the temporal course of the expesure, and the source of the exposure. Weighing each type of exposure equally in a cumulative index (in total hours) may be incorrect because it assumes that all sources of exposure should be qua.ntified in the same way and that each source of tobacco smoke contributes C<luaily, disregarding intimacy of contact and proximity to smokers nnd conditions of exposure (e.g., room size, ventilatory factors). Thas, random misclassification of the exposure vari~ibla by inclusion of data from less relevant exposures than spousal smoking may ohscure an association of.involuntary smoking exposure with lung cancer risk. In this study, interviewer and respondent bias should also be considered because a structured questionnaire was not used. ~]
Page 51: TI07870661
An Ongoing Study el Tobacco-Related Cancers All of the cases of primary lung cancer in nonsmokers were selected (Kabat and Wynder 1984) froin an ongoing case-control study of tobacco-related cuncer conducted in five U.S. cities between 1971 and 1980 (Wynder and Stellman 1977). For each case, one control was individually matched by age (+5 years), sex, race, hospital, date of interview (-I-2 years), and nonsmoking status. Controls were selected from a large pool of hespltali:~ed patients who were interviewed over the same time period as the cases and had diseases not related to tobacco smoking. Information on demo- graphic factors, residence, height and'weight, drinking habits, previous diseases, and occupational exposure were obtained. Ques- tions on tobacco mnoke espesure at work, at home, mid frmn current spouss were added in 1978 and revised in 1979. Information on exposure was available for 25 of 37 nonsmoking male cases, 63 of 97 nonsmoking female cases, and their respective matched controls. A higher percentage of female controls reported exposure to at home (32 percent), at work (89 percent), and from spouses (60 percent) than did female cases. The percent of female cases who reported exposure at home, at work, and from spouses were 30, 49, and 64 percent, respectively. None of the case-control differences in women were statistically significant. Male cases reported more frequent exposu're at work (OR 3.27, p = 0.045) and at home (OR 1.26), but no difference in the smoking status of their spouses (OR 1.00). The process for selecting the nonmuoking controls front the larger pool of controls in the ongoing study and for selecting the non- smoking cases and controls who were questioned with regard to ETS exposure were not described adequately. It is not clear whether the 25 ol'37 male and 53 o1"97 female nonsmoking cases and controls who provided information on involuntary smoking were all interviewed during or after 1978 when the questions on involuntary smoking were introduced. The proportion seemed high, since it represented 68 percent or male and 55 percent of female nonsmoking cases interviewed during the 10 years o1. data collection. The study was not designed to specifically address the effect of involuntary smoking, and a variable subset of questipns on involuntary smoking was asked, depending on when the subjects were interviewed. Misclassifi. cation of the exposure is possible because it is not clear whether the cases and controls answered the same set of questions aml whether a comparable amount of information was obtained. The researchers acknowledged the limitations of this study and presented its resull~ as preliminary findings. 82 The Los An!leles Counly Sludy In the c~,.~,~--co.trol study by Wu and colleagues (1985), 220 white female ]m~g cancer patients (149 with adenocarcinoma and 71 with squamous cell carcinonm) and 220 l~pulation controls were individu- ally matched on sex, race, age (±5 years), and neighborhood of residence. C==ses were ideqtified from the population-based tumor registry of Los Angeles County. All cases were histologically confirmed; t.he histological type was based on the pathology report from the Im:~pital of diagnosis. Using a sl.ructared ques~;ionnaire, cases and controls were directly interviewed by telephone and were asked about their own personal smoking Imbits and the smoking habits (amount and years of smoking) of current and former husbands, parents, and other household members during childhood and adult life, Exposure to tobacco smol~e at work (in hours per day) was obtained for each job o1. at least 6 n,mtbs' duration. Information on medical and reproduc- tive history, beating and cooking sources, and dietary intake of vitamin A w~:re obtained. Of 149 patients with adenocarcinoma of the lung, 29 had never smoked, nor had 2 of 71 patients with squamous cell carcinoma. The analysis of i,vol~ntary smoking was based on 29 nonsmokers among the 149 adenocarclnoma cases and 62 nonsmokers among the controls. A subject was classified as' married to a smoker if any of her husbands h~d ever smoked. Similarly, a subject was considered exposed at work if she was exposed to tobacco smoke for at least 1 hour per dtty at any of her jobs. There were small, but nonsignifi- cantly increased risks associated with ETS exposure from spouse or spouses (OR 1.2; 95 percent C.I. 0.2, 1.7), and from cowarkers (OR 1,3; 95 percent C.I. 0.5, 3.3). Increased risk was not associated with smoke exposure from either parent (OR 0.6; 95 percent C,L 0.2, Exposure t~, tobacco smoke from spouses and from coworkers was combi==ed in an index representing smoke exposure during adult life, There was an increasing trend in risk with increasing years of exposure. The ORs were 1.0, 1.2, and 2.0 for O, I to 30, and 31 or more years .of involuntary mnoking exposure during adult life, respective- ly, but the results were not statistically significant. Because the exposures may have occurred concurrently, the years of exposure represented units of exposur~ rather than calendar years o1. expo- sure. This study is limited by the small number of itonsmoking cases and controls. Unlike the two. case-control studies that excluded adenocarci,oma or bronchioalveolar cell carcinoma (Trichopoulos et el. 1981; Correa et el. 1983), cases in this analysis were of these cell types (17 adenocarcinoma, 12 bronchioalveolar); this case mix may explain the weak association observed. 83
Page 52: TI07870662
The Four Hospitals Study A case-control study by Garfinkel and colleagues (1985) included 134 nonsmoking female .lung cancer cases selected from three hospitals in New Jersey and one in Ohio over an 11-Year period, 1971-1981. Medical records served as the initial source of informa- tion on smoking status of the subject, and the nonsmoking status of each case and control was verified at interview. Three conl~rols, colorectal cancer patients matched to cases by age (:l:5 years) aml hospital, were iuterviewed for each ease, giving a total of 402 controls. All diagnoses of cases and controls .were pathologically confirmed. Interviewers, blinded to the diagnosis of the subjects and to the study hypothesis, administered a standard questionnaire to subjects or their next of kin. Information on the smoking habits of current spouse (total and amount smoked at homo), tobacco smoke from other sources (in hours per day at home, at work, and in other settings), and exposure to tobacco smoke during childhood were obtained. Subjec.ts were classified according to the smoking habits of current husbands. Smoking habits of a cohabitant in the same household was used for single women or those who no longer, lived with their spouses. Of the cases, 57 percent were classified according to the smoking habits of husbands; the corresponding percentage iu controls was not provided. N~nsmoking women livi~g with a smoker showed an elevated risk for lung cancer (OR 1.31). The ORs for lung cancer in nonsmoking women were 1.00, 1.15, 1.08, and 2.11 when the husbands were nonsmokers, daily smokers'of less than 10, 10 to 19, and 20 or more cigarettes at home, respectively (one-sided p for trend, <0.025). Similarly, a significant positive linear trend (one- sided p < 0.025) was shown when the husbands' total amount smoked was categorized into four levels. However, there was no apparent dose-related trend by years of exposure to tile husbands' s,noking (0, < 20, 20-29, 30-39, 40+ years). There was no apparent association between lung cancer and tobacco smoke exposure from other sources. Cases and controls did not differ in their reported exposure to tobacco smoke during childhood or in their average hours of exposure per day to other's tobacco smoke during the last 5 years and 25 years before diagnosis. The results remainc~l unchanged when exposures at home, at work, and in other settings were examined separately. The odds ratios were highest for exposure in other settings, but they were based on a small number of positive responses. There was no consistent pattern by histelogic type. Squamous cell carcinoma showed the strongest relationship with involuntary smoking, based on the husbands' smoking habits at home (RIt 5.0, 95 percent C.I. 1.4, 20.D, hut failed to show any relationship when involuntary smoking exposure was classified by hours of daily exposure. 84 This cuss-control study has the largest number of nonsmoking lung cancer cases to date and p~;ovides estimates of the mlaclassifica- ties of disease and of the smoking status of the subjects. Among the published studies on involuntary smoking, this is tile only one involvi~g imlependent verification of the diagnoses of all cases. This verification showed that 1~ perceut of the cases classified as lung cancer were not primary cancers of the lung. This study showed that 40 percent of the women with lung cancer who had been classified as nonsmokers tor smoking not stated) on hospital records had actually smoked, compared with 9 percent of the controls. The inclusion of lung cancer patients who had actually smoked would have substan- tially increased the odds ratios with involuntary smoking, because 81 percent of the potentially misclassified cases had husbands who smoked compared with 68 percent of the "true" nousmoking patients with lung censer. It should be noted that none of the other studies on involuntary smoking and lung cancer based class!fication of smoking status solely on data from medical records. The measure of involun- tary smoking based on smoking habits of husbands attempted to dilTereutiatv between current total smoking habits and current smoking habits at home. The interview also included ETS exposure not only at home but at work and in other settings. The exposure information presented in this study is potentially limited by its extensive reliance on surrogate interviews, Owing to the need to ttssemble sufficient nonsmoking cases, diagnoses as early as 1971 were included, so proxies were interviewed for a high percentage of the deceased cases. Among the cases, 12 percent of the interviews were conducted with the subject, 25 percent with the husband, 3ti percent with offspring, and 27 percent with an informant who had known the subject for at least 25 years. The corresponding distribution of informants in the control series was not present~i. Although the ORs did not vary consistently by respondent group, the OR for smoke exposure based on the hus- bands' smoking tended to be lower when husbands Were the respondents. Presumably, the husbands reported their own smoking habits, and it cannot be determined whether bias resulted. The information provided by surrogates may be particularly inaccurate for exposures outside the home. Systematic bias between personal and surrogate interviews and systematic bias by informant status must also be considered. Given that the topic .of involuntary smoking is potentially sensitive for the family of a lung cancer patient, it is possible that some surrogates may not have provided accurate histories, particularly with regard to their own smoking habits. Surrogate |'espondents for cases might have been more likely ~o underrelmrl, exposure titan those for controls; such differential reporting would have led to an underestimation of the true effect, The multiple regression analysis performed in this study did take 85
Page 53: TI07870663
respondent status into consideration, and it was de,ordained that this factor could not account for the relationship with husband's smoking status (Garfinkel et al. 19~6). It is not clear if the colorectal cancer controls were diagnosed in the same years as the lung cancer cases. Because the response patterns of relatives who are interviewed after the recent death of a subject may differ from responses obtained lung after the subject has died, another source of bias may have beeu intruduced. A United Kingdom Study In an ongoing hospital-based case-cont.rol study of lung cancer, chronic bronchitis, ischemic heart disease, and stroke, Lee and colleagues (1986) examined the role of involuntary smoking in a group of inpatlents interviewed after 1979, when, to cover involun- tary smoking, the questimmaire was extended to married patients. An attempt was also made to interview the spouses of the married nonsmoking lung cancer patients and the spouses of the comparisou group. The interview on involuntary smoking ad~ninistered to hospital lnpatlents included questions on the smoking habits of their first spouse and on ETS exposure at home, at work, during travel, and during leisure, based on a subjective four-point scale. Spouses of nonsmokers were asked about their own smoking habits at the time of interview, during the year of admission of the subject, and during the course of their marriage. A total of 56 lung cancer cases among married lifelong nonsmok- ers was identified; two controls were selected for each. case and individually matched on noasmoking status, sex, marital status, age, and hospital. Among the 66 cases and I12 controls, information on spouses' smoking habits was available for 29 (52 percent) cases and ~9 (56 percent) 9ontrols from an interview conducted while the patient was still in the hospital. Interviews with spouses were obtained for 34 (61 percent) of the cases and 80 (71 percent) of the controls. Using both of these sources of information, the smoking habits of spouses were available for 47 (84 percent) of the eases and 96 (86 percent) of the controls. Nine risk estimates were presented for spouses' smoking, for each of the three sources of information (subject, spouse, and both), separately for men and women and for both sexes combined. The researchers concluded that spousal smoking was not associated with lung cancer because ri~ks were not consistently elevated. When their spouses reported about their own smoking, a RR of 1.60 (95 percent C.I. 0.44, 5.78) was found for lung cancer in the women. In contrast, a RR of 0.75 (9[$ percent C.I. 0.24, 2.40) was found when the female subjects reported about the smoking habits of their spooses. On the o0~er hand, a RR of t.01 (95 percent C.[. 0.9.3, 4.41) was found for male lung cancer patients when 86 their sl,ouse:~ reported about their own smoking, whereas the risk was 1.5:l (.95 percent C.I. 0.37, 6.34) when the male patients evaluated their spoascs' smoking habits. As might be expected, the combined risk in relation to spouses' smoking for both sexes and both sources of informati~n was near unity, at 1.11 (95 percent C.I, 0.59, Using u secn==d group of cootrols, presumably all of the nonsmokers who had responded to the hospital inpatient interview on involun- tary smokl,g, the researchers reported no significant case and control diff,,rences in .exposure to ETS at home, at work, during travel or leimtre, from spouses, or for all sources combined. This study has several limitations that must be cunsidered in interpreting its results. Although the study attempted to verify involuntary smoking front spouses by using two sources of informa- tion, dtml n,ports were obtained for only 16 (29 percent) of the cases and 43 (38 i,ercent) of the controls. The questions on involuntary smoking included exposure from other sources, but they were based on a subjective scale, and different groups of controls were used for the amdyses. Information was not presented on the accuracy of the diagnusis of lung cancer or on the histological types included in the study. Moreover, the investigators did not verify the smoking status of the subjects during the interviews with spouses. The study's inconsistent findings by source of information and by sex m==y telleer the absence of an association between involun~ry smoki==g and lung cancer in this population, or may reflect method- oiogical problems in the design or conduct of the study. The main study was not originally designed to investigate the effects of involuutary smoking. However, because of interest in this issue, the investigato~'~ decided to "increase the number of interviews of married lung cancer cases and controls." The representatlven~ss of the ca.~es a==d the controls cannot be determined because there may have been differential selection factors in enrolling nonsmoking lung cancer caeca and controls into the study; thus, selection bias cannot be ruled out. The method for selecting thiz 112 nonsmoking controls was not adcquately described in the report; it is not clear whether they were .selected from the pool of all controls for lung cancer or from the pool of controls for the four diseases under study. There is also an apparent discrepancy in the number of nonsmoking cases cited in th*~ text and presented in the results. The report cited 44 never smolcers among a total of 792 lung cancer patients who comploted the involuntary smoking questio~maires when they were in the hospital. However, the analysis for an involuntary smoking effect based on interviews with subjects in the hospital showed only 29 lung can~:er patients; this discrepancy was not explained, The risk~ in relation to smoking by spouses varied with the source of informal.ion. The risk estimates tended to be higher when the raspendentn were men, either reporting abou~ their own s.moktng,
Page 54: TI07870664
h~bits or the smoking habits of their spouses. Tibia pattern could result if the male respondents overestimated exposure to environ- mental tobacco smoke or if the female respondents uuderestimated exposure. An analysis of the patients (16 cases and 43 controls) for whom data were provided by the spouses and by the subjects themselves showed a 97 percent concordance for spouses" smoking. during the year of the interview and 85 percent concordance for spouses' smoking some time during the marriage. Lack of specificity in the question asked regarding spouses' smoking any time during the marriage may partly explain the discrepancy in response. To the extent that there is no co,tsistent pattern in the direction of this discrepancy, it can be assumed that a spouse was a smoker sometime during the marriage if either respondent answered positively. On the basis of this assumption, RRs of 1.47 (spouses of 4 of 7 cases and 7 of 18 male coatrols smoked) and 1.39 (spouses orb of 9 female cases and 16 of 25 female controls) were found for the men and the women, respectively, in relation to their spouses' smoking. The risk estimates were not statistically significant, but the number o1" subjects was small. The Japanese Case-Control Sludy The study by Akiba and colleagues (1986) included 428 (264 men, 164 women) incident primary lung cancer cases diegnosed between 1971 and 1980 in a cohort o1" 110,000 Hiroshima and Nagasaki atomic bomb survivors. Coatrols were selected among coho,'t members who did not have cancer. For deceased cases, correspondi,tg controls were selected from among cohort members who died o1" causes other than cancer or chronic respiratory disease. The controls were individually matched to cases on a number of factors, including age, sex, birth year (:i:2 years), city of residence, and vital status; a variable number of controls was interviewed, depending on the place of residence. Of the lung cancers, 29 percent were pathologically confirmed, 43 percent were radiologically or clinically diag~msed, and the remain- der were found at autopsy. Subjects or their next of kin were interviewed regarding the subjects' personal smoking, smoking habits of current spouses a,~d parents, and occupation. Less than 10 percent of the interviews with the men and about 20 percent of the interviews with the women were conducted with the subjects themselves. The diutributions of the next of kin interviewed were similar I'or the cases and the controls. Among the cases, 103 (19 me,~, 84 women) had =lever smoked, compared with 380 controls (110 men, 270 women). An elevated lung cancer risk associated with smoking habits of spouses was observed for men and women. An OR of 1.8 (95 percent C.[. 0.5, 5.6) was found. for nonsmoking me~= married to wives who smoked a,~d au OR of 1.5 (95 percent C.I. 1.0, 2.5) for nonsmoking women married to husbands who smoked. Lung cancer risk increased with the amount smoked per day by the husband, with an OR of 2.1 for women whese husbands smoked 30 or more cigarettes per day. The OR was higher (1:8) among women who had been exposed within the past 10 years cempared with those who bad been exposed before that time (OR 1.3). However, an increasing duration of exposure to husbands' smoking was not associated with a monotonic trend of increasing risk. The relation between lung cancer and husbands' smoking was observed regardless of the occupation of wives .(housewife, white- 'collar, blue-collar), but the highest odds ratio was for women who worked in hi,recoiler jobs and whose husbands were heavy smokers (OR 3.2). Despite a high proportion of proxy interviews, the distribution of informant tyim was comparable for cases and controls; this compara- bility minimizes the possibility of recall bias. The high concordance between the subjects' reported smoking status in a previous survey and the information from the next of kin is reassuring. Although a high propertion of cases had no histological confirmation, an increased risk was observed regardless of the method of diagnosis. This study also provided an opportunity to test for potential confounding factors, including radiation exposure and occupation, but none were identified. The Swedisl~ Study The study by Pershagen and associates (in press) included 67 incidents of primary lung cancer cases from a cohort of 27,409 nonsmoking Swedish women who were participants in a national census survey or in a twin registry. Two controls were selected from each source and were matched to cases on year of birth, and on vital status if they were selected from the twin registry. Subjects or ~heir next of kin (excluding husbands) were mailed a questionnaire that assessed their exposure to tobacco smoke from parents and the husband with whom the subject had lived the longest time. Information on residential and occupational .history was also obt~dned. Elevated lung cancer risk associated with the smoking habits of spouses was observed. For all lung cancers, ORs of 1,0, 1.0, and 3.2 were observed for women who had no, low (< 15 cigarettes/day or < 1 pack of pipe tobacco/week or <30 years of marriage), and high exposure to their husbands' smoking, respectively, The increased risk was fotmd primarily for squamous and small cell carcinomas (OR 3.3); consistent effects could not be detected for other histologic types. On the basis of the approximately 75 percent of responddnts who p~.ovidcd information on parental smoking, there was no effect 89
Page 55: TI07870665
of parental smokiug on risk for all lung cancers, al~r controlling for , the husbands'smoking. The study is similar in design to the Japanese case-control study (Akiba et sl. 1986), except that the Swedish investigators obtained histologie confirmation for all of the cases under study. Moreover, this study excluded husbands as inl'ormants, so that a potential bias associated with husbands' reporting their own smoking habits could be eliminated. The investigators contended that the finding of an association only for squamous cell and small cell carcinomas argue~ against a spurious fii~ding because it is unlikely that the next-of-kin informers would have been aware of the histologtc types diagnosed in the cases. The German Sludy The last in this description of studies to date based ou the case- control design is a German study (Kneth et el. 1983), interpreted by the investigators as showing a role for involuntary smoking in the etiology of lung cancer. Of 39 nonsmoking women with lung cancer, 24 (62 percent) had lived with smokers. Although a comparison group was not interviewed, the investigators surmised that this frequency of smokers in the household was about three times higher thaa expected from census-based smoking statistics for men in the age group 60 to 69. The limitations of this study ~re evident; the researchers assumed that smoking prevalences for men were indicn- tire of smoking prevalences for members of the cases' households and a specific control series was not enrolled. Other Sources of Tobacco Smoke Exposu're Parenlal Smoking Recently evaluated as a risk factor I'or lung cancer, parental smoking is of interest because of the large number o1" exposed children, the age nt which it begins, and its duration. Results of this association are variable, demoustratlng no association, association with just mothers' smoking, or association with both mothers', and fathers' smoking. Correa and colleagues (1983) rel~rted an associa- tion between lung cancer risk and the mothers' smoking in the men, which persisted arter adjusting for personal mnoking habits (OR 1.5, p<0.01). This association was not observed in the women, and increased risk was not related to fathers' smoking in either the men or the women. A positive association between the mother's smoking and lung cancer risk was reported in a study of female lung cancer, but the result was not statistically significant after adjusting for personal smoking habits (()R 1.7, 95 percent C.I. 0.8, 3.5) (Wu et el. 198~). Another study suggested that the father's smoking (OR 2.5) and the mother's smoking (OR 1.8) were each relatc~l to increased lung cancer risk after adjusting for age and individual smoking habits (Slmdler, Wilcox, Everson 1985b). These results were based on small numb,~rs, however, particularly for the mother's smoking (in 2 of 15 cases, the mother smoked). Significant associations with maternal or paternal smoking were not found in two other studies (Akiba eL el. 1986; Pershagen et el. in pre~); however, information was lacking for about one-tidrd of the subjects. Since smoking habits of children are highly correlated with smoking habits of parents, it is difficult, ew,n after adjusting for personal smoking habits, to be certain that an iridependent effect of parental smoking has been observed. Hone of tl~e studies with data on parental mnoking had sufficient numbers to examine the effects of parental smoking on nonsmokers, In Louisiamt, one nonsmoking case had a mother who smoked (Correa et zd. 1983). In Hang Kong, 6 percent (5/88) of the nonsmokiag cases reported that their parents smoked compared with 2 perct~zzt (3/137) of the nonsmoking controls (Ken et el. 1984). in Los Angeles, the frequencies of smoking by mothers and fathers were lower I'or nonsmoking cases (4 percent mothers, 28 percent fathers) th=m for nonsmoking co|ztrols (11 percent mothers, 35 percent fathers) (Wuet el. 1985). Exposure to tobacco products during childhood was not significantly different between cases and controls (nit 0.91, 95 percent C.I. 0.74, 1.12) in another study (Garfinkel et el. 1985). It is diffi¢:ult to obtain accurate information regarding remote childhood events, so data on parental smoking tend to be crude or unavailable. Information on maternal smoking during pregnancy would not be available unless the parents could be interviewed. Because lung cancer occurs most often among older persons, interview with a parent will generally be impossible. Moreover, information on parental smoking will most likely be unavailable or meaningle~, if surrogate interviews are conducted. Coworker's Smoking • The workplace, an important source of tobacco smoke,exposure, was not co~sidered in the early studies on involuntary smoking, Later case-,'ontrol studies provided some informntlon on tobacco .exposure at work, but the data were limited and inconclusive, l~abat and Wyndcr (1984) reported a statistically significant positive association between tobacco smoke exposure at work for men but not for women. In comparison with controls, patients with cancer in Hang Kong reported more hours and years of exposure at the workplace, hut only two cases and four controls had exposure to tobacco ram,lie at work (Ken et el. 1984). Data in the Los Angeles study suggc,ted that the workplace may be an important source of exposure to tobacco smoke. A small increased risk wbs observed for
Page 56: TI07870666
any exposure at work, and an index combining exposure from coworkers and spouse or spouses indicated a trend of increusing risk with increasing exposure (Wuet al. 198~). Garfinkel and colleagues (1986) found no differences between cases and cnntrols in thei~ exposure to tobacco smoke at work during either the/~ years or the 25 years before diagnosis, and a similar lack of an association was also repof~d by Lee and colleagues (1986). Dose-Response Relationship An important factor in the appraisal of the relatiozzship between involuntary smoking and lung cancer is the assessment of dose- respouse relationships. However, this analysis hing~m on the defini- tion of exposure. Data on act|re smoking and lung cancer suggest that exposure measures consid.ering amount, duration, and recency of exposure should be employed in examinb~g dosc-respoase rela- tionships in active smokers {Doll and Pete 1978; Pathak et al. 1986). Misclassification of exposure to ETS may be expected when exposure categorization is based on the amount or the duratio,~ of smoking by the current spouse or cohabitant, as current exposure from one source may not adequately measure past exposure or cumulati.ve exposure. Moreover, these exposure variables may not be indicfitive of the exposure dose to the respiratory tract because dose determi- nants such as ventilation rates, breathing pattern, and deposition factors are unaccouuted for. Research is now being directed toward the integration of informa- tion from questionnaire resl~ases, biochemical studies, and environ- mental sampling to determine the most accurate meusures of exposure to the respiratory tract. However, exposure assessme.nta for epidemiological studies of lung cancer and involuntary smoking will remain limited by tlm inaccurate recall of exposures that occurred as much as 40 to 50 years earlier. Nevertheless, research on exposure should resolve several poi,Rs of uncertainty. The comparability between exposure dose measured by amount smoked and by hours or years of smoking should be assessed. The relative importance of. sources of ETS should also be clarified, so there Will be some agreement on whether cumulative dose should differentiate between sources of exposure. In the absence of data showing a particular exposure measure to be optimal, an index of involuntary smoking based o,~ the amount smoked by spouses shows the most consistent dose-response relation- ship with lung cancer risk (ltlrayama 1981a; Trichopoulos etal. 1981; Correa et al. 1983; Garfinkel et al. 1985; Akiba etal. 1986). Other indices of involuntary smoking exposure have act been as well studied and have not shown a consistent dose-respoase relationship with lung cancer risk, These exposure variables included total years of exposure to spouses' smnking, average dully hours of exposure 92 from nil mmrces, and cumulative lifetime hours and year~ of exposure. , Amoag the studies that have found a dose-response relationship with amount smoked by a spouse, three have also examined the relationship by duration of spouse's smoking (Correa etal, 1983; Garfinkel et al. 1981~; Akiba etal. 1986), but only one study showed similarly increased risk using a dose and duration variable (Correa et al. 1983). In the study by Oarfinkel and coworkere (198~), only years nf sin.king by the current husband or cohabitant was asked; therefore, differences in the duration of living with current husband or cohabitant may account for the less consistent dose-response relatiouship. In their Japanese case-control study, Akiba and colleagues (1986) suggest that intensity (amount smoked per day and recency ef exposure) may be the key index of ETS in studies of lung cancer risk. Two stadium have assessed total involuntary smoking exposure to ETS. The method used by Koo and coworkers (1984) relied on respondents to describe the expo~uras from each source separately, and a summary measure of exposure was derived by the investiga- tors. The method used by Oarfinkel and eoworkera (1985) relied on the respondents to average their exposures from nil sources for specific time periods. The former method of Koo and coworkers (1984) may not have adequately considered intensity of exposure; therefore, an association may have been obscured by combining and high iutensity exposures as if they were equally important, In the latter study of Garfinkel and coworkers (1985), a high percentage of case interviews and, presumably, control interviews was conduct. ed with surrogates.. Although information provided by surrogates regarding dt~mographic variables is generally valid, as are responses on cigarette smoking status (current, prior, never), more dehiiled information on the cigarette smoking of a deceased spouse has more limited validity (Lerchen and Semet 1986). Surrogate interviews may provide adequate information about tobacco smoke exposure at home, but may be Inaccurate for describing gradients of total tobacco smoke exlamure from all sources. Expected 10ung Cancer Risk An extensive data base describes the relationship between active smoking and lung cancer (US DHEW 1979, US DHHS 1982; IARC 1986). 'ri~is information has been utilized to construct mathematical models to describe the relationship of dose, duration, initiation, and cessation of active smoking for risk of lung cancer. For several reasons, comparable models have not yet been developed for involuntary smoking and lung cancer. First, research on involuntary smokiag and lung cancer is recent. Second, involuntary smoking is not as re~,lily quantified as active smoking; tobacco smoke is 93
Page 57: TI07870667
ubiquitous in the environment and present in variable but generally " low concentrations in comparison with MS, and inhaled dose varies with ventilation and other phyMological factors (Hiller 1984; Hoegg .1972; Hoffmann et el. 1984; Schmeltz et el. 1976; St6ber 1984; US DllliS 1984), Neverthele~, theoretical models, originally developed to describe the relationship of active smoking and lung cancer, have been used to predict lung cancer risk from involuntary smoking, t/sing Doll and Pete's (19?8) model [(0.273 x 10-t9 (cigarette/day :1- 6)~ (age 22.5)t~] for active mnoking and lung cancer, Vutuc (1984) calculated expected lung cancer risks for various exposure levels, ranging from 0.1 to 5.0 cigarettes per day. For exposure levels of 0.1, 1.0, 2.0, and 5,0 cigarettes per day, the corresponding risk estimates were 1.03, 1.38, 1.78, and 3,36, respectively. These low-dose active smoking risk estimates are comparisons of active smokers with all nonsmokers (those with high E'P3 exposure and those with low ETS exposure). The risk estlmatos in involuntary smoking studies are a comparison of nonsmokers with higher levels of involuntary smoking exposure with nonsmokers who have lower levels of involuntary smoking exposure. As a result, the uumericel values of the risk estimates In active mnoking studies are not directly compa~:able to those in the involuntary smoking studies. The appropriateness of extrapolating from the active smoking ' model hinges on the actual exposure d s nonsmoker. Estimates of exposure have been derived from various sources, Experimental conditions have been used to quantify the involuntary smoker's exposure to ETS. l[ugod and colleagues (1978) reported that under conditions heavily pollute! with sidestream smoke (to maintain a carbon monoxide concentration of 20 ppm), the particulates of tobacco smoke inhaled by involuntary smokers was small, the equlvalen~ of one-half to one cigarette per day. Exl~ures may also be ~t|matod from biochemical measurements. Studies comparing cotinine levels in nonsmokers and smokers show cotinine levels in nonsmokers that correspond to about one-sixth to one-third or a cigarette per day (Jarvis et sl. lg84; Weld et el. 1984). Higher cotinine levels in nonsmokers, comparable to about two cigarettes per day, have been reported (Mntsukura et el. 1984, 198~), but the results were questioned (Adlkofer et el. 1985; Pittenger 1985) and await confirmation. The epldemiologic evidence on the lung cancer risk ~oc.iatod w|th marriage of a nonsmoker to a smoker has been criticized as implausible on the basis of predictions from Doll and Pete's model (Lee 1982a,b; Vutuc 1984~. It has been argued that rehttive risks of 2 or 3 from involuntary smoking correspond to active smoking of two to five cigarettes per day and that this equivalent level of active smoking is too large to be realistic. This argument fails to consider 94 the differ~m:e in the comparison groups used to generate the risk estimates i~ studies of active smoking and involuntary smoking. The risk e~l,imal.es for studies of active smoking use as a comparison group all ntmsmokers, which includes those with and without high levels of exposure to ETS. Studies of involuntary smoking use risk estimates that are derived by comparing nonsmokers with higher levels of exposure to E'I'~ with nonsmokers with lower levels of exposure to ETS. Because the risk estimates in active and involun- tary mnokb~g studies use different comparison groups, the numerical values are ~mt directly co~nparable. In order ~.o make them comparable, the risk estimates in involun- tary s|,~okl,g and active smoking studies would have to be calculated using the same reference group. If the reference population used is all nons,nohers, then the risk estimates for nonsmokers married to nonsmoker, are reduced to below 1 (i.e., their lung cancer risk would be lower titan the risk for all nonsmokers as a group), The risk estimates for nonsmokers married to smokers would be above 1 (i.e,, would be gr~ater than the risk of all nonsmokers as a group), but the numerical value of the risk earls|ate would be reduced from the value obtai~ed by corn parlson with nonexpased nonsmokers. If the data from the Japanese cohort study (Hirayama 1981a) are' recalculated to use all nonsmokers as the reference population, the risk estlmnte for lung cancer in nonsmoking wives of nonsmoking husbands would be 0.63 and the risk estimate for nonsmoking women ms, ried to smokers (current or former) would be 1.12. The • alue of 1.12 compares the risk for nonsmoking wives o1" smoking hnsbands with the risk for all nonsmokers in the studies of active smoking. This magnitude of risk is within the range of risk that would be predicted using the Doll and Pete (1978) model for calculating active smoking risk for smokers of 0.1 (risk estimate 1.03) and 1 (risk estimate 1.38) cigarette per day. The evidence for exposure to environmental tobacco smoke bm~od oa biologic markers of tolmcco smoke exposure indicate that involuntary smoking exlmsure results in levels of biologic markers (e.g., cotinine) that are similar to h.wels expected in smokers of 0.1 to I cigarette per day, Thus, estimates derived using similar comparison groups suggest that the hmg cancer mortality experience due to involuntary smoking is similar to that which would have been expected from an extension of the dose-response data for active smoking to involun- tary mnoking exposures. An alternative method of estimating expected lung cancer rates has been prnpesed by Repace and Lowrey (1985). They compared the age-standardized lung cancer mortality rates of Seventh-Day Ad- ventists (S])As) who had never smoked with a demographically comp.rabh, group of nonsmoking non~qDAs and attributed the difference in lung cancer deaths solely to involuntary smoking. This
Page 58: TI07870668
analysis was based on the following assumptions: (t) thai. SDAs had no exposure to passive smoking, whereas all of the uon-SDAs wel'e exposed, (2) that men and women had equal lung c~mcer death rates, and (3) that there were no other differences between the two group~. Summary Previous Reports of the Surgeon General bare reviewed the data establishing active cigarel.te smoking as the major cause of lung cancer. The absence of s threshold for respiratory carcinogenesis in active smoking, the presence of the same carcinogens in mainstream smoke and sides[ream smoke, the demonstrated uptake of tobacco smoke constituents by lnw~luntary smokers, and the demonstration of an increased lung cancer risk in some populations with exposures to ETS leads to the conclusion that involuntary smoking is a cause of lung cancer. The quantification of the risk associated with inw~luntary smoking for the U.S. population is dependent on a number of factors for which only a limited amount of data are currently available. The first of these factors is the absolute magnitude of the lu~g cancer risk associated with involuntary smoking. As was previously described, the studies that have been performed to assess the lung cancer risk of involuntary smoking do not contain a zero-exposure group. Some exposure to tobacco smoke is essentially a universal experience; therefore, studies of involuntary smoking compare a low-exposure group with a high-exposure group. The magnitude of the risk estimate obtained is a function of the increase in risk produced by the difference in tobacco smoke expceure betwsen the two groups examined, rather than an absolute measure of the risk of exposure in comparison with no exposure. The magnitude of the difference in tobacco smoke exposure between groups identified by spousal smoking habits may vary from study to study; this variation may partially explain the differences in risk estimates a,nong the studies. The extrapolation of the risk estimate data to the tJ.S. impulation would therefore require a better understanding of the magnitude of the exposure to e,~vironmental tobacco smoke that occurs in the populations examined in the studies of involuntary smoking and lung cancer. Of particular interest is the magnitude of the difference in exposure between the high-exposure group and th~ low-exposure group. A second set of data that would be needed to estimate the risk for the U.S. population is the dose and distribution of exp,;sure to i,.~I'S in the population. The studies that have been perl'ormed bare attempt- ed to identify groups with different exposul"es, but little is know,~ about the magnitude of the exposures that oc~:u~" in differenl, segments of the U.S. population or about the variability of exposure with time of day or season of the year. The cl~anging norms about. 96 smoking in public and the changing prevalence of active smoking during this. century suggest that ETS exposure may have varied. substantially over this century. A better understanding of the expeeu|'es that are actually occurring in the United States, and of past exposures, would be needed to accurately assess the risk for the U.S. population. The epidemiological evid~nca that involuntary smoking can signif- icantly increase the risk of lung cancer in nonsmokers is compelling when considered as an examination of low-dose exposure to a known carcinogen (i.e., tobacco smoke). Eleven of the thirteen epidemiologi. cai studies t~ date show a modest (10 to 300 percent) olden[ion of the risk of lung cancer among nonsmoker~ exposed to involuntary smoking; in six studies positive asaociations were statistically significa~tt. The studies showing no or nonsignificantly pozitive findings were generally the weakest in terms of sample size (Gllliset al. 1984; Chan and Fang 1982; Koo et al. 1984; Kabat and Wynder 1984; Wu et al. 1985; Leo etal. 1986), study design (Kabat and Wynder I984; Lee etal. I986), or quality of data (Chan and Fang 1982). In Table 11) are shown the sources and types of bias, and in Table 11, the statistical power, of the various case-control studies (Schles. • elman 1982). On the basis of the observed relative risks reported in the studies, the respective expe~ure fraction in the control popula- tions, and an a=0.05 for a two-sided significance test, only the studies by Trichopoulce and colleagues (1983) and Co[tea and colleagues (1983) have a probability of above 80 percent of fin~ling a statistically significant result, whereas the majority of the case- control studies show a study power of about 0.10 to 0.20, The power of the study, as expected, improves when a one-sided significance test is considert~l. Among the studies in which information on involun. tary smoking was available to conduct a trend test for dose, the power Ibr dc~ecting the observed trend wan above 50 percent for five of the studies. However, the power for a two-sided test and a one- sided test, basad on observed relative risk, and the pew,e[ fur's one- sided trend test, based on observed results, are difficult to interpret because the power is a function both of design aspects (sample case-control ratio, exposure prevalence) and of the observed relative risk. To focus on comparisons of the d~ign differences between studies, the power estimates for a fixed relative risk of 2 show that five of the studies would bare a power of 0.75 or greater to detect a statistically significant result. Thus, it is not surprising that some studies failed to achieve statistical' significance, but the lack of statistical significance in all btudies should not invalidate the positive sigltificant associations for involuntary smoking that have been obserw,d. 97
Page 59: TI07870669
4- TABLE ll.--Study l~ower for case-control study bssed on an unmatched analysis Otmrwd relative Power ~oe Power toe Pz~or~oa of rilk for N~mbee Con~rak ~n~rals" s~ Study o( ~ ca~e rarao who smoked ~x~u.~e~" ~mokfl~ Power one-sided trend Pow~ rot T~szd ~n P.P.:~. for Trichopo~io~ ~, ak "/8 2.~ 0.52 2.11 0,9'9 ~ ~ ~ ~ ~ ~ ~7~ 0.17 O~ ~ ~ ~ ~ ~ ~71' ~ 0.10 ~ ~ W~ ~ ~ ~ ~ 0.~ 0,10 G~ ~ ~ ~ ~ 0.61 1~ ~4 O~ ~ ~ ~ 67 ~ O~ ~1 ~ 0.~ (1~ ~ ~ ~ ~ ~ 0.~ L47 ~ O~ 0.88 O97 0.10 NA' 0.16 021 0.,58 O,8O O.64 O.29 0.37 O.94 O.52 0.,'~, T!07870669
Page 60: TI07870670
~ TABI..E 1L---Cont£nued O~rmd ml~dve Pm~r for Pmpot~o~ of risk for ~ver v~ two~id~l rest Number Cont~l: ~ntrols" sI~es n~r e~ Io l~sed on Sm~y of ~ ~ ra~o who ~moked ip~uses' imm]r~ obler~d RR for Pml-~en et aL 67 5.18 0.44 L23 0.12 (~n prmal Pooled • bW6 2.96 0~2 L~ Pool~d ' 509 3.40 0.~2 T!07870670
Page 61: TI07870671
Other Cancers Several recent studies provide data on the relatln,lshlp of ETS exposure to cancer at sites other than the lung. Two published reports address' the risk of other cancers in adults from exlx~ure to tobacco smoke froln spouses. Using the same Japanese cohort described previously, Hirayama (1984a) reported excess mortality For cancers or the paranasal sinus (N 28) and brain (N 34) among nonsmoking women who were married to smokers. The stm~dardized mortality ratios (SMRs) for nasal sinus cancer were 1.00, 1.67, 2.02, and 2.55 for women whose husbands never smoked, or had smoked I0 to 14, 15 to, 19, or 20 or more cigarettes per day, respectively (one- sided p for trend, 0.03). The corresponding SMRs for brain tumors were 1.00, 3.03, 6.25, and 4.32, respectively (one-slded p for trend, 0.004). The total number of deaths due to nasal cancer and brain tumors was small, and the numerators in the risk calculations were unstable, based on five nasal cancers and three brain cancers in women whose husbands were nonsmokers. In one study (Brinton et al. 1984), active tobacco smoking was associated with an increased risk of sinus cancer, particularly squamous cell tumors. Sidestream smoke has also been suggested to be of etiological importance in brain tumors in children (Preston-Martin etal. 1962). In a case-control study of ~idult cancers in relation to childhood and adult exposure to involuntary smoking, Sandler and coworkers (1985a, 1986) reported an overall cancer risk of 1.6 (9{~ percent C.I. 1.2, 2.1) associated .with exposure to spouses' smoking, which was more marked in mmsmoker~ than smoker~. Significant increases were observed for cancer of the breast (OR 1.8), cervix (OR 1.8), and endocrine organs (OR 3.2). This study has been criticized in its choice of controls and in the exclusion of certain cancer~ by the design of the study. The biological plausibility of the stady's findings was also questioned because the highest risk estimates were observed for cancers that bare not been consistently related to active smoking and because higher risks were observed for nonsmokers than for smokers. Failure to control for potential confounding factors and known risk factors for the individual cancer sites under study may bare produced artifactual results (Friedman 1986; Mantel 1986; Burch 1986). in a subsequent analysis of the same study population, Sandier, Wilcox, and Everson (1986a,b) reported increasing cancer risks with increasing exposure to involuntary smoking as measured by the number of smokers in the household and by the time periods of exposure. The biologic plausibility of these findings was also questioned (Burch 1985; Higgins 1985; Lee 1985). The effect of parental smoking on the development of cancers beth during childhood and in adult life is also of interest. '/'he relationship of parental smoking to overall cancer risk in children or in adults has been assessed b, three studies. A prospective survey (Neutel and 102 Buck 1971) of about 90,000 infants in Canada and the United Kingd~m~ f~llowed for a maximu,n of 10 years found an overall cancer risk ,,f 1.3 (9~ percent C.I. 0.8, 2.2) associated with maternal', smoking d~ring pregnancy. No dose-response relationship was observed, bt~t there were few heavy smokers (> 1 pack/day) in this study. A Swedish case-control study (Stjernfeldt et al. 1986) of all cancers [om~d a risk of 1.~ (95 percent C.I. 1.0, 1.9) for maternal smoking during pregnancy./~ dose-response relationship was dem- nnstra[ed; the risk was highest in the most exposed group, those smoking ~0 ,r more cigarettes per day (RR 1.6, p<O.01). On the basis of the smoki,tg hsbil~ of the parents of subjects up to.10 years of age, Sandier, Ew, rson, Wilcox, and Browder (1985) reported no significant differe,~ce between all cancer cases and controls with respect to the mother's smoking (RR 1.1, 95 percent C.I. 0.7, 1.6), but the father's smoking was related to an overall increased risk (RR 1.~, 95 percent C.I. 1.1, 2.0). In tliese three studies, analysis by specific cancer site revealed an increased risk of leukemia associated with parental smoking. Neural aml Buck (1971) found an almost twofold increased risk of leukemia in children of mothers who smoked during pregnancy, but the association was not statistically significant. Stjernfeldt and colleagues 0986) reported a significant positive association between mater~,al smoking and acute lymphoblastie leukemia. The relative risks were I.O, 1.3, and 2.1 (p for trend, <0.01) for mothers who smoked O, ~ to 9, and 10 or more cigarettes per day, respectively, Similm" sig~i ficant positive associations with maternal smoking were • not observed l'or other cancer sites, but the risk assessments were based o~ a small' number of cases. This study suggests that the relationship between nmternal smoking and leukemia was strongest for smoki1~g during the 5-ycar period before pregnancy, intermediate for smoking during pregnancy, and lowest for smoking after pregnancy. In the study by Sandier, Everson, Wilcox, and Browder (1965), the ~tother's smoking and the father's smoking were sepa- rately and jointly associated with an increased risk for leukemia and lymphoma. The relative risk was 1.7 when one parent smoked and 4.6 when I~th parents smoked (p for trend, < 0.001), The increased risk with parental smoking was observed regardless of .the personal smoki~g st~ttus of the subjec.t. No other cancer site was associated with the mother's smoking, although the father's smoking was associated with increased risks for other cancer "sites, including the brain and Ihe cervix. Two studies of leukemia in children found no relatin,~sbil~ with parental smoking (Manning and Carroll 1957; Van SteenseI-Ml~ll etal. 1985). in the study by Manning and Carroll (1957), the mothers' general smoking habits were assessed, whereas Van SteenscI-Moll and colleagues (1985) obtained information on the smoki~g habits of both parents in the year before the pregnancy.
Page 62: TI07870672
Stewart and colleagues (1958) reported a statistically sigl~ificunt risk of 1.1 (p=0.04) for" leukemia in association with the mothers' smoking, but cautioned that the smoking information on the mothers pertained to their habits at the time of interview, which took place after the deaths of the patients and may have been affected by bereavement. The effect of parental smoking habits has been examined in epidemiological studies of brain, tumors, rhabdomyosarcoma, and tcsticular cancer in children. Gold and colleagues (1979) reported an association between maternal smoking prior to and during pregnan- cy and brain tumors in children. A relative risk of 6.0 (p=0.22)was found, but the result was based on a small number of patients and was not etotistica[iy significant. No relationship between maternal smoking during pregnancy (RR 1.1, one-sided p-~0.,t2) and brain tumors in children was found in another study (Preston-Martin et el. 1982), but a significantly increased risk (RR 1.5, one-sided p=0.03) associated with mothers living with a smoker (usually the child's father) during pregnancy was observed. A significa~ttly increased risk with the father's smoking, but not the mother's smoking was also reported in a study of rhabdomyosarcoma (Grufferman et al. 1982). The father's smoking conferred a significant increase in risk (RR 3.9, 95 percent C.I. 1.3, 9.6), but the mother's smoking during and after the pregnancy was not significantly different between cases and controls (RR 0.8, 95 percent C.I. 0.3, 2.0). A history of maternal smoking during pregnancy, did not differ for testicular cancer cases and controls (RR 1.0, p=0.57) in one study (Henderson et el. 1979). There are at present insufficient data to adequately evaluate the role of involuntary smoking in adult cancers other than primary carcinoma of the lung. In addition, active amokm~ necessarily receive greater exposure to ETS than nonsmokers. Thus; effects w(;uld not be anticipated in involuntary smokers that do not occur in active smokers (IARC 1986), and the biological plausibility of associations between I~,~S exposure and cancer of sites not associated with active smoking must be questioned. The findings of Hirayama (1984a) and Sandier, Rverson, and Wilcox (1985) need confirmation in studies that take into account the potential confounding factors and the known risk factors for these individual sites. The evidence ~'or parental smoking and childhood cancer is also not clear, and evaluation of this association is made difficult by the various definitions of exposure that have been used, including materaal and paternal smoking before, during, and after the pregnancy. Mothers and fathers who smoke during a pregnancy generally smoked before the conception and continue tt~ smoke after tire pregnancy. Thus, an effect of involuntary smoking after birth cannot readily be distin- guished from genetic or transplacentally mediated effects. 104 Cardiovascular Diseases A causal a~ociation between active cigarette smoking and curdle- vascular diso=tse is well established (US DIIHS 1983), The relation- ship between cardiovascular disease and involuntary smoking has been examim.<i in one case-control study and three prospective studies, h= the case--centre! study by Lee and colleagues (1986), described prvviously, ischemic heart disease cases and controls did not show a statistically significant difference in their exposure to involuntary smoking, based on the smoking habits of spouses or on an index accuunting for expesure at home, at work, and during travel and leisure. In the Japanese cohort study, Hirayama (1984b, 1985) relmrted an elevated risk for ischemic heart disease (N=494) in nonsmoking women married to smokers. The standardized mortality ratios when the husbands were nonembkers, ex-smokers or smokers of 19 or more cigarettes per day, and smokers of 20 or more cigarettes per day were 1.0, 1.10, and 1.31, respectively (one-sided p for trend, 0.019). in the Scottish followup study (Gillie et el. 1984), nonsmokers not exposed to tobacco smoke were compared with nonsmokers exposed to tobacco s|noke with respect to the prevalence of cardiovascular symptoms at entry and mortality due to coronary heart disease, There was n¢~ consistent pattern of differences in coronary heart disease or symptoms between nonsmoking men exposed to tobacco smoke and their nonexposed counterparts. Nonemoking women exposed to h=bacco smoke exhibited a higher prevalence of angina and major E(.13 abnormality at entry, and also a higher mortality rates for all coronary diseases. However, rates of myocardial infarction m~rtolity were higher for exposed nonsmoking men and women compared with the nonexposed nonsmokers. The rates were 31 and 4 per 10,000, respectively, for the nonexpesed nonsmoking men and women, and 45 and 12 per 10,000, respectively, for the exposed nonsmoking men and women. None of the differences were tested for statistical significance. I.n the Jap=mese and the Scottish studies, other known risk factors for cardiovascular diseases, i.e., systolic blood pressure, plasma cholesterol, were not accounted for in the analysis. In a study ,f heart disease, Garland and coworkers (1985) enrolled 82 percent of adults aged 50 to 79 between 1972' and 1974 in a predominantly white, upper-middle-class community in San Diego, California. Blood pressure and plasma cholesterol were measured at entry, and all participants responded to a standard interview that asked about smoking habits, history of heart disease, and other health-related variables. Excluding women who bad a previous history of he:art disease or stroke or who had ever smoked, 695 currently married nonsmoking women were classified by their husbands' sell'-reported smoking status at enrolhnent. After 10 yeanl 105
Page 63: TI07870673
of followup, there were 19 deaths due to ischemic heart disease; the age.standardlzed mortality rates for nonsmoking wives whese hus- bands were nonsmokers, ca-smokers, and current smokers were 1.2, 3.6, and 2.7, respectively (one-slded p for trend, g0.10). After adjustment for age, systolic blood pressure, total plasma cholesterol, obesity index, and years of marriege, the relative risk for death due to isehemic heart disease for women nmrried to current or former smokers at entry compared with women married to never smokers was 2.7 (one-sided p <0.10). The study's findings are not convincing from the point of view of sample stability. The total number of deaths due to ischemie heart disease was small, and the denominator in the relative risk calculation is unstable, based on the deaths of two women whose husbands had never smoked. Moreover, it is well established that the risk of coronary heart disease is substantially lower among those who have stopped smoking {US DHHS 1983), although the amount of time required for this change aRer cessation of smoking is not clear (Kannel 1981). In this study, 15 of 19 deaths occurred in nonsmoklng women married to husbands who had stopped smoki,tg at entry, and the age-standardized rate for ischemic heart disease was highest in this group. The high proportion of deaths in nonsmoking women nmrrled to men who became ex.smokers implies that the excess resulted from a sustained effect of involuntary smoking. More detailed characterizations of ~xpesure to ETS and specific types of cardiovascular disease associated with this exposure .are needed before an effect of involuntary smoking on the etiology of cardiovas- cular disease can be established. One study {Aronow 197Ba,b} suggested that involuntary smoking oggravates angina pecteris, This study was criticized because the end point, angina, was based on subjective evaluation, and because other factors such as stress were not controlled for (Coodley 1978; Robinsen 1978; WaRe 1978; Wakehan 1978). More important, the validity of Aronow's work has been questioned ~Budiansky 1983). Conclusions 1. luvoluntury smoking can cause lung cancer in nonsmokers. 2. Although a substantial number of the lung cancdrs that occur in nonsmokers can be attributed to involuntary mnoking, more data on the dose and distribution of IZrS exposure in the population are needed in order to accurately estinmte the magnitude of risk in the U.S. population. 3. The children of parents who smoke have an increased frequen- cy of hospitalization for bronchitis and pneumonia during the first year of life when compared with the children of nmmmok- ers. 106 4. The childre, C' !)=~rents who smoke have an increased frequen- cy of ~ variety of acute respiratory illnesses and infections, i,cludi,g chest illnesses before 2 years of age and physician- diagno~ed bronchitis, tracheltls, and laryngitis, when com- p;wed with the children of nonsmokers. 5. Chronic cough and phlegm are more frequent in children whose parents smoke'compared with children of nonsmokers. The i,~plications of chronic respiratory symptoms for respira- tory health .as an adult are unknown and deserve further study. 6. The children of parents who smoke have small differences in tests ~r pulmonary function when compared with the children of nonsmokers. Although this decrement is insufficient to cause symptoms, the pe~ibility that it may increase suscepti- bility {.~ chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., active smoking or occupation- al exl~sures, needs investigation.' 7. llcaltby adults exposed to environmental tobacco smoke may' have small changes on pulmonary function testing, but are, uulikely t~ experience clinically significant deficits in pulmo- nary function as a result of exposure to environmental tobacco smoke alone. 8. A number of studies report that chronic middle ear effusions are more common in young children whose parents smoke than in chihlren of nonsmoklng parents. 9. Validated questionnaires are needed for the assessment of recent' and remote exposure to environmental tobacco smoke in the home, workplace, and other environments. 10. The associations between cancers, other than cancer of the lung, end involuntary smoking require further investigation before a determination can be made about the relationship of involuntary smoking to these cancers. 11.Further studies on the relationship between involuntary smoki~g and cardiovascular disease are needed in order to dctermlne whether involuntary smoking increases the risk of cardiovascular disease. • 107
Page 64: TI07870674
References ABEL,,E.L. Smoking during pregnnocy: A review of effects on g~owLh a.d develop- ment of offspring. Human BioioK~' ~2(4):.593-62fi, December 1980. ADLKOFER, F., SCtlEIiER. G., Van HEES, U. Passive smoking. (letter). New England Journal of Medicine 312~ I I k719--720. March 14, 1985, AKIBA, S,, KA'iD, 11., BLOT, W,J, Passive smoking and lung cancer among Japanese women. Cancer Re, catch 46(91:48~ki-4807, September 1986. ARONOW, W~. Effect.of pa~ive sl.ektug on a,tgine pectoris, New Englaud Journal of Medlcinr 299(11:21-24, July 6, 1978a. AItONOW, W.S. Effects of passive smoking, (letter). JVew England Journal o[Medi¢ine 299(16):897, October 19, 1978b. BACKHOUSE. C.I. Peak expiratory Row in youths with w, rying cigarette emok|ug habits, British Medical Journal 1(59541:.380-362, February 1~, !~.~75. RARRON, B.A. The effects of ml~cl-,mificatlon on the eetimatieu of relative risk. Biometrics 33(2):414-418, June 1977. BECK, G.J., DOYLE, C.A.0 ,~CI|ACI ITER° R.N. Smoking attd lung tuner'ion. American Review of Respirolory I)i,¢oJ¢ 12~1(21:i49-155, February 1981. BERKEY, C3., WARE, J.II., DOCKER¥, D.W., FERRIS, B.G., Jr,, SPEIZ~:R, F.E. Indoor air pollution and pulmonary function growth in preadolescent children, American Journal of Epidemiolot~y 123(2P.250-260, Februury 191~6. BEWLEY, B.R., llALIL, T., SNAITH, A.il. Smoking by prinmry schoolchildren: Prevalence end s~aoeiated respiratory symptoms. British Journal of Pret~ntiv¢ and Social Medicine 27(3):. 150-153, August 1973. BLACK, N. The sociology of glue ear: A case-control study. International Journal of Pediatric OlorhtnotaO'n~oloKv 9(2~.i21-133, July 1985. BLAND, M., BEWLBY, II.R.. POLLARD, V., BANKS, M.ll, Elle~t of children's and parents' smoking on respiratory, aymptonm. Archive, o[ l~iaeuse in Childhood 53(2): 100-105, February 1978. BLOT, W,J., McLAUGllLIN, J.K. I'ructicJd it~ue~ in the design .nd conduct of control studies: U~e of next-of-kln Intervlewa. In: Blot, WJ., Ilirnyama, T., lluel, It' O.G, lads), Statistical l~ues in C.ncer Epidemiology, }llru~hima, Sonel Pubibher~ 1985, pp. 46.62. BRINTON, L.A., BLOT, WJ., B~CKEII, J.A., WINN, D.M., BItOWD~'.R, J.P., FARMER, J,C., Jr., FRAUMENI, J.F., Jr. A case-control study of cancers of nasal cavity and paranesal ,intro. American Journal of Epidemiology I ~)6, June 1984. BRUNEKREEF, B., FISCHER, P., REMIJN, B., Van Der LENDI~, It., SCllOUTEN, J., QUANJER, P, Indoor air pollution and its effect on pulmonnry funtinn of adult nonsmoktng women: 3. Passive smoking and pulnmnary fuuction. International Journal of Epidemiob,gy 14(21:227-2300 June 1985, BRUNNEMANN, K.D., ADAMS, J.D., lie, D.P.S., ItOFFMANN, !). The influe,tce of tobacco smoke on indoor atmospheres. 2. Volatile and tobacco slu-~cific nitremamlues in main- and sidestream smoke and their contribution to i.door pollution. Preceding, o/" the 4th Joint Conference on Sensing of Enuironnwntal Polhdant~, New Orleans, Louisiana, 1977. American Chemical Society, 197~, I~p. 876-880. BUDIANSKY, S. Food and drug date fudged. Nature 302159091:fi60. April 14, 1983. RURC|I, P.RJ, Passive smoking attd lung cancer. (letter). Briti,~h Medical Journal 282162731:1393, April 25, 1981. BURCH, P.R.J. Lifetime passive sneaking and cancer risk. (letter). L~ncet 1|84331:866, April 13, 1985. BURCII, P,R,J. Passive smoking in adulthood and cancer risk. (letter). American Journal of Epidemioi.gy 123(2Y,;168-359, February 19811, 108 BURCIlFIEL, C.M., HiGGINS, M.W., KELLER, J.B., HOWATT, W.F., BUTLER, HIG(|INS, LT.T. Pa~alve smoking in childhood: Respiratory conditions and pulmanary function in Tecumseh, Michigan. American Reuiew o[ Respiratory Disease 133(fiP,966-973, June 1986. BURROWS, B.,. KI~UDSON, R.J., CLINE, M.G., LEBOWITZ, M,D, Quantitative relatianehil~* between cigarette smoking and ventilstery function. American Review i~f li,'apica~ory Disease 11f~2~.19~-206, February 1977. BURROWS, B., KNUDSON, R.J:, LEBOWlTZ, M.D. The relatlonsh.ip of ©hildhoed respiratory illness to adult obstructive airway disease. American Reulem of ReepirutorylKK, a~e 1l~5P.'/51-760, May 1977. CAMERON, P., KOSTIN, J.S., ZAKS0 J.M., WOLFE, J.H,, TIGHEo G. OSELI~I~, STOCKEIt, It., WINTON, J. The health of smokerd and nonemoken' children, Journal ofA Ilergy 43(6~,336-34 I, June 1969. CHAN, W.C,, COLBOURNB, M.J., FUN(], S.C., He, 11.(3. Bronchial cancer in Ilong Kong 1976-1977. British JournniofConcer39(21:.182-192, February 1979, CHAN° W.C., FUNG, S.C. Lung cancer in nottsmoke|l in Hang Kong, in: Grundmann, E., Clemme~en, J., Muir, C.S. lade). Geographies| Potholog.y in Cancer Epidcmiolog.r. Cancer Campaign, Vol. 6, New York, Gustav Fischer Verlag, 1983~ pp. 109-20201982. CHARL'I~)N0 A. Children's coughs related to parental smoking. British Medical Journal 288(6431P.1647-1649, June 2,1984.. CHEN, Y., LI, W.-X. The effect of pa~ive mnoklng on children's pulmonary function in Shongha|. American Journal of Public Health 76(~):.51fi-.518, May 1988. COLLEY0 J.R.T, Respiratory disease in childhoed, Brit/~b Medical Bulletin 27(1);9-14, January 197 I. COLLEY, J.R.T. Respiratory symptoms in children and parental smoking and phlegm production, I)ritieh Medical Journal 2(~912?,201-204, April 27,1974, COLLEY, J.R.T., HOLLAND, W.W., CORKIIILL, R.T. Influence of p~aive smoking and parental phlegm on pneumonia aud bronchlti~ in early childhood. Lancet 2(7888):1031-1034, November 2, 1974. COLLINS, M.II.0 MOESSINGER, A.C.0 KLEINERMAN, J., BASSI, J., ROSSO, P,, COLLINS, A.M., JAMES, L.S., BLANC, W.A. Fetal lung hypopla~la emaciated with mnter,ml mnoklug: A morphometrt¢ analysis, Pediatric lle~earch 11~4):406- 412, April COMSTOCK, t.I.W., MEYER, M.B., HELSING, K,J.0 TOCKMAN, M,S. Respiratory effects of household exposures to tobacco smoke and ga~ seeking. American Review ofl~e~piruto~.v l)~ea~e 124{21;143-148, August 1981. COODLEY, A. P~fl'ects of passive smoking. (letter). New England Journal of Medidn¢ 299Hti):t197. Iktober 19,1978. COPELAND, i(.T., CHECKOWAY, H,, McMICIIAEL, A.J., HOLBROOK, R,tl, ales due to mi~.lo~ification in the estimation of relative risk. American Journat of Epidt.miolol~ 105(51:488-495, May 19"/7. CORREA. P., PICKLE, L.W., FONTHAM, E., LIN, Y., HAENSZEL, W, Palllva emoklng and lung cancer, Lancet 2(8350):1195-~97, September 10, 1983. ~ CRIQUI. M.H. Response bias and risk rotlo~ In epidemioldgie studies, American Jaurnnl of Epidemlology 109(41:394-399, April 1979. DAHMS, T.E., flOLIN, J.F,, SLAVIN, R,G, PaMive smoking: Effects on bronchial asthma. Chest 80(5P.530-534, November 1981. DODGE, IL The effect~ of indoor pollution on Arizona children, Archives of Environmental Health 37(31:151-155, May.June 1982. DOLL, It., PETe, R. Cigarette smoking and bronchial carcinoma: Does and time relationsbil~ among regular smokers and lifelong non.smokers. Journal of Epidemiololo' and Community Health 32(41;303-313, December 1978, 109
Page 65: TI07870675
DUTAU, O., CORBEEANI}, J., LE~PIIONTI~, P., E~II~IOLI, ~. resplrutolr~s ll~es n l'inhml~Uon p~ive de famine de ~bnc eh~ l'l.fant d'~ge pr~ '~ol~lre ~Eesplratory ai~.s 8~lnt~ with p~ive inhala~lon of ~lm~ smoke ~nfan~). 1~ Poumon ¢l le C~ur 3~2):6~9, 1979. EKWO, E,E., WEiNBEROER, M.M., LACHENBR~CH, P.A,, IIUNTLEY, W.Ii. Relationship o[ parental smoking and gas ~klng ~ resplm~ry d~m children. Client ~(6):~2~, ~em~r 19~. FER~U~ON, D.M., IIOltW~D, LJ. Parental emokln~ and r~pire~ during early childh~: A six year longitudinal study. P~iutdc ~(2):~-i~, March-April 1986. FERGU~N, D.M., HOI~W~D, I,.J., SHANNON, ~.T., TAYI~IL B. Paren~ ~moking end lower r~pir~tovy IIInm in the fi~t ~r~ yearn of )ire. Epid¢miolo~ and Community H~I~h ~3}:1~, ~p~m~r 198L FEYEEABEND, C. HIGENB~HAM, T, RU~ELL, M.A.H. Ni~tine ~n~ntr~tlon~ In urine and eellv~ of smokers e~ nonsmokem. Bdtbb M~i~l 284(~21~1~-!~, April 3, 1982. FOLIAET, D., BENOWI~, N.L., 8~KE~ C.E. P~lve a~rptlon airline flight at~ndan~. (let~rL ~ew England ~mot ofM~i¢bm ~18~11~, FEISDMAN, O.D. P~l~e ~moking In edulth~ and ~r ~bk. (later). Journal ofEpidemtot~ 1~2~7, February 19~. FRIEDMAN, G.D., P~JTI, D.B., BAWOL, KD. P~valen~ and ~r~la~ smoking. Am¢rlcon Jou~ol of ~blle H~lth 7~4~40~, April OARFINKEL, L. Time t~n~ In lung ~n~r mo~lity among non~moke~ nnd ~ n~ on p~ive ~moking. Joa~al of th~ ~tionel ~n~r l~titute ~O~l~l-l~, June ~I{FINKBL, L, AUERDACII, O., OOUBEET, L. lnvolun~ smoking ~nd lung can~r~ A c~nt~l study. ~oumel of ~he Na~io~l ~r l~titu~ 4~, ~pttm~r 198~. GARLAND, C., BARR~NNOIL K, SUAEE~ L, CRIQUI, MJL, W~NOARD, D.L. ~ff~ of p~ive ~moking on ~hemle heart d~ mo~ilty ~ none~ke~: A pr~tlve study. Amed~n Jou~I ofEpldemiolo~ 121(6~, May 19~. men~l ~ smoke In two urbnn ~mmunitl~ in the w~t o~tle~. Joeraal of R~plmto~ I~ ~Suppl. 133):121-198, 19~. GOLD, E., GORDtS, L., ~NA~iA, J., SZK~, M. Rbk fae~ for b~ln tu~ in ehildren. Ameri~ Journal o[ Epidtmtolo~ 1~3~19, Mesh GORDIS, L. Should de~d ~ ~ m~h~ ~ dead ~ntrol~? Am~ ~1 ~pld~mioto~ 1 l~l~l~, ~enue~ 1982. smoking end the risk uf ~ildh~ ~thma. Ame~n ~ou~d o[~bl~ Hml~h 7~0):~7~79, June 198~. GR~ENBERO, R.A., ltALEY, N.J., ~E~ R.A., ~DA, F~. M~uring the ex~ure o~ infan~ to ~bn~ smoke: Nl~tlne end cotlnlne in ud.~ mud England Journal ofMe,lictn¢ 31~ 17~1~1~8, A~I ~, GREENLAND, S. The eff~t of m~lmiflcatio, in the p~n~ Amedmn ~ouma[ of ~idemio[~ 11~4~, ~r 19~. GRUFFERMAN, S., WANG, ILH., ~NO, KK, KIMM, ~.Y~., D~ELK ~.~., FALL~A, J.M, Environmen~l facto in the etiol~ of rhe~omy~ma in childh~. Journal of the Hotionol ~ncer Imtitute ~1~!07-113, Janua~ 1982. GRUNDMANN, ~., MULL~ K.-M,, WINTE~ K.D., ~E~ING, T.D. Nmt~moking wiv. at heavy smoke, have a higher r~k of lung ~n~r. fleer). Hde~h Journal ~6270):1 i~, April 4, 1~181, 110 HALEY, N,J., HOFFMANN, D. Analysis fur nicotine and cotinine in hair to determl.e ~'ignrette ~moker status. Clinical Chemistry 3l(10):159B-1600, October IIAMM()ND, I': C., SELIKOFF, I.J. P~ive smoking snd lung cancer with comm~n~ on Lwa uow Pnl~vrs. ~nuirunnte~l~ R~I~ 24{2):44~52, April 198L HARLAI'. S., I)AVI~% A.M. Infant admi~iona ~ h~pi~! and mammal smoking. ~nc~.t 1(78i;7):52g-~32, March 30, 1974. IIARRIS, J.E.. D.MOUCllEL, W.IL Nonmnoklng wiv~ o~ heavy smokers h~ve higln,r ri~ -f lung cancer. (IctterV British M~icol Journol ~3(6296):915, ~Lo~r 3, 1981, llA~EI,~LAD, V., llUM~LE, C.G~. GRAHAM, M,G,, ANDE~N, It,S, Ind~r envlromue.tal determlmm~ of lung function in children. American Review of R~piev too" I)ise~e 12~5):479~, May 198 L. IIENDEI~ON, B.E., BENIN, B,, JING, J., YU, M.C., PIKS, M.C. Rink ~actors for canc~,r of tho testis In young men. International Journal of ~n~r May Z979. HLOOINS, !, I.ifetime p~ive smoking and caner risk. (later), ~ncet ~7, April 13, 1985. HIGGINS, M.W,, KJE~BP~RG, M,, M~NER, H. Charec~ristl~ of ~mokem and nonsmokers In Tecumseh Michigan. ]: ~e dl~tributivn o~ ~moklng hebJ~ ~r~nt~ and families and their relationship ~ ~lal characteristic, Jonrnol nfEpidemiolv~ ~ I h4~9, July IIILLSI¢, F.C. I)e~sitlon o~ eid~tream cig~Rt~ smoke In the human tract, l'~utit,e M~dicDee 1~6):~7, Novem~r 1984. HIRAYAMA, T. Non-smoking wives of heavy smokers hove a higher risk o~ lung cancer: A sludy from Jopan. Bdt~b M~i~i Jou~ai ~6~9):1~L~, Januaw 17, 1981n, HIRAYAMA, T. Fa~slve smoking and lung caner. (let~r), Brit~h M~ical ~6~3~UI93-1394. April 2~, 198lb. IIlRAY~MA, T. Nonsmoking wives of nmoke~ have a higher riek of lung cancer, (let~,r). Rritiele M~i~l Journal ~6~):91~917, ~r 3. HIRAYAMA, T. Nonmuoklng wiv~ or smoke~ have a higher risk of lung ~ncer. (later). I~ritish Medi~iJonraM ~}:146~14~, Novem~r 28, 1981d. llIRAYAMA, T. l'essive smoking and lung c~nR~ ~nsls~n~ or ~lotlon, ~m'el ~83(;4~:14~1426, ~m~r L7, 19~. HIRAYAMA, T. Cancer nmr~lity In nonsmoking women with smoking husbands ~1 on ~ lerge-~ale ~hort study in Japan. ~ntlve Medicine Novcml~r 1984a, HIRAYAMA, T, Lung cancer in Japan: EIf~ o[ nutrition and p~ive smoking. In: Mi~ll, M., Correu, P. (~IsL Lnng ~neer: ~ee and ~ntion. ~erfield ~acb, Florldn, VCII, 1984, pp. 176-195. HIRAYAMA, T. Passive smoking: A new ~rget of epldemlol~, Journal Ex~riuee.hol Cllnicoi M~icine ]~4~7-~3, 19~. HOEGG, U.R, Cigaret~ smoke in cl~ spa~. Enui~nmentol Health (2k177-1~, Octo~r 1972. HOFFMANN, D.. HALEY, N.J., ADAMS, J,D., BRUNNEMANN, K,D, To~c~ etd~trcnm smoke: Uptake by nonsmokers, P~nti~ Medicine Novem~r 1984. HORW(~)I), I,.J., FERGU~H. D.M., SIJANNON. F.T. ~ial and familial facto~ in the development of early childh~ aHhma, P~latri~ 7~5):~9~, May 1985, llUOOI), C., IIAWKINS, I,.H., A~RUP, !'. Ex~ure of pa~ive smoke~ ~ toba~ snmke constituents. Internntlonal A~Idt~s of ~cu~tioaal and llmlth 42~ l ~:21-29, 1978, 111
Page 66: TI07870676
INTERNATIONAL AGENCY lq)E EI~EARCII ON CANCEIt. '/~,l+acm IAltC Monographs on the Evalu.tion ~ the (~rcioo~e.ic Iti~k of ~emicais to Ilunmns, Volume 38, O~,now, Wile, IAEC 19~. pp. 1¢1-314. IVBI~ON, M., BIECti. L., LUNI~VI~, O.R,. [I.Itl(ONI). O. Middle ~nr children and the ind~r environment: An elddemiol~! study. A*¢Ai~ Rauinmmentol Ii¢~ltk ,1~£):~4-~9, M~rch-April 1985. Y. Bi~hemicai marken of smoke ~r~ton an~ ~lr re~rt~ ex~sure te smoking, Ju~rnol of ~ddemioh~v aad @anlnluail~ Hcalth 3~4k3:15~3~. ~em. ~r 1984. JON~, J.E., IHGGINS, I.¢.¢,, IIl(:GINS, M.W., KBLLBR. J.l~. l~fl'~ct~ ur ~kin8 fuels on I~n~ function in .onsmoki.l w~e.. A~ki~ ~[ Eum~mcat~i 38:219-222, 1983. I{ABA~, G.C., WYND~R, B,~. Lung caner in noosmokers. Can.r M~rch I, 1984. ~ANNEI,, W.B. UI~a~ o. the role ,d cigarette smokln~ in coronory ~rtery ~. A~lerica~ ~e~r~ Journol I01(3):319-3~8, March l~i. KASUGA, H., IIASEBE, A., OSAKA, F., MA~UKI. II. ~eapiralory symptom ~h~l children nnd tho role o~ p~Ive s~kln~. To~o~ Journal o[ end Clinical M~irine 412):J01 -!14. AI~il 1979. KAUFFMANN, P., T~IBR, J.-F.. ORIO~ P. ~dult pmive emoki.g in t~ ho~ environment: & risk factor for ch~n~ =ir~ow limi~tion. Ameri('an Epidendology 117131:269-~, March HAUFFMANN, P., ~KBRY, D.W., SPBIZBR, F,B., ~ERRIS, B.(L, Jr. lymptoms and lunE function In women with ~Ive and ac[ive smoking, la~tr~D. American Reuie=uo[R¢~pimto~Di=~ 1~4, ~rt 2~Al5~, April KENTNSR, M., TRI£BIG, G., w£~.'rLE, D. ~e influence of pa~ive Imoklng on pulmonary function: ~ study of 13~1 o~ce workers. ~¢¢a~i¢,e Medicine 669, Novem~r 1984. KNOTH, A., 9OHN, B., 5CliMI~, F. Pa=iv touches ale lunge.kr~,~.u~che nichtraucherinnen IP~lve smoking es a ~u~l ~ac~r of bronchial carcta~m ~emale .on=mokers~ M~izini.che Klinik 7~2~9, Feb~ 4, K~, L.C., He, J.It.~., SAW, D. A~Ive an~ ~ive Imoking amo.g [emele cancer pat[en~ and con~ois In Hang Kon~. ~ournol o[~rimene~d and Clini~l cancer R~ea~h 4(2L367~7~, ~h~r-~m~r 1983. K~, ~,C., He, J,)l.~,, SAW, D. I~ ~.ive smoking an add~ rt~k factor for lung cancer In Chinese women? Journal of Ex~meatal and Clinical C~mcer ~3):277-~, July~p~m~r 1984, gee, ~C, He, J.IL~., LI,:B, N. An analy~il of~me r~k [actors I~r lung Hang gong. lnternatioaal Journal of~n~r ~2k14~1~, February ID, 19~. ~ORNEOAY+ K.R., KA~ENBAUM, M.A. N~moking wives of heavy smoke~ have ¢ higher risk of lung ~n~r. {let~r). Bril~h M~ical Journal ~r 3, 1981. .,A~MER, M,J., RICHAI¢~N, M,A., W~I~, N3., FUJ(UKAWA, (:.T., ~IIAI'IRO e.G., PIE~ON, W.B,, BIBRMAN, C.W. Irish foc~ for ~rsisleut middle.at 0flus{one: at{tie m~is, ca~rrh, eigaRt~ smoke ex~ure, and atapy. Jou~al the An~ertcan Medi~l Ass~iation 24~8~10~-10~, February 25, 1!183. LEBOWI'~, M.D. Envire.men~l t~a~ smoke: 3.3. The effec~ of environmen~l rebate crooks ex~u~ and 8~ a~v~ on dally ~ak flow ra~s in asthmatic and non.asthmatic [mntli~. Eu~un Journal of Respi~o~ Discuses ~SuppI. 1331:~97, 1984, LEBOWI~, M.D., ARM~. D.B., KNU~N, R, The e[f~t of pa~ive smoking on pulmonary function in childRn. Rnui~nment lnternatioual ~1-6}:371-:173, 1982. LEBOWY£Z, M.D., llURHOWS, B. Jlesplra~ry symptoms rulut~ to smakln~ hubils of family edul~, Cl~ot 6~ 11:4~5~, Januaw 1976. 112 LI~E, P.N. Non-mnoking wives of heavy smokers have a higher risk of lung cancer. (letter), British Medical Journal 283(6300.1465-1466, November 28, 1981, LEE, P.N. Pus~lw~ smoking. (letter). Lancet 1(8275):'/91, April 3, 1982a. LEE; P.N. Passive. smoking. Food and Cosmetics Toxicalo~y 20(2):223-229, April 1982b. LEE, P.N. l,ifetlme passive smoking and cancer risk. {letter}. Lancet 1(84431:1444, June 22,1985. LEE, P.N., CllAMBERLAIN, J., AI~DERSON, M,R, Itelationship of passive smoking to risk ef lung cancer and other smoking-es~oclatod diseases. Brilish Journal of Cancer 54il):97-108, July 1986. LEEDER, ~LIt., CORKHILL, It.T., IRWIG, L.M., IlOLLAND, W,W. Influence of family factors ou asthma and wheezing during the tint. five years of Ills. IJri~hh Journn[ o[Pre,~entiue nnd Social Medicine 30(4P,213-218, December 1976a. LEI~DEE, S,R,, CORKHILL, It,T., IRW1G, LM., HOLLAND, W.W., COLLE¥, J,R,T, lnflue.ce of I:,mily factors on the incidence of lower respiratory ill.ego during the first year of Ills. ]~rili#'~ Journal o[ Preuentiue and ,.~ocial Medicine 30(4P,203--2|2, December 1976b. LEHNERT, G. lioundtable dlscuss/on. Prevost{us Medicine 13(6~,730-746, Noveml~r 1984. LERCHEN, M.L., SAMET, J,M. An assessment of the validity of questionnaire responses prnvlded by a surviving spouse. American Journal of ~pidcm'ioioto !?.3(3P.481-41i9, March 1986. LIM, T.P.K. Ah'way obstruction among h|gh ~hool student~l, American ReuicuJ of Reap{salary IHsease 108(4~,98~988, October 1973. MacDONALD, EJ. Nonsmoking wives o~" heavy smokers have a higher risk of lung ~ancer. (letter). British Medical Journal 283(62861;91~-916, October 3, 1981a, MacDONALD, b:J. Nonsmoking wives of heavy smokers have • higher risk of lung cancer. {lettorL arilish Medicat Journa12836304P.1465, ~ovember 28,1981b, MANNING, M.I)., CARROLL, B.E.. Some epidemiological alpec'* of leukemia in children. Journal o[ the Na~ioaal Cancer institute 19(6):1067-1094, December 1957, MANTEI~ N. N,)nsmoking wives o1" heavy smokers have a higher risk of lung cancer. (letter). ilrili~h Medical Journal 28~6296):914-915, October 3,1981, MANTEl,, N. Passive smoking in adulthood and cancer risk. ¢letter). Amcrlca;~ Journal o[F.Iddemiolo~y 123~21:367-3680 February 1986, MARTINIO~, F,, ANTOGNONI, G,, MACRI, F., LEBOWITZ, M., RONCHETTI, It, Distrihution of bronchial responsiveness to a constrlctivn dru~ in a random podiatric Pal,slat{on sample. (abstract). American Review of Respirn~ory Disease 13|(4, part 2~:A242, April 198~. MATSUHURA, S., TAMINAT(}, T., KITANO, N., SEINe, ¥,, IlAMADA, H,, UCHIIIASHI, M.. NAKAJIMA, It., HIRATA, Y. Effects of environmental tobacco smoke o,I url.ary ¢otinine excretion in nousmokers: Evidence for passive smokini/, He~e EaglnnJ Journal o[Medicine 31 !(13}:828-832, Septembp, r 27, 1984, MATSUI(URA, ~;., HAMADA, 11,, ~;EINO, Y., MURANAKA, H,, HIOAStlI, l~, Pa~ive smoking. (letter). New F.~glaad Journal of Medicine 312/11):'/20-721, March 14, 1985. McCONNOCIlII,:, K.M., ItOQHMANN, K,J, Bronchial{tie as a ix~ible cause or wheezing in (:hildhoed: New evidence. Pediab'ics 74(! P.I-'~O, July 1984. McCONNOCIIIF., K.M., ROGHMANN, K.J. Predicting clinically aJ/:nificant lower respiratory tract illness in childhood following mild bronchial{tie. American Joornol of Diseases o[C/~ildre~ 139(61:625-631, June 1985. MURRAY, A.B.. MORRISON, B.J. The effect of cigarette smoke from the mother on bronchial r,,.ponsiveness and severity of symptoms in children with asthma, Joara,d .[ Aller/Ly nnd Cliniral In,nmnoh, ,/,gy "/~(4}:575--581, April 19~6, NATIONAl, AI ~ADEMY OF ~CIHNC~S. Risk Asseasmenl in fhe Feder, d Gouernm'enl: Monal;iag tl.' Process. Wa~hington, D.C., National Academy Pre~, |983 113
Page 67: TI07870677
NEUTEI,, C.I., BUCK, C. F, frect of smoking during pre~n~1~cy on the risk ofczmcer , children. Jvurn~l of the, ~a~ion~t ~n~r Institnte 47(1):~9~3, Jnly 1971. O'C~N NOR, ~., WE[~, 8.T., TAGEI~ I., SPEIZER, F.E. The eff~ of p~ive smoking on nonsl~Clflc bronchial res~n~ivene~ in a ~pulatlon ~mple of children and young edul~. (e~tract). Clinical i~esea~h 34(2~1A, April 19~. P~'I'HAK, D.R., SAM~, J.M., HUMBLE. C.G., SKIPPER, B.J. ~terminen~ of lung cancer risk In eigeret~ smoke~ in Hew Mexi~ Journal of the ~aliooal C~ncer Inslitate T~4):~97~4, April 1986. ]nvolun~ry smoking nnd Incldeuee of r~piratory lllne~ during the life. ~dio~ce 7~3):694-597, Mmeh PE~HAOEN, O., ZDEHEK, H., SVEH~)H, C. Pa~Ive smokin8 a~ lun~ ~n~r ~wedizh women. American ~ourn,d of Epidemiolo~ , in p~ P~E~, J.M., FERRIS, B.a., Jr. Smoking, pulmonary func~ou, nnd r~pira~ry symptoms (n n ~ll~age Br~p. AmeH~n Re~ew ~ ~pi~to~ ~e 9~6~774-7B2, May 1967. PICKLe, ~.W,, DROWN, ~.M., B[~, W.J. [nformation available f~m surcoats res~ndents In eese~uLml Interview studio. Ame~n Joumoi uf ~idemioio~ I I~ 1):~-I(~, July 1983. PIMM, P.E., SI~VERMAH, F., SHEI'HARD, R.J. Physiol~iral eff~W ~ecu~ ~tve ex~ure [~ clg~t~e smoke. A~hiu~ of ~nui~nmenfnl H~lth July-August 1978. PI~NO~R, D.J. Pessi~ smoking. (later). ~em ~land Joo~el 31~[ 1):720, March 14, i9~. com~unds and cbildh~ brain tumors: A co~ntro] study. ~neer 4~ 12):624~6945, ~em~r 1982. PULLAH, C.R., H~Y, KH. Wh~zlne, asthma, end pulmona~ dysfu~timz 10 y~ offer In~llon with r~pJra~ eyneyZia] virus in infancy. Br~tbk M~i~l J~rnal ~(~30):1~1~, June 6, 1982. PUKAHDER, d., LU~H~N, ~., TIMOHgH, M., KAEMA, P. Rl~k fac~ the ~currence of acuto otitis m~lia among ~-~year~ld ur~n ehild~n. la~,n~o~i~ 1~3-4~5, ~plem~r-~to~r 19~. ~AHTAKAL~IO, P. Relatlonzhip of maternal smuking ~ morbidity nnd the child up to the nee of five. A¢Ia Pa~iat~ ~ndineui~ 67{6~621~1, ~ptem~r 1978. ~AWDOH~, R.G., KEE~IHG, C.A., .IEHKINS, A., GUZ, A. C~garet~ smokl~ amonE secondary ech~l children in 1976: Prevalence of resptre~ry sym~om~ kn~l~ge of health Im~rds, end a~tizud~ to smoking ~nd health. ~oumal and ~ommemity ~alth ~ l ~, Ma~h I{EPACE, J.~., ~WR~Y, A.H. A quantitative ~tim~te o~ nonsmokem' lunB ~r risk from pn~ive smoking, ~z,i~mment ]nternationat] ltD:~22, 19~. ItODIHSON, D,F. Effec~ of pa~ive smoking. (letter). ~ew E~Riand Jou~al of Medicine ~16):8~, ~r 19, 1978. RUSH, D. ~piratory ~ym~ome in a g~up of American ~onda~ ~h~l ~uden~: The overwhelming n~lstion with cigarette smoking, int~tionat d~ai of Eptdemiolo~. ~2):]63-1~5, June 1~4. RU~L, M.A.H., FEYERABEHD C. BI~ and uri~ry ni~tt~e in nons~ke~. I~ncet 7~11:179-18], Jenuery ~, 1976. RU~ELI,, M.A.H., JARVIg, M.~., W~, i[~. U~ of urinary nicotine to ~timate ex~sure ond.mor~llty f~m ~ive s~king in non~mokem Jmwnal of Addiction 8[:27~], 19~. ~U~C! I, M. Non-smoklng wlv~ o~ heavy smoker~ have ~ hiEher risk ~ June ~n~r. {letterL ~tish Medi~[Journal 9~6~E9~. March 2l. I~1. 114 SACI(~'I', D.L. Bi~s i~ analy(ic research. Juar~al uf Chronic Di.~ee.~es 32(!.2l:51-I~, 1979. SAID, G., ZAI.~I(AR, J,, L~LLOUCIt, J., PATOIS, E, Parent) smoking relat~ to adenoldccto.~y and tonsill~tomy in children. Journal of EpidemloloK~ a~id CommuniO. I leo lth 32(2):97-10], June ]978. SA~JEE. Y.. VF~EY, C.J., COLE, P.V., RU~ELL, M,A.H. Car~xyhem0glo~n and plnsmn Ibis)cygnets: Complemen~ry Jndic~tors of smoking ~huviour? Tlmmx 37/7):~21-525. July i982. SAM~. J.M., TAOER I.B., SPEIZER, F.E. The rei~tionship between resplrato~ illn~ in childh~ ~nd chronic alr.flow o~tructlon in adulth~, American Review of ~,'~pirato~ DL~c~e 127(4):60~23, April 19~, SANDLER, D.I'., EVE~ON, R.B., WI~X, A.J. Passive smoking In adulth~ and caner risk. ~tmericm, Journal of Epidemiolo~7 121(1):37~8, January 19~. SANDLER, D.I'., EVER~N, R.B., WI~X, A.J., BROWDER, J.P, Cancer sdulth~d l,,)m early life ex~ure ~ ~ren~' amoklng. American Journal of ~bllc llcalth 7~}:487~92, May 19~. SANDLEfl, D.I'., EVERSON, R.B., WI~X, A.J. P~ive smoking in adulth~ and caner risk. ~letter}. American Journal ufEpldendol~ 12~2):369-370~ Feb~ary 19~. SANDLI'3L D.I'., WIL~X, A.J., EVE~N, R.B. ~mul~tive eff~ of lifetime ~ive s,uokh~g on cancer risk. ~ncet I(~424~312~14, February 9, 19~a, SANDLER, D.I'., WI~X. A.J., EVE~}N, R.B. Lifetime pa~Ive smoking and ~nc~,r ri~k. Hatter). l~ncct II8433}:867. April 13, 19~b. ~HENKER. M.D., SAM~F, J.M., SPSIZEI{, F.E. Eff~t of eigaret~ ~r content and smoking lmhlts on re~plratory symptoms in women. Amedcan ~e~,iew to~ IHs~se 12~g61:~4~, June 1982. ~HEHKEI{, M.B., SAME~, J.M., SPEIZEfl, F.E. H~k racers for c~ildh~ r~pira. tory d~e~,: The effect of h~t fec~rs nnd home ¢n~i~nmen~l assure, Americun lir,~i~,w of ~espi~to~ ~e I~6~I~I043, ~em~r 19~. ~IIILLING, ILS.F.. L~AI, A.D., HUI, S.L., B~K, O.J., ~HOENBERO, ~UIIUYS. A.H. Lung function, r~pira~ry di~a~, and smoking in [amllJ~, America J,,urnal of Epidemiolo~ I~4}:274-~, ~to~r 1977. ~HL~I'3.M AN. J.J. C~se.~nt~I 3ludies: ~ign, ~nduct, AnaO'siq. Mon~.rephs in El,ldemi~dogy ~nd Bi~tisti~, Vol. 2, New York, Oxford Unive~ity Pre~, 1982. ~HMEINZ. I., HOFFMANN, D., WYNDER, E.L. The influence of tobn~ smoke on ind~,r ,tm~pher~: I. An overview. ~venti~ M~icin~ 4{I):~2, Ma~h 197~, SEELY, J.E., ZUSKIN, E., I]OUHUYS, A. Cigarette smoking: Obj~tlve evidence for lung dmnng,, in teen-age~. &ience 17~39~}:741-743, May 14, 1971. SHEPIIARD, ILJ., ~LLINS, R., SILVERMAN, F. 'Ta~ive" ex~ure of asthmutic sub~c~ ~ cigarette smoke. Envi~nmental ~h ~2):392~02, ~em~r I~9. SIMS, D.G.. ~ )WHIIAM, M.A.I~.S., GARDNE~ F.S., WEBB, J.K.G., WEIGHTMAN, D. Study of 8-yeermld children with n blstory of reeplr~tv~ syncytial virus b~nchiolili,, iu la[ancy. Brit~h M~ical Jot, rno[ I(6104~:II-14, January 7, 1978, SPEIZER, F.E., FERRIS, B., Jr, BISHOP, Y.M.M., SPENGLER J, Reeplra~ d[se~e ~ m~d pulmonary function in children a~ia~ wlth NO, ex~sure, ~evi,.u~ of li rspira to~ D~e~e 121(I):~I0, January 19~. SPEIZER, F.E., TAOER, I.B. Epldemivl~y o~ ch~nic mucus hydration and ~tructive uirwsys dl~ase. Epidemiologic Reviews 1:124-142,1979. SPINACI, S., A RO~A, W., B~RGIANI, M., NORTALE, P., BU~A, C., ~ ~NDU~ SION, E. The ef[ec~ of air ~llution on t~ r~plrato~ health of children: A s~tbmnl si,dy. Pediatric ~Imonolo~ J(5):~2-2~, 19~, ~ERLING, T.i). Non.smoking wives of heavy smoke~ have n higher risk o~ lung cancer. (let~r). ~ritisl~ M~icoi Journal ~70):I l~, April 4, 198J,
Page 68: TI07870678
STEWART, A.. WEBB, J., HEWITT, D. A survey of childbed{ malignanci~. Medical Journal ~: 1495- !~. June 18, 1958. ~TJERNPELDT, M,, B~ROLUND, K., LIN~N, J.. LUI)VIO~)N, J. M~rn.l smoking durin~ pregnancy a~ ~k ofcl, ildh~ cancer. ~neei [(8.194~13~I ~2, June 14, 1986. ~TOBER, W. Lung dynami~ and UlRake of smoke con~fltuen~ hy nonsmokem: A survey. ~evenlive M~icine I~6):fi8~I, Hovem~r SU~ON, O.C. Pa~ive smoking and lung ~n~r. (letter). li~tish Me~icial ~al 282(62~}:733, February ~, 1981. SVENDSEN, K.II., KELLER. L.II., HEA~N, J.D. Eff~ of p~ive smoking in Multiple Ri,k F~c~r In~rvuntlon Trial (MRFI3~. Ci~ulation, Part II, No. 4, ~r TAGER, I.B. Pa~ive smoking and ~Oru~ry heolth in cblldren: ~phistry or mu~ for concern'/Anwri~n R~uirw o[ R~pimlo~" ~e l~6):gSg-~l, June I~. TAUER, I.B., MU~OZ, A., BOSNEN, B., WEI~, S.T., CAI~EY, V.. SPEIZER, F.E. Ef~t of cigarette ~moking on the pulmonary function of children and American Review of Respi~ls~ ~e 131{5~752-7~9, May 1985. TAGER. I.B., WEI~, S.T., MU~OZ, A., R~NER, B., 8PEIZER, F.E. ~n~ltudin~l study of the effec~ of maternal ~moking on pulmonary function i,t children. Etlgland Journal of Medicine ~ 12~6~-703, ~ptem~r 22, 1983. TAGE~, I.B., WEI~, S.T., ROSNER. B., SPEIZEII, F,E, Eff~t o[ paren~l smoking on the pulmonary functiun of children. Ameri~#~ Journal of Epidemiolw gv I 1~I}:i~26, ,luly 1979. TASHKIN, D,, C~RK, V.A., SIMMONS, M,, REEMS, C., COU~N, A.H., BOURQUE, L,B., SAYIIE, J.W., I)~E~, R., ROKAW, S. The UCLA Impulat~ studies of chronic o~tructive r~piratory di~: 7. llelallonshil, ~tw~, smoking and c}dldren's lung funct[~. America Itevi~w of ~pimt~ !~6l:891~97, June 1984. TRICHOI~ULOS, D. Pa~ive ~mokin~ and lung caner,/let~r), l~ncet Mgrd, 24, 1984. TRICItOPOULOS, D., KALANDIDI, A., SPARROS, L Long caner and ~moklng: ~n~lu$ion of Greek study. (letter). ~n~t ~!}:677~78, ~p~m~r 17, 1983. TRICIIOi~LOS, D,, KALANDIDI, A., SPARR~, L., MacMAIION, B. I~ng ~r nnd pa~ive smoking, lnle~afional Journal of~nver 27{1~1~, Jmmnry 15, 1981. ~OKOS, C.P. Non-smoking wlv~ d heavy smokers h~ve a higher ri~k of'lung {letter}, Brilizh Medical Journal 2~k 14~- 14~, Novem~r ~, 1981. U.S, DEPARTMENT OF IIEALTH, EDUCATION, AND WELFAllE. Stocking and Health: A Re~rl of the ~ur~n (]enemt U.S. ~partmeut of I lealth, ~u~tlon, and Welfa~, Public lloalth ~rvlce, Of~ of the A~istant ~retary for H~lth, O~ce on Smoking ~nd lieallh, DIIEW Pub. No. {PlISJ79-~, 1979. U.S, DEPARTMENT OF HEALTH .AND liUMAN SERVICe. The Health ~- quences of Smoking for Women: A Re~rt of the Surgeon Gen¢t~i , ~,S. ~rtn~nt ,of Ilealtb and Human ~rvic~, Public lteaith ~rvice. Oifice of the A~l~nt ~eretary for Health. Office on Smoking ~nd Health. 19~. U.S. DEPARTMENT OF IIEALTH AND IIUM~N SEliVIC~. ~,e H~lth ql~enc~s of Smoking: ~ncer. A Rc~rl of the Sargon Gtn~'ra[. U.S. ~pnrtment of ileulth and tluman ~rvi~, Public Ile~lth ~rvice, Office of the ~ts~nt Secretary for Health, Office on Smoking and llealth, DIiHS I'uh. No. 50179, 1982. U,S, DEPARTMENT OF HEALTH AND IIUMAN SERVfC~. 77~e H~alth ~e- quenc~s of Smoking: Cardiov~cul~w Dise~e. A Re, re of the Su~flew~ Geseral. U.S. ~pnrtment o~ liealth and Ilumnn ~rvi~, Public Ilealth ~rvice. Oifico of the A~istant Secre~ry for llealth, Offi~ on Smoking and Ilealth, DlillS Pub. No. {PHS~4-~4, 10B& 116 U3, DEI'AIITMENT OF IIEALTH AND IIUMAN SERVICES, The H~alth quem'es of .timnking: Chronic Obstructive Lung ~. A Re, re of the Genemi. O.S. ~ment of Health and Human ~[~, Publi~ Health Office of the A~ls~nt ~re~ry for llealth, Offl~ on Smoking and Health, DIIHS Pub, No, ~Pl IS~-~, 1984. U.S. PUflLIC IIEALTH SERVICK ~moking and Hmllh. Re, re of the Adv~ ~mmille¢ h~ Ihe 8urg~n General of lhe ~bli~ Hmlth ~ruice . U.S, ~rtm~nt d Health. I,~u~tlon, and Welfare, Public ilealth ~rvi~, ~nte~ for DI~ ~ntrol, PIlS Pub. No. 1103, I~. VAN ~'EENSI,:~MOLL, H.A., VALKENBURG, H.A,, VANDENBROUCKE, J,P, Are maternal fertility problem, rela~ to chlldh~ leukaemla? International Jou~al ofEpidemb~h~K~' 14(4):~5~9, ~em~r 1~. VEDAL, S... ~:HENKER, M.B., SAM~, J.M., SPEIZER, 'F.E, Risk fac~n for childh~ rt~pira~ di~a~: Analysis of p~lmonery function, America ofR~pimto~7 I~zmze 1~:187-192, August 1~, VUTUC, C. Qtmnti~tive ae~ of ~ive smoking and lung cancer, M~icin. 136):~7~, Novem~r 19~. WAIT~ C.L. Elf~ of ~ive smoking. (later). New England Journal ~i6}:8~, (k~r 19, 1978. WAKEllAN, I I. Eff~ of ~ive smoking. Itetter). ~ew England Journal ~16k8~, (kto~r 19, 1978. WALD, N.J., BI )REllAM, J., BAIL~Y, A., RI~IIlE, C., llAD~W, J.E,, KNIGIIT, Urinary colinine ee marker of breathing other ~ple'a ~ba~o ~moke, (let~rk WALD, N.J., IDLE, M., BOREIIAM2., BAILEY, A. ~n monoxide in breath in telatlnn ~ smoking and ~r~xy~em~l~ln leveb. Th~ ~5~9, May I~1. WALD, N,J., Ill.tilE, C, Validatio~ of studi~ on lung caner in non~moke~ marrit~ b m~mke~. (letters). I~ncet ~lkl~, May 12, 19~. WALTEIL S., NANCY, N.R., ~LLIER, C.R. Chang~ in [ore~ expirato~ ~pl~ram in young male zmoke~. America Review of Rmpimlo~ D~e 11~k717-724, 1974. WAR~ J.ll. I~KERY, D.W., SPIRO, A. Iii, SP~IZER, F,E,, FERRIS, B,Qq P~ive stocking, g~ ~ing, and r~piratory health ff¢hildren living in ~ix ~itl~. Ameri(~n R*',,~eu, of Ropimto~ ~s~ 1~3}:~374, March 1984. WEINBE~/GglL S.g,, WEI~, S.T. Pu~m~ary dl~. Im Bur~w, G.N., FerrY, q~s}. M~i,'al Compli~tion. ~dng ~gnoncy 2nd ~, Phlladelphls, ~unde~, 19~i, pp. 4~34. WEI~, S,T., TAGER, LB., MUSOZ, A., SPEIZEll, F.E. ~e relationship of Inf~tio,m in early chlldb~ ~ the ~urren~ of incre~ levels of bronchial r~usivenc~ and a~py. Amed~n Review of R~pimto~ ~e April WEI~. S.T.. TAGER, I.B., SPEIZER, F.E., R{~NER, B. Pe~is~nt wh~: I~ ralston to r~piratery illne~, cigarette smoking, and level of pulmvnary funution ~pulution mtmple of children. Amerimn ~eview of ~oplmto~ D~e~e 707, Novemls~ WH1T~ J.R., FROEB, II.F. Small-airways dysfunction In nonemoke~ chronl~lly ex~l to h~t~ smoke. New EnglomI Journal of Medici*te ~13}:72~7~ March 27, WIII~'EMOII~:. A., AL]~llULEIt, B. I~ng cancer incidence In elgarett6 smokers: Further amdysis of ~11 and Hill's du~ &r Brlti~h phy~iclao,, Bion~elr[t'~ 3~4):~811;, ~em~r 1976. WIEDEMANN, H.P., MAHI.ER, D.A.," ~KE J., VIRGULTO, J.A., SNYDEII, MATI'IIAY, R.A. Acute eff~ of pa~ive smoking on lung function and nil'way reactivity in ,,sthmatic suhj~. Chest 8~2}:1~!~, February 1986, 117
Page 69: TI07870679
WOOI,C(.)CI(, A.J., I'I~AT. J.K., LEEDER, S.tL. IILACKBUI~N, C.I{.B, (ed~.L The development of lung function in Sydney childre**: E;rI~ ofr~pirntory illne~ and mnoklng. A ten year sl.udy, Eu~q~n Jou~ol of ~c~piralo~ I~ ~Suppl. 132):I-137, 1984. ~U, A.IL, II~NDE~SON, B.£., PIKI*:, M.C., VU, M.C. Smokb*g~nd other ri~k fnc~ for lung cnncer In women. Journcd oftAe ~otio~*al Ce.~r I~tilute 74(4~747-751, April 1985. WYNDER, g.l,., HOFFMANN, D. 7h~ ,~mohr ~di~ in Ex~n,eMal ~ino. ~#ne~is. New York, A~demic P~q, l~. WYNDER. E.L. ~UELLMAN, S,D. ~mpnrntive epldemioI~y of ~rela~ cau~. ~u~r ~e#~h 37~ 12~41~622, ~r 1977. YARNELL, J.W.G., ~. Lk]GER, A.S. R~pira~ry illnm, maternal pm,~king habit and }ung function I. children. B~lbh Jounml of Dis~a ~f the Ch~t 7~3~, July l~Tg. 118 CHAPTER 3 ENV IRONMENTAL TOBACCO SMOKE CHEMISTRY AND EXPOSURE OF NONSMOKERS
Page 70: TI07870680
CONTENTS Introduction Laboratory Smoking Hunmn Smoking Sidestremn Smoke Formation and Physicochemical Nature Chemical Analysis Radioactivity of Tobacco Smoke Enviromnental Tobacco Smoke Comparison of Toxic and Carcinogenic Agents in Main- stream Smoke and in Environmental Tobacco Smoke Number aml Size Distribution of Particles in Environ- mental Tobacco Smoke F~timating Human Exposure to Environmental Tobacco Smoke Time-Activity Patterns Temporal and Spatial Distribution of Smokers Determinations of Co'ncentration of Environmental Tobacco Smoke Microeavironmentai Measurements of Concentration Monitoring Studies Conclusions Beference~
Page 71: TI07870681
Introductlol) The phy.~icochemical nature of environmental tobacco smoke (ETS) is governed by the type and form of the tobacco product or products burned, by the prey.ailing enviro~imental conditions, and by secondnry rc~tctions. Mainstream smoke (MS) is the complex mixture that exits fr-m the mouthp.iece of n burning cigarette, cigar~ or pipe when a pull" is inhaled by the smoker. Sidestream smoke (SS) is formed between puff-drawings and is freely emitted into the air surrounding a smoldering tobacco product. Sidestream smoke repre- sents the m,.jor source for ETS. The exhaled portions of MS and the vapor phase components that diffuse through the wrapper into the surroundin~ air constitute minor contributors to ETS. In the sckmtific literature, the terms "passive smoking," "involun- tary smoki~tl.,," and "inhalation of I~I'S" are frequently used inter- changenbly (US DHSW 1979; US DIIHS 1982, 1984). Laboratory Smoking Data on the composition of MS and SS originate frown laboratory studies. For such studies, cigarettes, cigars, or pipes are smoked by machines mtder standardized reproducible conditions. It is a ma~or goal o1" these measurements to compare the yields of the specific components in the MS or SS or both of a variety of experimental or commercial tobacco products and to simulate, though not to repro- duce, humlm smoking habits. '['he most widely used standard conditions f~r machine smoking cigarettes and little cigars ( _< 1.5 g) are one 35 mL puff of 2-second duration drawn once a minute to a butt length of 23 ram, or the length of the filter tip plus the overwrap plus 3 m~n (l~runnemnnn et el. 1976). The annual reports of the U.S, Federal Trnde Commi~ion on the tar, nicotine, and carbon monox- ide content .r the smoke of U.S. commercial cigarettes are based on these labor, tory smoking conditions. For cigars, the standard smoking co;;ditions are a 20 mL puff of 1.5-second duration taken once every 40 seconds, and a butt length of 33 mm (International Committee I~or Cigar Smoke Study 1974). The most frequently used pipe-smoking conditions call for the bowl to be filled with 1 g of tobacco a~d a 50 mL puff of 1-second duration to be taken every 12 seconds (Miller 1964). Ant, mher of devices for collecting sidestream smoke have been developed (I)ube and Green 1982). The mo~t widely used device is a eollectio~t apparatus made of glass and cooled by water circulating through an outer .jacket. The air entering the chamber through a distributor has a flow rate of 25 mL per second (1.5 L/rain) (Brunnemam~ and Heft'mann 1974). Under these conditions, the yields of m, instream smoke component~ from a cigarette approxi- mate those ,btained from the same cigarette when it is being smokea 123
Page 72: TI07870682
in the open air. However, the velocity of the alrstream through the chamber has considerable influence on tl,e yields o1' individual compounds in SS (Klus and Kuhn 1982). To collect the particulate phase of MS and SS, the smoke aerosols are passed through a glass fiber filter (a Cambridge filter with a diameter of 45 ram) that traps more than 99 percent of all particles with a diameter of at least 0. I b (Wartman et al. 1959). The portion of the smoke that passes through the glas~ fiber filter is arbitrarily designated as vapor phase, although it is realized that this separa- tion does not fully reflect the actual physicochemicai conditions prevailing in MS and KS. For the analysis of individual components or a group of components, specific trapping devices a~d methods ',e been developed (Dubs and Green 1982). Ituman Smoking , The standardized machine-smoking conditions used it~ the tobacco laboratory were set up to simulate the parameters of human smoking as practiced 30 years ago. Tile examination of current smoking practices suggests that machine-smoking conditions no longer reflect current practices, ttuman smoking patterns depend on a number of factors, one of which is the delivery of nicotine. Dosimetry of smoke constituents has shown that low ~dcotlne delivery (<~0.6 to 1.0 rag/cigarette) generally induces the smoker to draw larger puff volumes (up to 55 mL per Imf0, to puff more frequently (three to live times a minute), and to inhale more deeply (Homing etal. 1981). Furthermore, many smokers of cigarettes with perforated filter tips tend tn obstruct the holes in these tips by pressing their lips around them; thus, they inhale more smoke than would be expected according to the machine-smoking data (Kosiow- ski et al. 1980). Smokers of cigarettes with a Iongitudi~ml air channel in the filter tip compress the tip in a similar manner so that the mainstream smoke delivery is increased over that measured with tile laboratory methodology (Hoffmann etal. 1983). ' These deviations from machine-smoking patterns cause a greater amount of tobacco to be co~sumed during MS generation. Conse- quently, the quantity of tobacco burned between puffu is diminished, and lower amounts of combustion prod,~cts are released as Because of the proximity to (he burning tobacco product, the active smoker usually inhales more of the SS and £TS tha~ ~ nonsmoker. . It is not known to what extent the different constitue~tts of inhaled ETS aerosols can be retained in the respiratory tract of nonsmokers. Studies with MS have shown that more than 90 percent of the volatile, hydrophilic components are retained by tile ~moker (Dal- hamn etal. 1968a) and that less than 50 percent of the volatile, hydrophobic MS components are retained by the smoker (l)alhamn et al. 1968b). On the basis of these data, it may be assumed that the 124 pa~ivo smoker re~aitm a high percentage of the vapor phase components of ETS and significantly less of its hydrophobic volati]es, Sldestraam Smoke Formation and Physlcoc.hemical Nature When no,lfllter cigarettes are being smoked under standardized conditions, approximately 45 percent of the tobacco column is consumed during the generation of MS (puff-drawing), whereas the remainder is burned between puffs and under conditions of a strongly reducing atmosphere. In addition, MS ,and SS is generated at distinctly higher temperatures than SS (Wynder and Hoffmann 1967). Thus, undiluted SS contains more tobacco-derived combustion product~ than does MS, and contains especially greater quantities of those combt,stion products that are formed by nitrosation or amination. Consequently, the composition of SS differs from that of MS. The SS or a smoldering cigarette enters the surrounding atmo- sphere about 3 mm in front of the paper burn line, at about 350° (3 • (Baker i~J84), In Table 1, ti~e MS and tile SS from nonfilter cigarettes are compart~l. Under standardized conditions, the formation of the MS of a nonfilter cigarette (80 ram, 1,230 rag) is completed during 10 puffs, requires 20 seconds, and consumes 347 mg of tobacco. The formation of SS from the same cigarette during smoldering requires 550 seconds and consumes 411 mg of tobacco (Neurath and Horst- mann 1963). The pl! of the MS era blended U.S. cigarette ranges from 6.0 to 6,2 and the pH of SS, from 6.7 to 7.5. Above pH 6, the proportion of unprotonatcd nicotine in undiluted smoke rises; at pH 7,.9, about 50 percent is m~protonated. Therefore, SS contains more free nicotine in the vapor phase than MS. The reported measurements of the pH of cigars were 6.5 to 8.5 for MS and 7,5 to 8.7 for B~; measurements for the pit o~" SS from pipes have not been published (Brunnemann and Hoffmasm 1974). Chemical Analysis In order I.o establish reproducible chemical-analytica| data, c'iga. rette SS is generated in a special chamber. This assures that the cigarettes burn evenly during puff intervals when an airstream at a velocity of 25 mL per second is drawn through the chamber. At this flow rate in the chamber, MS generation is quantitatively similar to that measu|'t.~i without the SS chamber (Neurath and Ehmke 1964; Brunnemam~ and Hoffmann 1974; Dubs and Green 1982), Through- out this ch~tpter the data refer primarily to MS, ~S, and ETS deriving from cigarettes and not from cigars or.pipes, because 125
Page 73: TI07870683
TABLE l,--Comparison of mainstream smoke (MS) and sidestream smoke (SS)'of a nonfllter cigarette: Some physicochemlcal data 119~I T~ ~r~ (~) ~47 411 Wynder snd lloffmann P~mk ~m~rslU~ du~l~ [~st~ ('~ ~ ~runnemsnn and pII d ~1 ~ 6.~6.~ 6.~-7.~ Iloffmann (1974) ~a~llatl~Ior~llnl HumOr d ~d~ ~r c~a~' I0.S ~ liP' end ~vino ~r~r ~ II~sws Pnfl~k sire Inm)' O.l-I.O 0.01~.8 (197~h tllller et el. Pn~le ~n d~r (rim)~ 0.4 Wy~r and II~mtnn ~ke dllu~ I~ %1s I1~ Keith ~rrkk (1~ ~n ~ ~ ~nker noffmsnn, D~nne~nn ~r~n dbl~ 8-11 Hyd~n 3-18 O.~L0 NOT£: ~el~ ob4~Ined under ssmndli~ h~bvt.tory ~ ~I~ d I ~ ~ m~w~ d ~ ~; cigoret~ smoke is the major ~urce or ~ in public phc~. Few da~ are available on the ~ and I~S from cigam and pi~s. About 3~ to 4~ of the several thousand individual ~m~unds identified in tobacco smoke have ~en quanti~tively de~rmin~ in both mainstream and eid~tream smoke. A listing of ~!~ agen~ in the MS or nonfilter cigaret~s with their re~r~ range of concentration and their relative ratio of distribution in ~ ~mpar~ with MS is presen~d in Table 2. Values greater than 1.0 fefl~t the greater relate or u given mm~und in~ ~ thou in~ MS. The grouping of the commands in Table 2 in~ va~r ph~e ~m~nen~ and particulate pha~ conetituen~ rares ~ the makeup of ~, but does not repr~ent the physic~hemical distribution of fl~ com- mands in ~. ~me o~ the volatile.commands in MS and ~ are compared. On the b~ts of the amount of ~boc~ burn~ in the MS and SS o~ a nonfllter clgaret~ (see Table 1), the ratio of ~ ~ MS ~hould be 1.2 ~ 1.6 If the c, mbustion conditions during ~th ph~ of smoke generation were comparable. However, this ~ not the ~e, 126 as is indicaled by tim higher SS to MS ratios for carbon monoxide (2.5-4.7), cmbon dioxide (8-11), acrolein (8-15), benzene (10), and other mnok,: constituents. The high 'yield of carbon monoxide and carbon dioxide in SS indicates th.t more carbon monoxkle is generated during smoldering than dr,ring puff-drawing, After peesing very briefly through the hot cone, most {,1" the carbon m~noxide gas in both MS and SS is oxidized ~to carbon dioxide, most likely owing to the high temperature gradie;tt nnd the sudden exposure to environmental oxygen upon emission. The higher yields of volatile pyridlnes in SS compared with MS are probably caused by the preferred formation of these compounds from the alkaloid, during smoldering (Schmeltz eL el. 1979). In ¢ontra~t~ hydrogen cyanide (HCN) is primarily formed from protein at temperatun:s above 700° C (Johnson and Kang 3971), and the smoldering .f tobacco at about 600° ~ does not yield the pyrosynthe- sis of lICN to the extent that it occurs at the higher temperatures present duri,g MS generation. The very high levels of ammonia~ nitrogen oxide, and the' volatile N-nitresamines in SS compared with the levels i. MS is striking. Studies with "N-nltrate have under- scored that the burning of tobacco results in the reductlon of nitrate to ammonia, and that the latter is released to a greater extent during SS formation than during puff-drawing (Johnson et el. 1973). In a blended cignrette, this higher level of ammonia in ~S causes its elevated pH to reach levels of 6.7 to 7.5, while the pH of MS is about 6 (Brunnem,nn and Hoffmann 1974). The increased release of the highly carcinogenic volatile N-nitrosa. mines into SS (20 to 100 times greater than in.to MS) has been well established ~Brunnemann et el. 1977). The carcinogenic potential of SS may also be affected by the levels el" the oxides of nitrogen Four to te, times more nitrogen oxide (NO) is released into the environmenl, in sldestream smoke than is inhaled with the main. +stream smoke. T.he smoker inhales more• than 95 percent of the NO, in the rorm of NO, and only a small portion is oxidized to the po.werful nil+rosating agent nitrogen dioxide (NOffi). Only a fraction of NO is expecl.ed to be retained in the respiratory system of smokers by being btmnd to hemoglobin. The NO. gases released into the environmenl, are partially oxidized to NO~ (Vilcins and Lephardt 1975). Therefore, sidestream smoke-polluted environments are ex- pected to contain the hydrophilic nitrosating agent NO~. Data for particulate m~tter and s~me of its constituents in MS and SS are also listed in Table 2. The release of tobacco-specific N- nitrosamlne~ inte SS is up to four times higher than that into MS. Whether the distribution of these agents in the vapor phase and the particulate phase of SS is of major consequence with respect to the carcinogenic potential of SS needs to be determined. It is equally 127
Page 74: TI07870684
TAJ~LE 2~Distribution of constituents in mainstream smoke (MS) and the ratio of si~estr~m smoke- (SS) to MS of nonfilter cigarettes MS SS/MS MS SStMS Vapor ph~e c~n~[tuents ~ r~n~e r~t~ Par,..icu~w phase eon~it~-n~'~ r~ ra'£o ~.Ni~imemyi~mme" 10-40 n~ N-Nitmso~yr'r~idine" 6-30 n~ Formk ~ ~" ~,I0.-4~0 ~ L4-L6 Acetic m:~ 3~0--810 ~ 1.9-3.6 T!07870684
Page 75: TI07870685
TABLE 3.~Distribution of selected component~ "in the sidestream smoke (SS) and the ratio of SS to mainstream smoke (MS) of fotu- U~. commercial cigarettes Componenr.s SS SS! MS SS SS/M~ SS S,S/MS 55 55; MS Tsr (m~,/g) 22.5 LI 24.4 1,6 2U.O 2.9 "° 14.1 15.6 N'mot~ne (m~/g| 4.6 ~ ¢0 ~7 ~4 4~ 3.0 ~.o ~n m~ox~e t~/g) ~ ~I ~6 ~T ~ 3~ ~.8 14.9 ~al~ (~/~l ~ ~ ~ ~ 51.7 4~ ~ ~.4 N'~it~~ {~/g~ ~ 0~ ~ ~ 1~ ~.~ ~ 5.1 Ti07870685
Page 76: TI07870686
also depend on the general occurrence of radon in l.he atmosphere and not on the local emanation of radon (Hill 1982). In recent years, it has been shown that relatively high levels of radon and short-lived radon daughters may occur in indoor air, and consistent observations in this regard have been made in several countries (Nero etal. 1985). In the air with a very low concentration of particles, the proportion of unattached rado,~ daughters is increased beyond that found with a higher concentration of particles. The unattached daughters are removed more rapidly than those that are attached by plating nut un walls and fixtures. The addition of an aerosol, such as tobacco smoke, increases the atiached fraction, elevates the concentration of radon daughters, and reduces the rate of removal of radon daughters (Bergman and Axeleon 1983). The dose.of a radiation received by the airway epithelimn defends not only on the concentration of radon daughters hat also on the unattoched fraction and on the size distribution of the inhaled particles. The interplay among these factors as they are m~lified by ETS has not yet been fully examined. Environmental Tobacco Smoke The air dilution of sidestream smoke, and of other contributors to ETS, causes several physic(chemical changes in the aerosol. The concentration of particles in ETS depends on the degree of air dilution and may range from 300 to 500 mg/m~ to a Jew pg/m~. At the same time, the median diameter of particles may decrease as undiluted SS is diluted to form ETS (Keith and Derrick 1960; Wynder and lloffmann 1967; Ingebrethsen and SearH 1986). Further- more, nicotine volatilizes during air dilution of SS, so that in ~ it occurs almost exclusively in the vapor phase (Eudy et ul. t985}. This is reflected in the fairly rapid occurrence of relatiw;ly high c~nosn- trations of nicotine in the sMiva of people entering =t smoke-polluted room (Hoffmann, Haley el. al. 1984). Most likely there are also redistributions between the vapor phase and the particulate, phase of other constituents in SS duo to air dilution, which may account for the presence of other semivolatiles in the vapor phase of E~PS. l lowever, evidence of such effects needs to be establi~|hed. Comparison of Toxic and Carcinogenic Agents In Mainstream Smoke and in Environmental Tobacco Smoke The combustion preducL~ of cigarettes are the s~)urce of both environmental tobacco smoke and mainstream smoke. Therefore, comparisons of the levels of specific toxins and carcinoge~m in ETS with the corresponding levels in the mainstream smoke are relevant to an estimation of the risk of I~I'S exposure. Although E'I~J is a.far 132 less concentrated aerosol than undiluted MS, both inhalants contain the same volatile and nonvolatile toxic agents and carcinogens. Thl~ fact and the current knowledge about the quantitative relationsh|p¢ between dose and effect that are commonly observed from exposure to carcinogens have led to the conclusion that the inhalation of ETS gives rise to some risk of cancer (IARC 1986).. However, comparisons of MS and ETS should include the consider- ation of the differences between the two aerosols with regard to their chemical composition, including pH levels, and their physicovhem|. cal nature (particle size, air dilution factors, and distribution agents between vapor phase and particulate phase), Another impor- tant conskh:ration pertains to the differences between inhaling ambient air and inhaling a concentrated smoke aerosol during puff- drawing. Finally, chendcal and physicochemical data established by the analysis of smoke generated by machlne-smoking are certainly not fully comparable to the levels and characteristics of compounds generated when a smoker inhales cigarette smoke. This caveat applies particularly to smoking of low-yield cigarettes, for which the yields of smoke constituents in machine-generated smoking and human mnaking activities may be most divergent (Herning et al, 1981). The leech; of certain smoke constituent~ in the mainstream stunk0 of one c|garette compared with the amounts of such compound~ inhaled as constituents of ETS in I hour at a respiratory rate of 10 L per minute are presented in Table 4. Unaged MS does not contain nitrogen dioxide (NOr < 5 pg/cigarette) because the nitrogen oxid~ gener~tted during tobacco combustion in the reducing atmosphere of the burning cone are transported in the smoke stream (~10 col % O~) to the exit of the cigarette mouthpiece in less than 0,2 seconds, and it takv~ 500 seconds for half of the nitrogen oxide in MS to oxidiz~ to nitrogen dioxide (Ne.urath 1972). The relatively low valuP~ for nicotim: reported in ETS may be explained, in part, by the inefficiency of the trapping devices for collecting all of the available nicotine; tim alkaloid is predominantly in the vapor phase, which escapes retention by the filters of such devices.. The assignment of benzene as a "human carcinogen," ben~ [a]pyrene ~ts a "suspected human carcinogen," and N.nitrosod|- methylami~te and N-nitresodiethylamine as "animal carcinogens" t~ based on d~:finitions by the International Agency for Re~earch on Cancer (19~16). Accordingly, a human carcinogen is an agent for which "sufficient evidence of carcinogentcity indicates tltat there is a causal relalionship between exposure and human cancer." A pected hunmn carcinogen is an agent for which "limited evidence carclnogeni,~ity indicates that a causal interpretation is credible, but that alterm~te explanations, such as chance, bins, or confounding~ could ~ot adequately be excluded." An animal carcinogen is an agent 133
Page 77: TI07870687
TABLE 4.--C~ncentrations of toxic and carcinogenic agents in nonfilter cigaz-et~e mainstream smoke and in environmental tobacco smoke (ETS) in indoor environments A~t Weight Conc~r~oa We~h~ C.o~c~ rnr~a W~ht Cor~nn'~ion Carb~. raon~.~e 10=23 m~ 24.~00-~7~0 p~m 1.2-22 n~ 1-18~5 ~ ~ ~ ~ ppm Nh~n ~ I~ ~ ~.~I.~ ~ 7-~ ~ ~I~ p~ I~ ~ 195 ppb ~ ~ ~ II.~ p~ I~I~ ~ ~ ~ I~ ~ 98 p~ ~-N[~y~i~e~ i~ ~ ~ ~ ~I~ ~ 0.~.~ ~ I~ ~ ~.~;2 p~ N~Ni~i~y~¢= @~ q ~17 p~ <~ ~ <~.~ ~ i~ M O-~ P@ Ni~ 1~ ~ ~,~L~.~ p~ 0.~ ~ 0,~7~ ~ ~ ~ 75 ppb T!07870687
Page 78: TI07870688
TABLE &--Summary of sidestream smoke size distribution stuvties Chamtmr m~ian m~Ran gand~rd Number Po~der ~ N~ ~ ~~ ~ ' N~ ~ 0~ Not ~ N~ ~ ~ x 10" ~e~ ~: ~ ~e~ ~ ~ Not ~ O~ Z1 No~ ~ T107870688
Page 79: TI07870689
measuremef~ ts o1" a single compound reflect exposure to whole smoke is limited by the changes in the composition of ETS with time and the condil.kms of ex~sure. For this reason, exposures to ETS are often asse~cd using several measures as marker~, including mark- ers of the v, por phase and the particulate pha~e as well as reactive and nonreat.tlve constituents. Although biological markers show promise as measures of exposure because they measure the absorp- tion of smoke constituents, they too h.ave limitations (discussed in Chapter 4). An individual's ex. posure is a dynamic integration of the concentrution in "various enviromnente and the time that the individual spends in those environments. in specifying an individual's exposure to specific components of ETS, consid~,~rution must be given to the time scale of exposure appropriate for the response of interest. Immediate exposures of seconds or hours would be most relevant for irritant and acute allergic responses. Time-averaged exposures, of hours or days, may be important for acute contemporary effsct~ such as upper and lower respiratory tract symptoms or infections; chronic exposures occur- ring over a year or a lifetime might be associated with increased prevalence ~r chronic diseases and rlsk of cancer. The spnti~d dimensions or the proximity of the individual to the source of smuke is important in asse~ing that individual's exposure to ETS. ~I'S is a complex, dynamic system that changes rapidly once emitted from n cigarette. Physical processes such as evaporation and dilutio~t of the particles, scavenging of vapors on surfaces, and chemical reactions of reactive compounds are continuously occurring and modify the mixture referred to as ETS. An individual located a few ce~timeters or a meter from a burning cigarette may be exposed to a high co~centratioa of ETS, ranging from 200 to 300 rag/mS0 and may inhale ~:omponents of the mestly undiluted smoke plume and of the exhaled,malnstream smoke. Ayer and Yeager (1982) reported cigarette plume concentrations of formaldehyde and acrolein in the core s~ssoke stream emitted from the cigarette of up to 100 times higher tha~ known irritation levels. Hirayama, a~ reported by Lehnert (19~14), cites the importance of this "proximity effect" in a~ses~ing exposure. Distant.~ on the order of e meter to tens of meters i~rom a burning cigarette are relevant for exposures in offices, restaurants, u room in a house, a car, or the cabin elr a commercial aircraft. At these distanc'ce, the mixing ot" ETS throughout the airspace and the factors that affect concentration are of importance in detcr,ni~fing exposure for people in the space. In many rooms, mixing is ~ot completely uniform throughout the volume, and significant concentration gredient~ can be demonstrated (Islfizu 1980). The.~e concentration gradients will affect an individual's exposure by modifying the effectiveness of ventilation in diluting or removlug I~,{lutants. The airborne muss concentration may vary by 139
Page 80: TI07870690
a factor of I0 or more within a room. Short-term mcasul-eJnents iu rooms with smokers can yield respirable particulate conceptrations of I00 to 1.000 pg/Ina (Repace and Lowrey 19B0). MulLihour measurements average out variations in smoking, mixing, and ventilation and yield concentrations in the range of 20 to 200 itg/m= (Spengler et el. 1981, 1985, 1986). Finally. on a systems scale, as in u house or building, concentrations are influenced by dispersion and dilution through the volume. Most time-integrated samples are taken on this larger scale. Using a piezobalance. Lebret (1985) found significazzt wzriaLion in respirable suspended particulate (RSP) levels between the Diving room, kitchen, and bedroom in homes in the Netherlands during smoking or within one-half hou,' of smoking. Ju sad Spengler (1981) studied the room-to-room variation in 24-hour average concentnz- Lions of respirable particles in various reside,ices. ~lthough differ- ences between some rooms were statistically sigpil~canL, absolute differences were relatively small, with a maximum difference of a factor of 2. Moschandreas end colle,gues (1978) released sull'ur hexafluorido, a tracer gas, in the living rooms of several residences and observed uniform concentrations in adjacent rooms withi,~ 30 to 90 minutes. RSP, which is slightly reactive, and nonreactive gases Would be expected to rapidly migrate through adjacent rooms. Therefore, in u ~etting Buch as the work environment, where the duration uf exposure is ~everal hours or more, ETS would be expected to disseminate throughout the airspace in which smoki.g is occurring. Smoke disse~nination may be reduced when air exchange rates are low, as may occur when internal doors are closed. Time-Activlty Patterns Individual tlme-activity patterns are a major determinant of exposure to E"~. The population of the United States is mobile, spending variable amounts of time in different Inicroenvironments. Individual activity patterns depend on age, occupation, season, soci.l class, and sex. For example, Letz and colleagues (1984) surveyed the time-activity patterns of 332 resident~ of Roa.e O~uuty, Tennessee, and found that 7~ percent of the person-hours were spent at horny, 10.8 percent at work. 8.6 percent in public places, 2.9 percent ia travel, and 2.8 percent in various other places. As expected, occupation nnd age were strong determinants of time-activity patterns. Housewives and unemployed or retired individuals spent 84.9 percent of their time at home, and occupational groups worked 21 to 24 percent of the hours. Students tended to spmtd the largest percentage of their time in public places, presumably schools, ranging from 14.7 percent lot the youngest group to 19.17 percent for the oldest group of students. 140 TABLE 7.--Mean percent and standard deviation of time allocation in various locations by work or school classification =ubgroup O~ioor Oflkel |nd,,-Lfi.ll To~l, all L~aflon |h)mcmaker ~.1 worker ~ ~t~n H~ ~.~ '~.91 49.97 ~.7( 67.~ 12.~)' 113.~) 113241 (8.7~1 (7.~) (13,~) ~ 5~2 ~ 8.~ 19.81 2.47 I0.~ 13.~) (~.~) (8.~) (t.49) (10.94) M~ veJ~kk 4.~ 5.tl 8.6~ 4.~ 7.~ t;I,19) (3.741 (6.15) (=.~1 1~,62J t;l~) (10.61) (5.~) (10.24) (12.~) 111.37) (I.~) ~.79) (0.~1 {3.~) (0.~) (I.~) N~r e~e~ ~ 5.~ 2.7~ U.13 12.~ 6,~ Nu~r ~ 02 4 12 B S(,~.IS~ ~ I1.~ I,,,m q~ck~kam ~d .I. I ll~l. The time allocations for various population subgroups in Portage, .Wisco.sin, ,re summarized in Table ? (Quackenbo~ et el. 1982). Tile data are eousistent with the findings of Letz and colleagues (1984) and show that the variability of individual nonsmokers' ekposure to smokers can be quite marked between the various occupational subgroul~. lnfa,ts have unique time-activity patterns; their mobility J~ limited and the locations where they epsnd their time depbnd primarily ou their caretakers. The time-location patterns for 46 infants is illustrated in half-hour segments in Figure 1 (Harlos et el. in prt:ss). Although infants spend most of their time in their bedrooms, they are in contact with a caretaker in traveling or in the ]ivingroom er the kitchen for approximately half of tile day. These infant time-activity patterns presumably correspond to the family patter,s a.d may significantly influence the infants' potential exposure. Altlmugh most people spend a.pproximately 90 percent o/" their time i. just two microenvironments (home and work) (Szalai 19.72), important exposures can be encountered in other environments. For instance, commuting or being "in transit" accounts fpr about 0.5 to 1.5 hours L~:r day for most people. Therefore, additional informati0u 141
Page 81: TI07870691
FIGURE l.~Tlme location patterns for 46 infants SOURcI~: lh*tlo* et *l. ¢l~ l~.ae t on the time spent and the I,,~I'S concentration in various microenvi. ronments may be~ useful in defining exposure. This exposure information can be obtained by questionnaire and validated by personal monitoring programs. The characterization of concentra- 142 tions o*' exp~sures or both in microenvironments should use time scales npprol*riate for the health effect of interest. These variations in location a~d time.activity patterns can make the reconstruction detailed WI'S exposure difficult in studies of long-term fiealth effects, The limitations in utilizing this tlme-activity approach in charac. terizing ezp,.~ures to other environmental pollutants also apply for ETS exposu,'es; they include the following: the extent to which overall population estimates can be generalized to individual pat- terns is ~orly understood; concentrations in various microenv.iron- meats are ~mly partially characterized; the, variation in time and activity patt~;rns and their effects on concentration levels are not established; c, xtrapolation to longer time scales either prospectively or retrospectively has not been validated; the differences within structures, i.e., room to room variations, are not well established, Temporal and Spatial Distribution of Smokers Exposure to ETS can occur in a wide variety of public and private locatJoas. At,proximately 30 percent of the U.S. adult population currently are cigarette mngkers. Nation'vide, 40'percent of homes. have one or more smokers (U.S. Dept. of Commerce 1985), In a survey of mare than 10,000 children in six U.S. cities, the percentage of children living with one or more smoking adults varied from a low of 60 percent to a high of 75 percent (Ferris et al. 1979), Lebowitz and Burrows (1976) reported that 54 percent of children in a study in Tucson had at least one smoker in the horde; Schilling and colleagues (1977) reported that 63 percent of homes in a Connecticut study had a smoker i, the home, These data indicate that the population potentially exposed to ~I'S in the home is greater than might be inferred from aggregated national statistics on the prevalence of smoking. A variation in the percentage of homes with smokers ~nay be observed among different regions. Furthermore, within house- holds, smoking does not take place uniformly in time or space, Smoking paLterns may change with activity, location, and time of day. These variables all serve to modify a nonsmoker's exposure to Exposure Lo ETS at home may also correlate with ETS exposures outside the home, possibly because nonsmokers married to smokers may have a t;reater tolerance for El'S-polluted environments or may be in the company of more smokers because of the spouses' tendency to associate with other smokers. Wald and Ritchie (1984) uded a biological marker and questionnaires to show tlmt nonsmoker~ married to smokers reported a duration of exposure to ET8 greater outside the home than was reported by nonsmokers married to nonsmokers (10.7 hours and 6.0 hours, respectively). Smoking prevalence varies widely among different groups (e.g.~ teenage girls, nonworking adults, and adults employed in various 143
Page 82: TI07870692
occupations); this variation modifies the exposure of .onsmokers to ETS. Smokers are present in nearly all enviromnents, including most workplaces, restaurants, and transit vehicles, making it almost impossible for a nonsmoker to avoid some exposure to ETS. The number of cigarettes consumed per hour by the smoker may vary at different times in the day, and the rate and density of smoking will also differ by the type of indoor environment a.d activity in such locales as schools, autos, planes, offices, shops, and b~rs. Although there have been numerous measurements of ETS concentrations in various indoor settings, these data do .at repre- sent a comprehensive description of the actual distribution of ETS exposures in the U.S. population. Spongier end colleagues (198~)and Sexton and colleagues (1984) demonstrated by the personal monitor- ing of respirable particles and the use of time-activity questionnaires that exposures to ETS both at home and at work are significant contributors to personal exlmeures. However, odditio.al data on the distribution of smokers in the nonsmokers' environment, as well as the distribution or ETS levels in that environment, are needed in order to characterize the actual I,.WS exposure of the U.S. population. Determinations of Concentration of Envlronmenlal Tobacco Smoke Environmental Tobacc~ Smoke is a complex mixture of chemical compounds that individually maybe in the particul.te phase, the vapor phase, or beth. ETS concentration varies with the generation rate of it~ tobacco-derived constituent~, usually given as mlcrometor per hour. The generation rate for ETS has been approximated by the number of cigarettes smoked or the number of p~lple present in a room who are actively smoking. Room-specific characteristics such as ventilation rate, decay rate, mixing rate. and room volume else modify the concentration. Because ETS particles have MMDs in the 0.2'to 0.4 Itm range, convective flows dominate their movement its air, they remain airborne for long periods of time, and they are rapidly distributed through a room by advection and a variety of mixing forces. Under many conditions, the ventilation rate of a space will dominate chemical or physical removal mecha.isms in deter- mining the levels of ETS particles. Nonreactive I~I'S compo.ents distribute rapidly through an air- space volume and their elimin.tion depends ahn~t solely on the ventilation rate. For example, Wads and colleagues (197~) simulte- nee. usly measured carbon monoxide, a nonreactive gas, and nitrogen dioxide, a reactive gas, in a house a~d determined their half-lives to be 2.1 and 0.6 hours, r~peetively. This study demo.strates the need for caution in extrapolating front one vapor plmse compound to another. Reactive gases and vapors may be rapidly lost to ~u|'faces or 144 may react with other chemical species. Their removal may be dominated by their reaction or absorption rates. Furthermore, the decay of I~S~icrived substances can be a function of the chemica[ ae well as the physical clmracteristics of room surfaces. For example,. Welsh and colleagues (1977) found that sulfur dioxide removal wtm greater for rooms with neutral and alkaline carpets than for rooms having carpets with acidic pH. Reactions with furnishings and other materials may occur for some ETS components as well, Mlcroonvlronmental Measurements of Concentration As was discum~l earlier, the complex chemical makeup of ETS makes the measurement~ of individual levels for each compound present in 1,71~ impossible with existing resources; thus, individual constituents have been measured as markers of overall smoke exposure. B,.~ause many of these conbtituent8 are also emitted from other sources in the environment, the contribution of ETS to the levels of these constituents is quantified by determining the enrich- ment of specific 'compounds found in smoke-polluted environments relative to the concentration measured in nonsmoking areas, Vari- ous gi~J components have been measured for this purpose, including acrolein, aldehydes, aromatic hydrocarbons, carbon monox'ide, nic- otine, .itrogen oxides, nitrceamines, phenols, and respirable parties. late matter. A summary of the levels found and the condition~ of measurement are presented in Tables 8 through 16. The major limitation of using most of these gases, vapors, and particles is their lack of specificity for ETS. The presence of sources, other than tobacco smoke, of these compounds may limit their utility for determining the absolute contribution made by ETS to room concentratious. Levels of nicotine and tabasco-specific nitrosamines, however, are specific for I~WS exposure. Obviously, no single measurement can completely charaeterlze the nonmnoker's exposure to ETS, and many studies have measured several of these componenLe in order to characterize the exposure. Markers should be chosen both because of their accuracy in estim.ting exposure and because of their relevance for the health outcome of iatoresL. One wi&~.ly reported marker of ETS is respirable suspended particulate (RSP) matter. Although lacking specificity for tobacco smoke, the prevalence and number of smokers correlates well with RSP levels ill hol~es and other enclosed areas. A study of the RSP levels in 80 homes in six ci~ies (Figure 2) (Spenh~lcr el. a!.,1981) showed that indoor concentrations were higher on aw:r.age ,nd had a greater range than the outdoor concentrations, Front I.hese d~ta, it is evident that even one smoker can significantly elevate i.&~or RSP levels. 145
Page 83: TI07870693
TABLE 8.--Acroleia m~sur~I under realistic condiUoms 0.~3-0.10 m~/m~ OA~ m~lm• 0.0~ u~m= 0~0 m~/m~ TABLE 9.--Aromatic hydrocarbons memnn~d under r~aIistic conditions Study pr~ O~-up*~7 V~dl~don .c':'ndRiom' Benzene 0.1C9 O.O~,.~.lO 0.O4 O.l,~ Ar~m 8.6¢'-tOJ8~ ~ M~,~i~ N~ ~ 7.1 12.0C0-12.~44 people 1~1,000.,.14.2T7 lx, op~ ~$ daya in th~ fall 0.04-L04 TI07870693
Page 84: TI07870694
TABLE 9.~Con/;i.nued study pmmbm" Occupancy TABLE lO.--Carbon monoxide messured under realistic conditions" T107870694
Page 85: TI07870695
TABLE lO.~mfinue~ TABLE lO.~Continued TI07870695
Page 86: TI07870696
~ TABL~ I0.---Continued Ty~e~ Seiff lnmr~, b~ No( ~m (1973) e~L 1-2 TABLE ll.--Nicotine measured under realistic conditions Vli | ~ VII | ~ V~ ~Ot ~ V~.I ~ ~ We~ a~l F~ 44 o~scm Varkd Va~d 140 x 3 bz o~ _ I-~ I~8 ~ V~lum no~ ~ (19~0}* iml~s T107870696
Page 87: TI07870697
TABLE ll.~Continued Study pr~ 132 2.7-.30.0 4c~m N~ N(x ~ N~x ~ N~x ~ N~x N~ N~ ~v~ NX ~ N(x ~ N(x ~ N~ ~ N(x ~ N~t ~ N~X ~ 47.7 TABLE 12.--Nitrogen oxides measured under realistic conditions W~b~ ~ ~t ~ Vm-i~d Vm'~ ~4~ '(1980) ~ NO~: 76 59-10~ NO:. 120 38.218 NO~ (;3 24-99 NO:. 80 14-21 NO~: 21 1-61 NO:. 195 6~-414 NO~: ~ 3~t03 N~ ~2 = ~0 ~0 (~k~ T107870697
Page 88: TI07870698
TABLE 13~Nitrosamlnes measured under re~distic conditions TABLE 14.--Particulates measured under realistic conditions Sm~y. ~ p~ Io0 m') V~il~i~m im~.l ~ N~ ~ t~jmD (1980) '~'T? ~47 0.74 O~ T107870698
Page 89: TI07870699
"fABLE 14.---C~ntinued prem/~ _-- lO TABLE 14.---Continued T107870699
Page 90: TI07870700
TABLE ~4~-- Continued ~ ~0-150/b~4 ~' 11 ~ 2,4 X ~0 m~u mmpl~ I~ l-~T 12 Aldeh.v~m Ip~lm') TI07870700
Page 91: TI07870701
8O ~0 ~0 FIGURE 2.--Monthly mean mass respirable imrticulate ~oncentrations (pg/m~) across six cries ~OUItCE2 Spemiler ,it ml. (II~IL TABLE 16.--Resplrable particulate levels as a function of number of smokers Smoker Iltatu8 Nun&er Mesa (p|lm¢) ~.amlsrd deviation smokers ~ homts/I,IN ~mp~ ~4.4 I1.~ s~e~ ~ ~nll~ um~ 70.4 42.9 smoke~ 4 ~m~ ~m~ 61.8 12.3 IlL ¢ |901 ). Spengler and colleagues (1981) collected respirable suspended particulate samples in 55 homes in six cities. The average concentrtl- tions observed between May 1977 and April 1978 are shown in Table 16. The quantity of tobacco smoked was not reported, nor was the number of houris each smoker spent in the home. The researchers concluded that the mean RSP levels increased by 20 ~g/m~ per smoker. Dockery and Spongier (1981) further analyzed theec data and considered the number of cigarettes smoked in the home. They concluded that the mean RSP concentration increased by 0.88 i~g/m~ 162 for every cil.,arette smoked per day in the house. A one-pack-a-day smoker in I.he home thus raises indoor respirable particulate levels by 17.(; pg/m~. Air conditioning increased the contribution of each cigarette by 1.23 ~g/m~, to a total of 2.11 I~g/m~ per cigurette in fully air-conditioned homes. These values are annual averages; air-condi- tioned barnes, in which air is recirculated during the warmer months, have higher levels: Repute and Lowrey (1980) measured RSP concentration using a piezobalance in several public and private locations~ including restaurants, cocktail lounges, and halls, in beth the presence and the absence of smoking. They then developed an empirical model utilizing the mass-balance equation. Using both measured and estimated parameters as input to the model, they validated the model for predicting an individual's exposure to the RSP constituent of ~I'S. 'rh~: model takes the form: C,q = 650 D,/n,; where C~q equals the eqoilibrium concentration of.the RSP component of ETS (ltg/m~), D, equals tl,; density of active smokers (number of burning cigarettes per 100 too#. undnv equals the ventilation rate (in air changes per hour, AC[U. The ventilation rate is a complex parameter that takes into account all the room-specific constants affecting the removal of ETS, such as ventilation, decay, and mixing. Measurements in a large number of locations using memmres of smoke generation such as the number of people smoking or the number of cigarettes being smoked have shown a definite relation. ship of smoke generation to particulate levels. First (1984) cautioned against the use of RSP measurements as a measure of ETS in public plac~ beca,se of its nonspecificity for ETS, and noted that other sources may contribute enough to the levels to invalidate the determine! ion of the ETS contribution. However, there are few other sourccs of ItSP in most U.S. homes, and therefore, the relationships of RSI' measurements to ETS levels are generally quite accurate in this setting. Nicotine appears to be a promising tracer for ~S because of its specificity G~r tobacco and its presence in relatively I/igh concentra- tions ill tolmcco smoke. It can also be measured in biological fluids to provide an indication o1" acute exi~sure to tobacco smoke. Cotinlne, nicotine'~ major metabollte, can be used as an indicator of more • chronic exposure. These biological markers are discussed in a separate clmpter of this Report. Recent studies have indicated that nicotine mi~y be primarily a~ociated with the vapor pha~e o~ ETS and theref, re not a surrogate for the particulate phase as once thought (F,~dy et el. 1986). However. the possible asefulne~q of th~ compound in estimating expiate to ETS warrants further evalu- ation. The nicotine content of sidestream smoke does not differ significantly from brand to brand when normalized on a per gram of tobacco basis (Richert et al. 1984). The use of nicotine, as a marker 163
Page 92: TI07870702
ETS must also give consi, leration to its loss to surfaces and its subsequent revolatilization and readmission to the r,om volume. Carbon monoxide, a marker fi~r gas phase comlmnt:nts, has been measured extensively as u surrogate for ETS. There are many sources of carbon monoxide other than cigarettes, indoors (e.g., stoves, grills} and outdoors (e.g., autqmobile). This nouspecificity for IZI'S seriously limits its usefulness for environmental measurements. In summary, no single compound definitively characterize~ an individual's exposure to E'I~. Additional research is currently under way to quantify the relationshilm among various constituents and ETS levels. Because of the complex nature of ETS, investigators may need to measure several markers or to separately record source variables (such as number of cigarettes smoked) in order to estimate exposure to ETS. Monitoring Studies Personal monitors can measure the concentrations of I~J in an individual's breathing zone. Personal monitoring is preferable to area monitoring because it integrates the teml~ral and spatial dimensions of an individual's exposures. At the present time, all of the studies that have used personal monitors to measure ETS constituents have utilized active samplers that provide integrated exposures over differing time periods. The markers assessed ia personal monitoring studies have the same lack of specificity found in area monitoring studies. However, in many of the personal monitoring studies, time-activity diaries were kept to permit greater re~iution in attributing exposure to specific sources. In Topeka, Kansas, 45 nonsmoking adults carried personal RSP monitors for 18 days, and area monitors were placed inside and out~ide their homes (Spengler and T~steson 1981). Tile indoor RSP levels were consistently higher than outdoor levels and th~ personal exposures levels were higher than either. The group was divided into those who reported ETS exposure and those who did not (Figure 3). Reported exposure to IZI~S clearly shifts the distribution to the right. On the average, reported E~I"S exposure increased an individual's personal concentration by 20 I~g/m~. Personal RSP monitors were carried by 101 nonsmoking volun- teers for 3 days in Kingsten-Harriman, Tennessee (Spengler et al. 19B5). The study population was divided into two groups: those who lived with a smoker and those who did not. ErI'S exposure was reported by 28 of the participants, with the remaining participants reporting none. The RSP distribution for the ambient samples is shown in Figure 4. Clearly, exposure to ~ significantly increases an individual's personal concentration profile. 164 16. 14 ~0 14- o. n n_. 0 S I0 I~ 20 ~ 30 35 40 45 50 SIS 60 6,5 ~0 75 ~0 e$ 90 ~5 FIGURE 3.--Percentage distribution of personal respirable particulate concentrations, non-smoke-exposed and smoke-exposed samples, Topeka, Kansas I~,J~JR(,,'E: ~nd~'~ ~*nd T~I~ 119~11, Sexton and colleagues (1984) monitored personal RSP exposure for 48 nonsmokers in Waterbury, Vermont, every other day for 2 weeks, The participnnts kept activity logs and had simultaneous indoor and outdoor liSP samples collected at their homes. The proportion of' ' time individuals spent exposed to E'I~ was the single most important determinmlt of their personal exposure. Volunteers who reported greater than 120 minutes of exposure to ~ had a mean RS]P exposure of ~0.1 pg/ms, whereas those volunteers who reported no exposure to !,','[~ had a mean exposure of 31.7 i~g/m~. 165
Page 93: TI07870703
240 FIGURE 4.--Cumulative frequency distributions of central site ambie.t and personal nmoke-exl~med and non.smoke-exposed respirable s.spemled particulate concentrations SOtlRCE: lSl~nller el ~!. (l~k Nicotine, a tobacco-specific compound, should make an excelle,lt tracer for ETS if its linage can be properly validated. Some considerations in its us.ge are detailed ill the section on area sampling. Currently, no published reports are awdlable that utilize this compound for the type of detailed personal monitoring studies carried out for RSP. However, a lightweight personal nicotine monitor has recently been developed (Muramats~l ct al. 1984) that may aid this type of research. The researchers measured average nicotine concentrations ranging from 3.0 itg/m~ in a hespital lobby to 38,7 Ixg/m~ in a conference room and 47.7 I~g/m~ in an automobile. No information on the duration of exposure or representativeness o1" these levels to the general population was given. However, this study does provide information as to the range of exposures an individual may encounter and demonstrates that high nicoti.e level~ can be encountered in various settings. It will be necess.ry to quantify th~ relationship between nicotine, a vapor phase coml~nent of ~TS, sad other components of interest such as RSP in order to fully utilize this tracer. Certain organic gases have been measured as possible indicat?rs of ETS exposure or of speci{ic effect~ such as irritatiou. These include formaldehyde and acrolein (Weber and Fischer 1980~ a.d aromatic Compounds such as benzene, toluene, xylene, and styrene (ltiggins et al. 1983), The U,S. Enviro.mental Protection Agency's recent TEAM study utilized personal monitors, employing Tenax cortridges, to develop profiles of individual exposures to volatile organics (Wallace 166 et al. in press). The TEAM study has found significantly increased exposure tt~ benzene for individuals exposed to ETS. Again, the nonspecificlty of these materials for ETS limits their applicability, Other mttterials such as carbon monoxide and nitrogen dioxide ha.re been measured in personal monitoring studies attempting to assess individuals' exposure to ETS. Their nonspeclficity and lack of sensitivity Ibr-low level ETS exposure make them inappropriate for populatio.-based studies. Personal monitoring techniques are currently available that will allow the a~sessment of individual exposures to various components of ETS. Although not wid, ely used in the past, they can provide valuable i.l,ut in developing exposure models and in validating other monitoring schemes. Their usefulness is primarily that they sample all of the microenvironments in which individuals find themselves .nd therefore automatically compensate for the nonuni- form temporal and spatial distributions of ETS that affect individual exposure profiles. Conclusions 1. Undiluted sidestream smoke is characterized by significantly higher concentrations of many of the toxic and carcinogenic conipotmds found in mainstream smoke, including ammonia, volatile amines, volatile nitrasamines, certain nicotine decom- positio, products, and aromatic amines. 2. Environmental tobacco smoke can be a substantial contributor to tl,e level of indoor air pollution concentrations of resplrable particles, benzene, acrolein, N-nitrasamine, pyrene, and carbon me.oxide. ETS is the only source of nicotihe and some N- nitros.mine compounds in the general environment, 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to environmental tobacco smoke. Exposures to Errs occur widely in the non- smoki.g population. 4, The small particle size of environmental tobacco smoke places it in the diffusion-controlled regime of movement in air for deposil ion and removal mechanisms, Because these submicron particles will follow air streams, convective currents will dondnate and the distribution of ETS will occur rapidly through the volume of a room. As a result, the simple separation of smokers and nonsmokers within the same airspat:e may reduce, but will not eliminate, exposure to ETS. 5, It has been demonstrated that b-'rs has resulted in elevated rcspin|bte suspe.ded particulate levels in enclosed places, 167
Page 94: TI07870704
References AYER, li.E,, YEAUER, D.W. Irr/tnnts In cigarette smoke piumee. American Journoi .of~blic Health 7~11~1~12~, Novem~r, 1982. ADAMS, J.I)., O'MARA-ADAMS. KJ., liOFFMANN. D. On The Mainetr~m.Side. Item Distribution of Ciga~tt¢ Smoke ~m~ntn~ P~r pre~en~ aL ~he Toba~o ChemiC' R~n~h ~nfer~n~, Montreal, ~nadn, Oct, ~, 19~. AMERICAN ~NFER~NCE OF GOVERNMENTAL INUU~'RiAL IIYGIENI~. Tbrelhold Limit Vala~ and Biol~icol Ex~su~ lndi~s for 1~ ~ond Printing, Cincinnati, A~ Hi, ig85, p. 1 BADRE, R., GUILLERM, K, ABRAN, N., BOURDIN. M., DUMAS, C. Pollution atm~phcrlqoe par lu fum~ ~ ~clAt~phertc ~llution by smoklng~ Annalez Pha~aceutiques ~ancai~s ~/IO~:44~5~. 1978. BAKER, R.R. The eff~t o~ ventll,tlo~ on clgnret~ ~lnb~stion m~han~ms. ~enl BERGMAN, H., AX~N, O. P~lve smoking and lnd~r ~don dauBh~r traflons. (letter). ~ncet ~2~1~1~, ~m~r 3, 1~. BRUNSKREEF, B., BOLEIJ, J~.M. ~ng.~rm nverage su~ad~ parti~dn~ trattons in Bmoke~' ~om~ ln~ernolional A~hi~ of ~cup~lbmal a~ men, tat H~l~h ~3~ 1982. BRUNNEMANN, K.D., ADAMS, J.D., IIO. D.P.S., IIOFFMAN, D. ~e l~fluen~ ~bac~ smoke on Ind~r atm~pher~: 2. Volatile and ~bacc~ific nitr~- min~ in main- and sid~trenm smo~e and their ~n~ibutlon ~ Ind~r ~e~i~gs of the Fourth Joint ~nfe~n~ o~ ~i~g of Em,iwnmental rants, New Od~, 197Z American Chem~l ~lety, 1978, pp. ~. BRUNNEMANN, K.D. HOFFMANN, D. Chemical studi~ on t~ac~ smoke: Analysis o~ volatile nltr~min~ in ~a~ snmke and ~llu~ ind~r envi~- menM. h~: Walker, ~.A., Grlclute, ~, ~naro, M., Lyle, R.E., Davb, W. E~utmnmental As~tl of N.Nit~ ~m~un~. IARC Puh. No. 19. International Agency for ll~arch on ~n~r, 1978, pp. BRUNNEMANN, K.D., HOFFMANN, D. ~e pll of ~ s~ko. F~ BHUNNEMANN, K.D., HOFFMANN, D., WYNDER, E.~, GOJtl, G.B. lt~di~ oa tobac~ luto~v: ~. I~rminatto~ of ~r, nl~tine, aml ~r~n ~noxldo in cigarette smoke. A ~m~rtBm ot in~rnati~nl smoking ~nditiona. in: Wynder, E.I.., lloffmann, D., Gori, G.B. (~s}..M~ifying ~he ~is~ for the Smuk~r. Pr~dlngs of t~ Third World ~n~eRn~ on Smoking and ll~lflt, New June 2-5, 1975, Vol. L U.S. ~mrtmvnl or llealth, ~ucafioa and Welfa~. ~blic Health ~rvice, National l~tltu~ or H~lth, Natlon~ Caner l~tltu~, DIIEW Pub. No. (NII1~7~1221, i~76, VP. 441-449. BRUNNEMANN, K.D., YU, ~, HOFFMANN, D. ~ment or~rcla~enie volatile 'N.nitr~amin~ in ~bac~ and In mainstreum and sld~tr~m smoke from rJgorettes. ~ncer R~m~h 37{9):~1~3222, ~p~m~r 1~7. BUREAU OF Tile CENSUS. ~r~nt ~putation Su~ U~. ~¢ment of ~mmerce, Bureau of the ~ns~l, CANO, J.P., CATALIN, J., BADlt~ R., DUM~, C., VIALA, A., GUILLERME, R. ~termination de la nl~tlne Imr ch~mat~raphie en ph~v gn~u~; 2. Applt~- tions [~termlnation of ni~tlae by g~-ph~ chromu~raphy: 2. Annnl~ Plmrmaeeuti~ues Fran~i~ ~1 I~0, Novemlmr 1970. CARTER, W.L., HAS~AWA, I. Fixation or ~ba~ ~moke ae~ ~or distribution ~tudl~. Journal of ~lloid and Interface ~ience 53:1~141, ~r CItAN, T.L., LIPPMAN, M. Ex~rlmen~l me~uRmen~ and empiric! m~elllng the regional de~itionl o[ inhal~ particl~ in humans. Ameri~ Indwell H~iene Ass~iatton Journal 41 (6):~, June 1980. 168 CHANG, I'.-T., I'b-'I'ERS, L.K., UENO, Y. Particle size distribution of malnltream cigarette smoke undergoing dilution. Aenmol Science and T~nolu~ 4:191-~, . 19~. CHAPPEI.L, S.II, PARK~, R.J. Smoking and ~r~n monoxide Ivvel~ in enel~ public plac~ lu New Brunswick. ~nadiaa Journal of~blie H~alth ~2):15~16i~ March-April 1977. ~BURN, R.F., ~ER, ~E.. KANE, P.B. ~mideratlo~ of the phy~lol~cal varisbl~ that de~rmine the ~1~ car~xyhem~l~in ~ncentratlon ~ man. Jou~alofCIbdcal in~ti~afion 44(11):18~1910, Novem~r I~. CUDDEBACK, J.E., ~NOVAN, J.R., BURG, W.R. ~u~tion~ ~ of lmokihg. Anwd~n lnd~fr~l Hygiene A~tion Journal 37(5):2~287, M~ 1976. DALHAMN, T., ED~, M.L., RYLANDER, R. Mouth a~rption of varloul tom,urals h, cigaret~ smoke. A~hi~ of Enuiwnmental t?eallA June Ilia. DALIIAMN, T., ED~, M.L., RY~NDER, R. ~n[lon of clgaret~ amok~ ~m~,enM b, human lungs. A~i~ of Environmental Heallh 17(5~74~748, Novem~r 1~. ~KERY, I).W., 8PENGLE~ J.D. lnd~r~r Riationshi~ o~ r~pirsbls sulfa~ and Imrticl~. Atm~phe~ Environment 1~3~3, I98L DUBE, M.F., Gi~EEN, C.R. Meth~s of ~ll~tlon of smoke for anslytl~l pur~. R~nt A~b~n,~ in To~ ~ien~ 8:4~1~, 1982. ELLIS, L.P., ROWE, D.K Air qusllty during public gatherings. Joumal of [h¢ Air ~dlution Cun¢nd A~iotivn ~6~, June 19~5. EUDY, LW., THOIINE, F.A., H~AVOR, D.L, GREEN, C.K, INGEBR~HSEN, 8~udi¢~ on the Va~r.Pha~ l~tdbution of Envi~nmental ~[~tlne By ~i~[~ 7~pping nml ~t~tion Meth~. Pa~r pr~n~ at t~ ~th ~n~ Chem/l~' It~a,'ch ~nl~ren~, Montreal, ~t. ~, 19~. EUDY, L.W., GI(BEN, C.R., IIEAVOR, D.~, INGEBR~SEN, B.J., THORNE, F.A. Studies on the Va~r-~rticulate Ph~e ~tdbution of Enuim~menlal ~i~tine ~l~ti,~ 7h,pping ~nd ~t~tlon Meth~. Pa~r p~n~ ut the 79th Annual M~ting of the Air Pollution ~nt~l A~iation, Minnea~lil, June 2~, lg~, FERRIS, B.G., Jr., SPEIZER, F.B., 8PENGLER, J.D., ~KERY, D,W,, Y.M.M., WOI,~N, M., HUMBLE, C. Eff~ of sulfur oxid~ and r~plrabl~ ~rtkl~ oa human health: Meth~ol~ and ~m~ra~y or ~pulntions in study, Ame~ran R,,viewof ~pirato~ ~ 1~4k7~-779, ~r 1~79. FI~, M.W. Envir~men~l ~ smoke me~uremen~: Bet~t and p~t, Enw~vn Jo,wnnl of Ropi~to~ ~ ~Supp. 1~);~!6, 19~, Fi~ilER, T., WEBER, A., GRAN~EAN, K LuRverunzelnlgung dutch ~krnuch in g~t~,, [Air ~llution due ~ ~nc~ smoke in ~ursn~]. Internalional A~hi,,~ o[ (~'cu~tional and Enui~nmental lleolth 41(4~267-~, 1~8, FLEI~ilBR, R.I,., PARUNGO, F.P. Aer~l ~di¢l~ on ~ trid~omes. ~62):1~[-159, July 12, 1974. GALUSKINOVA, V. 3,4.~nzpyrene de~rmination tn the smoky atm~phere m~tlng r~ms and r~uran~: A ~ntribution ~ the pr~lem o[ the n0xiousne~ of ~nlK~l p,t~ive smoking. N~pl~ma 1 l(6k4~, 1~. GODIN, (L, WRIGHT, ft., SIIEPHARD, R.J. U~an ex~ure ~ carla monoxide. A~hi~ ofkgwi~nmentaIH~ith 2~5~13, Novem~r 1972. GRIMMER, G., ~EHNKE, H., HARKE, II.P. Zu~ p~lem d~ ~ivrnuch~m: Aufnahme vnn ~lycyeli~hen s~mati~hen kohlenw~ffen durch vvn ~g~reth,,,rauchhBltiger lu~ [P~lem of ~ive ~moking: In,he of aromatic hy, lr~nr~n~ by breathing air ~n~ining cign~t~ smoke[ A~hit~ of iA.cu~tionol and Enviwnmental H~lth 4~2);9~9,1977, 169
Page 95: TI07870705
HARKI~, I|.P. Zum Problem des Passivrauchens: 1. Usher den callus8 des rauchens nuf die UO.kunzentration in buroramnen [The problem of pa~ive smoking: I. inlluen~ of mnaking on the C~ ~ncentratioa in afll~ r~ms]. A~,hivfi~rA~eil~medi~iu 3~3):1~-~, 19T4. liARI(£, H.P., I'~, H. Zum P~blem d~ Pa~ivrauehe~: 3. Ue~r den enflu~ des rnud~en~ ~uf die ~-kon~ntr~tion im kraRfah~ug ~i [ahr~n Im jThe problem of pa~i~e ~moking: 3. The influence of ~muking on the ~ucentratlon in driving au~mobil~[ ln~ern~fional~ A~Aiu fi~r Ar~R~m~l~in HABIt8, D.P., MARBURY, M., 8AM~[, J., 8P~N~L~I~ J.D. Relating lnd~r level~ to InFon[ ~nnl ex~r~. AIm~pherie~nuinmmcnl, In pre~. ItARMS~N, H., ~FF~NBBROEI~ ~. T~bakrauch in verkebrsmit~ln, wohn. and ~r~i~raumen [Toba~o emok~ In tr~nl~r~tion vehicle, living ~nd working r~ms]. ~hiu fur llygiene and Ba~leHologie 141~5h~, 19~7. HAWTiIORNB, R.B. lnd~r sir quMity ~tudy of £orty e~[ Tenn~ ~n~. ~k Ridge, Tennis. Oak Ridge National ~ra~ry, ORN~G~;5, I 9~. lt~HINO, ~.1., JON~, H.T., HACIIMAN, J., MIN~, A.tl. Puff volu~ Increa~ when Iow.ni~tin~ elga~z~ nre z~k~, B~is& M~ical ~rnol 189, July 18. 198L HILL, C.~. B~ioae~ivity in ciga~Z~ smoke. 0eZ~rL Hew En8lund Jou~ol Medicine ~(~311, July ~, 1982. H[~L, P., HAI,~Y, N.J., WYNDKR, ~.~ ~iga~ smoking: pl~ma nlcoUne, ~Unine and th[~ana~ ~. ~ff-re~r~ smoking du~ end cardiovn~ulnr dl~n~. Juurnnl o[Ch~nir ~e~ ~6~4~49, l~. HILLER, F.~., MeKUSKER, K,T., MA~UMD~R, M.~., WI~H, J.D., BONE, ~[tlon of m[d~£ream elgmret~ smoke I~ the humnn r~pira~ " America .Revi¢~ o~R~pi~to~ D~me 1~4~4~, April !~. HIH~, W.~. Si~ chn~riatl~ of ctgm~t~ smoke. Ame~m lnd~t~al Hy~ene A~s~ialion Journol ~ ]~4~4, Jmntln~ 1978. HINI~, W.~., Fi~, M.W. ~n~ntraUon~ of ni~tlne nnd ~bacco smoke In public pineal. New Eagland~ournnlo[M~icine ~1~:~5, April 1~, HOFFMAHH, D., BBUHH~MAHH, ~.D., ADAMS. J.D., IIAL~Y, HJ. ind~r ~llution by ~ba~ smoke: M~el etudl~ on the u~ke by nonsmoker. In: lnd~ Air, ~ado~ ~M~ ~moMn8, Particulat~ and Hoeing ~pidemiolo~v. P~ing~ of ~he ~rd ln~rnatlonal ~nferen~ on Ind~r Air Quality and Glimnle, S~khohn, Vel. ~, pp. ~t~tg, 1984. HOFFMANN, D., HAL~Y, H.J., ADAMS, J.D., BRUSHEMAHH, K.D. Tobae~ eldeetream *rooks: up~ke by. nonsmoker. ~nti~ M~ieine ~ovem~r HOFFMAHH, D., HALEY. N.J., BRUHH~MAHM. ~.D., ADAMS, J.D., WYHD~ E.~ Ciga~tte ~idesl~m ~mot~. Fo~ation. Anal~i* end M,~el ~[udi~ on the U~ta~e by ~o~mote~. Pa~r pr~n~ a~ the U.S.~apan m~tin$ en the new etlol~ of lung caner, llonolulu, March 21-~, 19~. ING~B~HS~N, B.J., SEA~, S.B. Panicle $ize ~t~bution n~ ~ide~m 8mo~e. Pa~r pr~nt~ at ~e ~gtlt Toba~ Chemb~' R~rch ~nfe~n~, . ~r ~, 198~. ,IHT~BHATIOHAL AG~H~ FOR B~AR~H OH CAHEER. ~o~ IARG Mon~zaph~ on the Evaluation of the ~arein~enie Ri~k of Chemi~le Human~, VoL ~8, L~n, IARE, IHT~RHATIOHAL ~MMI~Eg ~R ~lOAIt SMOK~ ~UD~. Machine smoking clean. ~ta Info~ation Bulletin 1:~4, 1~4. [SHIZU, Y, General ~uation for the intimation of indoor ~llutio,. Envi~nmental Science and T~hnol~ 14:1~@1257, 19~. 170 JOIlNSi~N, W.R., IIALE, lt.W.0 CLOU(311, S.C., CIIEN, P.II. Chemistry of the converalon *~f nitrate nitrogen to smoke products. Nature 243(540@.223-225, Msy'~ 25. 1973. JOHN~ IN, W.It., KANG, J.C. Mechanisms of hydrogen ~yanide formation from the pyrolysis of amin.o acids and related compounds. Journal of Organic 36(I):189-192, January 15, 1971. JU; C., SPENGLI,~R, J.D, Iloo,u-to-rcom variations in concentratinn of resplrabls particles iu residences. Environmental Science nud Technology 16~5):592-~96, May 1981. JUST, J., BOItKOWSKA, M., MAZIARKA, 8. Zanleczyszcenie dymen tytonlowym powietr~ knwlarn War~zawskich [Tobacco smoke in the a|,r of Warsaw coffee rooms], l~oc~nihi Pantslwowego Zakladu H)71ieny 23{2~.129-135~ 1972. KEITH. C.II., I)EItRICK, d.C. Measurement of the particle size distribution and concentrathm of cigarette smoke by the confuse. Journal of Colloid~cience 15:340- 356, 1960. KLUS, IL, KUIIN, He Verteflung verschiedener tabskrauehbestandteile auf hsupt und nebenslromraueh (sine ubersleht} [Distribution of various tobacco smoke components among mainstream and sldestresm smoke (a sur~eyl]. B¢iIrllge Taba~/br~chunl; International 11(5P.2£~-265, November 1982. KOZLOWSKI, L.T., FRECKER, R.(3., KHOUW, V., POPE, M.A. The misuse of "less- hazardous" cigarettes and Its detection: Hole-blocking of ventilated filters. American &mrnal of Public llealth 76(! 1):.1202-1203, hTovember 1980. KRUGER, J., NOTHLING, J.F. A comparlaon of the attachment af the decay products of rmlon-22{~ and radon.S22 to monodlspersed aerosols. Journal of Aerobe! ,~ience 10(6):.571-579, 1979. LEADEItER, ILP., CAII~, W.S., ISSEROFF, R. Ventilation requirements in buildings: 2. Porticulnle matter and carbon monoxide from cigarette smoking. Atmospheric Envi~mmeut 18(1l:99-106, 1984. LEBOWITZ, M.D., BURROWS, B. Respiratory symptoms related to smoking'habits of family adulls. Chest 69:48-50, 1976. LEBRI~'I', E. Air Pollution in Dutch Homes. Ph.D. Thesis, Wages|sEen Agricultural University, The Netherlands, 1985. LI~IINEIt]; G. Roundtoble d|scusalon. Preventive Medicine 13:730-746, 19S4. LETZ, It.E., S{ )CZEK, M.L., SPEHGLER, J.D. A survey of time-activity patterns in Klngston/Ihtrriman. In: Method~ and 8upporf for Modelled Data. Presented at Quality Asm,ronce in Air Pollution Measurements Conference, Boulder, Colorada~ October 14-18, 1984. MARTELI~ E.A. Tobbaco radleacivity and ~ancer in smokers. American 63(4):4(34-412, July-August 1975. McCUSKEIt, K., .HILLER, F.C., WILSON, J.D., MAZUMDER, M,K,, BONE, Aerodyaamic sizing of tobacco smoke particulate from commercial cigarettes. Archives of l,:nvironmentni Health 38(4}:.215-218, July-August 1983. MILLI~R. J.E. [~etermination of the components of pipe tobacco and'cigar smoke by means of n new smoking machine. Proceedings of the Third World Tobacco ,Scienti/i¢ ('~mgress. Salisbury, Southern Rhodesia, Februn.ry 18-26, 1963, Sallsbury Print~rs. Lid.. 1964, pp 564-595. MOSCilANDREAS, D.J., SI'ARK, J.W.C., McFADDigN, J.l~., MORSE, S,S. IndoorAir Polluthm in the Residential En~ironmenL Vol. I and 2, U.S, Env[ronmenial Prob~ctlon Agency Report No. EPA 600/?-78-229a and b, 1978, MURAMAI~t I, M., UMI~MURA, S., OKADA, T.0 TOMITA, H. Estimation of personal expomsre bt tobacco smoke with a newly developed nicotine per~nnl monitor. Enui~xmmenlol Research ~!):218-227, October 19El4. NI~AL, A.D.0 WAX)DISH, R.A.S., BOSENBEBG, S.1L ~valnntiou of indoor particulate conm:ntrntion for an urban hoepltal. American Industrial Hygiene Association Journal ~/9~71:578-5[32, July 19713. 171
Page 96: TI07870706
NEIIO, A.V., SEXTRO, R.G., DOYLE, S.M., MOED, B.A., NAZAROFF, W.W., REVZAN, K,L., SCIIWEIIR, M.B. Clmracterlziug the source~, rungs and envi~n- men~l influen~ of ra~on ~2 and i~ d~*y pr~uc~. ,%ience o[ ~he Total Enl,imnnlen/45:~3-244. ~lmr 19~. NEURATII, O.IL Nltr~amine Ibrmatiun Prom pr~ur~m I~ ~a~ smok+. In: B~ovsky, P,, Pmu~mmm, R. nnd Walker, E,A. ~s)+ N.Ni+m+o An.lysb and ~ommlion, Lye., In~rnattunal Agency for Rmearcb on IARC ~iontlAc Publication Nu. a, 19~ pp. NEUH~TH~ G., EHMKE, H. APl~tur ~r un~muchu.g des ne~nstromta.ches [Apparatus fur ~he Inv~tlgatlon of sid~tream smoke[ ~itrlige zur ~k~or- NEURATH, ~., IIO~'MANN, II. ElnAum d~ Feuchtigkei~gelmlt~ vnn cigaret~u nuf die zusnmme~ung d~ raueh~ and die ~lu~onentem~ratur ~Eff~t molslure conlenl of cignret~ un l~ ~m~Itlon nf the smoke m~d lhe NI~HHE, I,A., CLARHE, W.A., C~RKIN, M.E., ~AYNOR, U,W,, WADACII, J,B, Ind~r Air quality, l.filt~t~n at~ Yentilotio. in R~idential Buildln~ New York 8~ Ene~ ~atch ~nd ~v~lopm~nt AutborRy, NYSEI~DA 1985. OKADA. T., MA~NAMA, K. I~inmffon of ~rticleliz¢ and ~n~ngmtion cigarette ~m~k~ by a light ~ut~tlng ~. Jou~al o[ {blloid and ~i~nce 48:461~69, 1974. PERRY, J, ~t~n your ~at~l~: Na mnoklng. B~l~h ~lumhia M~i~l ~EN~RF~R, J., ~HRA~B, A. ~n~ntration and mea. pa~lcl~ ~ main and lids ~tr~am o[ clgaretl~ ~mok~. 8~aub. R~in. a2:3~16. 19~. ~RTllEINE, F. Zum Problem d~ ~lvrmuchena [A ~nttibution ~ th~ pr~lem pa~ive ~mokln[]. Munehen¢r M~i~tn~h¢ ~'6¢~chd~ 11~18~707-7~. 30, 1971. QffACKENBO~, JJ., KANAR~IK, M.8., 8PENGLER, J.D., LI~, R. monitort.g fi~r nRt~en dioxide ~x~ure: Metb~al~l~l co.sidar~tl~ tot n ~mmunity ~tudy. g.vi~umen¢ inl¢rnagional ~1~k~49-~8, 198~. QOANT, F.R,, NEON, P.A., ~M, ~.J. E~rimental m~aautemen~ ~ concenlration~ In oW~. Enuirtmmenl inle~ational ~l ~22/~227, ! ~ RAABR, O.O. ~ncerninB the in~raction~ that ~ur ~tw~n radon d~y and aermol,. Health Ph.~ice 17(2~177-1~, Au~s~ 1~9. RADFORO, ~,P., Jr., IIUHT, V.R. Polonium-2i~ A volatile radio element cigarettes. ~n~ 14~3~3):2~T-249, January 17,1~. R~PAC~, J.I.,, LOWR~Y, A.li. lnd~r air ~llufion. tobacco smoke, and public h~Rh. ~ience 208:464~72, May 2, REPA~E, J.L., IDWR£Y, A,lt, T(~ Imoke, ventilation, aud iudmr air quaIRy. American ~'iety o~ Hmtin$ Re~rigemti~, and Air-~ndiHoni.g ~ngin~ Inc., , ~t.actio~part 1):B9~914,198~ RIUH~RT, W.L., ROBIH~H, J.C., ~I,ISHAW, H.F. Ytel~ of ~r, alpine and ear~n monoxide In the lid.tream smoke from I~ bran~ of Canadian American ~ournal of ~blic H~llh 74(3k2~231, March 1934. 8AKUMA, 1i., ~U~AMA M., MUNAKATA, 8., OHSUMI, T., SU(;AWARA, distribution of cigarette ~moke mm~nen~ ~tw~n mainst~emn nnd sldmLream smoke: 1, Acidic comanche. Beil~ge zur Ta~k[onchung 1~2):6~71, June 1~3. 8AKUMA, ll:, KUSAMA, M,, YAMAGUCHI, K., MA'~UKI, T., SUGAWAIIA, S, The distribution of cigaret~ smoke ~m~ne.~ ~tw~n muinstr.au, and side strewn, smoke. 2: D~ce, Beilr@£e zur To~kfor~chang 12(4):l~-2~, Joly 1984. 172 SAKUMA, II., K USAMA, M., YAMAGUCHL K., 8UGAWAItA, S. The distribution of cigarette ~m.ke ¢cmp~neut~ l~tween mai.stream and ~id~tream smoke: 3. Midd[~ and bigher I~liing ~mlmnen~. Beit~e zur Ta~kfomchun8 Novem~r Itll~4. ~A~ELLATI.~RZOLIN I. G., SAVINO, A. Evaluation of a rapld index of amblen~ ~n~mi.nti.a by clgaret~ smoke In relation ~ the ~m~ition of g~ ph~ the smoke. R,e~to ie~llano dTsiene ~1-2~4~5, Jnnuary.Aprtl 1~. BOUIIUYS, A, Lung function, reepire~ry di~ ~nd smoking In families, Amerizxzn ,Io.rnal o[Epidomiulo~ 1~:274-2~, 197~. ~i[MEL'I~, I., I)EPAOLIS, A,, IIOFFMANH. D. Ph~tero[s in ~ba~: Live analysi~ and fate iu toba~ ~mbustion. ~il~e zur $4~11-218, I~em~r 1975. , ~[IMEL'~, I, WENGER, k., HOFFMANN, D., ~, T.C. On the f.~ of nicotine during py~lysle znd In a burnin[ clgaret~. AsrJeultuml and F~ Chemht~ ~(3):~1. MnyJune 19~9. SEBBEN, J., PIMM, E, SHEPARD, RJ. Cige~t~ smoke in en¢l~ public f~eillties. A~hiz~ of ~a~i~nmentol H~lth 3~g52~. Me.h-April 19~7. SKIFF, H.~ ~rl~n Monoxide ~ an lndimt~ o[ ~lte.~ ~llution ~ l.xe~ity B~a~,a U,S. ~partment of Trane~r~tion, F~eral Highway AdmlnJ,tr~. Lion, Bureau .f MoOr Carrier ~feLy, April 1973, SEX~N, K. FI'EHGLER, J.D., TREITMAH, ~.D. l)er~nal ex~u~ (o ~tcl~: A ~ study in Wa~rbury, Vermont. Aim~pher~ 18:1~1~11. 19~. • 8~VIN, It.~,, IIEIt~, M. [nd~rAir ~llution. Pa~r pr~n~ at the ~[h annual m~ting of the American A~dem~ of Aller8~, ~n Diego, February 1~19, 1975, SPENGLI,:R, J,I)., ~KERY, D,W., TURNER, W.A,, WOL~N, J,M,, B,G., Jr. ~ne.~rm me~uremen~ of r~plrable .ulfs~ ~d ~rticl. [~[de sad ou~ido Imzmm. Alm~phe~e Enuimnmen~ I~IE~, 1981, SPEHGLHn, J.D., T~EITMAN, lL.D.. T~N, T.D., MAGi, D.T., ~EK, M,L, Pemzml exl.mU~ ~ mpinzble ~rticula~ and Implications for air ~llutlo. epldemiol~y. E.pimnmeneai ~ien~ and ~hnolo~ l~8~q;, k.~ 1985, SPENOLE~, J.l)., REED, M.P., LEBR~, E., CHANG, B..H. WA~E, J,H., SPEIZEB, F.E., FEIIiIIS, B.G. Ho~ ~ lnd~r Air Poffution H~llh Study. Pa~r p~nt~ at the ~9th Aunu.I Mwting of the Air Pollution ~ntrol ~iation, Minnee~llz, ' June SPENGLER, J.I)., '~N, T.D. Star.till M~eb [or Pe~n~l Ex~um Pa~r pr~al~ st Environmetri~ 81, ~nferenw of the ~iety for Industrial .nd Appli~ Mathematic, Alexandria, Villain, April 1981. ~ERLING, T.I)., DIMICH, ll., KOBAYASill, b. Ind~r bypr~uc~ levels of ~b.cco smoke: A crll.icui review of tim ll~rature. Journal of the Air Pollution ~ntml A~fffion :1h~3):2~9, March 198~. ~ERLIHO, T.I)., ~ERLING, EM. Envlronmen~l T~ Smoke. 1,2, ]nv~tlga. tio~ on the .ff~t of regulating smoking on levels of jnd~r ~J]ut]o. and on ~rcepLion of heeRh and ~m[o~ of offi~ worke~. ~um~n ~ou~al to~ ~s~ I~Suppl. 133E17~2, 19~. SZAD~OWSKI, D., HARKE, H.P., AHOEIIER, J. ~ohlenmonox[d~l~tung dutch ~.ivrauehe. tn buroramen [~y burden of ~t~n monoxide from pmive smoklzzg i. olliccm], inne~ M~lizin ~6~3l~13, ~p~m~r 1976, SZA~I, A'. Thr U~e o[ ~me: ~ily Activitiet of Ur~n and Su&ur~n ~pula[~ ~lue ~uot~iee. The Hague, Mourn Publisbe~, 1972. 17~]
Page 97: TI07870707
U.S. DEPARTMENT OF II}'gALT/I AN/) IIUMAN SE//VICES. 7he HeaDh ~e. quences of Smo&ing: ~ncer. A Re~rl of the Sn~eon Gene~l. U.S. ~partment of Health nnd Humnn ~rvi~s, Public Ileulth ~ice, Offi~ of the ~r~tary for llealth, Ollice on $mo~ng nnd Ilealth. DIilIS Pub. No. {PH~2-- ~179, 1982. U.S. I)EPARTM~HT OF IlEALTII AND IIUMAH SERVICe. ~¢ ll~l~h quences: of ~moking: Chronic ObeIructi~ Lung D~e. A lte~rl of the Oen¢~E ~.$. ~partment of llealth and lluman ~i~, Public Heslth ~i~, Office of the A~Is~nt ~re~ry for llealth, Ofli~ on Smoking nnd llealth, DI Ills Pub. Ho. {PII$~, 19~. U.$. DEPAI~MEHT OF HEALTII, EDUCATION AHD WELFARE. ~mokiug and Health: A Re~rl of the ~urge~m Geneml. ~.~. ~pn~ment of llealth, ~u~tlon ~nd Welfare, Public He~Itb ~i~, O~ of tke A~is~nt ~re~ry for lieMth, O~ce on 8mnklng and Health, DHEW Pub. ~o. (PlISSe;6, 1979. O.S. I)EPARTMEHT OF TRAHSPOItTATION A~I) ~. DICPARTMEHT OF HEALTII, EDUCATION, AND WELFARE. Health As~l~ of ,~moking in ~. ~l Aia'~fl. U.8. l~rtme~R of Trans~rtatlon, F~leral Aviation Admlnietrn- Lion, end U.S. ~pertmea~ o[ )leelth, ~u~tioa, ~nd Welfare, Hatimml Instltu~ for Occupational Safety m~d Health, ~m~r 1971. U.S. FEDERAL T~DE ~MMI~SIOH. ~ar", Wi~oline and ~n Monoxide Smoke of 207 Varicti~ of ~meslic Cil~ft~. F~er~l Trade (~mmi~n, January 1985, pp. ~. VAINIO, It., IlEMMIHKI, K., WII,B~)URH, J. Data on t~e carcln~enlcity cbemicsls in the IARC monog~p~ pr~ramme. ~in~n~ie MI Hovem~r 1985. VI~INS, G., LEPHAR~, J.O. Aging pr~ of cigsret~ em¢~ke: Formation o? methyl nitrite. Chembl~and laduslry 22:97~975, Novem~r l~, 1975. WAD~, W.A. III, ~E, W.~., Y~M, J.E. A study" o~ ind~r o~r queli~y. Jou~gl of the Air Pollution ~ntwl A~iatinn ~9):93~939, ~p~m~r WALD, N., I{ITCHIE, C. V~lldetion o[st~Jdi~ on lung caner In noa~ke~ married to smokers. (later). l~n~t l{~, May 12, 1984. WALLACE, L.A., PELL[ZZARI, g.D., HARWEL, T. SPRACINO, C., ~N, Personal ex~ure~, Ind~r~uM~r ~l~tionsbi~ and breath levels ~ volatile o~unics In Hew Jersey. Atmospheric Envi~menl, in i~. " WA~II, M., BLACK, A., MORGAH, X., CRAWSHAW, G.H. A~r~ion of ~ by typical ind~r surfaces including w~l c~r~, wallpslmr, and paint. Alm~phe~ Enuimnmenl l I(I I):I I07-I l I I. 1977. WARTMAN, W.B.. Jr., C~BILL, E.C., I IAR~W, ~.$. ~termln~tlon of pa~lculste matter in con~n~rn~d ~er~Is: Application to analysis of cigaret~ ~moke. Analyticul Chembt~ 31(I0):17U~17~, ~r ~959. WEBER, A., FISHER, T. P~ive smoking a~ work. Interualional Amhi~ of ~u~lional and Envi~nmental ll~Ith 47(3):~221, 19~. WEBER, A., FISCHER, T., (JRKN~RAH, B. P~Ive smoking In ex~rimenlal and field conditions. Envi~men~al Res~h ~216,1979. WYNDER, E.L., HOFFMANN, D. ~c~ and ~o~c~ Smo~" Stndi~ in lal Ch~inogeneeb. New York, A~demle P~, I~7. 174 CIIAPTER 4 DEPOSITION AND ABSORPTION OF TOBACCO SMOKE CONSTITUENTS
Page 98: TI07870708
CONTENTS Introduetio~t Deposition Size Distribution of Cigarette Smoke Mainstream Smoke Sidestrcam Smoke Particle Delmsition in the Respiratory Tract Total Depoeition Regiomd Deposition Respiratory Tract Do~e of Environmental Tobacco Smoke Cigaretl~" Smoke Particulate Ma~ Depoeited The Concept of "Cigarette Equivalents" Markers of Absorption Carbon Monoxide Thiocy=mate Nicotine Cotinint~ Urinary Mutagenicity Populations in Which Exposure Has Been Demonstrated Experimental Studies Nonexperimental gxp~ure~ Quantification of Absorption Evidence of Absorption in Different Populations Quantification of F.xp~ure f~m~parison of Absorption From Environmental Tobacco Smoke and From Active Smoking Concinsiom~ References :
Page 99: TI07870709
Introductio~t An nnder~tanding of the deposition of cigarette smoke particles in the rcspir~ltory tract is .important because many o~" the toxic constituenL~ of cigarette smoke are contained in the particles, The quantity relained, which constitutes the dose, is some fraction of the quantity i~ll~aled. Measures of tobacco smoke constituent~ or their metabolites-are also important because they reflect the absorption of tobacco sml~ke by the individual smoker or nonsmoker, and therefore may be mo~'e accurate markers of the actual exposure experienced by an individual There is little experimental information describing the deposition of environmental tobacco smoke in the respiratory tract (Jarvis et al. 19~3). However, cigarette smoke particles probably behave in a manner similar to other inhaled particles. In contrast, there are a number of observations of different markers in the biologic~d fluids o1" smokers and nonsmokers. This review begins with a disc~,ssion of particle deposition in general and the factors that affect deposition. This undet~tanding is the~ applied to the existi;,g dal.n on tobacco smoke deposition in the human respiratory tract. Subsequently, a variety of biologic markers of smoke absorp- tion are exmnined, and the levels of these markers found in smokers and nonsm~lkers under a variety of circumstances are presented, Finally, an attempt is made to quantitate the exposure of nonsmok- er~ relative to that of active smokers using levels of these biologic markers. Depoelllon The term "delmsition" refers to the transfer of a particle from inhaled air to the surface of any portion of the respiratory tract~ from ~ese I.o alveolus. "Retention" is the quantity of deposited material remaining in the respiratory tract at a specified time following &:position. Retention decreases as clearance mechanisms suc.h as mt,cociliary action and absorption reduce the respiratory tract hurden of inhaled particles. Retention is not discussed in thin review. An aeros~d is a suspension of particles in a g~seous or vapor medium; cigarette smoke is such an aerosol. Aerosols are character- ized by such terms as mass median diameter (MMDI, the diameter below which lies one-half pf the particles by mass, and count median diameter (CMD), the diameter below- which lies half of the particlev by number. Most naturally ~ccurring aerosols have a log-normal dlstrlbutlo~, and the magnitude el" the spread of particle size i~ the geometric standard deviation (GSD~. Particle mass is a l'unction the cube of the diameter; a particle with a diameter of 0.5 i~m has 1/1000th o~" the mass of a 5 ttm pa~'ticle. Thus, for an aerosol with a large geom~:tric standard'deviation, the mass medidn diamel~r may 179
Page 100: TI07870710
be considerably greater than the count median diameter. The smaller particles of an aerosol, despite their relatively small mass, have a large total surface area because of their great number. A monodisperse aerosol has particles of one size, with CMD equal to MMD, and a GSD of 1. For practical purposes, a GSI I of 1.2 or less is accepted as monodisperse. Most naturally occurring aerosols are polydisperse, with GSDs in the 2 range. A lognormally distributed aerosol with a GSD of 2 and a CMD of 0.1 will have vn MMD of 0.42. in this discussion, when size is referred to, it is the MMD otherwise stated. Both total deposition and the deposition site in the respiratory tract vary substantially with particle size. Size Distribution o! Clgarelle Smoke Mainstream Smoke The size distribution of cigarette smoke has been of interest to investigators for many yeal~. TI,e important relationship between size and re,spiratory tract deposition is discussed belnw. Most studies have been performed using mainstream smoke. Mainstream smoke is the smoke exiting from the butt of the cigarette during puff- drawing, and sidestream smoke is the smoke pitons that drifts into the environment from the burni~tg tip of a cigaretb~ between puffs. Environmental tobacco smoke (E'I~) is the mnblent burden of sidestream smoke and the smoke exhaled by a smoker. Involuntary smoking is the consumptio~ of E?I'B by people, either smokers or nonsmokers, from the environment. One purpose in discussing the size distribution and respiratory tract deposition of p.articles is to illustrate the discrepancy between the measured p~rticle size of mainstream smoke and ire measured deposition il~ the human respiratory tract, The deposition fraction o1" mainstream smoke is several times higher than wouhl be predicted on the basis of its particulate size. The measured deposition of sidestrcam smoke is more in keeping with its measured size (Hiller, McCusker et al. 1982). The standard laboratory smoke generation technique is to force air through the cigarette us would be done by a smoker, followed by rapid dilution of the resulting mainstream smoke so that particle size can be measured. A standard 35 cm~, 2-second puff is usually used, alflmugh actual puff volume was shown to aver~ge 45 cm~ in one study (Mitchell 1962) and/56 cm' in another; for individuals, the puff volume can vary from 20 to 30 cm~ up to 70 to 80 cm~ (iliads et al. 1983). The size distribution of the diluted mainstream ~moke aerosol is then meesurcd by one of a variety of techniques such as light scattering devices, microscopic measurement, or imlmctor collecting devices. Using various diluting and sizing techniques, particle size 180 measurcme~ls of mainstream cigaret~ smoke have been reported from many h~boratories ('['able 1). One potential cause of error in measuring the size distribution of mainstream cigarette smoke is the relative insensitivity to ultrafine particles of some previously used measureme~d, methods. More recent studies using newer measure- ment techniques support the suggestions by the earlier investigators (Sinclair 195~}) ¢hat there is'an ultrafine (<0.1 I~m) component to the cigarette sm~ke. Size characteristics have been measured by electron microscopic metheds, following rapid fixation of undiluted fresh tobacco smoke, as CMD 0.2 i~m and GSD 1.6 (Keith 1982), The size distribution measured with an electrical aerosol analyzer has been reported as CMD 0.1 I~m, GSD 2.0, suggesting more ultrafine particles thlm previously recognized (Anderson and Hiller 1985), Smaller particles (<0.4 I~m) of tobacco smoke have been shown to have a chemical composition different from that of larger particles (St~ber 1984h possibly because of the large surface area of smaller particles. Laboratory metheds, such as rapid dilution, commonly used to study mainstream smoke, are highly artificial and may not accurate, ly duplicate tile generation, dilution, and inhalation of mainstream smoke by the smoker. Smoking technique and respiratory tract cenditions may promote changes in particle size. Therefore, the particulate siz~ in the respiratory tract may differ from the sizes measured when mainstream smoke is diluted for size analysis or when dilut~:d sidestream smoke is inhaled by the involuntary smoker. The smoker's puff is takes as a bolus in a relatively small volume elr air into the humid upper respiratory tract. Smoking technique varies widely (Grifflths and Henningfield 1982) and has been shown {.o vary significantly among groups classified as healthy smokers compared with those with emphysema and also between those with e,q~hysema and those with bronchogenic carcinoma and bronchitis (Medici et ai. 1985). Some smokers hold the puff in the mouth for several seconds prior to deep inhalat|on. The initial puff is highly concentrated, with approximately 10* particies/cm~. At this concentr~fion, particle coagulation can occur rapidly, causing a tenfold to n hundredfold reduction in particle number and an increase in particle size (Hinds 1982). Also, the accumulation of water in or en the particles in the high humidity of the respiratory tract can increase particle diameter (Muir 1974), and may increase the diameter as much as 30 percent (Mitchell 1962). Some evidence suggests, however, that at least for dilute cigarette smoke, hygro- scopic growth occurs o~tly under supersaturated' conditions (Kousaka et al. 1982). Coagulation and water uptake by particles in the respiratory tract may considerably alter particle size distributions so that measurements under laboratory conditions probably do not 181
Page 101: TI07870711
TABLE L--Size distribution of mainstream tobacco smoke Size I~a~. con~t~tian Study [no. pardch~/l:~| Di|~tion Method ~mment WeI~ ~d ~e ~D 119191 (1~ ~D 0.~ ~ w~er ~mu~fion ~Vatle ~ ~r and ~er ~D (1~ ~D 0.6 ~ ~l~i~ p~ipimd~ [2~ x IW] GSD L75 Kehh ~ ~ck ~D 0~ ~ ' Ae~l ~nt~f~ GSD I,~ I 1~ MMD 0.~ Mic~pic ~la~ ~h~ ~972~ [~7 x IW] of ~i~iv¢ d~y ~cle Pont~db~er ~D 0.42 I~I (19~ ~D 0~ ~I~! ~ d~ in spi~l ~t~f~ Q~ ~d ~D ~18 l~l ~ht ~ ~D l.~ ~a~unu~ ~D 0~ TABLE L--Continued Study [no. part l¢les/cra~l Dilution Method Commit Hind~ MMD 0.38-0.52 10:.1-700:.1 Aerosol centrifuge Size distribution decrea.s~ 11~8~ CMD 0.4 10:.1 dilution increases CMD 0".27, 3.100:.t GSD 1.3-1.,5 McCu~ker e~ at. MMD 0.:..'.'.'.'.'.'.'.'.~.3 I~6.000:A La.~er doppler ve|o~im~try Aerod.vrmmi¢ diameter GSD L4 ,19821 ;4"~ x Chang et aL C~ID 0.~4.-0.'~ 6:1-18:1 gl~-tnea~ a~r~ol anal)~.ar Bimodal digributzon ~1984~ [3.6 x lO'l IEAAt Primar~ mode (E,~A)'GSD 1.18 MMD 5.5 seconda~.' 1--~ x 10~ Anderson Cascade lmpactor .~'~nd mode tCI) -q~r-~Oe~r Of mode tCl~ SUT~t.~ID = oa~nt m~dcm dbmeter:..~|MD ~ n~,,, m~.m dhm~':.GSD = g~a~.,,tr~c ~t~duNd~-mtio~. T!07870711
Page 102: TI07870712
TABLE 2.--Size distribution of side,tream tobacco smoke Stud)' ~e (pin) D(lutt~m Method Ke|th and CMD 0.16 ~:1 Aerial Nntu~ . ~rrick ~ntdl~e ~ntri~e mt~ke generat~ ie.erafl~ x~ dllut~ Ililler, CMD 0.31 Hot gtvtm I,~er doppler McCu~ker el u|. velocimehT (19~2) NOTI~ C,MD - count median dinmete~ (k~;b - I~m,'~t rk standard devintkm. represent distributions fouud in actual inainstream smoking condi- tions. Sldestream Smoke Sidestream smoke is generated by cigarettes burning spontaneous- ly between puffs and is quantitatively the major contributor to ETS. Fifty-five percent of the tobacco in a cigarette is burned between puffs, forming sidestream smoke (see Chapter 3). Dilution takes plac~ as smoke rises in the ambient air currents. This dilution with air reduces, but probably does not eliminate entirely, the Omgulation that causes the particulate to increase in size, as they may in the highly concentrated state that occurs when a smoker draws a puffer mainstream smoke into the mouth and holds it briefly before inhalation. The size distribution of sidestream smoke might be expected to resemble that of diluted mat,stream smoke. The results o~ several reports of sidestream smoke size measurements (Table 2) support this impression. Particle Deposition In the Respiratory Tract Total Deposition Total deposition has been studied both theoretically and experi- ~nentally. Mathematical eqt,ations can be used to predict depositio,. by combining mathematical models of lung anatomy with equation~ describing the behavior of particles in tubes. The major property to be considered is particle size and its influence ()n impaction, sedimentation, and diffusiou. Inertial impaction is ti~e mechanism 184 that causes i~articles moving in an airstream to be unable, because of excessive m~tss, to follow the airstream around a bend. Large partich:s intlmct at the bend in the airsLreem or in the lung on or near a site o1" airway bl"auching. The larger the particle the greater its chance ~f depositing by impacLion, lmpaction is a relatively unimportant form of deposition for particles smaller than 0.~ The effect of gravity on suspended particles causes them te fall, process called sedimentation, which also becomes relatively unim- portant for particles less than 0.l~ pm in size. Larger particles faster, and I~r all particles, the greater the residence time (in the lung) the greater the likelihood of deposition by sedimentation, Diffusion is the net transport o1" particles caused by Brownish motion. It I~:comes increasingly important for particles less tha, 0,6 Im~ in size {liinds 1982). The mass median diameter of sidestream smoke is in the 0.3 to 0.5 Fm size range. Total deposition for inhaled partich:s i~ i. the 10 to 30 percent range for 0.5 pm sized particles, In Figure 1, Lippmann's review (1977) of the measurements total deposition of monodlsperse aerosols in human subjects is modified to include more recent data and data on ultrafine particle deposition. The respiratory pattern clearly affects particle deposition. Most important for all particles, including environmental tobacco ~moke, is the reside,ca time in the lung. Deposition increaeeh with slow deep inspiration (AILshuler et el. 1957) and with breath holding (Palmes et al. 1966; Anderson and Hiller 1985). In hamsters, the deposition of 0.38 pm particles rises in a nearly linear fashion with oxygen consumption ([Iarbison and Brain 1983). These data indicate that deposition el' ETS during involuntary smoking increases with the increasing activity level of the exposed individual, The pre~enca of an electrical charge on particles may increase deposition. Mainstream smoke is highly charged (Corn 1974), The addition of either a positive charge or a negative charge to inhaled particles iztcz.eases deposition in animals (Fraser 1966), and neutral- ization of the charge reduces deposition 21 percent in rats (Ferin et al. 1983). 'l'hore is little information describing the effect o£ a charge on the deposition of either mainstream or aidestream smoke in human subjects. Particle growth by absorbing water may affect deposition. Mathe- matical models that describe the effect of humidity on particle growth indicate the potential for a considerable change in size of some p~zrtich,s during transit in the humid respiratory tract (Fortes 1977; Cocks nnd Fernando 1982; Renninger eta], 1981; Mart0nen and PnLel laB1) and that these changes could significantly alter deposition (l"erron 1977). Growth of 0.4 to 0.5 pm particles should increase their deposition fraction, but growth era 0.07 pm particle to o.1 Izm, for example, would reduce its deposition (see Figure 1). Such
Page 103: TI07870713
I,{) "-'T--'-'-i ! I 0 I , I I. I O,OI 0.02 0.03 Figure L---Total respiratory tract deposition of inhaled inert particles during oral inhalation an effect has been shown for laboratory-generated aerosols in human subjects (Blanchard and Willeke 1983; Tu and Knutson 1984). While hygroscopic growth has been postulated for tobacco smoke (Muir 19741, it has been demonstrated in the laboratory to occur, at least for dilute smoke, only in supersaturated condltio.s (Kousaka et aL 1982). Many reports describe measured depositioi~ of mainstream ciga- rette smoke in the human respiratory tract (Table 3}. Although few studies of total sidestream smoke deposition are available, those few (Table 3) suggest that sidestrenm smoke does indeed deposit in a manner similar to that found for laboratory-designed research aerosols. The deposition fraction of mainstream smoke diluted 1:30 and inhaled by rats from chamber air containing t,68 mg/L (assuming a rat tidal volume of 1.5 mL and a respiratory rate oFBS) is 186 8.1 percent (Binns et el. 1978). Deposition for the sidestream smoke has bee. measured i. mouth-breathing human volunteers at 1~ percent, similar to that for similarly sized polystyrene latex sphbres (Hiller, Mazumder etal. 1982). Environmental tobacco smoke exposure frequently occurs with breathing through the nose rather than throug~ the mouth, but inert lmrtioles in the size range of ETS (0.2-0.4 itm) are not substnntially reduced in number by passage through the nose. The fraction of inert 0.2 Fm particles deposited in the alveolar region of the lung is similar for mouth breathing and nasal br~atldng (Raabe 1984). It is poesibl.e that the charged or reactive particles of ETS may behave somewhat differently than inert portlclcs, but it seems unlikely that nasal breathing substan- tially alter~ the deposition of the small particles of ETS in comparison with mouth breathing. Ilegto~al Deposition Total dep~sition is subdivided into the fractions depositing in the upper respiratory tract (larynx and above), the tracheobronchial region (trachea to and including terminal bronchioles), and the pulmo.ary ~egion (respiratory bronchioles and beyond) (Figure 2), Deposition i. these areas is referred to as regional deposition, Particle slzc is a major determinant of both total and regional deposition. A mathematical model prediction of regional deposition of polydisper~e aerosols is shown in Figure 2 (ICRP 1966). Experime.tol verification of mathematical models of regional deposit/on is limited. Using isotope-labeled particles, it is possible to quantiiate the upper respiratory tract deposition as a fraction of total depesiLion. By assuming that the aerosol depositing in the trach~bronchial region will be cleared within 24 hours, it is possible to measure alveolar deposition as the fraction of the total initial depositio, below the larynx that is remaining at 24 hours and trach~bront:hial deposition as the difference between the initial deposition a.d what is remaining at 24 hours, Using this method, the deposition of 3.~ I~m particles was this: total deposition, 0.79~ upper respiratory tract, 0.10; tracheobronchial region, 0.24; and pulmonary region {aive~lar), 0.4~ (Emmett et el. 1982). These measurements are below the estimated regional deposition for upper respiratory tract deposition m|d higher for the pulmonary deposition than are the measureme.Ls calculated by using the Task Group on Lung Dynam- ics model ([CI{P 1966). The regional deposition of mainstream cigarette smoke in smokers has alsd been studied. Subjects inhaled smoke from cigarettes labeled with radioactive 1-iodohexadecane (Black and P~itchard 1984; Pritcb.rd and Black 1984). The results indicate that less than 40 percent of the particulate mass deposited in the pulmonary region, compared with an expected 90 percent deposition in the
Page 104: TI07870714
TABLE ~--Respiratory tract deposition of mainstream and sidestream c~garette smoke Study l~'Ix~i~on fr'~ction tmL) tRcond) Smok~ dilution l~rntory p~ttern Mainstream smoke B~umber~er 88% No~ &iven Noc ~ive~ None In~tuzion (19~t Mi~ll tl~2~ ~ ~ = 9~ SO l~ ~ 0~ SD ~1 "~ inst." ~n~ ~ ~. (7% ~ None U~I Si~m smoke T107870714
Page 105: TI07870715
widely. Enhanced deposition at specific anatomic sites may b~ especially important for some inhalants. For example, the concentra- tion of carcinogenic substances at a site may favor that site for cancer development. This may be especially important for cigarette smoke, since lung cancer may occur at sites of high deposition such as airway bifurcations. Depesition of a 0.3 ~tm laboratory-generated stable aerosol has been shown to favor right upper lobe depesition, and on the basis of surface density of deposition, thu lobar bronchi (Schlesinger and Lippmann 1978). The deposition per airway genera- tion has been calculated for large particles, but h~m not received sufficient attention for particles in the size range of mainstream or sideetream smoke. A deposition peak has been predicted, using a lung model for the fourth airway generation (trachea is 0) for 5 particles, and a peak in airway surface concentration density was. predicted for 8 Ixm particles at the fourth generation (Gerrity et 19.79). Both of these deposition peaks are calculated for particles substantially larger than those of cigarette smoke. Depositions may be quite nonuniform even within a single airway generation. An enhanced deposition st bifurcations with highly concentrated deposition on'carina ridges within bifurcations has been demonstrated in a five airway generation model of the humm~ respiratory tract for both cigarette smoke (Matter,an mad Lowo 19B.3b) and research aerosols (Mnrtonen and Lows 1983a). Epldemiological studies ot" the pathophysi~iogic c~nsequences of involuntary smoking have emphasized, among other things, an increase in the incidence of respiratory illness in children (see Chapter 2). The issue of the resl~iratory tract deposition of particles in children has been addressed only recently. Using morphometrlc measurements ft;om casts of the lungs of children ~md young adults aged 11 days to 21 years, a mathematical growth model was created. Using this model and c~mventional methods for predicting the behavior of particles in tubes, the deposition of particles at various ages can be predicted. On the basis of these calculations, tracheo- bronchial depositions per kilogram of body weight lbr ~ Itm imrticles was estimated to be six times higher in the resting newborn than in n resting adult (Phalen et el. 1985). Differences are predicted also for particles the size of sidestream smoke, with tracheobronchial deposition in infancy being twofold to threefold higher in adulthood. Total deposition has also been estimated using mathematical model- ing, with the total depositien estimated at approximately 15 percent at age 6 months and at 10 percent in adults (Xu and Yu 19t~6). 190 Respiratory Tract Dose of Environmental Tobacco Smoke Cigarette Smoke Particulate Mass Deposited The dose of environmental tobacco smoke to the respiratory tract is the product of the mass in inhaled air and the deposition fraction. To this I~int, particle size and deposition fraction, which is related to both size and respiratory pattern as well as to other less understood factors such as particle charge and hygroscopicity, )~ave been addre~ed. To estimate dose, the content of smoke in inhaled air must be known, as well as the respired minute volume. Mass content in inhaled air varies widely, as does minute volume, which depends considerably on activity level. Sidestream smoke concentrations have be.an r~ised as high as 16.5 mg/m~ in experimental chambers (Hoegg 1972). lIigh levels, 2 to 4 mg/m~, have also been estimated using measured carbon monoxide concentrations for rooms 140 m~ |~ si~e containi~g ~0 to 70 persons (Bridge and Corn 1972). Such levels far exceed the RPA air quality standards for total suspended particulate ~,f 75 pg/m~ annual average and the 260 pg/m* 24-hour a~eragc in the United States and the 250 i~g/m~ 24-hour average for the United l(ingdom. Measuren,:nts of environmental smoke concentrations vary wide- ly, depending,, upon the location and measurement technique (Tables 4 and ~). I~:vels of total suspended particulates'(TSP) measured under realistic circumstances have been found to be from 20 to 60 pg/m~ in no.smoking areas, and can range from 100 to 700 pg/m~ ]n the presenc~ of smokers (Repace and Lowrey 1980). These men, are- manta inch, Is all suspended particulates, and so could include porticlcs other than tobocco smoke. However, in a smoky indoor setting where: measurements as high as 600 l~g/ms have been found, tobacco smohe is the m~jor contributor to particuloto mass, with the non-tohacco.,moke contribution being small and similar to that measured for nonsmoking areas, namely in the 20 to 60 itg/ms range, This concept is supported by studies in which tobacco smoke concen tratio~ in the environment'was determined by measuring the nicotine cow,tent of suspended particulates. Using this technique (Hinds and First 1976), E'U3 levels have been estimated to be 20 to 480 l~g/m* i~t bus and airline waiting rooms and as high as 640 l~g/m~ in cock tall hmnges. Thcse calculations of smoke concentrations were based on an average weighted nicotine fraction of 2.6 percent, an approach ~imt may underestimate tobacco smoke particulate concen- tration. The mass deposition in the respiratory tract can be estimated if the atmospheric burden of cigarette smoke particulates, mlnuts volume, aml deposition fraction .is known. Assuming a smoke concentrati,m orS00 ~g/ms, a minute volume of 12 liters per minute,
Page 106: TI07870716
TABLE 4.~Indoor concentration of total suspended particulates (TSP) measured in ordinary living or working situations Condltion~ of loc~tion. T~P Bad.round occupancy, smoking" iS}. S~udy Loc~don non.~no]~n~ IN$) ~rnlms z ~-SD ~n/m; CommenL~ Jus~ e~ al. Coffee shop 4 kx~$1ox~ LIfO 5~'O' *1972, Ax~m A At~*~nce 9.600 224 42 High volume sampler for A~r conditioned (S} ~x~p~nded p*rficuia~:. ~ A~ndm~ 14~00 ~I 42 m~u~ ~ at ~I TABLE 4.--C~ntinued ~ Coati.o-. of loea*.i~o~ T~P 8aci~:~und oecup~'~, smokinl Weber and F'mche¢ 44 o/l'we* Window ~fil~m*- 202 Su~ from TSP m*~,ured with All samplm co|lec~d using" pie~electric balance ~h very hizh cotlbcdoa efficiency at ~ ~m and 10~ ~ 4 ~,m; sample T107870716
Page 107: TI07870717
TABLE 4.--ConL~uued occupant, smoldng IS). Spengler et ~L 35 ~omes No ~moke~ .~.4 " 11.6' .21.1 "" 11.9 |1981~ 15 hom~ 1 smoker $ horn~ 2 smok~rz I h~n~* 2 smoker~. Ligh~y ~ed, 1,14 central gir conditlonln~ Annual m~n: r~plreb]e ~ ~l|ec~,,d on filter* m~r removal of nonr~spirable fmctim~ 2~hr r,~nple collected ever7 6 da~ TABLE 5:~Lndoor concentration of total suspended particulates (TPMr) generated by smoking cigarettes under ]aborator~ conditions Chamber. Cig~r~ TPM S',udy Te~t condi*iom ~'en¢i~fi~ s~ ~um~tion mq:m* ~mmen~ Pennia and Well mix~ N~e 9~ m= 3 simul~n~ly. 2 q 3.8 ~ Olive~ ,1975) ,19721 ex~men~r and ~ ci~lat~ ~r ~uipm~¢ in c~m~ ~i~t~ m~u~ ls mm dd~ s~ke ~11~ in ~king ~ ~ smoke ~. 150 rain p~ramokim~ ~ne ~ ~ ~. ~t2 ~ (t~) ~i~t~tmll~ c~ II ~ ff=/min/~t II m= 16/hr tb~ ~I 0.~ Mum~ ~i~nt~ll~ 15.4 air ~/hr ~ m~ 1/8 mm m ~ m~ 0.1~.;~ ~l~ ~n~ ec aL ,l~i ~n~l~ I~4 ~ ~lhr ~ m= 3 ~ul~y. t~n 0.47~.~ T107870717
Page 108: TI07870718
and a deposition fraction of 11 percent (Hiller, McCusker e~ el. 1982), mas~ deposition over an 8-hour work shift wouhl be 0.317 rag. The Concept of "Cigarette Equivalents" Many investigators have attempted to estimate the potential toxicity o1" involuntary sm~king for the nonsmoker by calculating "cigarette equivalents" (C.E.). To inhale one C.E. by involuntary smoking, the involuntary smoker would inhale the same mes~ quantity of ETS as is inhaled from one cigarette by a mainstream smoker. This approach has led to estimates from as low as 0.001 C.E. per hour to as high as 27 C.E. per day (Hoegg 1972; Hinds and First 1975; Hugod et el. 1978; Repace and Lowrey 1980). These differences of up to three orders of magnitude seem illogical when mo~t reports of measurements of environmental concentrations of smoke, from the most clean to the most polluted with environmental tobacco smoke, are within tenfold to fiftyfold of each other. The following discussion demonstratsa why the C.E. can vary so greatly as a meeaure of exposure. The calculation of C.E. is a~ follows: PMI~p~ - TSI' (mg/m where PMl~equals the particulate mass inhaled by passive smoking, TSP equals the total suspended particulate, and ~/~ equals the inhaled volume. C.E. =, PMi~/PM~,=~; where C.E. equals cigarette equivalent and PMI~ equals the mass inhaled by (mainstream) smoking one cigarette. (This is taken to b~ the tar content of a cigarette as reported by the IJ.S. Federal Trade Commission.) Cigarette equivalent~ can be calculated for any time interval chosen, i.e., per hour, per day. Although the example given is for particulate mass, C.E. can be calculated for any component of cigarette smoke, such as carbon muaoxids and benzt4s]pyrcne. The following calculations illustrate the difl'erent results I'rom two differeut approaches to the calculation of C.E. Exam.pie I Example 2 V~ 0.36 m~/hr 20 ~n~/d~y PMI~.~ 16.1 mg tar/cig 0.5~ mg tar/cig TSP 40 pg/m~ 700 p.g/m• Example, 1 PMI~ CE TSP x Vv. 40 p~/m~ x 0.36 m=/hr 14.4 pg/hr PMI~/PMI~..~ = (0.0144 mg/hr)/(16.1 mg/cig) 0.001 ciglhr 196 = TSP x V~: = 700 itg/m~ x 20 nP/day 14,000 rig/day = PMi,p,/PMI~,~ = (14 mg/day)/(0.~5 mg/cig) --- 25 cig/day These colculations of C.E. approximate the approaches used in two reports--Exmnple 1 by Hinds and Fit'st (1975) and Example 2 by Repace and I~wrey (1980)--and the results are similar, The exam- pies are the extremes used in the two studies, and are at the extremes of commonly cited reports of C.E. Even if the TSP concentration used in the two examples were the same, the result~ would differ 24-fold because Example 1 is calculated per hour and Example 2 is calculated per day; 2.3-fold because of the difference in inhaled minute volume; and 29-fold because of the difference in what is considered to be a "standard" cigarette. Even using the same TSP concentration, the results would be 1.6 x 10~ different. If C.E. is to be calculated, all of the factors used in the calculation should be standardized. The calcuh~tlon of C.E. is deficient in several other ways. The deposition b'action of the total inhaled particulate mass in the respiratory ~ract from mainstream smoke is higher than from involuntary smoking. The deposition fraction for involuntary smok- ing is approximately 11 percent for mouth breathing (Hiller, Mazumder e~ el. 1982). The deposition from mairistream smoke ha~ been rel~)rted to vary from 47 to 90 percent (Table 3). The cigarette equivalent calculation considers only the quantity inhaled, and if mass d~me &,posited is considered, one C.E. from passive smoking will cause ~cveral times less mass to be deposited than the mainstream smoke of one cigarette. The differs:aces in the chemical composition between sidestream smoke and mainstream smoke make the C.E, concept misleading unless C.E. is calculated for each smoke constituent, This has been accomplished (lluged et el. 1978) using measured levels of various smoke constituents in a chamber filled with sidestream smoke. The results indicnte ~hat one C.E. for carbon monoxide could be inhalcd 5.5 times faster, and for aldehyde, 2.9 times faster, than for particulate mass. Measurement8 of total particulate matter and benzo[a[pyrene taken in an arena with active smoking revealed a fivefold rise in TSP above background and an eighteenfold increase in benzola]pyrene over background. Using the measured ben- zo{a]pyrene concentration of 21,7 ng/m~, an inhaled volume of 2,4 m*, and 8.2 zzg benzo[aJpyrene per cigarette, the occupant of such an enviromnent would consume 6.4 C.E. for benzo{a]pyrene (WHO 1986, 197
Page 109: TI07870719
p. ST). The C.E. TSP would be 1.7. Therefore, a C.E. for the carcinogen benzo[a]pyrene would be inhaled 3.6 times more rapidly than a C.E, for TSP (Eiliott and l~owe 1975). The wide latitude in the results of C.E. calculations demonstratos the dependence of the C.E. calculation on the numerical values of the variables chosen, and correslmndingly demonstrates the marked limitations of the use of C.E. as an atmospheric measure of exposure to the agents in environmental tobacco smoke. When the quantifica- tion of an exposure ie needed, it ia far more precise to use terms that define the milligrams of exposure to the agent ol' interest per unit time. However, the term cigarette equivalent is fn.~uently used, not simply as a measure of exposure, but as a unit o~" disease risk that translates the measured exposures into a risk of diseas~ using the known dose-response relationships between the number of ciga- rettes smoked pe'i day and the risk of disease, if the term C.E. is to be used as a unit of risk, the variables used to convert atmospheric measures into levels of risk for the active smoker need to be determined on the basis of the deposition and smoke exposure measures for the average smoker. The deposition fraction of indlvld. ual smoke constituents in the population of active smokers is needed rather than the range observed in a few individuals. In addition, the actual average yield of the cigarettes s~noked by the subjects in the prospective mortalif~y studies would be needed to compare the do~- response relationships accurately. The yield using the Federal Trade Commission (FTC} method may dramatically underestimate tile actual yield of a cigarette when the puff volume, rate of draw, or number of puffs is increased; therefore, calculations usi!~g the FTC numbers may be inaccurate, particularly for the low-yield cigarettes. These limitations make extrapolation from atmospheric measuros {~ cigarette equivalent units of disease risk a complex and potentially meaningl.es~ process. Markers of Absorptlon In contrast, measures of absorption o!" environmental tobacco smoke, particularly cotinine levels, can potentially overcmne some of tile limitations in translating enviromnental tobacco smoke expo- sures into expected disease risk. Urinary coti~dne levels are a relatively accurate dosage measure of exposure to smoke; they have been measured in populations of smokers and nonsmokers, and are not subject to errors in estimates of the minute ventilation or yield of the average cigarette. Potential differences in the half-life of cotinine in smokers and nonsmokers, differences in the absorption of nicotine relative to other toxic el;eats in the smoke, and differences in the ratio of nicotine to other toxic agents in mainstream smoke and sidestream smoke remain sources of error, but the accuracy ~vith 198 which actiw: smoking and involuutary smoking exposure san be compared is almost certainly substantially greater with measures of abserption lhan with atmospheric measures. Tobncco s~noke contains many substances, but only a few have been measm'ed in human biological fluids, Of the gaseous ¢ompo~ nents, markers include carbon monoxide and thiecyanate, The latter is not n gas but a metabolit~ of gaseous hydrogen cyanide, Concentra- tions of nic.tiae and its metabelite cotinine are markers of nicotine intake, In mainstream smoke, nicotine intake reflects exposure to partic~dates. In ~nvironmental tobacco smoke, nicotine becomes vaporized trod therefore reflects ga~ phase exposure (Eudy et a|, 1985). Quantitating tar consumption is more difficult; urinary mutagenic i~ctivity has been used as an indirect marker. The relative exposures of nonsmokers to various tobacco smoke conatit~ent~ differs from that of smokers. Assuming that exposure to a single telmcco smoke constituent accurately quantifies the expo- sure of both smokers and nonsmokers to other constituents is inaccurate because the composition of mainstream smoke and enviro~mm~lal tobacco smoke differ (see Chapter 3). To understand the usefulness and limitations of various biocheml- cal markers, it is important to appreciate the factors that influence their absorption by the body and their disposition kinetics within it. Carbon Mmmxlde Carbon nmnoxide is absorbed in the lungs, where it diffuses across the alveolar membrane (Lawther 1975; Stewart 1975). it is not appreciably absorbed across mucous membranes or bronchioles, Within thc~ body, c~rbon monoxide binds, as does oxygen, to hemoglobin, where it can be measured as carbexyhemoglobin, Carbo~ mop,oxide may also be bound to myoglobin and to the cytochrome enzyme system, although quantitative details of binding to the latter sites are not available. Carbon monoxide is eliminated primarily by respiration. The amount of ventilation influences the rate of ellmina~ion. Thus, the hall-life of carbon monoxide during exercise may be less than 1 hour, where~ during sleep it may be greater tim. 8 hours (Castleden and Cole 1974). At rest, the half-life is 3 to 4 hotlrs. The disposition kinetics of carbon monoxide explain the temporal variation of carbon monoxide concentration in active smokers during a day of regular smoking. With a half-life averaging 3 hours and reasonably constant dosing (that is, a regular smoking rate) carbon monoxide h:vels will plateau after 9 to 12 hours of cigarette smoking, This has b~,cn observed in studies of circadian variation of carbon monoxide c.ncentrations in cigarette smokers (Benowitz, Kuyt et 1982). Smoldng is not a constant exposure ~ource, but results in pulsed dosi.g. There is a small increment in carboxyhemoglobin 199
Page 110: TI07870720
level immediately after smoking a si,tgle cigarette:, which then declines until the next cigarette is smoked. But alter svvcrai hours of smoking, the magnitude of rise and fall is small compared with ti~e trough values. For this reason, carbp, xyhemoglobin levels at the end of a day of smoking are satisfactory indic~ttors of cal'b~m monoxide exposure during that day. Carbon monoxide exposure may be more constant during environ- mental tobacco smoke exposure than during active smoking. The major limitation in using carbon monoxide as a means of measuring involuntary smoke exposure is its lack of specificity. Endogenous carbon monoxide generation from the metabolism of hemoglobin results in a low level of carboxyhemoglobin (up to I percent) (Lawther 1975; Stewart 1975). Carbon monoxide is generated by any source of combustion, including gas stoves, machinery, and automo- bile exhaust. Thus, nonsmokers in a community with moderate home and industrial carbon monoxide sources may have carboxyltemogio- bin levels of 2 or 3 percent (Weebkenberg etal. 1981). A carbon monoxide level of 10 in room air results in an increment of 0.4 and 1.4 percent carboxyhemoglobin at 1 and 8 hours of exposure time, respectively (Lawther 1975; Stewart 1975). Thus, small increments of carbon monoxide due to environmental tobacco smoke may be indistinguishable from that due to endogenous a~d non.tobacco- related sources. Measurement of carbon monoxide is straightforwa|'d and inexpen- sive. Alveolar carbon monoxide pressures are proportional to the concentration of carboxyhemoglobin in blood; therefore, end-tidal carbon.monoxide tension accurately reflect~ blood c~rhoxyhemoglo- bin (Jarvis and Russell 19t~0). Expired carbon m~moxide can be measured u~ing an instrument (Ecolyzer) that measures the rate of conversion of carbon monoxide to carbon dioxide ps it passes over a catalytically active electrode. Blood carboxyhemoglobin can be measured directly and quickly using a differential spcctrophotome- ter. Thiocyanate Hydrogen cyanide is metabolized by the liver to thiocyanate. In addition to tobacco smoke, cei'toin foods, particularly leafy vegeta- bles and some nuts, are sources of cyanide. Cyanide is also present in beer. Thiocyanate is distributed in extracellular fluid m,d is eliminated slowly by the kidneys. The half-life of thiocyanate is long, about 7 to 14 days. Thiocyanate is also secreted into saliva, with salivary levels about 10 times that of plasma levels (Haley etal. 1983). The long half-lil'e of thiocyanate means that there is litth: lluctuation in plasma thiocyanate concentrations during a day or I'rom day to day. Thus, the time of sampling is not critical. On the other hand, a given 20O level el' thi~yanate reflects exposdre to hydrogen cyanide over several weelts preceding the time of sampling. When a smoker stops smoking, it {.akes an estimated 3 to 6 weeks for thiocyanate levels to reach that individual's nonsmoking level. Because o1" the presence of cyanide in foods, thiocyanate is not specific for ,,xpesure to cigarette smoke. Although active smokers have plasma* levels of th'iocyanate two to four times those of nonsmokers (Vogt etal. 1979; Jacob etal. 1981), light smokers or involuntary ~mokers may have little or not elevation of thiocyanate. When thoas~,nds of subjects are studied, involuntary smokers have been found to have slightly higher thiocyanate levels than tl~ose without exp~sure (Friedman et al. 1983). Other studies of smaller numbers of subjects have shown no difference in thiocyanate level between exlz~d or nonexposad nonsmokers (Jarvis et al. 1984)0 Serum or plasma thiocyanate levels can be measured using spectrophot~metric methods or, alternatively, gas chromatography, Nicotine Nicotine i~ absorbed through the mucous .membranes o[" the mouth and bronchial tree as well as across the alveolar capillary mem- brane. The extent of mucosal absorption varies with the pH of the smoke, such that nicotine is absorbed in the mouth fiom alkaline (cigar) smoke or buffered chewing gum, but very little is absorbed from acidic (cigarette) mainstream smoke (Armitage and Turner 1970). With ~ging, environmental tobacco smoke becomes less acidic; pI-I may" rise to 7.5, and buccai or nasal absorption" of nicotine, by the' nonsm~ker could occur (see Chapter 3). Nicotine is distributed rapidly to body tissues and is rapidly and extensively metabolized by the liver. Urinary excretion el" unmetabo- lized ni~:otlne is responsible for from 2 to 25 percent of total nicotine elimination in alkaline and acid urine, respectively; nicotine excr~ ties also varies with urine flow (Rosenberg et ai. 1980). Exposure to environmenlal tobacco smoke, active smoking, and use el" smokeless tobacco markedly elevate salivary nicotine transiently out of propor- tion to serum and urinary levels (ltoffmann et al. 1984). Nicotine is present in b~'sast milk (Luck and Nau 1985), and the concentration in the milk is almost three times the serum concentration in,the mother (Luck and Nau 1984). The rate of nicotine metabolism varies considerably, as much as fourfold am,ng smokers (Benowitz, Jacob etal. 1982), There l~ evidence tlmt nicotine is metabolized less rapidly by nonsmokers than by smokers (Kyerematen etal. 1982). A given level of nicotine in the body ~'eflects the balance between nicotine absorption and the metabeiism and excretion rates. Thus, in comparing two persons with the sa~ze average blood concentration of nicotine, a rapid metabolizer may be absorbing up to fodr times as much nicotine as a
Page 111: TI07870721
slow metabolizer. To determine daily intake of nicotine directly, beth the nicotine blood concentrations and the rates of m~tabolism and excretion must be known. These variables can be measured ia experimental studies (Benowitz and Jacob 1984; Feyerabend etal. 1985), but are not feasible for large-scale epidemiologic studies. The time course of the decline of blood concentrations ef nicotine is multiexponential. Following the smoking of a single cigarette or an intravenous injection of nicotine, blood concentrnti~ms of nicotine decline rapidly owing to tissue uptake, with a half-life of 5 to 10 minutes, If concentrations are followed over a longer period of time or if nmltiple doses are consumed so that the tissues are saturated, a longer elimination half-life of about 2 hours becomes apparent (Benowitz, Jacob eL al. 1982; Feyerabend et al. 1985). Because of the rapid and extensive distribution in the tissues, there is considerable fluctuation in nicotine levels in cigarette smokers during and after smoking. As predicted by the 2-hour hall'-life, nicotine blood concen- tratlons increase progressively and plateau after 6 to 8 hours of regular smoking (Benowit~, Kuyt et al. 1982). Nicotin, e concentra- tions have been sampled in the afteruoon in studies of nicotine intake during active cigarette smoking (Benowilz and Jacob 19841, and similar timing might be appropriate in assessing the plateau levels that result from continuous ETS exposure, such as during a workday. Russell and colleagues (1985~ quantitated nicotine exposure by compari.ng blood nicotine concentrations during intravenous infu. siena (0.5 to 1.0 mg over 60 minutes) in nonsmokers to the blood nicotine concentrations in nonsmokers exposed to environment~d tobacco smoke. The data suggest that nicotine intake in a smoky bar in 2 I~ours averaged 0.20 mg per hour. The presence of nicotine in biologic fluids is highly spc~:ific for tobacco or tobacco smoke exposure. Nicotine concen(.ration is sensi- tive to recent exposure, because of nicotine's relatively rapid aml exteasive tissue distribution and its rapid metJ~bolism. Urinary nicotine concentration has been examined in a number of studies environmental tobacco smoke exposure. Although influenced by urine pH and flow rate, tl,e excretion rate of nicotine in the urine reflects the concentration of niceties in the bl~KI over the time per!o'd of urine sampling. In other word~, nicotiue exc~'etion in a timed urine collectioa is an integrated measure of the body's exposure to nicotine during that time. When timed urine collections are not available, nicotine exc~'etion is commonly expressed as a ratio of urinary nicotine to urinary creatinine, which is excreted at a relatively constant rate throughout the day. Urinary nicotim; excretion is highly sensitive to environmental tobac~.~ smoke expo- sure (Hoffmann et ai. laB.I; Russell and Feyeral~:nd 1975). Saliva levels of nicotine rise rapidly during exposure to sidcstream smok~: 202 and fall rapidly alter exposure has ended (Hoffmann etal. 1984). Presumably, this time course reflects local mouth coutaminat.ion, followed by ,bsurption or the swallowing of nicotine. Blo~l, urine, or saliva concentrations of nicotine can be measured by gas chromatography, radioimmunoassay, or high pressure liquid chronmtogr~q~hy. Sample preparation is problematic in that contam- ination of s.mples with even small amounts of tobacco smoke can substantially elevate the normally low concentrations of nicotine in the bh~J. Thus, careful precautions against contamination during sample coll,:ction and processing for analysis are essential. Because the concentrations are so low, the measurement of nicotine in blood has been difficult for many laboratories in the past, but with currently awdlable assays, it is feasible for large-scale epidemiologic studies. Cotinine Cotiniuc, the major metabolite of nicotine, is distributed to body tissues to a ~,mch lesser extent than nicotine. Cotinlne is eliminated primarily by metabolism with 15 to 20 percent excreted unchanged in the urine (Benowltz etal. 1983). Urinary pH does affect the renal elimination ,f cotinine, but the effect is not as great as for nicotine, Since renal clearance of cotinine is much less variable than that of nicotine, uriuary cotizdnc levels reflect blood cotinine levels better than urinary nicotine levels reflect blood nicotine levels. Plasma~ urine, and saliva cotinine concentrations correlate strongly with one another (llsley et al. 1983; Jarvis etal. 19114). The elimi,mtion half-life for cotinine averages 20 hours (range, 10 to 37 hoursl (Benowltz etal. 1983). Because of the relatively long half-life of cotinine, blood concentrations are relatively stable throughout the day for the active smoker, reaching a maximum near the eml of tlzc day. Because each cigarette adds relatively little to the overall ceLl,dee level, sampling time with respect to smoking is not critical. Assuming that smoke exposure occurs throughout the day, a midaftcrnoon or late afternoon level reflects the average cotlnine ~oncenl,ruti~,n. The specificity of cotinine as a marker for cigarette smoking is excellent, li~;cause of its long half-life and its high specificity, cotinine measurements have become the most widely accepted method for assessing the intake of nicotine from tobacco, for both active and in w~luntary smoking. Cotinine h:w;ls can be used to generate quantitative estimates of nicotine aba~,rption. Geleazzi and colleagues (1985) defined a linear relationship between nicotine intake and plasma cotinine levels six healthy vo|unteers who received several i.e. doses of nicotine (< 480 Itg/I(g/day) t'or 4 days. The ability to extrapolate from this model to h:vels in nons~nokers is limited, however, because the 2O3
Page 112: TI07870722
elimination haft-life of cotinine may I.. shorter ill slw,ke~ than in nonsmokers, as is the elimination half-life of nicotil~e (Kyercmaten et el. 1982)~ Cotinine can be assayed by radloimmunoaesay, gas chromatogra- phy, and high pressure liquid chromatography. Urinary Mutageniclty Tobacco smoke condensate is strongly mutagenic in bacterial test systems (Ames test) (Kier et el. 1974). A number of compoumls, including polyeyvlic aromatic hydrooarbons, contribute to this mutagenicity. The urine of cigarette smokers has been found to be mutagenlc, and the number of bacterial revertants per test plate is related to the number of cigarettes smoked per day (Ymnnsaki and Ames 1977). Urinary mutagenicity disappears withi~I 24 hours after smoking the last cigarette (Kndoet al. 1985). For several reasons, tile measurement of mutagenic activity of the urine is not s good quantitative measure of tar absorption. Individu- als metabolize polycyclic aromatic hydrocarbons and other mutagen- ic substances differently. Only a small percentage of what is absorbed is excreted in the urine as mutagenic ci~emicals. Tits bacterial system is differentially sensitive to different mutagenic compounds. The urine of smokers presumably contains a mixture of many mutagenie compounds. In addition, the test lacks specificity, in that other environmental exl~mures result in urinary mutagenicity. The test may also be insensitive to very low exposures such as involuntary smoking, floweret, one study, by Bos and colleagues (1983), indicated slightly increased mutagenic activity ill the urine of nonsmokers following tobacco smoke exposure. The presence of benzt~a]pyrene and 4-amino biphenyl covalently bound to DNA and hemoglobin in smokers (Tannenbaum ~t el. 1986) suggests other potential measures of carcinogenic exposure. Wheth- er such measures will be sensitive to IZI'S exposure is unknown. The development of specific chemical assays for human exposure to components of cigarette tar remains an important research goal. Populations In Which Exposure Has Been Demonstrated Abs~ption of tobacco smoke components by nonsmokers has been demonstrated in experimental and natural exposure conditions. Experimental Studies Nonsmokers have been studied after exposures in tobacco-smoke. filled rooms. The smoke may be generated by a cigarette smoking machine or by active smokers placed in the room by the investigator, or the location may be a predictably smoke-filled environment such as a bar.' The level of environmental smoke has mcx~t often been quantituted by measuring ambient carbon monoxide concentrations. In nonsmokcls exposed for 1 hour in a test room with a carbon • monoxide lew:l of 38 ppm, carboxyhemoglobin levels increased by 1 percent and uri;mry nicotine increased about eightfold {itu~ell and Feyerab~nd 1975). Seven subjects in n similar study eat for 2 hours in a public hour,: (bar) with a carbon monoxide level of 13 ppm; their expired carh.n monoxide "increased twofold and their urinary nicotine excr~:tion increased ninefold (Jarvjs et el. 1983). In a study exposing eight nonsmokers to a smoke-filled room for 6 hour~, a small increos~: in urinaiT inutagenic activity was measured (los et el. 1983). Nonexperlmental Exposures Exp~ure studies performed in real-life situations have compared biochemical markers of tobacco sm6ke exposure in different individ. uals with cliff's:rent self-reported exposures to tobacco smoke. Absorp- tion of nicotine (indicated by urinary cotinine levels) was found to be increased in ,dull nonsmokers if the spouse was a smoker (Weld and Ritchie 1984). In another study (Matsukura et el. 1984), urinary cotinine levels in nonsmokers were increased in proportion to the presence of smokers and tile number of cigarettes smoked at home and the preu:nee and number of smokers at work. llood and urinary nicotine I~vels were increased after occupational exposure to ETB such as a transoceanic flight by commercial airline flight attendants (Foliart et el. 1983). Nicotine absorption, documented by increased salivary cotinine concentration, has been shown in schoolchildren in relationship (,~ the smoking habits of the parents (Jarvis el, el. 1985)~ and using ph~sma, urinary, and saliva measures, in infants in relation to tht.~ smoking habits of the mother (Greenberg et el, 1984; Luck and Nail 1985; Pattishall et el. 1985). Quantification of Absorption Evidence of Absorption in Different Populations One questiunnaire survey indicated that 63 percent of individuals report exposure to some tobacco smoke (Friedman et el. 1983), Thirty-four Iz:rcent were exposed for 10 hours and 16 percent for 40 or more hours per week. The distribution of cotinine levels in a few populations has been relmrted. In men attending a medical screening examinntien, there was a tenfold difference in mean urinary cotinine in =.msmokers with .heavy exposure (20 to 80 hours per week~ compared with no reported ETS exposure (Weld et el, 1984), The median lind 90th percentile urinary cotinine concentrations for all nonsmokers who reported exposure to other people's smoke were 6.0 and 22.0 ,=g/mL, respectively, compared With a median of'1645 ng/mL for ~=ctive smokers. In 569 nonsmoking schoolchildren, 205
Page 113: TI07870723
T~BLE 6.wNicofine measures in nonsmokers with environment~l tobacco smoke (ETS) exposure and compa_,-isons with active smoking Mean or me.an con~encra~ou and ~-ange P~ ~ot~ Urine ~ico~ine ~liva nicotine Number of Smoking Study subjects st~t~J F~p~m~re le~,t Bet'ore Alter ~ot~ ?dter Before A~ter Ru.~sel! and 12 NS 78 men in 0.73 0.90 -- 80 (13-20~1 -- Feyerabend ~mok~4111~d room i19751 14 N~ ~ -- -- -- I~4 (0.~.3) -- 13 NS ~p~ -- -- 8~ t~ ~ 18 S A~ 24 ~y -- -- -- ~ (1~ -- Ti07870723
Page 114: TI07870724
TABLE &---Continued Number Plsanm nlc~ine Urine n~o~ine S~liv~ nic~ine (nzlmI.} (ng/mlJ tnz/mI.~ Greea~rg 32 HS Ia~a~a, e: aL (1984| 19 ~ lafznt, mother 12.7 t0-.lGG) 0 Luck and Nm.t 10 NS. nmtmms No *tl:otu~. -- -- -- 0t (0-14) (1985) 10 NS. n~tmtm N~ by. S 10 NS. infants S mot.l~r, not nursed -- -- -- 3.q (4-.21tt) 9 NS, ~ Nuned by. S moc..~r: -- -- -- 12 TABLE T.--4~otinine measures in nonsmokers with environmental smoke ~ and comparisons with active smoking M~sn ~r nm~tn concanu-ation and ran~ Numb~ m~ImZJ (rig/re.L) (2/mL jarvis 7 NS Bm'ore. 1130 Lm. e~aL ARer, pubtic ho~se x 2 hr (1983) 12.9 1~ 8.0 T107870724
Page 115: TI07870725
TABLE 7.~ntinued ~r (~/mL BeSom ~ Weld ( 19S4~ 221 NS 4~ NS 4~ NS 4~ NS 4~ NS 4S NS 131 S 42 . S ~4 14.7 3~6 {61-2138) 1920 (1006-4.569) M~t~ukur~ 2O0 NS 272 NS 2S NS ~ NS 99 NS ~ NS 2S NS 472 NS ~ .$ 76 NS 201 NS Sl0 ~0 31o 420 1030 1~60 68O 22O TABLE 7.--Continued o( Smokin¢ Stud), subjec~ ~attm Expo~r~ ~1 M~a* or median c~n~n~r~fi~n ~xi ~ l~'ore ~ B~fore ~r S~v~ cocinine Before AR~ GRe.bers 32 er. aL 19 NS, infzn'~ $ mod~r NS mo,.her .-- ~1 (t1-188~) 9 0 (0-3', 96 NS 76 NS 12~ NS ~ ~r~m SM 0.4 ~ (I.0} 3..(, ~ ~i 10 Nau 19 10 9 NS. ~nm N~ in~m N~r~d by S ~ S mother, no~ nurmd S mock', 100 327 (117-7m) Smoken in hom~ S~rum ¢otin~ T!07870725
Page 116: TI07870726
212 IIIIIIII IIIIIIIII IIIIIIIII IIIIIIII measureme.ts, cotinine appears to be the ~hort-term marker of choic9 for epidcmiological studies. (5) Mea. I(;vels o~" urinary nicotine and or cotinine in bodily fluids increase witl~ an Jncreasi.g sell-reported ETS exposure and with an increasing number of cigarettes smoked per day. There is consider- able variability in levels among individuals at any given level of self- reported exI. ~sure. Compnrison of Absorption From Environmental Tobacco Smoke and From Active Smoking Epidemiol~glc studies show a dose-response relationship between number of cigarettes smoked and lung cancer, coronary artery disease, and other smoking-related diseases. Assmning that dose- resin.ass relationships hold at the lower dose end of the exposure- response curve, risks for nonsmokers can be estimated by using measures of absorption of tobacco smoke constituents to compare the relative exl=mures of active smokers and involuntary smokers, As discussed previously, measures of nicotine uptake (i.e., nicotine or coti.ine) are the mos~ specific markers for ETS exposure end provide the best quantitative estimates o(" the dose ot" exposure, Although the ratio of nicotine to other tobacco smoke constituents differs in m.instream smoke and eidestream smoke, nicotine uptake may still be n valid marker of total ETS exposure. Nicotine uptake in nonsmokers can be estimated in several ways. Russell a.d colleagues (1985) infused nicotine intravenously to nonsmokers and compared resultant plasma and urine nicotine levels with I, htme observed in nonsmokers with ETS exposure. A.n inl'usio, of Img nicotine over 60 minutes resulted In an average plasma nicotine conce.tratlon of 6.6 ng/mL and an average urinary • nicotine concentration of 9.24 ng/mL. Using these' data in combina- tion with mt:asured plasma and urinary nicotine levels in nonsmok- ers after 2 hours in a smoky bar, nicotine uptake was e~timated a~ 0.22 mg per hour. Since the average nicotine uptake per cigarette is 1.0 mg (Ben.witz and Jacob 1984; Feyerabend et el. 1985). 0.22 mg of nicotine is equivalent to smoking about one-fifth of a cigarette per hour. In making these calculations, it Is assumed that the disposition kinetics o~ i.haled and intravenous nicotine are similar and that the rate of uicotizze exposure from Erl~J is constant. Steady st.te blood cotinine concentrations can also be used to estimate nicotine uptake. Galeazzi and colleagues (1985) measured eotinlne levels in smokers receivi.g various doses of intravenous nicotine, simulating cigarette smoking, for 4 days. They described the relatio.ship: [steady state plasma cotinine eoncentrativn] (ng/ml,) ---- ~0.783) x [daily nicotine uptake] (p~/kg/day). With such data, a 70 kl,' nonsmoker with a plasma eotinine concentration of 2.~ ng/mL wouhl Izave an estimated uptake of 3.2 pg nicotine/kg/day, or 213
Page 117: TI07870727
0.22 mg nicotine/day, equivalent to one-fifth of a cigarette. This approach assumes that the half-life for cotinine and nicotine eliminations is similar in smokers and nonsmokers, an ~msumption that may not be correct (Kyerematen et al, 1982). A third approach is to compare cotinine levels in nonsmokers with these in smokers, Jarvis and colleagues (1984) measured plasma,~ saliva, and urine nicotine and cotinino levels in 100 nonsmokers selected from outpatient medical clinics and in 94 smokers. Ratios of average values for nonsmokers compared with smokers were ns follows: plasma cotinlne, 0.5 percent; saliva coti~ti~e, 0.5 percent; urine cotinine, 0.4 percent; urine nicotine, 0.5 percent; and saliva nicotine, 0.7 percent. These data suggest that, on average, nonmnok- era absorb 0.5 percent of the amount of nicotine almorbed by smokers. Assuming that the a~erage smoker consumes 30 mg nicotine per day (Benowitz and Jacob 1984), this ratio prc~licts m~ exposure of 0.15 mg nicotine, or one-sixth of a cigarel.te per day. The most heavily exposed group or nonsmokers had levels ahnost twice the overall mean for nonsmokers, indicating that their exlmsure was equivalent to one-fourth of a cigarette per day. Must studies (see Tables 6 and 7) report similar ratios when comparing nonsmokers to smokers. The exception is Matsukura and colleagues (1984), who reported urine cotinine ratios in nonsmokers to mnokers oF6 percent. The reason for such high values in this one study is u~known. Personal air monitoring data for nicotine exposure can also be used to estimate nicotine uptake. For example, Muramat~u and colleagues (1984) used a pecketable personal air monitor to study environmental nicotine exposures in various livi,2g environments. They reported air levels of from 2 to 48 pg nicotine/m*. Assuming that respiration is 0.48 m~ per hour and exposure is for 8 hours per day, nicotine uptake is estimated to range from 8 to 320 itg per day. The average values are consistent with other estimates of one-sixth to one-third cigarette equivalents per day in general populations of nonsmokers exposed to ETS. As noted before, these estimates must be interpreted with caution. Relative absorption of nicotine in smokers and nonsmokers may substantially underestimate exposure to other compenents of ETS. Conclusions 1. Absorptionof tobacco-specific smoke constituents (i.e., nicotlne~ from environmental tobacco smoke exposures has been docu. moated in a number of samples of the general population of developed countries, suggesting that measun~ble exposure to environmental tobacco smoke is connnon. 2. Mean levels of nicotine and cotlnlne in body fluids incream., with self-reported E*I~ exposure. 214 3. Because.' of the stability of coti sine levels measured at different times during exposure and the availability of noninvasive ann|pli|tg techniques, cotinine appears to be the short-term msrkcr of choice in epidemiological studies, 4. Both mathematical modeling techniques and exporimbffttl[ data suggest that 10 to 20 percent of the particulate fraction of sidcstrca,n smoke would be deposited in the airway, 5. The dJ:velopment of specific chemical assays for human expo- sure ~o the' components of cigarette tar is au important rcsear~'h goal.
Page 118: TI07870728
References ALTSllULER, B., YARMUS, I,., PALMES, E.D., NELSON, N. A(.rtmol delmsitio, I in the human respirntory tract: L Experimental procedures and total delmmitlon. A.M.A. Archtues of lndustriaI Ht~,lth 15(4):.293-303, April [957. ANDEllSON, P.J., HILLER, F.C. l~zrficle Size Distribution of M~dnstream Tobacco and Martfl~ana Smo~¢¢ Using the ~leclrical Aerosol Analyzer. Palmr pre~ented at the American Asaoclatlon for Aerosol Research, Albuquerque, November 1985. ARMITAGE, A.K., TURNER° D.M. Absorption of nicotine in cigarette and cigar Imoke through the oral mucous. Nature ~26(525£):. 1231-1239., June ~.'/, 19/0. BAUMBER(IER, J.P. The amount o1" smoke produced from tobacco a,~d It~ absorption In smoking as determined by electrical precipitation. Journal at Pharmacology and Experimental Thernpe~#tics 21(1k47-57, Pebrunry 1923. BENOWITZ, N.L., JACOB, P. III, Daily intake of nicotine during cigarette smoking. Clinical Pharmacology and Therapeutics 3~4l:499-504, April 19B4. RRNOWIT~, N.L., JACOB, P. I/I, JONES, R.T., ROSF.NRERG, J. Inter|ndividuol vorlnbiIRy in the metabolism and cardiovascular effects of nicotine in man. Journal of Pharmacology and Experimental Therapcaticz 221(2):.368-379-, May 1989-. BENOWITZ, N,L., KUYT, F., ,IACOII, P. Ill. Circadian blood nicotine concentrations ' during cigarette smoking. Clinic~d Plsnrmacoiogy and Therope~ic~ ~2(6p.~58-~64, December BENOWITZ, N.L., KUYT, F., JAC()B, P. Ill, JONES, R.T., OSMAN, A..I,. Cotinine dispo~Rion and effect¢ Clinical elsarnm¢olugy and Theral~utic~ 34(5P.604-611, November 1983. BINNS, It. LUGTON, W.G.D., WILTON, L.V., DYAS. B.J. Inhalation toxicity studie~ on cigarette smoke: ft. Delx~ition o1 smoke particles |o the respiratory system of rats under various exposure ¢ondltion~. Toxic~lol~y 9(1-~-1:87-1(12o February 1978. BLACK, A., PRITCHARD, J.N, A ¢nmparlaon of the regional del~o~ition nnd short- term clearance of tar partlculoh~ material frmn cigarette smoke, with that pm polystyrene micro~pheres. Joarnnl of Aerosol ~cience 15(3~:224-227, 1984. BLANCIIARD, J.||., WILLEKI,:, K. An inhalation system for characterizing total lung deposition of ultrafine particles. American lnd~sb~al lty#iene Ass,ciati,n Journal 44(1 |):846-~56, November |983. BOg, R.P., THEUWS, J.L.O., IIENDERSON, P.T. Excretion of mul~|gens in human urine alter pa~ive smoking. Cancer I~tler~ 19( I kBfk-90, May 19143. BRIDGE, D.P., COLIN, M. Contribution to the assessment of exposure of nonsmokers to sir pollution from cigarette and cigar Imoko in occupic~l spn~. Enoironmenlai Research 512):192-209, 1972. CAIN, W.S., LEADEREB, B.P., IF+SEROFF, R., BI+;RGLUND, I,.(|., IIIIEY, lt.J., Lipaitt, E.D.. Parlman, D. ~enlllotion requ|remonta in bulidiogs: !. Control of occulmncy odor and tobacco snmke odor. Alm~pheric Enuir~mment 17(6P.1183- 1197, 1983. CASTLEDEN, C.M., COL~, P.V. Variations in carbosyhaemnglobi|, level~ in smokers. British Medical Jonrnai 415947):7:~-738, December 28, 1974. CIIANG, P.T., PE'I'ERS, L.K., UENO, Y. Particle size dlatrlbutlun of n,ni,~strenm cigarette smoke undergolnl~ dilation. In: Liu, B.Y.II., Pui, D.Y.II., Fismm, ll.J. (ods.). Aer~ot~: Science, Tcchn~dog.y, ¢~nd lndastrial Applie~m~ms ,f Airborn Par~icle¢ New York. Elsevier Science Publishing Compnny, Inc., 1984, pp. 737-740. COCKS, A.T., FEItNANIX), R.P. The grnwth of sulphate aerosols in the human airways, Journ,lofAero~ol,~cienre 13(I}:9-19, 1982. CORN, M. Characteristics of tobac~ sideatreem smoke and fach~ra influencing lt~ concentration and distribution tn occupied spaces. In: Rylander, it. (adj. Environ- mental Tobacc~ Effec~ on the Ncm-Smuker. ,°~candanauian Journal uflle~pirutury Diseases 91(Sul~pl.l:21-36, 1974. 211] COULTAS, l).lt., SAM~', J.M., HOWARD, C,A,, PEAKE, O,T,, SKIPPER, B,J, Salivary cotlnlue levell and passive tobacco smoke ex~urs in the homl, (a~tr~ct), America Review ofR~pimlo~ D~e 13~4, part 2):~157-A1~, April 19~. CUDDEBACK, J.$., ~NOVAN, J.R., BURG, W.R, ~u~tional ~ of smoking. America Ind~tdal Hygien¢ A~ia~ion Jou~i 37(5):2~7, 1976. DA~MN, T., ED~. M.-L.~ RYLAHDE~ R. ~ntion of clgare[~ smoks ~m~nen~ In human lung. A~hi~ of Envi~nmenlal HtaIIA 17(5~74~74B, Novem~r DAL~VALLE, J.M., ORR, C. JK HINKLE, B.L ~e ~atlon of aer~ls, Brit~h Journal nf Appti~ Ph~i~ ~Suppl 3~519~, 1954. EL~, L.P., ItOW~ D.R. Air quality during ~bllc gathering. Jou~l of the Air ~lluti~ ~twl A~iation ~8):~, June 1975. EMM~I', P.C., AITKEN, R.J., HANNAN, WJ. Meuursmvn~ of th~ ~! ~o..1 dopmltion of inh.l~ ~icl~ In t~ hum~ r~pir~ff tract. Jou~l of Ae~d ~iem~ I~6):~, 1~2. EffDY. ~W., TIIOME, F.A., II~VNER, D.L,, OREEN. C.R., INOEBR~HS~H, B.J. 8tudi~ on ~he Va~r-~rtku~te Ph~ ~t~bu~ion of ~nvi~nmen~l Pa~r pr~.~ s~ th~ ~h T~ ~m~' ~¢h ~n(eren~ Montrenl, ~n~a, Hovem~r 19~. ~d clesranco of T~. ~Icl~ In ra~. Env~n~n¢al R~h 31(I~14~151, Jun~ I~. FERROH, G,A, 'l~e si~ of ~luble ae~I porfld~ ~ a function of th~ h~midRy tho al~ Appll~tion ~ th~ hum~ ~pira~ tra~ Jou~[ ofA¢~] ~ie~ ~4k~ I-~, 1977. FEYR~IIEND, C, HIGRH~HAM, T., RU~EL~ M,A,H, Hi~fins ~n~ntr~tlons In urlns and ~llva of smoke~ ~ n~moke~, B~f~ M~I ~oumal ~(~21}:I~I~, April 3,19~2. ~Y~IIRND, C, INOS, R.MJ., RU~EL~ M.A.H. Hl~tlne phnrm~nefl~ snd I~ api,li~tkm ~ In.ks from smo~, B~t~h J~na] of~linical I~2~247, Feb~a~ 19~. ~LIA~', D., IIRHOWI~ ~.~, B~KE~ ~.g. P~lve a~rption of nl~tlns airllne flight at~ndan~. {Ist~r). ~w ~la~ ~1 of M~i¢[ne Mny 5.1~3. F~BB, B.A. The de.ilion of unifier chn~ ~dlcl~ in ~e I~gs of A~hi~,~ ofEnui~nmentaIH~lth 1~2~15~157, Auger 1~, F~EDMAN, G.I)., P~ITI, D.B., BAWO~ R.D. PRv~en~ and ~rRIn~ of amo~ng. Amed~n J~alof~bl~Hmlth 7~4~401~, April lg~. QALEAZZI, R.L., DAENENS, P., OUTER, M. S~ndy-a~ ~ntration of ~tlnina ~ a meaam'o of ni~tin~ln~ke by muoke~. Eum~n Jou~al of Cilniml GEBRITY, T.It, LEg, P.S,, HA~, F.J., M~RINE~I, A,, WERNE~ P,, ~UREN~ B. ~lcula~l de.Ilion or inhel~ ~icl~ In the ei~ay generations of normal aubj~t~. Jomwal of Applied Ph~iolo~ 47(4):~73, ~r GREENBERG. R.A., HAL~Y. N.J., ~E~ hA,, ~DA, F.A. Me~urlng the of tnfnn~ to ~ smoke: Nl~tlne and ~tinina tn urine ~d ~llva. E~land Jam hal of Medicine 31~17):1~1~8, April ~, GRIFFITi IS, It.it., ltENN1NGFIELD, J.E. Ex~rimen~i annly~b of human clgaret~ ~moklng ~b~tdor. F~tion l~t~i~ 41(21:~240, February 1982, HALEY, NJ., AXELRAD, CM., TIL~N, K.A, Validation of RIf-R~ smoking ~havh~ llim'hemi~l analy~s at ~tinine and thl~y~a~. Ame~can Journal of ~blic lt~ld~ 73(10~1~ t~7, ~r 19~. 217
Page 119: TI07870729
llARBISON, M.L., BRAIN, J.D. Effect. of exercl~ on particle det~ition in Syrian golden hamsters. American Rc.iew of Respiratory Disease 12~5}:~8, Novem- ~r 6, 1983, HILLER, F.C., MAZOMDER, M.K., WI~N, J.D., McLEOD, P.C, BONE. R.C. Iluman respiretory tract de~ition using multim~a[ n¢r~i~, ,loumoi of A¢~ol ~ience i~4}:337-343, 19B2. HILLER, F.C., M~USRER, K,T., MAZOMDER, M.K., WI~N, J.D., BONE, R.C. ~ition of ~ld~tream cigarette ~mokv In the humnn r~pira~ry tritct. American Be.iew of ResplmtoO' Db~se 1~4}:4~, 1982. HINDS, W.C, Aewsol ~hnolo~, New York, John Wiley nnd ~tt~, 1982, pp. 11~119, 143-148. HINDS, W,C, Size ¢harscteristl~ of cigeretm smoke. Amed~n lnd~tdal A~iation Journal 3~1~4~, J~nun~ 1978. HINDS, W.C., Ft~, M.W. ~ncontratiom of nl~tine and t~n~ smoke in public place. New England Journal of M~idne ~16}:844~5, April 17,1975. HINDS, W., FIR~, M.W., HUIIER, G.L., SIIEA, J.W. A meth~ for me~suflng resplra~ry de~ltion of cigaret~ smoky during smoking. America lnd~tdal lt~icae A~s~iation Journal 44{2~ 1 ! 3-116. Febru~ 19~, HOERS, U.R, Cigarette ~moke ia el~ ~pac~. Envi~mentol II~i~h 2:117-128, ~r 1972. HOFFMANN, D., HALEY, N.J., ADAMS, J.D., BRUNNEMANN, K.D. sid~tream ~moke: Up.ks by nonmnokers. ~n*i~ M~iivine 1~6~17, Novem~r 1984. HUGOD, C,, HAWKINS, ~.!1., ~RUP. P. ~x~uR to p~ive alnoke~ ~ smoke constituent. International A~hi~s of ~u~tio~l and Euvi~ment~! llcaltb 4~1}:21~, 1978. INTERNATIONAL ~MMI'I~EE ON RADIATION PR~'ION, TASK GHOUl' ON LUNG DYNAMIC. ~ition aud ~ntt~ m~el~ for internitl d~lmet~ of th~ human r~pir~ry tract. H~lth l'h~i~ 1~2917~, Fcbrua~ 1~. 'JAMB, P. 111, WI~N, M., llENOWI~, N.L. Improv~ g~ ch~ma~phie methM for the de~rmlnntion ~ ni~tin~ and ~tinine in biohgle floi~ doumoi of Cb~matogmpby 22~1):61-70, January ~, 198L JARVIS, M.J., IIU~ELL, M.A.H. ExplrtM air car~n monoxide: A ,implv bre~ t~t for tobacco ~mokv in.ks. British M~iml Joumal ~1(6~):4~, A~u~t 16, 1980. JARVIS, M.J., RU~EL~ M.A.II., FEYERABEND, C. A~rption d nl~inv and c~r~n monvgidv from Im~ivv tmoklng under natural ~ndlti~! d Tho~ 3~ 11 ):8~33, Novemlmr 1 JARVIS, M.J., RU~ELL, M.A.IL, FEYERABEND, C., EISER. J.IL, MORGAN, M, OAMMAOE, P,, GRAY, E.M, P~ive eg~ure ~ ~a~ $llBke: ~li~ ~tinine canctntration~ in ~ repr~n~tive ~puhtion ~mldo of non~moking ~h~l children. Bdt~h M~i~iJournai ~1i~):9~-~, ~r 6, 19~. JARVIS, MJ., TUN~ALDPE~E, H., FEYE~BEND, C., V~Y, ~., SALI~- 3EE, Y. Bi~hemi~l m~rke~ of smoke a~rption and ~lf-relmr~ ex~ure tn pa~ivv ~moking, Journal of Epid,miolR~ and ~mmu~ity Hcalth ~em~r 1984. JUST, J., BORKOWSKA, M., MAZIARKA, S. Air ~llution I~y ~e~ ~moke Wnr$~w cotf~ hou~. l~zniii Pa~t~go ~&ladu Hi~ic.y. ~2~l~1~. 1972. KAY, N.Y., MANSON. C., BSEN~'A~ E., IISIEII, D.P.ll. ~ ktnetic~ mu~gen egvretion in the urine of cigarette ~moke~. Mutation 1~7(2/3):227-232, Au~st.~ptem~v KEITII, C.IL Particle ,izo ~tudit,s on tobo~ ,muke. Belt~ge t.r lntenm6onal lH3gl~131,1982. 218 KEITH, C.II., DERRICK, J.C, Measurement of the particle size distribution and concetttretlo, of cigarette sntoke by the "conifuge." Journal of Colloid 15(4}:34U-356, August 1960. K1ER, L.I)., YAMASAKI, ,~, AMES, B.N. Detection of mutagenic uctivi'ty in cigarette .smoke canal,nantes. Pvo~'eedings of the Na6onal Academy of Science, USA 71(10l:4159-4163, October 1974. KOUSARA, ¥., OKUYAMA, K., W/i.NG, C.-S. Response of cigarette smoke particles to chn.ge i,, humidity. Journal of Chemical Engineering of Japan 1~1);75-76, 1982. KYEREMATEN, G.A., DAMIANO, M.D., DVORCHIK, B.H., VESELL, E,S. Smoking. induced changes in. nicotine dispesition: Application of a new IIPLC a~ay for nicotine and its metabolites. Clinical Pharmacology and Theropeutic~ 32(6):769- 780, December 1982. LANGEIt, G., I,'ISIIER, M.A. Concentration and particle size of cigitrette-~moke particles. A~¢ hi~,ea of Indu.~trial Hcallh 13~4):372-378, April 1956. LAWTilKR, P.,I. Carbon monoxide. British Medical Bulletin 31(3):256-260, Septem. bet 1978. LIPPMANN, M. Regional depceition of Imrticle~ in the human respiratory tract. In: Lee, I).II.K., Falk, ILL., Murphy, S.D., Geiger, S.R. (eds). Handbook vfPhy~iology. Vol. 9, 1977, pp. 213.232. LUCK, W., NAIl, H. Nicotine and cotinine concentrations in serum and milk of nursing mo~ hers. British Journal of Clinical Pharmacology 18{1):9-15, July 1984, LUCK, 'W., NA|I, H. Nicotine .rid catinine concentrations in ~erum Itnd url,e of infant, exp,,seal via pa~ive smoking or milk from smoking mother~. Journal of Pediatrics il)7(~1:816-820, November 198~. MARTONSN, T.B., LOWE, J.E. Cigarette smoke patterns in n human respiratory tract model. In: Marple, V.A., Liu, R.Y.II, (eds). Fundamentals and Aero~ds in Mining Itnd lqdustrial Work Environment., VoL L Ann Arbor, Ann Arbor Sciem:*~ Publishers, 1983a, p. 171. MARTONEN, T.B., LOWE, J. A~essment of aerosol deposition pittterns in human respirntery Irect casts. In: Marple, V.A,, Liu, B.Y.H. (eds). Fundumental~ and Statu~, Acre.Dis in Mining and Industrial Work Envlronmenta, Vo|, I. Ann Arbor, Ann Arbor S,:ience Publisltem, 1983b, pp, 1~1-164. MARTONEN, 'r.B., PATEL, M. Computation of ammonium bisulfate aerosol depo~lo alan in conducting airways, Journal of Toxicology and Environmental Health 8(~/6):10OI- 1014, November-December 1981. MATSUKURA, S., TAMINATO, T., KITANO, N., SEINO, Y,, llAMADA, UCIlll IASI II, M., NAKAJIMA, H., HlitATA, Y. Effects of environmental Sobered smok,: at) m i..ry cotlnine excretion in nonsmokers: Evidence for pa~lve smoking, ~Vew England J(,,rnal of Medicine 311(13?,8 .287832, September 2?, 1984. McCUSRBR, K., IIILLER, F.C,, WILSON, J.D., McLEOD, P., SIMS, R,, BONE, Dilution of ,.lg~rette smoke for real ,time aerodynamic sizing with It SPART analyzer. Jo.roal of AerwoI Science 13(2}:.103-110, 1982. MEDICI, T.C., lINGER, S., RUk'GGER, M. Smoking pattern of smoker~ with and without teh.cco-smoke-related lung dlsoese. American Review of Re~plratory Disease 131(3):385-388, March 1985. MI'i~:HELL, It I. Controlled measurement of smoke-particle retention in the re, plrit- tory t,'act. A.*v'ican Reuicw o[Respirotory Diseases 85(4):526-533, April 1962. MUIR, i).C.F. Tobacco smuke inhalation. In: Rylander, R. (ed,). Environmental Tobacco Smoke Effects on the Non-Smoker. Scandinavian Jo~trnul o[Re~piratory Diseo,~es 91(Htqqd.):44-46, 1974. MI.IItAMA'I~U, M., UMEMURA, S., OKADA, T., TOMITA, H. F, stimotion of personal expce.ro tu Iobocca smoke with a newly developed nicotine personal monitor, Envit.nment,d Research :1r~1):218-227, October 1984. 219
Page 120: TI07870730
MURAMAT~U, T., WP-BER, A., MURAMATBU, 8, AKERMAN,. ~. An Itudy on irri~tlon and annoyanc~ due ~ ~ive smoking. [nlernal~nai of ~cn~lional and ~wimumcntal H~lthSl(4k~317, 19~1. NEAL, A.D., WADDEN, II.A., R~ENBERQ, 8.H. Evaluation of lnd~r ~rticuln~ concentraHon~ for an urban ~pi~l. Ameri~m lad~l~,d Hysie~¢ A~iation Journal 3~7):57~82, July 1978, , OKADA, J., MATSUNUMA, K. ~termlnatlon of partlch~-sb~ distribution and concentration of cigarette smoke by a llght-scattering meth~. Journal of ~lloid and Interface ~ience 4~3~461~69, ~p~m~r 1974, PALM~. KD., AL~HULER, B., NEON N. ~Jtion o~ aer~ls In t~ bunmn reapira~ry tract during breath holding. In: Dav~, C.N. (~.). Inhal~ ~r¢irl~ and Va~ !1. Oxfo~, Pcrgnmon, H~, pp. 339-~9. PAq~ISHALL. E.N., ~ROPE, G.L, ~EL, R.A., HELMS, It.W., liALEY, NJ., I)ENN Y, F,W. ~rum ~tlnlno as a*ne,~ure of tob~o smoke e~aR in ¢htldreu. American Joarnai of i~e~ of C~ildh~ I3~ll~llOf 1104, Novem~r 1~. PENKALA, SJ., DE OLIVEIRA, G. l~e l[mul~tu~ analya~ of ~n mananas and sus~nd~ par~icula~ nmt~r pr~c~ by cigarvl~ ~amking. Enutwnmenlal Resean.h ~2~-114, April 1975. PHALEN, R.F., OLDIIAM, M.J., BEAIICAOE, C.B., CR(~KER. T.T., MORTENSHN, J,D. P, mtnntal enlargement ,d humnn trnch~&ronchial alrw~ys and implications for particle de~itlon. The A~,atnmi~l R~ 21~4~3~, Augnst ~LY~I/OVA, M. An ot~mpt ~ de~rmine the ~lention o~ ~a~ amo&e by means of membrane filters, In: ~v~, C.N. (~}. Inhal~ l'articl~ and Vul~ Oxfo~, Pergamon Pr~, I~ I, pp, 142-147. ~R~EN~HFER, J. Die ~flmmung der gr~nvertilung vm, set--lea mit hills der radioaktlven markieru~ und tier apiral~ntrlruge, Ae*wol ~ieace 4:~H,' 1973. ~RSTEN~RFER, J,, ~HRAUB. A. ~n~ntratton a~ m,,~u ~rtlcle sl~ of tim main sod side B[ream of ¢igaret~ anmke, ~laub-Reiahailung der Lu~ 3~10);~, ~to~r 1972. PRI~HARD, J.N., BLACK. A, An ~tlmation of the tar I~artict,la~ ma~rial debiting in the r~pira~ry trae~ ~ ~althy male middh~- aud Iow-~r clga~t~ smokers. In: Ltu, B,Y.H., Pui. D.Y.H,. F~n, lI.J. (eds). Aenm~b: ~haology, and ]nd~sldal Applimtion~ of Ai~rae Parlicle#, New Yor~, ~ience Publishing ~nt~ny, Inc., !~, pp. 98~2. RAABE, O.G. Slze-~l~tlve ~u,pling criteria for fl~e flmracic and r,mpirabl~ fractions, AnnaI~ of the Amerimn (bnftren~ o[ ~rnmv, tal lad,~ldal Hygi,'n- ~ts ( 11 ):53-~, 1984, RENNINGER, R.G., IlILLER, F.C., I~N~ R.C. The evn~,ration ~nd g~w~ of dropie~ hn#ing more than one volatile ~natituent. Journal of Ae~ 1~6}:~1fi, 1981. REPAC~ J.L., ~WREY. A.ll. i,~r ~lr ~llution: T~a~ smoke and public health. ~'itnce ~:464~72, May 2,1~. ROSENBERG, J., BENOWI~, N.L.. d~B. P. fil, WI~ON, K.M. klnetl~ and e[fec~ of intraveno~ nl~tine. Cli~i~l Pharmaodo~ and lies ~4):517~22, ~tolmr RU~ELL, M.A.Ii., ~LE, P.V.. BROWN, E. A~tion by am,smokers of carom monoxide from r~m air ~llu~ by ~ba~ ~moke. ~,ncet 1(7~3~7~79, March 17, 1973. RU~ELL, M.A.iI., FEYEliABEND, C. BI~ a,~d urin,~ry nicotine in nonsmoker. ~aeet 1(7~):17~18l, Janu,,ry ~, RU~ELL, M.A.II., W~, RJ., JARVIS, MJ. lutravenous nicotine simulation of pa~lve smoking ~ ~tlma~ d~ge ~ ea~ no.makers. Bd~iah Journal of Addiclion ~g£):~l-~. Juno 19~. 220 SCIILF~INGEll, It.B. LIPPMANN, M. Selective particle depo~ition oltd bronchogenlc carcilmnm. I,:nl,iraumenhd Re:~cnw~:h 1B3}:424--431, June 1978. SCI IMAI,, I)., t ~ )NSBRUCI I. U., DRUCKREY, Ii. Fluore~zenzmc-~ungen on 7.1garat. tenrm,cb, A~,~m.imittel F~r~chnng 4(2P.71-75, February 19~4. SINCLAIR, U, (~ptical properties of aerosols. In: [/andbool~ on Aen~.i~, From the Summary 'l'~,chnical Re~rt of Division I0, National ~fen~ lt~rcl~ ~mmit~, 8PENGLEIt, J.I)., ~KEItY, ~.W., TURNER, W,A,, WOL~N, J,M,, FER~IS, B.G., Jr. I~=~g ~rm me~uremen~ of r~plrable sulfa~ ~nd particl~ inlide and ou~i,le hom,~. Alm~p~eric Environment i ~:2~, 1981. ~EWAItT, R.D. The eliot of carla monoxide on humane. Annual Reulcw of ffl~BEIt, W. I,nng dynami~ nttd uptake of smoke ~nstituen~ by nonsmoker: T~NNENBAUM, S.R., BRYANT, M.S:, 8KIPPER, P.~, MACLURE, M. HemoBlobln TU, K.U., KNH'I~N, E.O. '!'~1 de~ltlon ~ ultrafine hydrophoblc ~nd hygr~opl~ aer~d~ in I he human r~plrn~ry tract. A¢~ol ~i¢~ and T~hnolo~ 3:453~65, 1984. V~T, T.M,. SHI,VIN, S., IIULLEY, S.B. ~m~ri~n of bi~hemical and qu~tlon, Urinury ~liniue ~ marker of breathing other ~ple'~ ~a~ smoke, WALD, N., IH'I~:III~ C. Validatiou ofet~ on lung ~n~r in non~moke~ married ~muokera, llet~r). ~ncet l(~):~, May 12, 19~. WEBER, A., FISHER, T. Pv~ive ~moking at work. lnte~atio~ml A~hiutl ~ul~tiomd mid Envi~nmentol H~lth 47(3~, 19~. WEL~, P.V., GI~RKE, R,ll. An ~illatlon meth~ %r me~urh~g the ~l~ ultramicr~-npic particl~. Jou~al of the Amtri~n Chemical ~i¢ly 3~, March 1919. WOEBKENIIEI~G, N.R,, MO~ARDI, R.A., I~LY, D.L., WO~ELL, D, ~r~xyhem~ 81~b~ m~d meO~em~l~iu level~ in r~iden~ living in ind~trhl and nonindu~tri, al ~umuuiti~, End~mental R~h ~2~7-~2, ~em~r 1981, XU, G.B., YU, C.P. Erf~ of age on domitian of InhBl~ aer~ls in the human lung, YAMASAKI, !~, AM~, B.N. ~n~ntratlon or tautens from urine by ad~rption with the n.nlmlar r~in XA~ ClgaRt~ ~moke~ have mu~genlc ~ings ~f the Natiuaai Academy of ~icn~ 74(8k~5~59, Augult 1977, 221
Page 121: TI07870731
CHAPTER 5 TOXICITY, ACUTE IRRITANT EFFECTS, AND CARCINOGENICITY OF ENVIRONMENTAL TOBACCO SMOKE
Page 122: TI07870732
CONTENTS Irritation: Acute Exl~mure Irritants in Environmental Tobacco Smoke Irritating and Amaoying Effects of Environmental Tobacco Smoke Studies of Healthy Individuals Field Studies Igxperimentai Studies Studies of Ek:nsitive Individuals Children Allergic Individuals Effects on the Lung Effects of Cigarette Smoking on Respiratory Epitheli- um: Studies in Humans Effect i~f Cigarette Smoking on Lung Inflammatory Cells Studies in Humane igx perimental Models Effects nf Cigarette Smoking on Lung Parenchyma: Studit.~ in Humans Summary of Lung Effects Carcinogenicity of Environmental Tobacco Smoke Inhalation Experiments Other lzt Vivo Bioassays In Vitrl~ Assays SummazT o1" Carcinogenicity Conclusions References 225
Page 123: TI07870733
TABLE l.--Major irritants in environmental tobacco smoke lETS), their concentrations in mainstream Smoke (MS), sides,ream smoke (SS) to mainstream smoke (MS) ratios, and levels in smoky air under realistic and natural conditions Irritant (per dprctt~) (ratio) Acrolel. 10-140 pg 10-20 6-120 ppb Forra=ldehyde 20-90 ~g s, ~) 3060 ppb, ico; 1-43 Amnmnln IO-f~0 Hi,rage. oxldt~ 16-e~O pg 4.7--~0 1-370 ~ 0 60 pbb Pyrldine 32 I~ l0 Sulfur di.xide 1-76 ppb NA I-~J Phenol 20-150 i~ 2.8 7.4-11~ pglm Toluene I0~ pg ~.6 0.04-1.04 I]espbable I,,rtix'.l.te~ 0.1-4~ n~ i.3-L9 55-962 mg/m Irritation: Acute Exposure Irritants iu Envtro.mental Tobacco Smoke . Tolmcco smoke is a complex aerosol that contains several thousand differe.t constituents (Hoffmann, Haley, Brunnemann 1983), Little is know. about the health effects of most o~ these compounds individually and even less is known about their interactions. Tobacco smoke co..sins compounds established as irritants, toxins, muta- gens. a.d carcinogens. The main irritants identified iu environmeno tal tobacc, smoke lETS) to date are respirable particul,ates, certain aldehydes, phenol, ammonia, nitrogen oxides, sulfur dioxide, and tolueae. The range o[ concentrations of these irritants measured in mainstream smoke, in sidestream smoke, and in smoky air under "realistic" a.d "natural" conditions or as results of field studies is summariz~d in Table 1. The levels of irritants in air contaminated with ETS vary considerably (Table 1), Some of this variation is due to differences in the number of cigarettes smoked, the amount of ventilation, the adsorptive properties of the surroundings, and measurement me,h- 227
Page 124: TI07870734
odology. Triebig and Zober (1984} compared the measured concentra- tions of these irritants with the maximum permissible c~ncentration (MAK) values for working areas and tl~e maximum emission concentration (MIK) values t'or outdoor air pollution in the Federal Republic of Ger=nany. They concluded that concentrations approxi- mating or in excess of the M [K values can be found for resplrable particulates, nitrogen dioxide, and acrolein. The other irritants generally do not reach the existing threshold limit values under realistic conditions. For phenol there is no MIK value. An evaluation of the hygienic and medical importance of the compounds in ETS based on threshold limit values is problematic for two reasons: first, MAK values for industries are established for healthy adults with an 8-lmur exposure per'day, aud MIK values are for the outdoor environment and no indoor limit values exist for "everyday life." Second, the threshold limit values are valid only for single com- pounds--ETS contains many different irritants, which might inter- act to produce more toxicity than anticipated from the concentra- tions of individual compounds. Many of the constituents of tobacco smoke are also produced by other sources that contribute contaminants to the indoor or outdoor e::vironment. For example, sources unrelated to smoking such as "ca formaldehyde foam insulation or certain wood materials can emit formaldehyde and may give rise to mean air concentrations as high as 100 to 400 ppb (Triebig and 7,chef 1984). In measuring the contribution o1" tobacco smoke to the levels o1" these constituents, some researchers (Weber et el. 1979a; Weber and Fischer 1980) have subtracted the measured indoor concentrations front the levels measured either in the unoccupied room or in the outdoor environ- ment near the room. The measured concentrations of irritants listed in Table 1 are primarily the mean values in air sample~ collected over intervals of one-half hour to several hours. Substantial variation in levels can occur, depending on, the proximity to a smoker and the air-mixing conditions in the room. Weber and Fischer (1983) t=~easured peak concentrations of 3,330 to 99JJS0 ng/m= l'or the pzwtlculates and 4/to 760 ppb for hitrogen oxide in the "blowing cloud" I meter from the smoker immediately alter smoke exhalation. These high concentra- tions decreased very rapidly with time (half-life between 2 and 20 seconds) and distance from the smoker. Ayer and Yeager (1982) measured formaldehyde and a~rolein co=mentrations in the side- stream Brooke plume rising from a cigarette between puffs and obtained concentrations of some constituents up to three orders of magnitude above the occupational limits establlsl~ed for more extended exposures. 228 FIGURE l.--Places of Impact, and irritants in the eyes and respiratory tract In relation to water solubility Irritating a=td Annoying Effects of Environmental Tobacco Smoke The main effects of the irritants present in ETS occur in the conjunctive of the eyes and in the mucous membranes of the nose, throat, m~d lower respiratory tract, The main ocular symptoms.are reddening, itching, and increased lachrymation; the main respira- tory tract symptoms are itching, cough, and sore throat, The relationship uf the site of the effect of some irritants in the eyes and in the respiratory tract to their water solubility is illustrated in Figure L Tb~ penetration of the particulates into the lung depends on their size; becaase most of the particulates in tobacco smoke are smaller than [itm, they can penetrate to the smallest airways. Studies of ll~.,althy Individuals Field Sludies Several studies have shown that annoyance anti irritation are the most common acute effects el' ETS exposure. Shepherd and Labarre (1978) surveyed more than 1,000 Canadian citizens aged 10 to 80 years. The i==tcrviewed population was representative o1" southern 229
Page 125: TI07870735
Ontario with respect to both iacome apd profession but underrepre- sentative of the elderly. Seventy-three percent .f the nonsmokers were disturbed by tobacct; smoke in restaurants a.d 53 percent by tobacco smoke in offices. The most frequently reported symptom was eye irritation. Complaints of nausea, dizziness, and wheezing as well as rhinorrliea were also repel'ted, although much less frequently than stinging eyes. Similar results were obtained in a survey ctmductod in three restaurants in Switzerla.d (Weber etal. 1979a). A multiple-choice questionnaire' was admipistered to 220 guests: O.e-tl=ird to two- thirds of the respondents complained about insulficlent air qualil.y, and up to 12 percent reported eye irritation. In a=tothor survey of more than 2,100 white~:ullar employees, Barad (1979) fou.d that nearly one-fourth of the nonsmokers reacted to smoke exposure with frustration and hostility. Weber and Fischer (1980) surveyed employees in 44 worksite workrooms, located in seven different companies, that included offices, rooms for design and technical and clerical work, conference rooms, The choice of companies and worksites was based on availability and therefore was not a random sample. In workrooms, the concentrations of carbon monoxide (CO), nitrogen oxide (NO), acrolein, particulate matter (PM), and nicotine were measured in the air. The contribution of tobacco smoke to these levels was obtained by subtracting background levels obtained before working hours from the concentrations during working hours. These differences from the background levels were called $CO, 6NO, and so on. Measurements were conducted in each room on 2 successive days (12 t-hour mean values per workroom). A total of 472 employees was questioned about irritation and annoyance as well as about their opinions on involuntary smoking. Some of the exposure results are aummarize~l in Table 2. The comparison of these 5 values with the measured absolute indoor concentrations revealed that 30 to 70 percent of the measured indoor concentrations of carbon monoxide, nitrogen oxide, and particulate matter were due to tobacco sznuke. The correlatlozis between the gas phase components 6CO and 6NO were relatively high (l~earson correlation coefficient r=0.73). However, the correlations of with 6nicotine and 6PM were low. Nicotine values were I:e.erally in the range of the lower dete~tlo, limit of the method z~f measurement used (gas chromatography). 'l%e low correlatiost of the gaseoas components with the particulate matter is probably due to Use different physical properties (sedimentotion, adsorption, and desorl~- ties of the particulates) a.d to the fact that the ~]'M values i'nclude particulptes from sources .ther than tobacco smoke. Apprdximately one-third of the employees descrii~.d the quality o]" air at work as "bad" witlt reg.rd to tobacco smoke. Forty pereent 230 TABLI'~ 2.~Air pollution due to tobacco smoke in 44 workrooms N.mber d Mean Standard Component ~amples valu~ deviation Maximum Iq(Xrl~: b vnlu*. ~ "'|mlu~r ©oncrnllr.t I~m du,in| work" minus "indoor ¢mlc~nl rzztlon I~orr work.'* were disturbed by smoke. One-fourth reported eye irritation at work, Seventy-two, percent of the interviewed nonsmokers and 67 percent of the smokers were in favor of a separation of the workrooms into smoki~*g and nonsmoking sections; 49 percent supported a partial or total p,,ohibitiun of smoking at work. Contredictory results were reported by Sterling and Sterling (1984), who found no relationship between smoking conditions in offices and comfort complaints. A self-adrdinistered work environ- ment questionnaire was given to approximately 1,100 employees working in nine buildings. Data were analyzed according to the sm~)king hvhits of the respondents and the office rules regulating smoking. The distribution of the responses to questions assessing the presence of symptoms (headache; fatigue; nose, throat, and eye irritations; sore throat and cold symptoms) were similar in environ- ' meats with a.d without smoking. The researchers concluded that "smoking is not a pivotal source of indoor pollution of health-related building complaints." No 'objective measurements of air pollution were carried out, however, and there were no descriptions of building ventilation. The researehers used a "l~uilding illness index" that included several different symptoms in addition to irritation (e.g,, headache, fatigue), and the irritating effects on the most sensitive organ--the ~:yes--may have been mesked by this use of an overall sympt~nn index. Experimental Studies tlarke a,,d Bleichert (1972) examined the acute physiological response to ETS in a 170 m~ room. The electrocardiogram, blood pressure, h~:art rate, and skin temperature showed no change with expel.re t. ]~S, even at extremely high exposure levels (160 cigarettes s~.oked in 30 minutes, corresponding to a carbon monox. ide co.ce.t,ation o1" 6() ppm at the end of the exposure). 231
Page 126: TI07870736
The influeuce of fl~e temperatm e and humidity of room air on odor perception anti irritation was investigated by Kerka a,ld llumphrey (1956). They found that odor intensity was somewlmt reduced by increasing the temperature at a constant humidity. Both odor and irritation intensity were reduced by increasing the humidity. Johans~on and Range (1966) also observed that acute irritation is increased in warm and dry air. Jobansson (1976) exposed 12 subjects in a 6.7 m~ climatic chum, bar for 29 minutes to the ETS produced by the smoking of 10 cigarettes. The air in the chamber was cold (lB° or 19° C) or warm (25° or 26° C), and at each temperature, the relative humidity was evaluated at three levels from 30 to 80 Ia~rcent. Under all conditions, subjective irritation, assessed by a questio,maire, increased during exposure; eye irritation increased more than nose irritation. No marked effect of temperature on the degree of irritation was observed, prohably owing to the limited temperature range studied (18~ to 26~ C). Kerka and Humphrey (1956) demon- strated a thermal effect when the temperature tin,go was greater than 8° C. The low relative humidity (7 to 20 percent# i~i aircraft may be responsible for the substantial level of perceived irritation due to ETS among passengers, despite the low levels of peilutants measured in aircraft (W110 1984). Base and colleagues (1978) studied the effects of E'I~J on human tear film and observed n reduction in the stability of the precorneal tear film in subjects exposed tO a smoke concentration corresponding to approximately 20 ppm CO. In the presence of ~-']'S, the tear film breakup time was significm~tly reduced by 36 to 40 percent com- pared with baseline measurements without smoke. The researchers suggested that this reflects an alteration in the relative proportions of the constituents of tear fihn. In these studies, the quantitative exposures to E'l~ were either not measured or determined in a relatively imprecise way. More systematic studies, including measurements of saver:fl compeunds of ~'rs, were carried out by Weber and collaborators (Weber etal. 1976, 1979a,b; Weber, Fischer, Grandjean 1977; Weber, Fischer, Gierer et al. 1977; Weber and Fischer 1983) and Muramatsu, Weber, and colleagues (1983). Tbesa experiments were carried out in a climatic chamber of 30 m~, with an air temperature of 20° to 24° C and a relative humidity between 40 and 60 percent. The ventilation rate could be varied between O.l and 16 air changes per hour. The smoke was produced by a Borgwald mnoklng muchiue under standardized conditions, and only the sidestream smoke of cigarettes was used. Healthy students were exposed to the sidestream smake of cigarettes in groups of two or three ih the climatic chamber. They all also participated in a control exposure with identical conditions, but without sidestream smoke in the air. The conce~trations of the following co,npounds were continuously recorded: cttrbon monoxide, 232 nitrogen oxide., formaldehyde, acrolvin0 and particulate matter, The background levels before smoke production were subtracted from the measured cmwentrations'during smok.ing; the resulting values were called 5CO, ~NO, and so forth. The degree of irritating and annoying effects of the ~:xpesed subjects was determined every 10 minutes by means of qm:stionnaires and by measuring the eye blink rate, considered un objective measure for eye irritation. In the fi~t study, 33 subjects were exposed to co~,tinuoasly increasing an,eke concentrations (Weber et ai. 1976). The main results are summarized in Figure 2. The concentrations of carbon monoxide, oxides of nitrogen, formaldehyde (HCHO), and acrolein increased wilh the number of cigarettes smoked, Both mean subjective eye irritation and mean eye blink rate increased with increasing smoke concentration. Subjective nose and throat irrita- tion was also ~.vnluated. Nasal symptoms were less pronounced than eye symptoms, and the threat was the lea~t affected. In a second series of studies, acute effects were analyzed in relation tO smoke concentrntion and duration of exposure (Weber et al. 1979) (Mt,ramatsu, Weber et al. 1983). The tobacco smoke concentrations correspendod to 1.3, 2.5, 5, and 10 ppm CO (5CO). Subjects were exposed to these smoke concentrations for I hour, each smoke concentration increasing linearly di~ring the first 5 to 10 minutes and Ihen remaining constant at the desired level for the rest of the hour. B~cause very high correlations (r >0.9) were obtained in the first expe.rlmental series between ~CO and each of the other compom~ds, m~iy ~iCO w~s used to quantify the level of exposure to The results obtained for subjective eye irritation and eye blink rate are shown in Figures 3 and 4. The mean r6ported level of eye irritation as well as the eye blink rate increased with increasing smoke concentration. Both irritation parameters also increased with the duration o'f exposure under conditions of constant smoke concentration. The same, but less pronounced, results were observed • for nose and fl~roat irritation. Annoya,~ce increased rapidly as soon as smoke production began and increased with increasing smoke concentration, but after 10 to 15 minutes the level of annoyance remained approximately constant during the rest of the exposure. Thus, the intensity of exposure was important ih determining the degree of annoyance and the duration of exposure w~,s less important. These experiments demonstrated an objective irritant response in healthy adult subjects at levels of smoke exposure substantially lower than the levels at which an airway response has been demonstrated. Whether this difference represents a difference in threshold for irritation in the eye and airway or a limitation in the ability to measure subtle changes in the airway is uncertain, 233
Page 127: TI07870737
Eye Irdl-tion Stool 4 M~ium 2 Weak 0 I | I I I 0 10 20 win fr .... i i I t I ! ! ! 22 32 42 43 ppm O.H 0.42 0.ll~ l.ll t.45 1.50 ppm I I I I I I 0.03 o.10 0~2 0.47 o.02 o.~ ~ 0 o.o5 o, tl 0,10 0.20 o,.~o .ppm | i 0 I0 i ....... EI~ blnk tall FIGURE 2.--Mean subjective eye Irritation, mean eye blink rate, and concentrations of some pollutanto during contlnuotm smoke protection lit an unventilated clhnatic chamber IqOTl~: ~ lUbJeetl: O rain: nwllul~n~nt tm,f¢~'~ ~ ~m ~IUILCE Weber el II. 119761 Hugod and colleagues (1978) End Weber aad colleagues (Weber, Fischer, Grandjean 1977; Weber, Fischer, Gierer et al. 1977; Weber et al. 1979b) carried out mweral experiments in order to determine which compounds in ]s~'S are responsible for irritation and annoy- once. The result~ of the two studies were somewhat conflicting. Hugod and colleagues exposed 10 subjects in an unventiluted 68 m~ room to high concentrations of sidestream seek, {concentrations corresponding to 20 ppm CO), tv the gas phase of side~tream smoke alone, and to acrolein alone at concentrations three times tlt(me found in sidestream smoke alone. Irritation was asse~med via a 234 Smokl concenlrellon (DeCtn .llxm monoxide) Exp~e du~ali~ FIGURE 3.--Mean subjective eye irritation related to smoke concentrations (ppm delt,a CO~ and duration of exposure NO~r~: 32 tit 43 ~.bj¢~tl; 0 mitt: iniiliur~rnenl bcftlie or ~ the t~ pk~e o,1t. ~i~lort. We~r ~ml ~olleat~es (We~r, trou~ or l~ or lk~ee i~ ~ ~0 Ill= ~lim~li~ ¢~a~ber lo vll~l~ gas phase of smoke. Suhjective irri~tlon and annoyance ~ well ae eye bli.k tale were measure. The resul~ indicated that acrolein and formaldehyde did not pr~uce su~ntial irri~tlon or annoy- ance at the levels used. The gas ph~e ex~ure r~ul~ in high levels of reported annoyance, but w~ !~ imprint ~ a dextral. nant of irrital.ion. The obj~tively measured eye blink rato~ as well subjective eyd irritation, was much lower with the g~ phase alone
Page 128: TI07870738
I ~ 2S.0- IS.O o:o .l 0 10 ~ 30 40 50 ~0 |rain) Expolwe di~sikm FIGURE 4.--Mean effects of environmental tobacco smoke on eye blink rate NOTE: 32 (o 4;! llui,ir~il; 0 rain: ~ul"r.mll ~ smilke plidocUon; 0 l~ II rain: Inciemil~ lllmke ¢~llic'Plltlr ill kin: 5 to 110 rnln: ronlltinl llmak t pii<llil~.llll. than with the ~tai sldestream smoke, suggesting that the par.ticu- late phase is the major determinant or irritation. The ret~earehers postulated that the irritating effects o1" the particuhil.e phase are due to the semivolatile irritant compounds. These comp~mnds, which volatilize rapidly during the process of combustion, recondeuse on the particulates with coolinl,, and may deposit irritanbt in relatively high concentrations on Ihe mucous membranes. Studies ,,f ,%,Isitive ltldivid,ale Ohlldrerl Severnl invesl, igators have used questionnaires hi examine the subjective sylllptoms of children and young people with ~ ekposurc (Cameron 1972; Muramntlm 1977; Muramatsu, Murnmatsu et al. 1!183). The last.group found that 81 percent of 13-year-old children disliked involuntary smoking and 82 percent complained of o,e or more kinds of irritation, the most common being eye irritation. Several epldemiulogical studies have shown that children with parents who smqke have an increased risk for respiratory illness (see Chapter 2~. Allergic Ir[lividuala A few studies have assessed the effect~ of ETS on allergic individuals. SI)eer (1968) reported that allergic individuals report irritatioll n..'e frequently than healthy individuals. Weber and Fischer l1981ll observed that employees suffering from hay fever reported significantly more eye irritation at work than those without hay fever. Effects on the Lung Cigar,:tto smoking is associated with prominent changes'in the numbers, tyl.:s, and functions of respiratory epithelial and inflam- matary cells. These alterations have been implicated in the develop- ment of pulmonary emphysema, chronic bronchitis, and respiratory tract cancers Imd in an increased susceptibility to infections. Chronic exposure to environmental tobacco smoke might cause similar changes, ll~cnuse studies that directly address the effect o1" chronic 'exposure to ~nvironmental tobacco smoke on lung structure and biochemistry have not been conducted, this section reviews those studies in h.mans and animals that provide evidence on smoke exposures tlmt may be relevant to ETS exposure. Effects of Cigarette Smoking on Respiratory Epithelium: Studies in llpmans Exte|isive evidence shows that exposure to cigarette smoke adverse effects on respiratory epithelial cells, and dose=response relationships have been e~tablished from these changes (Auerbach et aL 1961; Auvrbach, Hammond, Garfinkel 1970). Studies involving the systenmtic examination of the bronchial mucosa from large numbers of human smokers have recorded three principal types of epitheli.l chlml;es: epithelial hyperplasia, loss of cilia, and nuvlear atypia. In u. atttopsy sl.udy of 402 adult male subje~t.s (Auerbach et ai. 196D, 98 Percent of the sections of the tracheal and bronchial 237
Page 129: TI07870739
TABLE 3.----Sections with one or more epithelial chnngcs, by packs of cigarettes per day T,~I wilh Humber o~ Mumlver ef Group sul,,lec~a sections Number |'erce.l~e Subjcctz without |~n! ¢zn~r Never smoked ~ulzrly ~ 3.324 ~9 16.8 Smok~ < 112 p~kl~y ~ l,R24 I,~3 92.3 S~oked 112-1 ~cklda~ ~ 3.~fl6 2.~ 97.4 8mok~ I-2 peck/day 113 7,~$2 7,~21 Sub~ with lung caner ~ ~ 2,778 To~II 41~ 19,797 111,7~ Average ~.~ SOU I1(:~: Aue~oa(h el ml. ! I~h. epithelium of the men who had smoked had epithelial changes. 1'he most common abnormality observed was atypical nuclei, and a large proportion of sections had hyperplasin. Denudatio. of tl~e ciliated epithelium was also present in mtmt of those who had smoked. Other studies have observed that goblet cells were frequently increased in the airways of cigarette smokers (Ragland et el. 1976; Jones 1981). The extent and severity of the abnormalities have been closely related to the intensity of. smoking. A similar rclathmship of smoking habits to laryngeal lesions hem been observed (Auerbach, Hbmmond, Garfinkel 1970), although the laryngeal lesions were less frequent and less advanced than those in the bronchi for a given smoking history. The frequency and severity of epithelial lesions observed in smokers contrasts sharply with those in individuals who do not smoke regularly, in the study by Auerbach and colleagues (1961) (Table 3), 98 percent of the sections from the trach~)bronchial tree from smokers contained abnormal epithelial changes; however,. similar changes were observed in only 16.8 percent of the ~eetions from nonsmokers. The most common lesion in nonsmokers was epithelial hyperplasia (9.4 percent); atypical cells were seen in oaly 4,.8 percent of the sections from nonsmokers. If it is assumed that the nonsmoking group included a subgroup of individuals who were chronically exposed to environmental tobacco smoke, an assumption that seems reasonable in light of the largely U.S. veteran populati.n under consJderatio, in the Auerbach group's study, then some infbrmation on the effect of chronic exposure to environmental tobacco smoke on the respirato~T epithe- 238 lium can be inferred. Epithelial hyperplasia or nuclear atypia due to chronic CXl~IS. re to envi ran mental tobacco smoke may occur in some nonsmokers, but these findings are not common in the majority of nonsmok ere. Cigarette smoking also has adverse effects on the bronchial wall beneath the epithelium. Submucosal gland hypertrophy has been observed frequently (Auerba~h et al. 1961; Ragland etal. 1976; Jones 1981). The prevalence is related to the intensity of cigarette smoking. Mucous ghmd hypertrophy is seen in nonsmokers, but is not prevale.t and is usually not extensive (Auerbach etal, 1961), The loss oi" ciliary epithelium, the increased numbers of goblet cells, a.d tlw mucous gland hypertrophy frequently observed in cigarette m,.d~ers would predict mucociliary dysfunction. Indeed, availablo evidence indicates that long-term cigarette smoking im- pairs mucociliary transport (Wanner 1977). Once a cigarette smoker develops chronic bronchitis, mucus transport appears ta be irrevers- ibly damaged. Impairment persists even in patients who have abstained from cigarette smoking for many years (Santa Cruz etal. 1974). Prior to the development of chronic bronchitis, however, partial recovery of function has been observed (Camner eL al. 1973), Studies examining mucocillary dysfunction in humans due solely to chronic envlr.mnental mnoke exposure have not been reported. Effect of Cigarette Smelting on Lung Inflammatory Cells ~tudies in H,man~ One of the earliest pathologic lesions found in the lungs of young smokers is a resplratery bronchiolitis (Anderson and Foraker 1961; McLaughlin aml Tueller 1971; Niewoehner et el. 1974). Clusters of pigment-laden phagocytes, predominantly alveolar macrophages (AM), lodge ia the respiratory bronchiolas of cigarette smokers precisely at the sites of the earliest lung injury. The infiltration by AM precede~ the development of emphysema and focal fibrosis (Cosio et el. 1978). Analyses of cells harvost~d by bronchoal.veolar lavage Complement the morphologic studies. Lavage fluid yields five to seven thncs more AM from the lungs of cigarette smokers than from nonsmokers' lungs (Harris et el. 1970; Reynolds and Newball 1974; Wart el, el. 1976; Hunninghake et el. 1979; Hoidal et el. 1981), The alveolar macrophages from smokers appear to be activated morphologically and metabolically. The AM from smokers have increased size, endoplasmic reticulum, Golgi apparatus, glucose metabolism, hydrolytic and proteolytic enzyme activities (Pratt etal. 1971; Coheu and Cline 1971; Harris et el. 1970; Rodriguez et el. 1977; ttinman eL el. 1980; Martin 1973; Car~trell et el. 1973), and increased rates of oxidative metabolism resulting in increased production of reactive oxygen species (superoxide radical, hydrogen peroxide, and hydroxyl radical) (Hoidal et el. 1981; Hoidal and Niewoehner 1982), 239
Page 130: TI07870740
The strategic location of the alveolar macr,~phages and their altered function have led to the hypothesis that they may coutribute to alteration of the protease-antiprotease bahmce of the lower respiratory tract and thus foster the development of emphysema in smokers. Two plausible mechanisms have been identified by which AM may influence the protease-antiprotease bulance in cigarette smokers. The first is by directly increasing the lung pretense burden. Human AM release enzymes with elastolytic activity in vitro, whereas those from non~mokers do not (Rodrigucz etal. 1977). The activity tony originate from endogenous or exogenous sources. A metalloer~zyme with activity against synthetic amide substrates, which have specificity for elastase, was detected in the bronchoalveo- lar washings of cigarette smokers (Janoff et al. 1983; Niederman et al. 1984) and was also fouud in the cell culture fluid of smokers' AM (Hiuman et al. 1980). Alveolar macrophages can synthesize a metallopretease capable of selubilizing elastin; they also contain a thiolprotease with such uctivity (Chapman and Stone 1984). The metelloprotease, if analogous to that of murlne macrophnge elastase, would be resistant to inactivation by alpba,-protease inhibitor (atl'l) (Bands et al. 1980). These enzymes have not beau demonstrated to cause emphysema. The content of elastolytic activity in AM at a given time is less than thut of equal numbers of polymorphon.uclear leukerytes (PMN); thus, AM may be only a minor source of enzymes capable of lung parenchymal destruction. However, their potential importance must be considered in light of their demonstrated ability to degrade elastin in itho presence of serum pretense inhibitors (Chapman and Stone 1984) and their capability of ongoing synthesis of elastolytic enzyme~. Cell matrix contact amy be critical for their matrix-degrading action, since the AM-derived enzymes are likely to be membrane bound. Human AM also acquire elastolytic activity from exogenous sources. AM can bind and internalize neutrophil elas~ase by virtue of possessing a specific membrane receptor for this and other ~eutro- phil glycopreteins (Campbell et al. 1979; Campbell 1982; MvGowan et al. 1983). Studies to date suggest that the scaveng~l elastase accounts for much of the vlastolytic activity in AM lysotes. Seques- tered PMN elastase may sub~quently be released by AM over nn extended period of time. The second mechanism by which AM may influ¢,nce the proteas~ antlprotease balance in cigarette smokers is by inuctivating v~=PI, a major antiprotease of the lower respiratory tract iu humans (Gadek et al. 1981). Smokers' AM can inactivate u~PI through oxidant mechanisms in vitro (Carp and Janoff 1980). Studies on bronchoal- veolar lavage fluids have identified oxidatively inactivated u~Pl in some human smokers (Gadek etal. 1979; Carp et ul. 1982), but this has not been a consistent finding (Stone et al. 1986; Boudier et aL 24O 1983). Studies that directly a~ess the status of a~PI activity in,the. alveolar space and interstitium of cigarette smokers are needed to clarify this issue. • The phat,q,:ytic capabilities of AM from cigarette smokers attd nonsmokers are similar in most studies (ttarris etal. 1970; Cohen and Cline 1971; Reynohls etal. 1975; Territo and Guide 1979), although a few studies (Martin and Warr 1977; Fisher et al. 1982) have suggetzted a modest decrease in the phagocytic abilities of KM from smokers. The experimental design of these studies has differed considerably, and teci~nica] factors may be responsible for the variable results. In particular, there are differences in cellular culture conditions. In view of the increased number of AM in cigarette sn|okers, it seems unlikely that a primary phagocytic defect of AM wouhi account for the bacterial colonization observed in some cigarette snzokers. The po~ibility that increased numbers of PMN may be present in the lungs of cigarette smokers ha~ been examined primarily because of the attetd,ion given these cells iu the study of the pathogenesis of emphysema. PMN elasta~e is the only purified human enzyme with ready accem~ to the lung parenchyma that has been demonstrated to cause emphysema when administered to animals. The number of PMN is increased in the distal airways and lung parenchyma of cigarette smokers. Bronchoalveolar lavage from some smokers yiplds increased PMN (Reynolds and Newball 1974; Hunninghake etal, 1979). More compelling evidence for.increased PMN in the lungs of smokers comes from the morphologic evaluation and direct cellular analysis of the lung parenchyma. A fourfold increase in PMN infiltrntion has been observed in the lungs of cigarette smokers compared with the lungs of nonsmokers, using morphometrlc techniques (Ludwig et al. 1985). Aualysis of cell suspensions from lung hi6psi~:s has also demonstrated increa~l PMN in the lung parenchyma of smokers (Hunninghake and Crystal 1983). The alveolar septa are the primary site of the PMN accumulation, Increased ]'MN are present in the alveolar walls of smokers both with and without emphysema, which suggests that other factors must also Im involved in the development of tize destructive lesion, Factors that might influence the destruction of lung parenchyma • by PMN elnst~se include the intensity of PMN influx, the amount of elasta~e pet' cell, the quantity and site of elastase released, and factors that enhance or inhibit the elastolytic activity, Investigations of the relnl.lon of PMN elastase levels and the development of emphysenm bare provided discrepant results. Some studies have shown elevut~M levels of PMN elastase in patients with chronic obstructive pulmonary disease (Galdston etal. 1977; Rodriquez etal, 1979; Kranq~ etal. 1980), but others have not (Taylor and Keuppers 1977; Abbeud etal. 1979). Other alterations in the PMN function of 241
Page 131: TI07870741
cigarette smokers include the e~hauccd generation of reactive oxygen species in certain smokers (Ludwig aml Hoid~d 1982). After stimulation, the release of superoxide anion by PMN was 50 percent greater from smokers with peripheral white blood counts (WBC) greater than 9,000 per ms1~ than from nonsmokers with similar WBC or from smokers or nonsmokers with WBC lens than 9,000 per mm~. (Cigarette smokers have increased peripheral WBC counts compared with nonsmokers.) The influence of cigarette smoking on many aspects of the i~nmune system has been examined. Immunoglobulin (lg) levels in the peripheral blood of smokers have been reported to be decreased {Gerrard et al. 1980; Ferson et al. 1979), but similar results have not been observed in all studies (Bell et al. 1981; Merrill ctal. 1985). In contrast to the decrease of lgG in peripheral blood, cigarette smokers appear to have increased lgG levels in bronchoalveolar lavage fluid (Bell et al. 1981), primarily owing to an increase in lgG, (Merrill et al. 1985). Cell-mediated immunity may also be affected by cigarette smoking, but again, the results are somewhat conflicting. Peripheral blood T.lymphecytes and mitegen responsiveness have been reported to be increased (Silverman et al. 1975), unchanged (Daniele et al. 1977), or decreased (Petersen et al. 1983). Natural killer-cell activity in the peripheral blood of cigarette smokers aplmars decreased (Ginns et al. 1985; Ferson et al. 1979). Analysis of peripheral blood lymphocyte populations by monoclonal antibodies has demonstrated increased T-lymphocytes (OKT3-I-), with a decreased proportion of OKT4+ (helper/inducer), aud an increased proportio~i of OKTS+, suppre~or/cytotoxic subsets in smokers with greater than 50 pack- years of smoking (Miller et al. 1982). A;mlysis of bronchoalveolar lavage fluid from cigarette smokers with a mean smoking history of 14 --.+ 9 pack-years demunstrated a decreased proportion of OKT4+ lymphocytes and an increased proportion of OKTS+ lymphocytes (Costabel et al. 1986). In the latter study, the alte|'ations in T- lymphocyte subsets observed in bronchoalveolar htvage were not present in peripheral blood. This finding nnd the increase in IgG in bronchoalveolar lavage fluid, but not in serum, rais~ the possibility of regional effects of cigarette smoking on the immun{., system. The extent to which the alterations of i*~flammatory cell numbers and functions observed in smoker's are also present in indlvldmlls who are chrnnically exposed to environmental tohacco smoke remains unknown~ Studies in humans have not directly addressed this issue. Studies of dose-response relationships are absent, except for those cited that document a relationship of peripheral white blood cell count and lymphocyte "l-cell subsets. If it is a~sumed that a subgroup of nonsmokers is composed of individuals who are chroni- cally exposed to envlromnenl.al tobacco smoke, then some i*~ferences • are possible. A~ has been stated, the most common pathologic feature 242 in the lung.~ o[ young cigarette smokers is an accumulation of pigment-lade|~ ~ac~oplmges in the respiratory bronchioles. In" the study by Nicwoehner ~md colleagues (1974), all 19 male cigarette smokers wh~ died suddenly elsewhere than in a hospital had such lesions, which were present in all sections studied in 16 of the 19 subjects. In ~-m~trast, o~ly 5 of 20 nonsmokers had similar lesions, and they were minimal in all but 2. One of the two individuals was a stoker i~ a fol~ndry aud the other was undergoing desensitization for severe hay [ever. Although the inflammatory cell accumulation cannot be absolutely attributed to these extenuating circumstances, it is clear theft the respiratory bronchiolitls is not common in young, healthy imlividuals who do not smoke regularly. In contrast, autopsy studies have observed I'ocal inflammatory changes quite frequently in older subj~.cts who had not smoked, but the lesions were of much less severity than in age-matched subjects who had smoked (Cosio et al. 1978). Similar changes have not been observed in studies on bronchoalve~,lar lavage fluids. The metabolic activation of the AM from youage~" and older nonsmokers is similar (Hoidal al~d Niewoeh- net 1982). These finding~ suggest that the characteristic inflammato- ry lesions B.,cn in the lungs of smokers are usually absent or are modest in th~se individuals who do not smoke cigarettes and who are not exposed to an alternative inciting agent. Experimented Models The effect ~lf cigarette s~noke inhalation on lung inflammation and inflammatory cell function has been extensively studied in experi- mental animal models; however, studies have not investigated inflammato~y cell alterations in models intended to simulate.ehrdnic envirostmentnl tobacco smoke exposure. Several studies have demon- strated that chronic cigarette smoke exposure produces an accumu- lation of AM within the respiratory bronchioles of many animal species, incltsding dogs (Ilernandez et al. 1966; Frasca et al, 1971, 1983; Park ctal. 1977), rats (Kendrick et al. 1976, Coggins et al, 1980; Huber et al. 1981), hamsters (Bernfeld, Homburger, Soto et al. 1979; Hoidai and Niewoehner 1982), and mice (Matulionis and Traurig 1977), that is strikingly similar to that seen in human smokers. In most studies, the accumulation of AM has been dependent on the duration and intensity of the smoke exposure (Hoidal and Niewoeh- net 19~12; l.lnbcr et al. 198t). Increases in lyso~omal enzyme activities have hecn observed in rats (Etherton et al. 1979) and mice (Matuliolfis a~sd Traurig 1977) following tobacco smoke exposure. Increa~ed elastase secretion by alveolar macrophages from mice chronically ~xposed to cigarette smoke has also been observed (White et al. 1979). O~ygen consumption, superoxide anion release, hydro- gen peroxid~ production, and hexose monophosphate shunt activity were repert~:d to be increased in AM harvested by bronchoalveolar 243
Page 132: TI07870742
lavage from hanmters (Hoidal ,md Niewoehner 1982) and rats (Drath et al. 1978; lluber et al. 1981) chronically exposed to tobacco smoke. Accumulatiou of PMN iu the alveolar septa of cigarette smoke- exposed hamsters, strikingly similar to that observed in human smokers, has also been reported {Ludwig et al. 1985). ILl contrast to the focal nature of the AM accumulation, the accumulation of PMN was diffuse. Studies of PMN function have not been sys~emutically evaluated in smoke-exposed animals. One distinctive fcal.ure in rats has been a lymphocytic periairway infiltration {lnnes et al. 1956; _uber etal. 1981). Similar alterations are not seen in Immans. The lymphocytic infiltration may be due to complicating respiratory infections with mycoplasma or a respiratory virus, which have been common in rats. Effects of Cigarette Smoking on Lung 'Parenchyma: Studies in Humans The most striking alteration of the lung pareachynm associated with cigarette smoking is centrilobular e~nphysema. 'rite relation- ships between smoking history, age, and the degree of emphysema bays been examined. 'rbe effect of smoking on tile development of emphysema is believed to be cumulative (Anderson et al. 1972; Auerbacb etal. 1974~. in a study of 1,824 autopsies from individuals who had died in the hospital, Auerbach and associates, usi;;g a semiquantitative scoring system, detected emphysematous lesions in all individuals who had smoked two or more packs of cigarettes per day, incldding 111 who had been under 60 years of age at the time of death. The extent of emphysema strongly correlated with the number of cigarettes smoked per day. ltowever, some emphyselna- tous changes, usually of a mihl degree, were noted in 94 perceat of the individuals who had regularly smoked less than one-half pack per day. In contrast, no emphysema was detected in 95 percent of the 175 individuals who had not smoked regularly, and only one case of emphysema of moderate severity had occurred in a person who had not smoked. These findings suggest that emphysema is rare in individuals who do not smoke regularly and do not have a genetic predisposition for the disease. Summary of Lung Effects Substantial evidence dt~untents that active cigarette smoking produces adverse effects on respiratory epithelial cells and causes lung inflamnmtion and alveolar septal disruption. Wlmther these effects occur following chronic exposure to environmental tobacco smoke cannot be definitively answered by the frngmenlary data now available. It is possible that clinically significant pulmouary conse- quences of chronic exposure l.o environmental tobacco smoke in adults might occur only whe~ this exposure interacts with other 244 factors in pm'ticularly susceptible individuals. In this regard, future studies directed at selected high-risk populations or animal models incorporvti|q; exposure to enviromnental tobacco smoke along with other exlrosm'es might be the most fruitful areas of investigation into the effects of chronic ezposure to environmental tobacco smoke. Carcinogenhdty of Environmental Tobacco Smoke This seeLion reviews some of the more widely employed meLhods of evaluation of tile carcinogenicity of mainstream smoke that may also be extend~l to the evaluation of ETS. The similarities, differences, and technical difficulties in employing these various bioassays with MS, smoke cundeasate, and ]~TS are discussed. Inhalation gxperiments Because inhalation is the primary mode of exposure for both active and involunl ary smoking, animal inhalational assays would appear to be the ideal approach to developing an animal system for carcinogenicity testing. However, the acute toxicity (mainly due to carbon monoxide and nicotine} have limited the exposures to whole smoke that con be tolerated by laboratory animals. 'INvo types of passive exposure systems offer the primary ap- proach¢~ to iqhalation studies with small laboratory animals, These systems provide either the forced exposure of the whole body to tobacco smoke or exposure of the head only. The amount of smoke that is retained in the lower respiratory tract of the animals is the dosage varialde of interest in assessing these studies. The particulate matter content of whole smoke is probably of greater importance than the vapor phase con~ent (Wynder and Hoffmann 1967; Davis et al. 1975) for studies of carcinogenesis. Labeled particulate phase componenis have been used for determining the deposition of the particulate phase in the respiratory tract in smoke inhalation studies (Mohr and Reznik 1978). However, since such markers are applied to ll~e tobacco column, they may be partially volatilized during smoking. Thus, some of the values reported in deposition studies of inhaled smoke aerosols in mice, rats, and hamsters reflect the deposition of the trapped particulate phase plus the gas phase of cigarette smoke in the respiratory tract. A less ambiguous tracer is decachlorobilthenyl (DCBP). It is added to the tobacco column of cigarettes, mtd after exposure of the animals to the smoke of the treated cigarettes, this tracer can be determined in extracts of various segments of the resp|ratory tract by gas chromatography with an elecl.ron capture detector (GC-ECD). The detection limit of DCBP is < 5 x 10~n g (Lewis etal. 1973; Hoffmann et al. t979). Using these t~hniques, only a small percentage of the smoke particulates of cigarette mainstream smoke can be shown to reach regions in the 24~
Page 133: TI07870743
lower respiratory tract of small laborotory animals. This may explain, at least in part, why tile tifetime inlmlation exposures of small animals to tobacco smoke have led only to limited numbers of lung tumors. In mice, inhalation assays with cigarette smoke have generally led to hyperplasia and metaphmia in the trachea and bronchi of the animals (Wynder and lloflnmnn 1967; Mohr and ]teznik 197B}. In one of the most extensive studies, the Leuchtenbergers (1970) induced pulmonary adenoma and adenocarcinoma in Shell's mice. tlowever, only the gas phase, not the total smoke, iaduced a statistically significant number of lung tumors. In another inhalation bioassay, male and female C57BI mice (100 in each group~ were eXlmsed, nose only, to fresh mainstream smoke diluted with air (1:39) for 12 minutes every other day for the duration of their lives. Four lung tumors were detected in both the treated male mice and the treated female mice. No hmg tumors were found among controls. A similar experimental design was used to examine the possible differences between the smnke of flu-cured Bright tobacco cigarettes a,,d the smoke of alr-cured Bright tobacco cigarettes (Harris et al. 1974). Female Wistar rats (4~8 animals) were exposed, nose only, to a 1:l~ smoke-to-air mixture for 15 seconds of every minute during an 11-minute exposure twice a day, 5 days per week, for the. lifespan of the animals. Three of the rats exposed to cigarette smoke developed pulmouary squnmous neophmms of uncer- tain malignancy and one animal had an invasive squamous-cell carcinoma of the lung. No tumors were found in the 104 sham- . control animals or in the 104 untreated female rl|ts (Davis et al. 1975). Fischer-344 rats (80 animals) were exl~sed, nose oaly, to a 1:10 smoke-to-air mixture for approximately 30 seconds of every minute that a cigarette was being smoked (Dalbey et al. 1980~. In this manner, tile animals were exposed to the smoke oI'~me cigarette per hour, 7 hours per day, 5 days per week, for 128 weeks. The mean pulmonary particulate deposition during the smoke-aerosol expoeure was 0.25 mg per cigarette, or 1.75 mg per rat Imr day. Ten respiratory tumors were observed in seven smoke-exposed rats. One alveologenic carcinoma and two adenomatoid lesions were obeer~ed in 3 of the 93 control rats employed in this study. A similar protocol was used to evaluate the effects of the inhalation of the smoke of cigarette~ with varying tar deliveries. In this study (Wehner et al. 1981), squamous metaplasia of the laryngeal and tracheal epitheli- um was significantly increased in tile smoke-exposed Fischer-344 rats. Syrian golden hamsters (80 males and 80 females) were exposed, nose only, to n 1:7 smoke-to-air mixture for 10 to 30 minutes, 5 days per week, for a period no longer than t~2 weeks. The incidence of larynge~d le,koplakias ranged from 11.3 percent for the animal receiving tile low dose to 30.6 percent for those animals receiving the highest do.qe ,~f cigarette smoke. Such changes were not observed in the controls or in the hamsters exposed to the ga~ phase only (Dontenwiil 1974). Exposing 102 male BIO 87.20 and BIO 1~,16 hamster's, no~e only. twice a day, 5 days a week, for up to 100 weeks, resulted ia almost 90 pcrce~t of the animals having hyperplastlc or neoplastic changes in the larynx {Bernfeld et ai. 1974). Laryngeal cancer was five ti..mes more frequent in the BIO 1~.16 strain. Two animals in this strain also developed nasopharyngeai tumors, Another study using nose-only exposures and similar extents of exposure rel~orted similar changes in the larynx of the smoke- exposed ani~imls (Wehner et al. 1974). Increasing the exposure duration to I.l~e lifespan of the animals resulted in the development ofsquamous i~spilloma of the larynx.. Thirty rabbits in an inhalation chamber were exposed to the smoke generated from 20 cigarettes for up to 5 1/2 years. Thirty-one animals were used as controls. No tumors were found among the treated nainmls that c~mld be related to the exposure.to cigarette smoke {llolh~td et al. 1963). Eighty.six beagle dogs, trained to inhale cigarette smoke through tracheo~tom~ts, were actively exposed to smoke from either filter or nonfilter cig~rettes {Auerbach, Hammond, Kirman et al. 1970). Tumors o1" the lung were reported in 23 of the 62 dogs exposed to smoke from the nonfilter cigarettes. Two of the dogs in this group had small bronchial carcinomas. Noninvasive bronchioaiveolar tumors were reported in 4 of the 12 dogs exposed to the smoke of filter cigarettes and in 2 of the 8 control dogs, The bronchioalveola.r tumors ten&,d to be multiple, with as many as 20 per lung, and were reported in ~ of the 203 lung lobes in the 29 dogs with such tum6r~, Inhalation ~tudies with ~ or ETS have not been reported thus far with any of i.he laboratory animal inhalational assays. This lack of exl~riments has in large part been due to the absence of exposure devices that ~dlow the appropriate delivery of the inhalant without incurrblg the loss of the test animals' due to the toxicity of carbon monoxide and nicotine. Other In Vice Bioassays Amoltg al~:r~mtive rnetheds used to assess the relative carcinoge- nicity of mainstream cigarette smoke, the most widely utilized test ia to collect the cigarette smoke condensate (CSC) and to biopsy this material for carcinogenicity, In the process of preparing C~C, many of the volatile and semivolatile components are lost. Furthermore, there are serious concerns regarding the influence of aging of the CSC, which can affect both the chemical composition and the biological act ivity. Despite these shortcomings, bioassays ~sing C~ 247
Page 134: TI07870744
have providc~l insight into mechaulsms by which tum~r induction tn animal ti~ues is likely to ~ur. The applieaUon of ~0 ~ mou~ 0kin h~ helped ~o idonUfy ~h~ aR~n~ Lha~ are active as ~umor inl~ia~ and ha~ ~hown ~l~a~ within ~ho ~0 ~ubfl'aa~ion~ are eom~n~n~ ~ha~ ~an ae~ ~s ~umor promoter~ or re~pe~Uwly. ~hus, ~hi~ ~pproaCh ~dlow~ Um ~omparison of variou~ condensable, ~p~ially when larR~ grou~ of animals are u~ (>~ p~r ~roup). The application of ~C ~ mouse skin is the most widely e~nploy~ assay for the evaluation of i~ carcinogenic ~ntial. The mou~ skin bioa~ays in rebate carcinogenesis have ~en reviewed (Hoffmann, Wynder et el. I983). A typical ex~riment as~ two h~ thr~ d~ levels of condensa~, generally 25, ~, and 75 mg of ~C, which are administered topically to the shaw backs of mice three to six tim~ weekly for approximately 78 wee~. The ~C is most frequently applied as an acetone nun~nsion (25, 33, or ~ ~rccnt). At the conclusion of such a study, skin tumors, ~me of which arp malignant, generally are obsc~ among the treat~ animals in a do~e.related fashiou. Such studies have shown that the carcin~enic activity of ~C is also a function of ~bacco variety, is influenc~ by replacement materials such as ~bacco. sheet or ~misyntheti~, and nmy be infl~ienc~ by the use of additives. Although such bio~ys haw ~en extensively perform~ for the ~rs from mainstream cigarette smoke, only one study has examin~ tht~ carcin~enic pbtential of the condensat.e of sid~tream cigaret~ era'eke. Cigarette tar from the sidcstream smoke of uonfilter cigaret~ that had eettl~ on the funue[ covering a multiple-unit smoking machine was sus~nd~ in accuse and appli~ to mouse skin for 1~ months (Wynder and HolTmann 1~7). Out of a group of 30 Sw~ ICR mice, 14 animals develol~d ~nign skin tumors and 3 animals had carcinomas. In a parallel a~ay o~ MS from the same cigaret~, a ~0 percent ~e~ne suspension applied to deliver a comparable dose of ~C ~ 1~ Swi~-ICR Ibmale znice !~ ~ ~nign skin tumors in 24 mice and to mali~tant skin tumo~ in 6 mice. This iudica~ that this smoke condensate of ~ had greater tumorigenicity on mouse skin than MS tar (p >0.05). In Vitro Assays Several short-term bioassays have been performed to evaluate the genotoxicity of the MS of cil;arettes. These studies hare been the subject of two reviews (DeMarini 1983; abe et hi. 1984). Although most ot" these studies have evaluated the effects of CSU, come investigations were focused on either the gas phase or the whole smoke. In recent years, there has been increased use o1' short-term assays to attempt to evaluate the relative genotoxic potential of environmental tobacco smoke. 248 • The most rummonly employed assay for muU~genJc activity is done with curious sl.rains of Salmonella typhimurium. Whol~ smoke as well as ~C fro=n four types of tobacco were found to be mutagenic in S. typhimurium TA1538 (Basrur et el. 1978). Sidestream smoke was al~ found t. be mu~genic in a system where the smoke was ~sted directly ou the bacterial plates (O=~g et el. 1984). These studies lend sup~rl, to the extensive u=ays ~rform~ with ~C that establish that ~bacco smoke h~ significant mu~geniv ~ntial. ~veral of the studies with ~ from mainstream smoke have aimed ut comparing the eff~ of various ~baccos, various tes~r strains, and various sys~ms select~ for me~lic activation. Most of the mutal~enic activity w~ a~ia~d with the b~ic ffactiou ~ (~Mm'ini 1983). For the ~ from mainstream smoke, genlc activity was primarily de~cted with the strains TA1538 and TA98, thus indicating the pr~nce of the fram~shift ty~ mu~eus. ICxcept for studies on the eff~ of nitra~trea~d cigarettes, nm~bolic activation was r~uir~ ~ demonstrate mu~- genJc activity ~or m~t o~ the ~ s~udJed. ~veral short-term t~ have ~n ~rformed in eukaryotiv eystemeL A s~lution of the gas phase of mainstream cigaret~ smoke di~lw~ in ~ phoepha~ buffer induc~ r~ipr~ai minnie recombi- nation lit Succharom~'es cereu~iae D~ and ~ti~ mu~n~ in an i~la~ of etruins D~ (l~rd et el. 19~). Whole mainstream cig~ret~ smoke indm'ed mi~tic gene conve~ion, revere mu~tion, and r~ipr~al mi~tic r~ombination in strain D7 orS. ce~uieiae (G~irola 1982). Transformation of mammalian cells was also induced in several cell sys~m~ using the ~ from mainstream cigarette smoke (~nitzkl 1~)68; lnui and Takayama 1971; Rhim and Huebner 1973; Handier et ul. 197~; Takayama et el. 1978; Rlvedal and Sonnet 19~). Tranel~la~n~l ex~ure ~ mainstream ~ was re~r~d to transform Syrian hamster f~l cells (~emu~n et el, 1981). '['ranBfi~rnd~lf activity w~ reared in the acidic and basic fractions ~ well as the neutral fractions of ~. Studies on subfractione ~ Imve shown that the b~ic fraction and ~me of the acidic fructione nr~ the most active in cell transformation (Benedict et aL 197~). The m~utral fracLion of~C was al~ re~r~ to inhibit DNA repair in urn'real human iymph~yt~ (Gaudin et el. 1972), Transfor- mation of mmnmalian cells with ~ or ~ h~ not been re~r~d, Summ~ry of Carcinogenicity At pre~ent, the scientific literature offeg~ some information on the physicochemical nature of the sidestream smoke from tobacco products ~md el" environmental tohacco smoke, Chemical analytical studies haw: already demonstrated that SS and ETS contain ~ wide spectrum a~" csrcinogez~s such as polynuclear aromatic hydrocarbons:
Page 135: TI07870745
volatile and tobacco-specific N-nitrosamines, nnd polo, dam-210. To date, only one study, has demonstrated the carcinogenic activity of the particulate matter of sidestream smoke and a few isolated reports have dealt with the genotoxlcity of SS and li,'TS. Titerefore, bioassay studies with the mainstream smoke and the environmental tobacco smoke of cigarettes are needed. Although the resulting bioassay data will derive from tests of concentrations of environmen- tal smoke that do not realistically occur in the human setting° these results will provide information about the relative carcinogenic potential of sidestream smoke in comparison with the mainstream gmoke of the same cigarettes. In a comprehensive analytical approach, data should be generuted to systematically determine the concentrations of toxic and tumorigenic agents in the ETS samples and to simultaneously measure the uptake of tobacco-speclfic agents by the body fluids of nonsmokers exposed to E']'S. Concluslons I. The main effects of the irritants present in E'I'S eccur in the conjunctlva of the eyes and the mucous nzembranes of the nose, throat, and lower respiratory tract. These irritant effects are a frequent cause of complaints.about poor sir quality due to environmental tobacco smoke. 2. Active cigarette smoking is associated with prominent changes in the number, type, and ~'unctlon of respiratory epithelial and inflammatory cells; the potential for environmental tobacco smoke exposure to produce similar changes should be investi- gated. 3. Animal models have demonstrated the carcim~gencity of ciga- rette smoke, and the limited data that exist suggest that more carcinogenic activity per milligram of cigarette smoke concen- trate may be containc~i in sldestrvam smoke than. in main- stream cigarette smoke. References ABI|OUI), ICI'., I(iJSI-ITUN, J.-M., GRZYIIOWSKI, S. Interrelationships between' ueutrol,hil elasl~*se, serum alphu,-nntitryl~i*~, lung function and chest rudlogra. phy i~ pzzlie~ds with chronic airflow ~lruction. American Reuiew ufR~pi~lo~ Dis~¢ 121~ I 1:31 ~0, July 1979. ANI)EI~ON, A.I~., Jr., FOItAKER, A.G. Peth~en[~ impllcutions of alv~litls pulmo~mry emphy~ma. A#~hi~ ofPa~hol~gy 7~6):~34, Novem~r 1~!. ANDEI~)N, J.A., DUNNILL, M.S., RYDEIL R,C. ~ndence of the Inclden~ entphy~emn m~ smoking, age and ~x. Thor~ 27(6):~7~5l, ~p~m~r 1972. AUERBACII, O., STOUT, A.P., HAMMOND, E.C., GARFINKEL, L. Changes [n bronchial epithelium in relation ~ cigarette smoking and in relation ~ lung cancer. New I.;~zgland Jour~mi ~fM~iclne ~G):~7, August 10, I~1, AUERBACI{, ()., IIAMMOND, E.C., GARFINKEL, ~ llis~l~ie changes in the le~nx iz~ reht~iod to smoking Imbi~. ~ncer ~1):92-1~, Janua~ 1970, AUEIIBACll, O., GARFINKEL, !,.. HAMMOND, E.C. Relation o£smoklng and age to fizzdings in hmg parenchyms: A micr~oplc study. Ch~t ~l):2~, January 1974. AUERBACll, O., IIAMMOND, E.C., KIRMAN, D., GARFINKEL, L, Eff~ of ¢igareite sm~klztg on d~s: • Pulmonary n~p]~. A~hi~ Iteailh 21(6):754-7~, ~m~r 1970. AYER, H.E., Y~:AGER, B.S. Irri~n~ in clgaret~ smoke plum~. Amerimn Journal of ~bllc Health 72:12~!~, [982. BANDA, M.J., ('.LARK, E.J., WERB, Z. Limi~ p~lysls by mac~phage Inactivates human a~-pro~in~ tn~lbt~. Jou~al of Ex~rimental 1~6~ 1663-1670. ~em~r BARAD, C.K S~mkJng on the ~ob: The ~ntrove~y hea~ up. ~c,~tioual H~lth and ~fety 4~ 1 ):21-24, January.February 1979. BASRUR, P.](., M~LURE, S., ZILKEY, B. A ~mpari~n or short term bioa~y r~u]~ with rarcin~enl~ty of ex~rlmen~l cigarette. In: Niebur~, H.E. ~n~ion at~d ~t~tion of~acer. ~OJ. L, Mabel ~kker, New York, 1978, pp, ~I-~MS. B~O, P.K., PIMM, P.K, SHEPHARD, R.J., SILVERMAN, F. The eff~t of cigarette smoke on the, human ~ar film. ~nadian Jou~al of ~hthalmolo~ J~nuery 1971t. BELL, D.Y.. llASEMAN, J.A., SI~, A., McLENNAN, G., H~K, G,E,R. praline o~ the hronchoalv~lnr surfa~ of the lungs of smokerz and nonsmoker, Amerira~ ~e~,iew of Respirato~ ~e 12~!):72-79, July 1981. BENEDI(~F, W.I,'., RUCKER, N., FAUn, J., KOURI, R.E. Malignant transformation of motz~ ceils by cigarette smoke ~nden~. ~ncer ~esea~h March 1975. BSHNFEI,D. P.. IlOMBURGER, F., RU~FIELD, A.B. Strain difference in the' res~nse of i~zbr~ Syrian bamste~ ~ ¢lgeret~ smoke inhalation. Jou~al Natiot~l C~rer i~lilu I¢ 5~4 ~ 1141-11~7, ~r 1974. BERNFEI,D, P., ilt)MBORGER, F., ~, E., PAl, K,J. Cigarette zmoke inhalation studi~ in Inl~red Syrian gulden h~ms~. Journal elias ~ational Ca~cer ~3E67~9, ~ptem~r 1979. BOUDIEIt, C., I'I,'.LL~IER, A., PAULI, G., BI~H, J.G. ~e functional activity of pro~iu~e inhibitor in brouchoalv~lar lavage fluids fro~ healthy human zmoke~ and nmzsnzol~e~. Clinics Chimica Acts 13~3~16, Au~st 31~ 1983, CAMERON, P. ~econd-hand tob~o smoke: ~tldrenz' reactions. Journal of.~h~l Health G~5):2~-~4. May 1972. CAMNER, P.. ]'111].]P~N, R., ARVI~N, T. Withdrawal o~ cigarette smoking: study ozz tra~'h~bronchi~l clearance. A~hi~s of Envi~nmental Health 92, Fehruary 1973.
Page 136: TI07870746
CAMPBELL, E.J, I luman leukocyte elastase, cuthel~in G, and hctol~rrin: Family of ncutrophil granule glycoprotein~ tlmt bind to an alveolar mucroldmge r~eptor. ~t~ing~ of the ~.tionnl A~,demy of ~icnr~ 7~22):694 I~945, Nove,n~r ~982, ~AMPB~Lb, .E.J, WIIITE, RR., SEN~OR, R.M., RODRI{;UEZ. R.J., ~eptor.m~i~d binding and In~rnali~tlon of leuk~yte elns~se by m~crophagc~ h, ~i~ro. Journal of Clini~l Investigation Cd(3):824~33, 1979. CANTRELL, E., B~;SBEE, D., WARR, G., MARTIN, R. Induction o~ aryl hydrogen hydro~yla~ In human ly,aph~'y~ and pulmouary air.Jar nmcrophag~: comparl~n. Li/~ ~i~nce~ i~!2~1~9-1654, ~cem~r 16, 1973. CARP, I1., JANOFF, A. Potential m~tntor ~ inflammation: Pl~ag~y~eriv~ oxidan~ auppreM the elas~-inhlbltow ca~city of alphn,-prolein~e iuhibl~r in vitro. Journal o[Clinicqi lm,esli~ttion ~5~987-~J5, Novem~r 19~. ' CARP, IL, MILLER, F,, HOIDAh, J.R., JANOFF, A, Potential m~batdsm of emphysema: al protein~ lnhihitor ~ver~ from lungs of cigarette smoke~ con~in, oxidiz~ methionine m~d h~ d~re~d elnstase inhibitory ca~clty. ~e~ings o[ the National Acad~'my o[ ~ien~s 7~K6~ 1-~5, ~arch 1~2. CIIAPMAN, H.A,, ~FONE, O.L. ~lnpar~n of live human neutrophtl and ~v~lar macrophoge elastolytic activity In vitro: Relative resistance of nmc~ph~e elas~lytic activity to ~rum and alv~lar p~in~ inhibits. ,laurel o[Ciini~l " ln¢'~ti~tion 74(5):169~17~,Novem~r ~GINS, C,R.E., ~UII.L~. X.LM., ~M, R., MORGAN, K,T. Cigar*,t~ Induc~ patholo~ of the ~t r~pira~ry tr~ A ~mpart~n of the efl~ of tl~ particulate and your phi. To~i~la~ 1~2~lO1, August ~HEN, A.B., CLINE, M,J, The human alv~lar macrophage: I~lntion, cultivati~ in vitro, and studies of morphol~ an~l functional characteristic. Jou~al of Clinical int,tsligation ~7~1~ 1398, July ~71. ~LLEY, J,R,T., ~UGLAS, J.W.B,, REID, D.D.R.pim~W diR~ In yoong adul~ Influence u~ early childh~ lower r~piratow tract illn~, ~ial cl~, air ~flulion, and smoking. Bril~h M~iml Journal ~73~19~19B. July ~, 1~3. ~LLISliAW, N.B., KIRKBRIDg, J., WIOhE, D.T, T~)a~ smoke In the workplace: An ~upatlo.al health h~. ~nadion M~ical A¢~'iation Joumai 131(10):11~-1~4, Novem~r 15, 19~. ~SIO, M,, GIIEZZO, H., linG, J.C,, ~RBIN, R., ~VEI~ND, M., ~MAN, J., MACKLEM, P.T, ~e relutlo~ ~twRn ~m~urnl chnng, in small ai~ays and pulmunaw function ~. ~*w P:~l~d Jou~al of M~icin~ ~1~7-1~1, June 8, [978, C~STABEL, U,, BRO~, K.J., REUTER. (:.,,ROtlLE, K.-H., MA'VI'I'IYS, It. Alter- ntion~ in immunoregulatory T~'nll sul~ in cigarette smoke~: A l,henotypic analysis of bronchoalv~lnr and Id~ lymph~y~, Ch~t ~1~39~4, July 19~. ,~LBEY, W.E,, N~HBIM, P., GRi~EMER. R,, CATON, J.E., GUERIN, M.R. Chronic inhalation Of cigaret~ muoke by ~44 ra~. Journal of the Natimml Cancer Institute 64(2):38~388, February 19~. DANIELE, R.P., DAUBER, J.II., AI,~SE, MD., ROW~N~, D.T., GOitBNBERG, D,J. [,ymph~yte studi~ in ~ym~matic cigaret~ smokers. America Review of Respimlo~ Dhc~e 11~6~7-1(~, ~:em~r 1977. ' DAVIS, B.R., WIIITEIIEAD, J.K., (;ILI~ M.~, LEE, P.N., 9U~J'ERWORTIi, ROE, FJ.C. Res~nse of rat lung ~ InhM~ Valmur ph~e ~mstituen~ (VP) of ~bacco smoke alone or in conjunction with smoke ~ndensa~ or ~rac¢ions of smoke condo~ given by Intratr~cheu[ Instillation. Brit~h Journal ofC'~ncer 31(4~46~ 468, April 1975, ~MARINI, D,M. GenotoxicRy of tobac~ smoke nnd t~a~o .make cnnden~. Mutation R~seo~h ! 14(1):59~9, January 19~. 252 I~)NTENWIhI,, W.P. Tumorigenic effect of chronic cigarette smok~, inhalation on Syrimz goldl,n hamsters. In: Karl)e, 1% Park, J.F. (eds). ~,xperimcnl~ll Lung Cancer: C~in.gene.~is and Bi~eays, International Sym~ium, ~attle, June 1974. New Y.rk, Springer-Verlag, 1974, pp. ~1-~2. DRATII, I).IL, IIARPER, A., GllARIBIAN, J.. KAItNOVSKY, M,L., IIUBER, G,L, The effect .1' I~bac~ snzoke on the me~lism and function o£ rat alv~lar mac~pheg~. J, mrnal o[Cellul~r Physioh~gy 9~ !):1~113, April 1978. E~IIBR'I'ON, J,l,:,, C~NNING, D.M,, PURCI IASB, I.F.ll. Quanti~tive compari~ne of the pubuon~l~ ~xicity of ~ba~ and NSM smoke. Journal of 127{4~:I~US~, April 1979. FERN, M,, I,:I)WAR~, A., LIND, A,, MILAN, G,W., HE~EY, P, ~w n~tur~l killer~ll aclivlty and immun~l~ulln levels a~ia~ with smoking In human sub~. Int,,rm~tional Journal of~ncer ~5):~, M~y 1979. FI~IIEIt, A. P~t~ivrsuchen: Ausma~ und wi~kungen der lu~vvrunrvlnlgung dutch ~krauch unter ex~rimen~llen ~ingungen und In f~Idvv~uchen lP~lw smoking: Eatent and inlluen~ of air imllution due ~ ~ba~ ~moke under ex~rimea~l amditions ~nd In field studi~J. D~r~tlon Eldgen~Iche T~h. niche ll~:hnle, ZErich, Swi~rland, Di~. ~II Nr. 6~, 1979. ~SIIER, G.L., McNEILL, K.I~,, FINCII, G.L., WI~N, F,D., GOLDE, D.W, Function. al evulu~tiou of lung macrophag~ from clgaret~ smoke~ and non~moklr~, Jou~al ~f the Reticul~ndolhdial ~iety 3~4):311-321, ~r 1982. FRA~A, J.M., AUERBACII. O., CARTE~t, II.W., PARKS, V,R. Morphol~ic atlons Induc~ hy short-~rm cigaret~ smoking, Amtd~n Journal of lll(l~ll-~, April 1983. F~A, J.M., AUBRBACH, O., PARKS, V.II., JAMI~N, J.D. Bl~tron mlc~p ~ ~atlum on pulmmmry fibrmis sod emphy~ma in ~moking d~s. Ex~d. mental and Muh¢uinr Pothoh~ 1~ 1):1~1~, ~uguat 1971, GAD~K, J.IC., FEL~, G.A., CRY~A~ R.6. Clgaret~ ~moking indu~ functional antlprntea~ ~flciency iu the lower r~pirato~ trac~ of humans. ~4424ki3ff~1316, ~em~r 1979. GADBK, J.~,, I"EL~, G.A., ZIMMBRMAN, R.L, RBNNARD~ ~.1,, CRY~A~, R,G, Antielasta~ of the human alv~lar ztructu~: Impli~tlun~ for the pro~ antlpro~a~ therapy of emphy~ma. Journal of Cliniml In~sti~tio~ 898, ~lmr 19BI. GAIROLA, C (hmetic eff~ of f~h ciga~t~ amahs in ~ha~m~ Mutati.a Ite~m:ch 10~2~:12~1~, ~p~m~r 1982. GAI,~)N, M., M BLNICK, R,~, GOUDRING, R.M., b~V~KA, V., CURASI, C,A,~ DAVI~, A,U. Interactions of neutrophil elns~, Rrum try~tn inhibi~w activiW~ and ~moking hiu~ry as ri~k fac~ for chronic o~tructive pulmonaw di~ patlenl~ with MM, M~ and Z~ phen~y~ for alphacantitry~in, An~edca~ o[R~ldrntoO" Diseme ! !~5~:837~46, Novem~r 197~. GAUDIN, D., GIIBfIG, R.S., YIBI,DING, K.L, inhibition of DNA repair by gens. lli~:hemic~d and Bio#h~icai R~ea~h ~mnmnimtio~ 4~4~94~949~ 1972. GBRRARI), J.W., iI~INBR, I).C., MINK, J., MBYB~, A., ~SMAN, J.A, 1mmun~ globulin lurch iu smoke~ and nonsmokers. Annah o[Alta~ ~4(~);261-262~ May 19~. CJ. Natural killer cell activity In cigarettte amoke~ and ~ worke~, Ameri~m Re,,Jew o[Respimto~ D~e 131(6~1~, June 19~. HARKS, II,-P., I~bEICH~RT, A. Zum P~blem d~ P~lvtauchens {R~gn~ing problem of p.~ive smoking], h, ternationai~ A~hiu ~r Ar~i~m~in 322, 1972, 253
Page 137: TI07870747
HARRIS, J.O., SWENSON, E.W., JOl iNSON, J.F~ III. llunma alva, let macrophoge~: CompnrLson of phagocytic ability, ~luc~ utilimtio, and ultr~tr.cture in smokers and .onsmoke.. Jou~o[ of Clinical Jn~ti~olion 4~11~-~. Novem~r 1970. HARRIS, R.J.C., N~RONI, G., LUNATE, S., PICK, C.R., CII~'ERMAN, F.C., MAIDMENT, B.J. The incidenre of lung tumors In ~TBL mi~ clgarttte smok~:air mlxtur~ for p~olong~ ~ri~. Internmlonal JnurnaI of ~nc~r 14(D:130-136, July l~, 1974. HERNANDEZ, J.A., ANDE~N, A.E., Jz., HOLMS, W.~, ~)RAKER, A.G. Pulmonary parenchymal duf~ in d~s following p~longel cigarette mnokv ex~sure. Am~d~n R~vitw of Rezpimto~ D~ 9~I);7~, Jumm~ ~. HINMAN, L.M., ~VENS, C.A., MATrHAY, R.A., flEE, J.ILL. EI~ and ly~ozyme activil[~ in human alw~lar mncrophag~ E[f~ o[ c[ga~et~ ~moking. American Review of ~pi~to~ D~e 121(2k26~271, February HOFFMANN, D. IlAL~Y. NJ., BRUNNEMANN. K.D. Cign~ttv sidc~tream ~moke: Formation, annly~[$ and m~el ~tudie~ on the up.ks by non-sm~,ke~. Pr~n~ nt the U.S.~apan M~ting on New Etiol~y d Lung ~n~r, ltonolulu, Ms~]t 21-~, 1983. HOFFMANN, D., RIVENSON, A,, H~H'r. S.S., IIILFRICII, J., K~}BAYASIII, N., WYNDER, E.L. M~el ~tudie~ in ~ba~ carcin~en~i~ with the Syrian golden hamster. ~g~ss in ~dmenlal ~mor R~h 24:37~, 1979. HOFFMANN, D., WYNDER, E,L. ItlVEN~N, A. ~VOIE, E~:, HI.~IIT, S.S, Skin bioa~ay~ in ~ba~ ~rcln~en~l~. ~ in ~mentai 26:4~7, 1983. HOIDAL, J.R.. ~X, R.B., ~MARBE, P.A., FERRI, R. REPINE, J.E. Alte~ oxidative metallic r~n~ in vitro of alveolar mnc~plmg~ f~m ~ympt~tatlv cigarette smokem, American Be~,iew of R~pt~lo~ D~e !~1):~, January 1981. HOIDAL, J.R. NIEWOEHNER, D.~ Lung phng~yte r~mitn.mt and m~lic. olterntion~ induc~ by cigaret~ ~moke i~ hum.n~ and in ~eview of~spim#o~ ~e1~3~:~48-5~2, ~p~m~r 1982. HOLLAND, R.H,. KOZ~WSKL E.J., ~KER, L "~tv eff~t of Hg.ret~ snmkv on th~ re~pira~ry ~ys~m of tho rmbbit. Ca.cer 1~}:~ 12~16. Muy HUBER, G.L., DAVI~. P., ZWILLIN(L O.fi., I~IIAY, V.K, HIN~, W,C. NICIIOLAS, H,A., MAHAJAN, V.K.. ltAYASI II, M., FIi~, M.W. A nod physiologic bioa~ay ~or qumttilying al~r~timm in th~ lung f~ilowing ex~Hmenta~ chronic inhalation of ~bu~ ~mokv. Cliniod it¢spirnlo~ Ph~iolo~ 17~2}:269-327. August 1981. IIUGOD, C,, IIAWKINS. LH., A~'RUP, P. E~l~mure of ~ivv mm~kem smoke c~)nsfltuen~, lnlernalionnl A~hit~s of ~u~tbmal and Envi~umcntal llcalth 42:21-~J, 1978. H~NNINGHAKE, G.W., CRY~AI,, R.G. Ctg~ret~ mno~i.g and hmg d~t~uction: Accumulation uf neutrophil~ in the lung~ of c~gnrctte mnokem. Americas ~evlew Re#pirato~ D~e~e [~5~838, No,emir 1983. ltUNNINGliAKE, G.W. GADEK. J.E., KAWANAMI, O., FERRANS, V.J. CRY~ TAL, R.G. lnflnmm~ and immune pr~ i. the humnn lung in he.IHt and disease: Ewim~tion by broncho.Ickier lavnge. Ameri~m Journal 97(D:!49-2~, (~r 1~9. I~N~, J.R.M., McADAMS, A.J., YEVICH, F. Full,unary disuse ht rn~: A m~ey with commen~ on chronic routine pneumonia. American Jour~al 32{D:141-159, Janus.-February 1956. INUI, N., TAKAYAMA, S, A~.elernflon of proH[vrM.ion and tumor pr~uction ~strain cell~ hy treatment with cigar,,tee ~r. Gain 6~4k315~, August i~1. 254 IZARI}. C., VAI,ADAUD.BARItlEU. D., FAYEULLE, J.-P,, TESTA, A, Influence des param,,I.rc, d,. fn,nage sur I'activite genotoxique de }u phase gazeu~e de fumt.e de cigaretle, lm,~.Ir,,e sur le lymph~yte humain et In 'levure lEff~t bf machine. smoking Imrm.eters on the genotoxlc activity of gas pha~ cigarette smoke ~ward human lympl.~yt~ and yeantJ. Mutation ~ta~h 77(4);341-344, April JANOFF, A., tgA,IU. L., DEAIHNG, R. I~vels of el~ activity in brnnchonlv~lnr lavage Iluids .f healthy sin.kern and nonsmokers, Ameri~ Review 1)~e~qe 1~(51:54~44, May 19~. JOIIAN~ON, C.R. Tobacco smoke in ~m air: An ex~rimen~l Invmtlgatlon ~our imrcvplioa and irritating ef[~. lJuilding &mi~ En~inter 43:25~26~ Morel, 1976. JOilAN~ON, C.R,, RONGE, !!, Klimettnverkan pa lukt ~h irrl~tlon~ffekt ~akm'ok pn,liminart m~delande [Climatic Influence on smell and lrri~tion ~ff~ front t**l*acco emoke], No~k Hygien~k ~kdfl 47:3~39, 1~. JON~, N,L. 'rl.. pathophysiol~icnl ~n~uen~ of smoking on the renplra~ry system. Canadian Journal of ~blic H~lth 7~6):~, Novem~r.~em~r 1981. KENDRICK, J., N~IIEIM, P,, GUERIN, M., CAqDN, J. DALBEY, W,, GRI~EMER, R., RUBIN, I., MAD~X, W. T~a~o smoke inhalation studies in ra~. ~xlcologv and ~pplicd Pharmom~ogy 37(3):657~9, ~ptem~r 1976. KERK~, W.F., IIOMPIIREY C.M. Tem~rnture and hnmidlty erf~ on ~rceptlon. A,~HI~AE ~n.~actio~ 62:531~62, KRAM~, J.A., I IAKKER, W., DIJKMAN, J.H. A maChO-pair study or the leuk~yte elnet~.-Ilke m:tivlty in normsl ~n~ and In emphy~matoue patlen~ with and without alpha,-nntltry~ln deficiency. Aa,edcan Reuiew of Re~piralo~ D~e~e 121(2~253-261, February 19~. ~SNI~I(I, L The eff~t of a hydr~nr~n~nrich~ fructlon of clgaret~ condensate o** human fe~,l ludg grown in view. ~n~r ~ea~h March I~. LEUCllTENBEII~]ER. C., LEUCIITENBER(]ER, R. Eff~ of chronic inhalation of whole fresh ciRaret~ smoke and of I~ g~ ph~ on pulmonary tum0rlgenesl= In Snail's mice, In: Net~heim, P., Hanna, M,G., Jr., ~dtherage, J,W. Jr. Mo~holoKy ¢~/" Ex~dmenlal il~pimlo~ ~in~nea~, Oak Ridge, ~.S. Ene~ ~mmi~ion, Divisivn of T~hnical Information, ~em~r ~970, pp, 329- 346. LEWIS, C.I., Mcl =EADY, J.C., '~NG, H.K, ~IIUL~, F.J., SPEARS, A,W. CIg~ret~ ~moke trnce=e: (=~ chronm~raphic analysia of d~achlorobiphe~l, American ~¢t~iew nf Resl*ir.to~ D~e.~ 1~2):~7-370, Augugt 1973. LUDWIG, P.W., il()iDAL, J.lt. Alterations in leuk~y~ oxidative nmta~lism ciga~tte mauh era. Amedcm= Review ofR~pimlo~ D~e=e 12~6):977-9~, ~cem. ~r 19H2. LUDWIG, I~.W., ~IIWAR~, B.A., ltOIDA~ J.R., NIEWOEHNER, D.E. Cigarette smoking cuum*s accumulation of ~lymorphonuclear leuk~ytes In alv~lar turn. Americcm Review ofJ¢t~pimlo~e 131(6);8~0, June 19~. MARTIN, R,R. Al~*r~ run.holly and incre~ acid hydrol~ content of pulm~ na~ .macrol,hag~ from clgaret~ vmokv~, Americon ~¢vlew of D&e=c 11~(4 ~:Sgl~t, April 1973. MARTIN, R.R., WAItR, G.A. Cigaret~ smoking and human pulmonn~ mncrophnges. H~pitul l~m'tice 1~9):97-1~, ~ptem~r 1977. MATULI()NIS, I).!1., TRAURIG. H.H. In situ r~nse or lun~ mncrophag~ and hydrola~ acliviti~ ~ cigaret~ smoke. ~mto~ Investigation 37(3):31~326, ~p~m~r l~r17. M~OWAN, S,E., SIDNS, P,J., CADRE, J.D,, SNIDER, G.L,, FRANZBLAU, C, The fn~ of nentr.phil el~e incor~ra~ by human alveolar mncr0phages, can Be.Jew o/" llespimto~ Disease 127(4~44~55, April 1983,
Page 138: TI07870748
McLAUGIILIN, R.F., TUELLEII, E.I':. Anotom|c ond blstol~ic thin,gee in eorly emphysema. Chest 59~6):592-599, June 1971. MERRILL, W.W., NAEOE~ 0,1'., Oi~[IOWSKI, J,J.. REYNOLD~, II.V. hmonn~ globulin G ~u~l~ pro~in~ In ~rum end Iawge fluid of ,to, ma[ ~ub~: Quantitation and compari~n with immun~lobulin. A and S. An,erican lleuieiu of ~espimto~ D~e~e 131(4):~84~7, April 19~. MILLER, L,G,, GOLDSTEIN, 0., MURPHY, M., GINNS, L.C. Reve~ibh, alter~stiona In [mmunoregula~ry T~oIIs tn emoking: Analysis by mon~iouat anti~i~ and flow cy~metry. Che~ 8~5):~2~5~J, Novem~r 1982. MOIIR, U., H~NIK, G. Tobe~u carcln~ene~ia. In: ilurrle. C.C.h.d.L Patho~en~i~ and Therapy of Lung Cancer. Mar~l ~kker, Inc,, New York, 1978. pp. ~. MURAMA~, T. A study on smoking e~l~rlen~ end crooking Imhi~ lte~rt 3. Paren~l ~moklng hebl~ and ~.hand ~ emoke of high ~'h~l student. Go#~o Hogan K~n~yu ~Ja~m~ Jonrnnl of~h~l llealth) 1~2~:~95, 1977. MURAMA~U, S., MURAMA~U, T. W~E~ A. A ~urvey on nttitud~ ~war~ p~tve ~moklng among ~h~l children end ~tuden~ in Swi~rlm~d. ~z~l- und MURAMA~U, T,, WEBER, A., MURAMAI~U, S., AKERMANN, F. An exlmrlmen- ~1 study on irri~tion ~nd annuye~ due ~ p~lve emoklng. A~hip~ of ~cu~tional ~ Envi~nmen~ai li~lth filH~317, April 1~. NIEDERMAN, M~., FRi'~, L.L., MERItlI,~ W.W. FICK, It.B. MA'I~ilAY. R.A., REYNOL~, H.Y., GEE, J,B.~ ~ation of a ~r~ ela~iytic in human lung lavege fluid end i~ relatten~hlp ~ ~lphat-unttprute~. Amelia ~evitw nf ~tspimto~ ~a~e I~6~94~947, June NII~WOEIINER, D.E., KLEIHERMAN, J., RICE, D.B. P~thol~ic changes In the ~rlpheral ai~ays of young clgsrvt~ smoke~. ~¢w Ensland Journal of M~icine 291{I~}:75~758, {~to~r I0. 1974. OBE, G., IIELLER, W.D., V~T, llJ. Mu~genlc activity of cigarette ~moke. In:'~, G. {~J. Mutations in Man. ~rfln, Springer-Verl~g, 19~, pp. ~- 246. ONO, T.M., ~EWART, J., WIIONG, W.Z. A ~imple In situ mu~geniclty ~t for de~tlon of mu~genlc air ~llu~n~. Mutation ~h 13~4~:177-18l, Al~rll 19B4. PARK, S.S., KIKKAWA, ~., GOLDRING, I.P,, DALY, M.~., ZELEI'~KY, M., SHIM, C., SPIERER, M., MORITA, T. An mdmal ~el of cigaret~ smoking in dogs: ~rrelutive evaluation o[ eff~ on puimona~ ~unvtion, de£en~ and morpho[~. American Review of R~pim~ Dis~e I I~6~971-979, June 1977. P~E~EN, B.II., ~E[MEL, LF., CAL~GIIAN, J.T. Suppr~s[o,, of mi~en- indu~ [ympb~y~ transformathm in cigaret~ smuke~. Clinical Immuno]~ and Immunolmtl~olo~ 27{I}:I~140, April 19~. P}iA~, S.A., SMITH, ~.ll., LADMAN, A.J., FINLEY, T.N. The ultr~tructu~ alveolar macropimg~ from human ciguret~ smoke~ and nonsmoker. REGLAND, B., CAJANDER, S., WIMAN, L.O., FALKNER, S. ~nnlng el~t~n mtcr~opy of the bronchial muc,~ in ~me lung di~ usiog b~nch~py ~imens: A pilot study including cau~ of b~nddnl ~rcinuma, ~*'~i~ silicosis, end tu~ulmla. ~.ndinauian Jm~rnal o[ R~pin~to~ l)i~ 57N~171- 182, 1976. RASMU~EN, ILE., BOVD, CII., DANSIE, D.R., KOURI, R.E, III,:NRY, C~. DNA repltcntlon nud un~h~ul~ DNA synth~ in lungs of mi~ exl~ ~ eigare~ smoke. Caner ~,.s~h 41:~25~, July 1981. REMMER, tl. P~ivrnuchen nm n~i~ldn~: G~undheilneh~dlich ~vr nieht7 IPa~ive smoking at the workplo~:e: Inju~ to he~dth or notT[ Zc~tmlblatt Ar~it~medizin 3rd I I):33~35 I, Novem~r 1985. 7.56 REYNOLDS, II.Y., NEWBALL, ]LH. Analysis of proteins and re~plratory mils obtaim~d From Izumon lurlgs by b~nchiul Invage. Journal of ~mlo~ Cliniod M~lirine 84(4):55~}~73, ~r [974. REYNOLIIS, I I.Y., KAZMIEROWSKI, J.A., NEWBALL, It.~, S~lflclty of o~onio nntil~liea ~ ,mhan~ pllag~y~ia of~ez~domon~ aerugin~ by human mncrol)hog~..&~urnal of Clinical ln~tigation ~2]:~7~, August 1975, RII1M, J.S., Illll~llNER, R.J. In vitro transformation ~y of m~or [ract[on~ cigarette snmke ~nden~tl~ (~} In m~mmalinn cell lin~. ~e~ings of ~iety for ~t i~rimentai llioio~ and Medicine [4~3):1~1~7, March 1973, RIVEDAI,, E., SANNER, T. Po~ntiating eff~t of clgaret~ smoke extract on morphoh~ic, I transformation of hams~r embffo ~ll~ by ~n~n]pyrene. [~ffer 1~3~ I II~ 198, ~p~m~r 1~. RODRIGUEZ. ,Lit., SEA~, J.~., RADIN, A., LIN, J.8., MAND~ 1., TURINO, Neutrophil ly~m~l ela~ activity in normal subj~ and In ~tlen~ with carnie ~t,'uctive pulmonary d~. Ame~n Review of R~pimto~ ! 1~3):4~J~ I'l, March 1~9. RODRIGI IEZ, ILL, WHITE, R.R., SENIOR, IL~., LEVINE, E.A. EI~ rele~ from human alveolar maeroph~: ~m~ri~n ~tw~n smoke~ and nons~ke~, ~ience 19~43141:31~314, ~r 21,197Z SANTA CRUZ. R., LANDA, J., HI~H, J., 8ACKNER, M.A, Tracheal mucus vel~liy in normal man and ~tien~ with ~tructive lung d~: E[f~ ~utaliue. Ameri~n ~euiew o[ ~piml~ ~e 1~4~4~63, April 6H~PHARD, ILJ., ~BARRE, R. Attitud~ of t~ public ~ws~ cigaret~ smoke imbllc place, C~,nadlan Journct o[~blic ~tfh 6~4):~310, July-Augua[ 1978, SILVBBMAN, N.A., ~VIN, C, ALEXANU~ J.C, Jr., CllR~J£N, RB, In lymphocyte r~,activity and ¢<ell levels in chronic cigaret~ smokers. Cllnt~l ~ment.l Imnmnolo~ 2~2~2, Novem~r SPgB~. F. Tob.~,~ en~ the nonsmoker: A Itu~y or euH~tiva ~ymp~me, A~i~ Env[nmnwnl(d llmlth I~3~44~4B, March I~. ~ERLING, T.D., ~ERLING, E.M. ~rl~n of Nonsmoker' and ~mok~ ~ptlon of environmvn~l ~nditlons ~nd health and ~mfo~ symp~m~ In enrichments with and without ~moking. In: Grandjean, E. (~}. Er~nomi~ and H~ith i~ M~M~ra Offi~. Phlladelphl~,T~ylor and F~a~, ~HK P.J., CALORY, J.D., M~OWAN, S,E., BERNaRd, J. SNIDE~, F~NZBLA~ I, C. Fun~tloaal a~-pro~ Inhibl~r In the lower respiratory tract of vlg~rvtW sm.ke~ ~ not d~r~, ~ien~ ~l{4616}:llBT-llBg, ~p~m~r 1~, TAKAYAMA, S., KA~II, Y,, HIRAKAWA, T. TANAKA, M, In vitro morphol~l~al transfnrmntl.n of cryopr~ hams~r embryo ~1~ with ~a~ ~r. Gan~ 6~1~8~, ~bru~ry 1978. TAY~R, J,C., KE~PPE~, F. El~t~opho~eti~ m~ility of Icuk~ ¢1~ normal ~ub~*'~ ~nd ~tlva~ with chronic ~tru~tiv~ puJmon~ dl~, can Rrview eJ'Respimlo~ ~e~e 11~3~531-~, ~p~m~r 1977, TERR[~, M,C., GOLDE, D.W. The function d human slv~lnr macroph~g~. Journal of~he lleticul,~ndothdial ~ie(v ~lkl I I-I~, January 1979. TRIEBIG, G., Z~BER, M.A. Ind~r air ~llution by zmoke constituent: A ~eventi,~ M,,dicine 1~6}:57~1, Novem~r 19~. U.S. DEPAlfFMENT OF HEALTH AND HUMAN SERVIC~. :The Health quencez of Smoking. CArnie Obstructi~ Lung D~e: A Re, re of the Genend. U.S. ~pa~ment of Ilealth and llum~n ~ic~, Public liealth Office on Sm.klng and Health, DHliS Pub. No. {PIlSner, VALENTIN, It, Arl~i~medltin. Vol. 2, G~rge Thteme Verlgg, 1985, pp.298, WANNER, A. Clinical ~ of mu~ilia~ trans~rt, American Review of R~pir~ffo~ i,~se~e 11~1):7~125, ~uly 19~7. 257
Page 139: TI07870749
WARR, G.A., MARTIN, R.R., IIOLLEMAN, C.L., CRISWELL, B.S. Cla~ific,,tlon of "bronchial lymphocytes from nonmnakers and smokers. American Review of l~espi~to~' D~ 1 l~l~l~, Jnnun~ 1976. W~B~R, A., FISCHER, T. P~iye smoking at work. ]~te~nalional ~u~tional and En~i~nmenlat Health 47:~-221, 19~. WEBER, A., FISCHER T, ~hndstollkonmntrationen hn bh~feld van r~uchern. JConcentratlon of ~llu~n~ In the blowing field of smokersJ. ]nternationat ~hiv~s of ~cn~tiona/ and Environmental Health fi~1):47~, [9~. W~D~R, A., FISCHER, T., GIERER, R., GRAN~EAN. E. ~x~rimen~lle ~zwlr- kungen van akrolein euf den men~he~ lEx~rimentnlly lnduc~ Irri~ting eff~ of acroleln in man]. International A~hi~ of ~Ul~tional and Enui~amental Ikollh 4~2):I17-130,1977. WEBER, A., FISHER, T., GRAN~EAN, g. Objek~ve und subjektivv physlol~i~he wlrkun~n dee pnssivrauchens [Obj~tlve end eub]ectlve ph~lel~i~l p~Ive smoking]. International A~hiue* of ~CUlmllonal end ll¢alth 37(4):277-288, ~ptember 6, 1976. WEBER, A., FISHER, T., ORAND,IEAH, E. Relzwlrkungen d~ [ormeldehyds {HCHOI auf den men,hen ~Irri~ti~g eff~ of formaldehyde In mnn al A~hi~s of ~cu~tional and ~m,i~nmental ll~Ith 3~4~-218, I ~77a. WEBER, A., FISCHER, T., ORAN~EAH, E. Pmlve amoklng in ex~rimea~l and field ~ndRions. E~wimnmental R~h ~:~216, 1979a. WEBER, A., FISCHER, ~., GRAH~RAN, E. P~ive smoking: Irri~tlng eff~ or the ~i smoke and ~he g~ pha~. Inte~agional A~hi~ of O~u~tional and . Enui~nmcntal~Ith 4~3~I~193,1979b. WEHNER, A.P., BUSH, KH., O~H, R.J., CRAIG, D.K. Eff~t of chronle ex~ure ~ cigarette smoke on tumor Inddence In the Syrian golden hams~r, In: Ex~rlmen~l Lung Cancer, Car~la~en~i~ and Bio~y~, Katie, E. mid Park, J.F. (~a.), Hew York, Sprlnger.Yedag, 1974, pp. WEH~ER, A.P., DAGL~, O.E., MILLIMAH, ~.M., PHEL~, D.W., CARR, D.B., DECKER, J.R., FILIPY, R.E. Inhalation blowy of ¢Ignret~ m~ke In ra~. Toxicology and Applied Pha~l~,~ 6[O~-17, ~r WHITE, R., WII ITE, J., JANOFF, A. Eff~ or e~a~tte ~moke on el~ ~retlon by routine mac~phag,. Jou~el of ~mt~ and Cliai~l Medicine 94(3~48~ 4~, ~l)[em~r ]979. WOItLD H~ALTH OROANIZATIUH. Smo£in~ in Ai~m~: Re~rt of a WIIO/IATA/ICAO ~ullatlon. Oenev~ World Health Organi~tion, WI]O/gMO/~.3,1984, 44 pp. WYNDBR, E.L., HOFFMANN, D. To~ and To~c~ Smoke: Studi~ In Ea~rlmen- tel Carc]n~en~s, Academle Prin. New York, New York. ]~7, 7~ pp. 258 CItAPTER 6 POLICIES RESTRICTING SMOKING IN PUBLIC PLACES AND THE WORKPLACE
Page 140: TI07870750
CONTENTS Introdudtion Currant Status of Restrictions on Smoking in Pubho Places Legislative Approaches Fc~iernl Legislation StaLe Legislation ~l~al Legislation Regulatory Approaches Smoking Reguhfion in Specific Public Places Public Transportation Retail Stores Rest,mrants lloh;Is and Motels Sch~mls llenlth Care Faciligies Current Status o£ Smoking Regulation~ in the Workplace Smoking Policies Prevalence of Smoking Policies Reasons I'or Adopting Smoking Policiea Barriers Lo Adopting. Smoking Policies Types of Smoking Policies The "Individual 8elation" Approach Environmental Alterations Restrictions on Employee Smoking Benuing Smoking at the Workplace l'relhrential lliring of Nonsmokers lmpleme,ttation of Smoking Policies lmpa~t of P~dicies ResLricting Smoking in Public Places and in the Workplace Poh,.ntial hnpacts of Smoking Policies Policy Implementation and Approval Direct i~ffects: Air quality and Smoking Behav- Indh'ect gffecla: Knowledge,, Attitudes, Serial Norms, and Smoking Behavior Methodologic Consideratiofis in Policy Evaluation
Page 141: TI07870751
Study Design Assessing the Effects of Smoking Policies Review of Current Evidence on Impact Workplace Smoking Policies Policy Implementation Air Quality Policy Approval Smoking Behavior Attitudes About Smoking Management Issues Legislation Restricting Smoking in Public Pla~ Policy Implement~ttion and Enforcement Policy Approval Attitudes and Social No, ms Smoking Behavior Recommendations for Future Research Conclusions Appendix: The Comprehensiveness Index of State Laws References 262 introduction Since the 1!170s, the accumulating evidence on the health risks of involuntary .rooking has been accompanied by a wave of social action reguh~l,ing tobacco smoking in public places. Initiatives in the public and tile private sectors have aimed at protecting individuals, from ex|msu! e to sldestream, smoke by regulating the circumstances where smokl,g is permitted. Smoking in public places has been regulated primarily by government action at the local level and at the Federal h:vel. Legislation has been the most common vehicle at the loc~l and State level; agency regulations have predominated in the Federal Governmeut. There has been relatively little judicial action to restrict smoking in public places; most cases have focused on nonsmokh~g employees' right to a smoke-free workplace (Feldman et al. 1978; Eriksen, in press; Walsh and Gordon 1986). Private sector initiatives Imve gained momentum in the 1980s. Businesses in a wide variety of i,d~mtries have adopted smoking policies to protect employee I,,~dth. Other private initiatives include nonsmoking sections in restaurants, nonsmoking rooms in hotels and motels, and • smoking restrictions in hospitals. Though this trend was fueled by growing evidence about the health off'eels of invvluntary smoking, it also reflects the changing public attitmiea about smoking since 1964, when public attention was focused vu the health hazards of cigarette smoking by the Report of the Advisory Committee to the Surgeon General (US P.HS 1964). The acceptability and desirability of tobacco smoking in public places Ires fallen dranmtically over time, as reflected in public opinion surw:ys. A majority now support the right of nonsmokers to breathe smoke-free air and favor policies that ensure that .right (ALA 1985b; I hmauer et al. 1986; BNA 1986; US DHEW 1969). This chapter addresses the scope and impact of these diverse policies. It begins with a review of the current status of policies restricting smoking. Issues specific to smoking regulation in trans- portatkm vehicles and motels, restaurants, stores, schools, health bare facilities, and the workplace are addressed. The effects of smoking policies on air quality, attitudes, and smoking behavior are considered. Current Status of Restrictions on Smoking In Public Places Smoking r~gulations in public places represent a mix of public and private actio,m. A public place may be defined as any enclosed area in which the public is permitted or to which the public is invited, Smoking restrictions are generally limited to indoor enclosed spaces (Hanauer el, al. 1986). This broad definition of a public place encompasseH a diverse group of facilities that differ in the degree to which smokb~g is restricted, the ease of introducing new regulations, 263
Page 142: TI07870752
and the methods by which new smoking restrictions have been proposed and adopted. Smoking il~ Federal, State, and local government facilities has been addressed by legislative ~lnd regulatory action. These facilities include government offices, public ~choois and libraries, and publicly owned transportatio.n and health care, cultural, and sports facilities. In public facilities under priv.ate ownership, smoking restrictions are s mixture of government-sponsored regulation and priw~te initiative. These facilities include retail stores, restaurants and bars, hotels and motels, and privately owned transportation and health care, cultur- al, and sports facilities. The extent and acceptability of smoking restrictions in public places is influenced by (1) whether ownership is public or private; (2) the' historical acceptance of smoking in the facility; (3) the degree to which nonsmokers are exposed to involuntary smoking, determined by the facility's size, degree of ventilation, and ease of separating smokers and nonsmokers; and (4~ the degree of inconvenience that smoking restrictions po~e to smokers. Smoking restrictions are still most widespread and least controversial in I'acilities where smoking has traditionally been prohibiled by fire codes, such as theaters or libraries, or where smoking is negativ.ely associated with the activity taking place, such vs gyms or health care facilities (Feldmm| et al. 1978~. Snmll crowded areas with pe~r ventilation, such as elevators and public transit vehicles, are also frequeutly regulated. On tile other hand, the strong association of smoking with eating and drinking contributes to the controversial nature of smoking restric- tions in restaurants and bars. Legislative Approaches Federal Legislation Congress has enacted no Federal legislation restrictiltg smoking in public places, although hills have been introduced in Congress several times since 1973 (Feldman et al. 1978). State Legislatio~= Most leglslution restricting smoking has been enacte,l nt the State level. Although legislation regulating smoking for heslth reasons is largely a phenomenon of the pest decade, cigarette smoking has been tile subject of restrictive legislation for nearly a century. Early legislation had two different rationales. The first, a relatively noncontroversial rationale, wa~ the protectio'n of the pt~blic from fire or other safety hazards, largely in the workplace (W~rner t981bl. The second, more confreres'sial motivation for ea~ly legislative action was a moral crusade a~;ainst cigaretteS simila;' i;t tone and coincide;it with the moral crusade ngalnst alcohol that emerged at the turn of I I~e century (Dillow 1981; Sobel 1978). Its goal was a total ban on ciga~ ettes, which were blamed for social evils and physical ills, ba~ed Im'gely on u~lfounded claims. By 1887, three States (North Dakota, low~, and Tennessee~ had completely banned the ~ale and use of cigarettes. At the peak of the movement, cigarettes were banned in a dozen States (Nuehring and Markle 1974; Sobel 1978). Most were itt the Midwest ~here cigarette consumption was low and anticigarettc l~ling high. The movement lost momentum when enforcing the'regulations pro.red controversial. As part of the strong reactlou to ~lcohol prohibition, all State laws banning smoking were repealed by 1927. Durillg th~ 1960s, as the health risks of smoking became widely recognized, public policy on smoking began to focus on encouraging the smoker to quit. However, the few existing State laws regulating smoking in public places were old and limited in scope. Even newly enacted law,--in Delaware (1960) and in Michigan (1967, 1968~-- restricted smoking in limited areas: public buses and trolleys, elevators, a~ld retail food establishments (US DHHS 1985b). Protec- ting the health or comfort of nonsmokers was not cited as a rationale of these laws. As of 1970, statutes restricting smoking were in force in 14 States ~.LIS DHHS 1985b). In the early 1970s, a new wave of smoking legislation emerged. |t covered smelting in a larger number of places and extended for the first time to privately owned facilities. The language became more restrictive, moving from permitting a nonsmoking section to requir- ing one and making nonsmoking the principal or assumed condition, The language also changed to make it clear that the specific intent was the safety and comfort of nonsmokers. The pace of new legislation increased in the mid-1970~. Between 1970 and 1974, 9 laws were enacted in 8 States; between 197~ and 1979, 29 new laws were passed and 15 additional States adopted smoking regulations. Minnesota passed its landmark Clean Indoor Air Act in 1975 "to protect the public health, coml'ort, and environment by prohibiting smoking in public places and at public meetings except in designated smoking areas" (Minnesota Statutes Annual 1985). It covered restaurants, private worksites, and a large number of pt~blic places, and soon became the model for other State legislation. Within the next 5 years, Utah, Montana, and Nebraska enacted similar comprehensive legislation (IJS DHHS 1985b). The language of statutes passed by 11 States during the 1970s made it clear that the specific purpose was to protect nonsmokers from involuntary smoking (US DHHS 198~b). Model legislation and advice ~tbeut successful enactment of State laws can be found in several ~ourccs (Hanauer et al, 1986; Feidman et al, 1978; Walsh and Gordon 1986). 265
Page 143: TI07870753
40 35 10 0 FIGURE l.--Prevalence anti restrictiveness of Slate laws regulating smoking in public places, 1960-1985 NOTE:; ~ ~ppcndix f~" dt~Init km~ d ~t ~l~.m d The rate of enactment of state legislation increased throughout the seventies (Figure 1, Table 1). The pace of ,ew legislation continues into the 1980s, with 23 new laws enacted by 16 States between 1980 and 1985 (Table 1). As of 1986, 41 SLates and the District of Columbia have enacted Inws regulating smoking in at least one public place (Figure 1). Eighty percent of the U.S. population currently resides in States with some smoking restric- tion, compared with 8 percent in 1971 (Warner. 1981bL Most of the nine States with no smoking legislation are concentr~,ted in the southeast United States and include three of the six major tobacco- producing States (North Carolina, Virginia, and Tennessee) (Figure 2). Current State legislation varies in comprehensiveness a,d lan- guage, The number of public places in which smoking is rcgulatod by State law ranges from 1 (Delaware, Mississippi, and S, uth Carolina regulate smoking on public transportation only) to ~6 (Minnesota and Florida) (US DHHS 198fib, T,'i-Agency Tobacco Free Project 9.66 ' TABLE l.--Stote |~ws restricting smoking, 1970-1985 Number of Cumulative number .ewly enncted o1" $late~ with Reetrlctlvene~ or r~trlct|venm 1892-19~9 1970 0 • 14 -- .250 1971 2 16 .250 ,2,50 1972 I 17 .2~0 1973 3 29 .330 .263 IEq4 3 22 ,417 ,295 19715 12 27 .~79 .389 1976 1971 6 ~1 ,~4'~ ,462 1978 2 M .62~ 478 19~9 4 37 .688 19eO ! 1964 3 4 196~ 8 42 .719 .619 1986). State laws most often restrict smoking in public transports. tion (35 Stal.~.~), hospitals (33 States), elevators (31 States), indoor ca!tarsi or recreational facilities (29 States), schools (27 States), public meeti,~g rooms (21 States),. and libraries (19 States)(Table 2). Other public places specifically mentioned in State smoking legisla- tion are public restreoms and waiting rooms, jury rooms, polling places, prlso,s, hallways, stairwells, and stables. Most laws restrict smokin~ in these places to designated areas, thereby making honsmoking the norm; in a few States smoking is banned entirely in these places. For example, smoking on public transportation is banned entir,.ly in four States (Florida, Georgia, Massachusetts, and Washington) and one (Washington) bans smoking Jn theatere, museums, a,diLoriums, and indoor sports arenas. Smoking restrJc- 267
Page 144: TI07870754
TABLE ~.--State laws regulating smoking in public places and worksites Star4 AL AK AZ AR CA CO C'I" DE DC FL GA HI ID IL I~ IA KS I.."Y 19~i.76 1973 192~ Y,~,'(I) |~ 19';3 19T3 19~ 19e0.St 19T7 19~4 19~3 19TS ~=a~ad -- ISe4 IS61 I~ ~ ~ ~ I~ 1960 ;379 1985 1975 1976 ibm,5 ~ 19~3 1975 1972 PUBLIC PLACES WH~1E SMOKING ~ PROH]~rI'ED (EXCEI~ IN DESIGNATED AREAS) T107870754
Page 145: TI07870755
TABLE 2.--Continued St~ LA ME MD MA MI ~ MS ]dO MT NE l~/ NH NJ Nit NY NC ND OH 1954 1~24 1967 19~ ~ Ye~s) ]~tion 1981,~3 1957 194T t968 197l L911 I9~ 1975 1981 ~ -- t~ 1975 19/5 1.q78 1975 1942 -- 1.9~9 Lq"m 1.9/5 L.~I 1~ 1985 19~6 -- 19T7 L.o84 pUBLiC PLACES WHERE SMOIGI~G IS PROHIBITED (EXcEFr ]1~ DESIGNATED AREAS) TABLE 2.--Con~nued N Ti07870755
Page 146: TI07870756
TABLE 2.~Co~[Inued t..~ootnotes) " T107870756
Page 147: TI07870757
0.05 ~ o.~o I0.40 0.35 0.30 0.25 I I I I ' I I I I FIGURE 3.--Average restrictiveness of State laws in effect, 1960-1985 NOTI~I CodlnK d restrlct|w.m dlaw; ~ete.dve. I.~ M~r~ - 0.75; ~ . O~ N~ntad ~ 0.~. ~ $tates, Compared with other States, major tobacco States are less likely to have enacted smoking legislation and more likely to have onacted less stringent laws, TABLE 3.--ltegional variation in State laws restricting smoking I~io. N N I%1 Total Slate Aver,ge StaLes with laws ' Average r~trk:LlveneM effective dote of Imwz in erf~c| of first law Nmtheut II II 11¢~0) 1944 ,61,1 Noc'th C~.trnl . 12 0 t75! 1976 .694 We~t 15 14 (93) 19£~ .714 * I~l~h~ ~ly Sh~ with I*~ In eff~t 1~ ~le I ~ I~ ~ R~r~lvenml, ~al ~gi~lation In the 198{~, the momentum of nonsmoker' righ~ legislation spread from the S~ ~ the I~al level, s~arheaded by actions in California {Warner et al. 19~)~ Although not the first I~al action, th~ succce;ful p~age of San Franci~o's Pro~sition P in 1983 d~pite heavily .u~idi~ ~ba~o industry op~ition attrac~d wid~pread publicity and w~ follow~ by the p~sage of comprehen- sive legislation in a num~r of other I~al communiti~ (Doyle 1984). Many Im'al ordinances ex~nd existing State policies ~ res~u- ran~ and wor~it~. A~ording ~ a March 1986 .u~ey, 74 Califor- nia cities ..d counti~ have ~ smoking ordinances, including 62 r~uiring .onsmoking sections in r.~uran~ and ~4 r~trlcting smoking in radii s~res (Ameri~n. for Nonsmokers' Righ~ Founda- tion 1986). in the su~ey, ~ of thee citi~ and counties require private employers ~ have a smoking ~licy or ~ identify non- smokiug areas. As a result, 44 ~rcent of California's population lives in communiti~ that have enac~ workplace smoking ordi- nanc~ evea though California private workplace. According to the Toba~ Institu~, by the end of 1985, 89 cities and counti.s nationwide had restric~d smoking in the privat~ workplace. As s~ above, three-fourths of these were in California (BNA 1986). Workplace smoking ordinances have also been p~ in Cincimmti (Ohio), Kansas City (Mi~ouri), Tu~on (Arizona), Aspen
Page 148: TI07870758
(Colorado), San Antonio, Austin, and Fort Worth (Texas), Newton (Massachusetts), and Suffolk O~unty (New York). In New York City, a bill to prohibit smoking in all enclosed public places has been proposed by the mayor (New Yo~'k Times 7/6/86). lte~ulatory Approaches Administrative agencies have become involved i,~ sm~klng regula- tion in two ways: (1) the enforcement of smoking legislation enacted by State and Ioc~,l govermnent is commonly delegated to a specific agency, usually the public health department; or (2) an agency may initiate smoking regulation as part of the activities it has been authorized to' supervise ~Feldman et al. 1978). Agency ~'egulations have been the major mode of regulation at the Federal level, where smoking by Government emplnyees and by passengers in interstate t|'ansportation have been addressed. Smoking by State and Ioc.al employees has also been addressed by the actions of administrators; e.g., smoking by municipal employees and in public areas of municipal buildings was banned by a recent mayoral order i~ New York City (New York Times 6/26/86). Smoking Regulation in Specific Public Places Public Transportation Because high concentrations of enviromnental t~bacco smoke can accumulate inside public transport vehicles, smoking is often restricted or banned in public transportation. Smoking is likely to.be banned entirely in vehicles where smokers spend relatively little time (e.g., city buses), and confined to designuted areas in situations where smokers spend several hours (e.g., intercity buses, trains, and airplanes). Such restrictions are relatively well accepted. Smoking on interstate transporbgtion vehicles is regulated by Federal agencies. The Civil Aer~mautics Board, under it~ jurisdiction to "ensure safe and adequate service, equipment, and facilities," initially regulated smoking on ~,irl~lanes, requiri~g, since 1972, that every commercial air flight provide a nonsmoki~g section [or all' passengers requesting such seating (l,'eldman et al. 1978; Walsh and Gordon 1986). Airline control is currently part of the autl~ority of the U.S. Department of Traasport~ttion. Likewise, the lnt~:rstate Com- merce Commission has restricted smoking on buses and trains to designated areas since the early 197(~s (Feldman et ai. 1978; Walsh 1984). Additionally, States and local governments have regt,htted smok- ing in public transportation vehicles. Tlfirty-one States lmve e,tacted legislation to restrict smoking to designated areas in public tr.ansit vehicles; an additional four (Florida, Georgia, Massachusetts, and 276 Washingto,~) ban smoking entirely on these vehicles (Table 2). Local ordinances al~ frequently address public transportation. Retail In general, State and local legislation prohibiting smoking in retail stores is well accepted. Eighteen States currently prohibit smoking in retail s~orcs (Table 2). Proprietors and their trade associations have generally supported smoking restrictions out of concern for the costs of ciga,'ette burns to merchandise and facilities and for the image prese~tod to customers by employees. Furthermore, their business is le~ likely to be affected than, for instance, the restaurant trade because: smoking is not as closely associated with shopping as it is with eating and drinking. Re, taut'ants The average American, who according to National Restaurant Association (NItA) statistics eats out 3.7 times per week, has the potenthd for repeated environmental tobacco smoke (ETS) exposure (NRA 1986). This is a problem particularly in small restaurants, where ventih~tion may not be able to remove smoke and room size precludes a meaningful separation of smokers and nonsmokers, Public opini~m polls document support for restaurant smoking restrictions mnong smokers and nonsmokers. Ninety-one percent of nonsmokers and 86 percent of smokers responding to a 1983 Gallup poll favored cither restricting or banning restaurant smoking, with most preferring restriction (Gallup 1983). Similar results were reported by two regional polls in 1984 (UC SRC 1984~ Hollander~ Cohen Associates 1984). Roper polls in 1976 and 1978 demonstrated the growth i~ this sentiment during the mid-seventles; the proper. ties of |'espo||dents supporting restrictions grew from 57 percent to 73 percent in 2 years (Roper 1978). Yet little is known about how restrictions affect decisions to dine out or the choice of restaurant, A 1981 telephone survey of 949 individuals conducted by the Nationul Restaurant Asseciation (1982) found that the existence of a non. smoking section was near the bottom of a list of 13 attributes influencing an individual's choice ot" restaurant. On the other hand, 47 percent of 1,038 adults answering a 1984 Gallup Monthly Report on Eating Out stated that one reason they did not eat out more w~ that they web's: bothered by smoke (Gallup 1984). As in oth~:r privately owned facilities, smoking regulations in restaurants have come about through private initiative and public mandate, l'rivate initiatives have sometimes occurred in anticipa. ties of a local ordinance, but the number o1" restaurants that haw volunta,'ily ~.st~bllshed nonsmoking sections is not known, Tho 277
Page 149: TI07870759
Ontario ltestaursnt and Food Services Association 1198t5~ published a handbook of guidellnes for estahlishi~tg nonsmoklng sectio~is. In 1974, Connecticut became the first State to requirn restaurants to have nonsmoking sections. By 1980, eight other Sta~es also regulated restaurant smoking. At present, laws in 18 States and an unknown number of localities regulate smoking in restaurants. Although a nationwide accot~nting of local regulations is not available, data are available for several States ('['able 2). Most State nnd local ordinances specify (1) the minimum number of seats that must be included in a nonsmoking section, (2) the smallest restau- rant for which rules apply, and (3~ the manner in which customers are to be informed about nonsmoking sections. 'Bars that do not serve rosa.Is are uniformly excluded from restrictions. Most current State legislation specifies that a minimum of 30 percent of seats be designated as nonsmoking and exempts facilities with fewer than ~0 seats. Local ordinances are generally more restrictive, specifying that a higher percentage of seats be designated nonsmoking and extending coverage to smaller establishments. Model ordinances" (Hanauer etal. 1986) suggest that a minimum of ~0 percent of seats be designated as nonsmoking, require the posting of signs Inside and outside the facility, and specify that owners ask patrone about smoking preference rather than respond only to customer requests. Thers has been more opposition to smoking restrictions in restaurants than in other privately owned public places (I lannuer et al. 1988). Opposition has come primarily from restaurant asm~ia- tions and centers on three conceras: (D government i~t~'asion into business practice, (2~ practica! problems in coordinathtg seating of smokers and nonsmokers, and {3) losing the business of smokers who chose to leave a facility rather than to dine in a nonsmuklng section or wait for an available table in a smoking section. These concerns assume that the supply of nonsmoldng tables will exceed demand. While the proportion of tables allocated by most laws to nonsmoking sections greatly underrepresents the proportion of nonsmokers, mixed parties of smokers aml nonsmokers would have to decide which section to sit in. Restaurant owners appear to perceive little customer demand for nonsmoking areas, or are unaware of the very high percentage of smokers a~d nonsmokers responding to public opinion polls who support smoking restrictions. In anecdotal reports, the experience of restaurant owners who have implemented restrictions is that they are well accepted by customers and less difficult to implement than expected (Leiiman 1984). There is little inibrmation on the extent of restaurant compliance with State and local laws. In Park City, (Jtah, the Chamber of Commerce polled its 32 member restaura~tts, and only 25 percent had complied with State |aw to set up nonsmoking areas (Park Record 6/13/85). However, a random survey of Minneapolis 278 restaur~mts i~ 1976, 1 year after enactment of the comprehensive Minnes~ta Clean Indoor Air Act, found near-total compliance with the State's smoking regulations (Sandell 1984). In a 1978 Minnesota survey, 66 p~'ccnt of nonsmokers and 81 percent of smokers felt that there were a~lequate nonsmoking areas in that State's restaurants (Minne~tpo[is T~'ibune 1978).. Hotels ~md Motels Over the I,ust decade, hotel and motel operators have begun to offer guest rnoms in which smoking is prohibited. In some facilities, no-smoking #tress in lobbies and restaurants are also provided, Hotels ~re mdque among public places in the manner and ease with which smoki~g has been addressed. Unlike the situation in restau. rants, the nn.smoking room policy is uniformly a private initiative, introduced by management in response to perceived customer demand (Lim~ell 1986). Hotel and motel rooms are not covered by State and local regulations and have not been addressed by nonsmokers' ~'ights advocates. Designating guestrooms as no-smoking began in the early 1970s in smaller hotel and motel chains. In the 1980s, the concept has spread to larger chat~s, including Hyatt ttotels in 1984 and Hilton Hotels in 1986 (L~s Angeles Times 198~). According to a 1985 survey of 98 hotel .and motel chains, 37 of 41 respondents provided no-smoking rooms, 23 by chainwide policy. The four respondents ~vho did not offer no-smoking rooms were considering doing so (Linnel] 198~). The percentage of rooms allocated as no-smoking varied from ~ to 30. percent, far less than the prevalence of nonsmokers iu the adult~. population (7(} percent). As a result, demand often exceeds supply, leading seve~'al chains to increase the percentage of no-smoklng rooms (LinnclI 1986; Vettel 1986). The only entirely no-smoking facility is the Non-Smokers Inn, a 134-room motel in Dallas, Texas, which has be~:n open since 1982 and reports a 96 percent occupancy rate (Vettol !!}8(J). Although there are nnecdotal reports of problems with complimtce, hotels do not have penalties for violators. The exception is Ihe Non-Smokers Inn, where at check-in'guests sign an agreement to abide by the rule; $2~O is charged to cover the costs of cleaning if thv management detects smoking by occupants, Whether m~-smoking guestrooms offer significant protection from sidestream smoke exposure is ~ot clear. It is not known whether nonsmokers #~re exposed to significant quantities of ETS by staying in hotel rooms previously, but not currently, occupied by smokers. Rooms desigm~tod as no-smoking may primarily allow nonsmokers to avoid stole tobacco odors. The rcgulal.io~ of smoking in hotels and motels is supported by public opinio~t. Fifty to sixty percent of respondents to recent opinion polls favor restrictions on smoking in hotel rooms, and an additional
Page 150: TI07870760
7 to 18 percent favor outright bnns on smoking (Gallup 1983, UC SRC 1984, Hollnnder-Cohen ./~esociutes 1984). In ttie 1~.)83 Gallup poll, 60 percent of nonsmokers and 49 percent of smok~.~rs supported smoking restrictions in hotels, with an additioual 15 percent smokers and 7 percent of nonsmokers" favoring outright smoking bans. Hotel manage~nent regards such l~licy as a marketin); tool. Cost savings do not appear to be a motivating force in the trend, despite am~ecdotal reports of reduced cleaning and maintenance costs in no- smoking rooms (Linnell 1986). Preparing no-smoking rooms requires an up-front co~t for the thorough cleaning of furnishings and often the repainting of walls. For instance, Quality Inns estimnuted that it spent $138 per room when it allocated 10 percent of its rooms as smoking in 1984 (Vettel 1986). Sclzools Smoking by students in schools has been the subject of State legislation, State and local school board regulations, and individual school policies. Colleges and universities are not discussed in this section. In 27 States, schools are among the public places where smoking is restricted to designated areas (Table 2). School board policies often combine restrictions on tobacco use in schools with educational programs about the hazards of tobacco use. Smoking by teachers, for whom school is the workplace, is also regulated by many school boards. Smoking has traditionally been regulated in schools for reasons other than concern about sidestream smoke exposure. The two rationales have been to comply with State law and to prevent the initiation of smoking by adolescents. The sale or use of tobacco by minors is prohibited in 35 States (Breslow 1982). Many of these laws are rendered ineffective by the availability of cigarett~m in vending machines and by cultural norms that discourage the laws' enforce- ment (US DIIEW 1969). Nonethele~, the laws do provide u legal incentive for schools to regulate student smoking. The second reason for restricting smoking in schools is that adolescents are making decisions about whether to begin smoking and the influe,tce of peers as well as of adult role models who smoke is recognized to be important (~S DHHS 1980, 1982). Recognition of the health efl'ects o1" involuntary smoking provides an additional reason to address smoking in schools and a reason to expand attention from student~ to faculty. For teachers and staff, the ~chooi is the worksite, a location with the potential for substantial ETS exposure (Repace and Lowrey 1986). For students, school is the site where they spend the most time outsid~ of the home. A total p,~hibitiol~ ~f smoking o,~ school grounds provides the gm'eutest i~s'ol*.ction from sidestrean, smoke exposure and unwanted role m~lelin~; effects. In practice, however, this policy has often proved diFficmdt to enfo,'ce effectively (Rashak et al. 19/36). In some cases it has c,-e~tted major discipline problems and required substan- tial time aml la:rsonnel for enforcement. School officials, faced with the ma,mgensent of other social problems, may not wish to devote much o1" their" resources to enforcement of a strict smoking ban, Conseque,ttly, many schools have established student smoking areas inside or outside the school building. U~e of these are~ often requires purc~tal pern|is~ion. Smoking are~ for students are not popular with parents or teachers, according to survey data. Over three-fourths oF e03 adults responding to a 1977 Minnesota poll opposed allowing school beards to establish smoking areas for students. Only 13 percent of 1,677 public school teachers responding to a 1976 m~tinnwide survey thought students should be able to smoke oral school grounds. The nature al~d extent of school smoking policies nationwide is not known. Results of the I~w statewide surveys vary considerably. A Connecticut survey reported that 75 percent of the State's public high schools permitted smoking (Bailey 1983). In contrast~ in Arizona, where State law requires schools to restrict smoking on s~hooi grounds, 92 percent of the State's 169 public and private secondary schools surveyed had written smoking policies for stu- dents, and most policies prohibited all tobacco use by student~ (Rashak et al. 1986). Smoking by teachers at schools is generally prohibited in the classroom, but is often permitted in a lounge where students are not allowed. Nin~:ty perce~t of Arizona schools .permit smoking in teachers' Iouagc~, 40 percent in private o~fices, and 19 percent in meetings (R~mshak et al. 1986). Such policies attempt to avoid negative rol~ modeling effects; however, they create a double standard that may be a barrier to student compliance with smoking bans. There has been little concern for protecting teachers from involuntary smoke exposure at the worludte. Since smoking Is prohibited in ~he cla~room, their exposure is limited to offices and lounges. Health Care Facilities There are strong reasons for health care facilities to hav~ particularly stringent restrictions oil smoking. Many patients treat- ed in these f~toilities suffer from illnesses who~e symptoms can be worsened by ~tcute exposure to tobacco smoke. Hospitals also convey rne~ages abo~t health to patients and visitor~; permitting smoking on the premi,~es may undermine, the messages delivered to many patient~ about the importance of not smoking (Kottke et al. 19B6). 281
Page 151: TI07870761
Stringent restrictions on smoki=tg in hospitals have been endorsed by l~he American Academy of Pediatrics (1986), the American Medical Association (1984), and the American College of Physici=ms (1986). Hospital smoking policies have been opposed by some who are concerned about inconveniencing smokers at times of illness and stress. Proponents of hospital mPsmoking policies, on the other hand, are concerned about inconveniencing the 1~on~moking patient or visitor at these stressful times. Public opinion supports smoking restrictions in health care facilities. In the 1978 Roper survey, 69 percent of respondents favored a ban on smoking in doctors" and .dentists' offices and waiting rooms lAMA 1984). Of the more than 3,000 individuals interviewed in hospitals and restaurants, 66 percent favored restric- ting or banning smoking in these areas (Barr and Lambert 1982). Over 80 percent of patients and faculty and 68 percent of employees agreed that "a smoke-free hospital would be an improvement in patient care" at the University of Minnesota hospital IKottke et el. 1986). Ssnoki|~g in health care facilities has been addressed through State and local legislation, Federal regulation, and private initiative. In most States, hospitals and numing homes are included among public. places where smoking is restricted to designated ureas fl'able 2). In many cas~s, these legislative efforts have not led to strong protection of patients from involuntary smoke exposure because patient care .~ areas may be included among the designated areas where stocking is I permitted. Federally run hospitals have adopted incre~mingly strin- gent restrictions on smoking. For i,=stance, Veterans Administration ., hospitals and clinics adopted a new stocking policy in 1986, and a i large number of indian HeaKh Service hospitals are entirely now ~smoke free (eTA 1986; Rhoades and FaJrbanks 1985). ]iealth care tfacllities run by some States, such as M==ssacbusetlJ~, have also adopted nonsmoking policies (Nainmrk 1986). la no~government hospitals, most smoking restriction has bee== the rest=It of private initiative, often spearheaded by the medical staff. Much of this action has taken place in the 1980s. Hospital smoking policies can be complex. Within a single institution, smoking may be handled differently in inpatient, outpa- ' tient, and administrative areas. Patients, visitors, and employees may be subject to different sets of restrictio,ts. Consequently, ismoking policies vary widely among hospitals (Ernster ~lnd Wilner 1985). The least stringent policy prohibits smoking only where it is a safety hazard, such as near oxygel.~, and may permit the sale of cigarettes on the premises. Mihl policies often assign patients to beds by smoking status, prohibit staff from smoking in patie=lt care areas, and provide areas in cafeterias and waiting rooms for nonsmokers. Moderately stringent policies prohibit smoking in shared patient 282 rooms or in z~ll patient rooms. Some hospitals permit patients to smoke with a do¢'tor's written order. The most stringent policies, the se-called amahs-free hospitals, prohibit smoking throughout the facility or limit smoking to a single room away from patient care areas (Kottke c.t ~d. 1986). Enforcement of a smoking policy is usually the responsibility of the nursing staff. Guidelines for implementing hospital smoki~g policies ba,/e been formulated (Kottke et el. 1986; Ernster and Wilner 1985; AlIA 1982). Despite anecdotal reports of the adoption of stringent smoking policies in individual hospitals (Andrews 1983), survey data indicate that smokh|g is still widely permitted in patient care areas. A survey of 360 randor~ly selected U.S. hospitals published ih 1979 found few restrictions on smoking; fewer than half elicited the patients' smoking pref~:rence on admission or had no~smoklng areas in cafeterias, wai~.ing rooms, or lobbies, and smoking was permitted on 76 percent of the wards (Kelly and Cohen 1979). A 1981 survey of '1,168 community hospitals reported in 1981 documented some change i~= policy prevalence (Jones 1981). More than 90 percent of the hospitals lind a written smoking policy, which restricted smoking to designated ~treas in 97 percent of cases. Over 85 percent of the hospitals offer=.~l no-smoking patient rooms, subject to availability (Jones 1981). A recent survey of 188 hospital administrators in Georgia reporl.ed that 70 percent continue to allow smoking in patient rooms, although only 6 percent permit it at nurses' stations (Barman et el. 1985). The proportion of hospitals allowing cigarette sales on the premises has dc~:lined from 66 to 58 percent in the late seventies (Kelly and Cohen 1979; Seffrin et el. 1978) to less than 30 percent in tl,; eighties (Ernster and Wilner 1985; Jones 1981; Barman ct el. 1986; Berteisen and Stolberg 198l), While there are little data on the prevalence of smoking policies in private physi- cians' offices, guidelines for physicians wanting to provide assistance in smoki,~g cessation are well developed (Lichtenstein and Danaher 1978; Shipley =rod Orleans 1982; US DHHS 1984). Current Status of Smoking Regulations In the Workplace Policies regulating smoking at the workplace for the protection of employees' hc, lth are a trend of the 1980s. As of 1986, smoking is restricted or b~mned in 35 to .40 percent of private sector businesses (HRPC 1985; I~NA 1986; US DHHS ~I986) and in an increasing number of Fe~leral, State, aud local government offices (eTA 1986), Private sector wJrkplace smoking is regulated by law in 9 States and over 70 commmtities (eTA 1986; US DHHS 1985b; ASH I986), Activns tu resI.Hct or ban smoking at the workplace are supported by a large majorily of beth smokers and nonsmokers (Gallup 198[i). 283
Page 152: TI07870762
'The workplace has becume the focus of particular attention as evidence about the heallh hazards of .involuntary smoking has accumulated. Urban adults sl..,nd more time at work than at any other location except home (l{epace and Lowrey 198,51. For adults living in a household where no one smokes (ltarris 1985), the workplace is the greatest source of Ib'TS exposure. Consequently, an individual's workplace ETS exlmsure can be substantial in.duration and intensity. This is of particular concern for individuals also exposed to industrial toxins whose effects may be sy~;ergistic with tobacco smoke (US DHHS 1985c). Furthermore, individuals have less "}~oice about their E~S exposure at work than they do in other .places, such as restaurants or auditariums. '['he nonsmoker's right to clean air on the job hss bee;t supported by common law precedent (US DIIHS 1985a; Welsh end Gordon 1986). Assuring clean air at work has received the growing attention of policymakers and nonsmokers' rights advocates. The worksite has also received attention because of its naturally occurring interper- sonal networks and intrinsic social norms. Behavioral scientists have attempted to take advantage of the social milieu of the workplace to increase the success of smoking cessation programs (US DIt|IS 1985c). Smoking policies have the potential to alter worksite norms about smoking and thereby to contribute to reductions ilz employee smoking rates or the prevention of smoking onset. A substantial. fraction of blue-collar workers, who smoke report the iuitiation of smoking at ages coincident with their entry into the workforce (LIS D~IHS 1985c). Smoking Policies Legislation mandating smoking policies in the private sector workplace has been more controversial and less widespread than legislation covering public places, llecause a worker's behavior off the job has'traditionally been viewed as beyond the employer's legitimate concern, private employers have been reluctant to impose rules on behavior not directly related to employment (Welsh 1984; Fielding 198~1. The concept of workplace smoki~g restriction has become more acceptable to employe~ and legislators as l.he hazards of involuntary smoking have become better known ~tnd as public attitudes about smoking have shifted. The rationale for policies has been refrained its guaranteeing an employee's right to a healthy work environment. Prevalence of Smoking Policies Despite the recent attention, regulating smoking at wtDrk is not a new idea. There is a long and noncontroversial tradition of smoking restrictions to insure the sal~ty of the worker, workplace, a'nd preduct (OTA 1986). Employers have restricted smoki~g to prevent 284 fires or e.xplo,~ions arom~d flammable materials or to prevent product . contami,tatio,=. The policies were supported by State legislation dating bacl¢ I.o 1892, whe~ Vermont authorized employers to ban smoking in I'~=ctories so long as a sign was posted (Warner 1982; US DIIIIS i98,%~, New Yo,'k, Nevada, and West Virginia had enacted similar legisl~=tion by 1921, and i=t 1924 Massachusetts banned smoking in stables because'of the fire hazard (US DHHS 1985b), Smoking restrictions remained uncommon throughout the 1960s, During the 197~}s, .workplace smoking regulations were includ.ed in the comprehc~tsive clea,t indoor air legislation being proposed at the State level. In 1975, Mi,mesota became the first State to enact regulati~ms fur private worksites for the purpose of protecting employee he=dth. Since then, eight other states have passed laws covering priwtte sector workplace smoking (Tri-Agency Tobacco Free Project 1986; eTA 1986; ASH 1986; US DHHS 1985b). Fifteen percent of the U.S. population lives in these nine States. The scope of this legislatiw~ effort widened in the 1980s to include local govern- ment. It has been strongest in California, where ordinances in 66 communities ~:over 44 percent of the State's population (Americans for Nonsmokers' Rights Foundation 1986). Despite this legislative activity, surveys of employers through the 1970s reveal that worksite smoking regulations remained limited overall {Tabh; 4~. Those in place applied primarily to blue-collar areas and were motivated by safety concerns (NICSH 1980; Bennett and Levy 19~01. Policies were more common in industries with product saft.~ty concerns (food, pharmaceuticals) or explosion hazards (chemic=dsl (ilRPC 19851. Safety was the prime reason for smoking policies in ~ survey of 128 large Massachusetts employers in I978- 1979. The pol.~:ntial for an adverse impact on clients, especially in service industries, was also cited (Bennett and Levy 1980), Concerns about the impact of smoki=tg or~ the health of employees or costa to employers--the focus of the current workplace smoking action-- were not mentioned. Fewer than I percent of 855 employers answeriag a nationwide survey in 1979 had calculated the costs qf e,nployee smoking (NICSH 1980). Five surveys of employers conducted between 1977 and 1980 document the situation just prior to the proliferation of workplace smoking policies. Estimates of the prevalence of smoking policies • ranged I¥om 14 to 64 percent, reflecting differences in. types of businesses sa~,tpled and response rates (Table 4). A survey conducted by the Natitmal tateraget=cy Council on Smoking and Health in 1979 had the largest sample size and the only random sample, but had a low reslm,~se ~'ate (29 pe='cent) (NICSH 1980a). Their estimate era ~0 percent prevalence of smoking policies is probably biased upward by the likelihood that companies with policies were more likely to 'respond. An even higher prevalence of smoking policies (64 percent)
Page 153: TI07870763
TABLE 4.--Surveys of worksite smoking policies TABLE 4.---Continued Warksi~ Inc*ndves Busine~ ~ Interview Rzst~-~ ce~a~oa for Survey. name Survey Samplini R~ponse r~te smok~g prorcam nonsmok~ (pub. date) year Number Workforce size Location method Method Who? N (%~ (%~ t%) (%~ U.,S. ~ 1985 1600 ~ u.m~: sm~l[ (50- U.S. Ra~dm= munple ~o~ meat & ~ ~). ~m-I~ (>1~) ~ ~ ~d H~ ~ I~ 13,58 (~5) 38 19 Bureau o*" 1986 19b'7 Prodommantly small- U~ Random Natio--t medium 80%-<1000 mmpk, m~cted Ptr~ Admi~ 662 (34) 36 41 4 Petene~ and 198~ 1100 Pwxiominantly ~ US. (1966) 16% - ~O0-tO00. 22% - and > IO(X) Pu~o ? ~ ? 5]7 (~3) ~ ~0 ,q T107870763
Page 154: TI07870764
TABLE 4.~ontinued Surv~ na~e Workpl~,~ (pub. ds~) ~ Dan~nell's ~e~ ~ No No No No Pr~ pn~duc~ ~quipa~nt ~ncy Council t54% ~ 46%) on Smoki~ ~d Blue,collar > whi~.collar Blu~l~r m 42%1~28%R. c~'eterias 19%IU2%B. ~ ~cil|ti~ ( < 1% czlc'uis~ ~okin~ role:. impoae TABLE 4.--Continued Sur,~y a~me Wor~p~c¢ br~s cc~m~ ~ 18%) compl,tinm T107870764
Page 155: TI07870765
TABLE 4.--Continuecl of prm~im~ 3,5~ B by some • ud Hum~ ~ > smsll Serric~ > Noc unionized ot~r industryw blue-collar TABLE 4.--C~ntinued Workp~:e size Other Typ~ of ,~ok~ poliO. Dumd~ Aft'airs. I~c. (1986~ We~ - -q2%. Nonlz~nm or ~ EN . 42~. nonmsmuf~urinz where NC - 29~, >a~nu~cturinz m0rkpt~e South - 23% lu~oki~g l~w in effect Open werk zrezt 19%R/41%B: Comp|y with laws ~y ~o~ 5% p~fer ~ ~ . 2% U) adopt 1986; 21% OnJy ~3~, .~ m~tl~ (<~ employem) haw Hea~th (:am (83~ fmm~ (61%L (4~1. where T107870765
Page 156: TI07870766
reported in a survey of large Massachusetts businesses n,uy reflect similar biases or regional variation or both. Smoking policies were reported in only 14 percent of white-collar ofl~ces in a nonrandom survey (Thomas 1980) and in 23 to 30 percent of large corporations responding to two nonrandom surveys by the sa=ne gro~=p (Petersen and Mnssengiil 1986). These~ surveys found that muoklng restrictions were moderate, worksite smoking cessation programs uncommon (9 to 15 percent), and incentives for nonsmoking rare (<3 percent). Outright smoking bans and preferential employment of nonsmokers were not men- tioned. However, employee complaints about smoking were reported by one.third of the businesses in two surveys (Petersen sad Masses- gill 1986; Thomas 1980), suggesting a growing pressure on employers For change. Smoking policies were stricter for blue-collar workers and larger worksites (NICSII 1980b; Bennett and Levy 1980). A second set of business surveys, conducted only 5 years later (1984-1986), shows a different picture (Table 4). Three large surveys, two based on random samples, reported a remarkably similar prevalence of workplace smoking restrictions, ranging from 32 to 38 percent (HRPC 1985; US DHHS 1986; BNA 1986). A fourth study reported that 56 imrcent of small and medium sized businesses had smoking policies, but only 38 percent of businesses restricted smoking to designated areas (Petersen and Massengill 1986). Because of uncertainty in the earlier (1977-1980) estimates, it is difficult to conclude that the most recent estimates of policy prevalence represent an increase. However, there is suggestive evidence on this Imint: half or more of policies reported in the 1984-- 1986 surveys were adopted within 5 years, indicating that the policies are largely products of the 1980s; a sizable number of companies without policies are considering them; in addition to the 86 percent of companies reporting policies in one 1986 report, 2 percent were planning to implement a smoking peiicy in 1986 and another 21 percent were considering adopting a policy (BNA 1986}. Finally, companies that adopt policies rarely reverse them: in the BNA 1986 survey, only 1 percent of companies without policies had .... ?r had one and rescinded it. These data support a contention that workplace smbking policies are a growing trend. The nature and scope of smoking restrictions also changed during the 1980s. The most common policy still restricted smoking to ,d, esignated areas, but those areas appeared to be shrinking. Despite several well-publicized examples (Pacific Northwest Bell Telephone, Group Health C~operative of Puget Sound), total workplace smoking bans were still rare (1 to 3 percent). An even more stringent'smoking policy now being adopted, giving preference to nonsmokers in/tiring or refusing to hire smbkers, was not even considered le~. than a decade before (BNA 1986; HRPC 1985; Petersen and Massengill 292 1986). l,'ewer than 5 percent of businesses have currently adopted such a policy. Workplace smoking cessation programs were more commo~, but incentives for nonmnoking remained rare. The 1984-19B6 surveys suggest tlmt the diffusion of workplace smoking peli~:ies throughout the private sector is occurring in a =tonunilbrm Fashion. Companies with policies differ from those without policies in workforce size, geographic location, and type of industry. Smoking policies, are slightly more prevalent in large companies than in small businesses (45 versus 33 percent) (Petersen and M=msengill 1986; BNA 19861. Policies also differ by company location, being more common in the West and Northeast than in the North Centr=d region or the South (BNA 1986; HRPC 1985), This i;eographic disparity is similar to the pattern of State smoking legislation~ and may in part be explained by it. Businesses in States with workph,ce smoking laws are more likely to have adopted smoking pelicies than are companies located elsewhere (HRPC 1985; BNA 1!186L Industries are adopting smoking policies at different rates, with more policies and more recent policies in nonmanufactur. ing industri,.s (finance, insurance, health care, pharmaceuticals) (HRPC 1985; Petersen and Ma~engili 1986; BNA 1986), This represents a shift from the earlier blue-collar predominance of smoking rcs~Hctions and reflects the change in policy orientation from workpb,ce safety to employee health. q~vo factors may explain the growth of workplace smoking policies in the 198~. Recently enacted State and local workplace smoking legislatJm~ is one factor influencing the private sector, Legal' mandates art: cited as a major reason for adopting policies, and as noted above, the prevalence of private sector smoking policies is higher in regions with legislation in place. Laws may encourage more rapid private action by putting smoking on the corporate agenda. A ~econd factor is public support. Support for an employer's right to restrict smoking to a designated area at work grew from 62 percent to 61 percent during the 1970s (Roper 1978) and continued to increase in the 1980s (Gallup 1983, 1985). In 1985, 79 percent of adults, including 76 percent of smokers, favored restricting smoking at work to designated areas. Only 8 percent favored a total workplace mnoking ban (Gailup 1985). These attitudes may also be manifest as employee pressures'to restrict smoking (Petersen and Massengill 1986; BNA.1986; HRPC 1985). Reasons for Adopting Smoking Policies it is not always easy to identify the motivations and goals for a specific workplace policy (eTA 1986). Explicit reasons for imple. meriting policies, according to the most recent employer surveys, are (1) to protect the health of the employee--especially the nonsmok. st--and assure a safe working environment, (2) to comply with State 293
Page 157: TI07870767
and local statutes mandating worksite smoking policies, and (3) to anticipate or handle demands from nonsmokiag employees for a smoke-free working environment. Other reasons may be the fear of possible legal liability for illnesses caused by sidestream smoke exposure in the workplace (Fiehling 1982; Walsh 1984), an opportuni- ty to symbolize a company's concern for employee welfare (Waish 1984; Eriksen 1985), as part of a general health promotion and wellness program, and the goal of saving the company money. Although it is generally agreed that employees who smoke co~t their employers more than do aonsmoking employees, there is as yet littl.e evidence that implementing policies will reduce the extra smoking-related costs (eTA 1986; Fielding 19~6; Eriksen in press). Corporations are keenly interested in stemming the rapid rise in health insurance costs, but may not see smoking policies as a means to that end. The top management at Xerox, for example, rejected a proposed smoking policy boom|so of concerns about the potentially adverse economic impact of excess smoking breaks on productivity (Walsh 1984). Actually, economic considerations do not appear to be a major reason why businesses adopt smoking policies, according to three recent surveys (HRPC 1985; BNA 1986; Petersen and Masses- gill 1986). Barriers to Adopting Smoking Policies Both survey data and case report~ give insights into reasons why employers have elected not to implement worksite smoking policies. According to a Tobacco Institute-sponsored survey, the 24 percent of large employers who had considered and rejected a smoking policy gave these reasons: policy not acceptable to employees (59 percent), employees can handle the problem on their own (58 percentS, implementation too difficult (39 percent) or too costly (5 percent), policy not acceptable to clients (10 percent), and no employee complaints about smoking (29 percent)(HRPC 1985). .Fear o~ worker discontent or union opp~itlon is the m~jor reason cited by employers who have considered and rejected a wmkplace smoking policy. Surveys consistently indicate that sm,~king policies are initiated by management, and are often adopted with little or no employee or union input (HItPC 1985; BNA 1986; NICSII 1980). Although most businesses thai. have surveyed their employe~ have found strong support for smoking restrictions (Pecilic Telephone 1983; Robert Finnigan Associ~tes 1985; Addison 1984; Ziady 1986; Marvit etal. 1980), some unions have actively opp~ed employer- mandated policies, both in individual cases-and at the national level. in 1986 the AFL-CIO Executive Council stated its opposition to unilateral policies and called for the case-by-case handling of workplace disputes between smoke~ and nonsmokers (BNA 1986). 294 Both employee organizations and e~nployers find i~ difficult to simultaneously balance the wishes of all their constituents, Another reason for reluctance to adopt smoking policies is concern about implementation (ItRPC 1985). In some cases, this means concerns abo~,t how to enforce the policy (BNA 1986) or whether it is enforceable (l~riksen, in press). Other reasons cited by companies were questions about the -legality of limiting employee smoking (BNA I986) m~d the nonsupport of top management who are smokers (BNA 1986). Some companies are dependent on business re}atlon- ships with t~bncco companies and businesses with tobacco-related interests, which they do not want to jeopardize (Kristein 1984; Wals,~ 1984). Types of Smoking Policies Private se~:tor businesses have addressed the issue oI" employee smoking in n variety ot~ ways. In addition to smoking policies, the umbrella co~eept of "worksite smoking control" can include educa- tional campaigns to motivate workers to quit, self-hel~ and organized .smoking treatment programs, medical advice, and incentives to encourage n,nsmoking (Orleans and Shlpley 1982; Windsor and Bartlett 198.D. Smoking programs ere sometimes subsumed as part of broader co~'porate wellness programs. Worksite smoking cassation programs were reviewed in the 1985 Report on the Health Conse- quences of Smoking (US DHHS 1985~). Businesses have taken a variety of approaches to a workaite~ smoking policy. The choices reflect the individual company's motive in adopting a policy and assessment of the potential for implementa- tion and enforcement. When protection from fire or explosion was the primary motive, policie~ primarily applied to blue-collar areas; when the goal was to avoid antagonizing customers, smoking bans applied only to client~outact areas (Bennett and Levy 1980), A company's s~lution also reflects its particular social environment, Recent study indicates considerable variability among individual worksites in attitudes and norms about smoking cessation (Sorensen et el. 1986). Because 'smoke travels, the desires of smokers and nonsmokers will inevitably come into conflict in common areas, and it is diJ'ficu]t to simultane~usly maximize the goals of smoke-free air, minimum employee disruption, and minimum co~t. A business adopting a policy primarily to avoid employee conflicts is likely to pay greater heed to snlokers' wishes at the expense of smoke-free air, and may consider solving the problem with increased ventilation (to avoid the necessily of behavioral change) or may separate smokers and non~mokers. A business whose primary goal is to reduce involuntary smoking ha~.ards will be more willing to sacrifice smokers' conve. nience and ~,~ay consider a total smoking ban. A business that aims 295
Page 158: TI07870768
to reduce costs may choose a minilnum of structural changes and maximum likelihood that the policy will result in employee smoking cessation; a total ban on workplace smoking or the hiring of only nonsmokers would be more likely to achieve these goals. Alternative- ly, adopting no policy may also be ine~'pe~wive, so long as Lhere are no employee conflicts over smoking. The myriad of current smokiug policies have been categorized several ways (US DHHS 1985a; BNA 1986; eTA 1986; ALA 1985a,b). The range, in ascending order of protection for the nonsmoker, include these: (1) No explicit policy (the "individual solution" approach) (2) Environmental alterations (separating smokers wltlz physical barriers, using air filters, or altering ventilation) (3) Restricting employee smoking, a range with these extremes: (el smoking permitted except in designated nonsmoklng areas; smoking prohibited except in designated areas (4) Banning employee smoking at the worksite (5) Preferential hiring of nonmnokers. Options (1) through (3a) effectively state that smoking at work is acceptable behavior; options (3b) through (5) indicate to employees that nonsmoking is the comlmny norm. Several groups have developed model policies of varying degrees of comprehensiveness to assist employers (ALA 1985a,b; G~,SP 1985; BNA 1986; Hanauer et al, 1986). Tile "Indiuidual Solution" Approach According to surveys, having no explicit policy is still the meet prevalent approach to smoking in the workplace (HRPC 1985; BNA 1986; US DHtlS 1986). Smokers and nonsmokers work out differ- ences on their own, using socelled common courtesy or |'inding an individual solution. According to a 1984 Tobacco Institute-sponsored survey, 70 percent of large employers encourage employees to work out differences on their own (HItPC 1985). When there is no explicit policy, there is the implicit message that environme~,bd tobacco smoke does not represent a hazard. So long as there are few disputes and they are easily settled, this approach is expedient. However, it is not likely to be a successful long-term policy. Nonsmokers in the late 1970s amy have been reticent to assert their rights and perceived a burden of confrontation (Roper 1978; Short and Williams 1978), but there is a growing consensus, eveu among smokers, that supports abstention in the presence of nonsmokers and that worl~sil.es should have smoking restrictions (Gallup 1983, 1985). 296 Enuironmex~l¢d Alter(ztio~ts Enviroamel~t~d alterations range/'rein simply separating smokers and nonsmoh.rs to different areas of a room to installing improv.ed ventilation systems to ,'emove environmental tobacco smoke. The advantage of this approach is that it requires no behavioral change of smokers nnd satisfies some of the wishes of nonsmokers. However, because toba~:c~ smoke easily diffuses beyond physical boundaries, simple harriers provide at best a slight reduction in involuntary smoke exposure (see chapters 3 and 4) (Olshansky 1982). More sophisticated ventilation systems can be prohibitively expensive, and even the best may not be able to clean the air adequately (Repace and Lowrcy 1985; Lefcoe et el. 19831. Workplace modification has sometimes be~,,~ utilized as a company's first step in the development of a more r~,strictive I~licy, as happened at the Control Data Corporation in Minneapolis (eTA 1986). Restrictions on Employee SmoMng The mest common workplace smoking policy is to restrict where employec~] may smoke (BNA 1986). This policy has broad publiv support; in a 1985 Gallup poll it was the approach favored by 79 percent of U.S. adults, including 76 percent ofsmokers (Gallup 1985), Policies differ in (1) the proportion of the workplace in which smoking is permitted, (2) whether the default condition is smoking, nonsmoking, or unspecified, (3) who has the authority to designate the smoking status of an area, and (4) whose wishes prevail when smokers and nonsmokers disagree. Policies often categorize the worksite into four areas that are subject to different rules: (1) private offices, (2) sh,red offices or work areas, (3) small common use areas (elevators, bathrooms), and (4) large common use areas (conference and meeting rl~,ns, auditoriums, cafeterias). The least r~:,trictive policies permit smoking except in designated nonsmoking areas, indicating that smoking is the company norm. Who has the authority to designate an area's smoking status and whether smokers' or nonsmokers' wishe~ prevail may not be explicit, The usmd pattern is for common use areas to be designated either totally noasmoking (elevators, bathrooms, conference rooms) or partly nuasmoking (cafeterias, auditoriums). Private offices are left to the db;creti~m of the occupant, who is often given the authority to declare it nonmnoking. In shared office areas, where the wishes smokers and nonsmokers may conflict, each individual may be given tile authority to designate his or her own immediate work area, or the policy may stipulate that a compromise be rea.ched. However~ this cau,~ot ensure that an employee's sell-designated nonsmoking area is free of sidestream smoke. Because the majority o~" an employee's ti,~e is spent in the immediate work area rather than in 297
Page 159: TI07870769
the nonsmoking common use areas, a policy that does ,lot specify nonsmoking in shared work are~ may not substantially reduce an employee's environmental tobacco smoke exposure. However, these policies may satisfy some nonsmokers' wishes with minimal disrup- tion to smokers. In some cases, companies seeking to limit smoking have adopted this type of policy as a first step to mare stringent restrictions or a total ban (e.g., Boeing, cited in O'rA 1986). The most restrictive policies specify that "smoking ie prohibited except in designated areas," establishing nonsmoking as the work- place norm. In the strictest policies, smoking is prohibitml in shared work areas (unless all occupants agree to desigmtte an area "smoking permitted") and in most common use areas. Policies may limit the areas that can be designated "smoking permitted" and predetermine that the wishes of nonsmokers prevail when conflict occurs. Even stricter regulatio=zs stipulate =lot only the location in which but also the time when smoking is allowed (e.g., work breaks only). So long as the smoking areas do zlot contaminate the air of work areas, these policies provide greater protection of employees from sidestream smoke at the cost of greater incozwenience to smokers, who may perceive the restrictions as coercive. The produc- tivity of smokers may suffer if they are permitted to take extra smoking breaks or if smoking areas are located too far from the work station. Ti~e variability of smoking restrictions in common work areas was demonstrated in a 1985 survey conducted by the Bureau of National Affairs. Of the 239 companies with smoking policies, 41 percent banned smoking in open work areas, and an additional 20 percent banned it if employees or supervisors wished. Only 8 percent permitted smoking in all open work arena, and 19 percent divided areas into smoking and no-smoking sections. There was more uniformity in treatment of common use areas. Over 50 per.cent of the companies banned smoking in hallways, conference rooms, rest- rooms, and ~ustomer contact areas, and smoking was partially banned in 58 percent of cafeterias (BNA 1986). In contrast to shared work areas~ smoking was permitted in 56 percent of the private offices in that survey, with occupants often given the authority to desig,mte the office as smoking or non- smoking. This has the potential lbr charges of unequal treatment and problems with employee morale (BNA 1986). Banning Smokb=g at the Workplace Some businesses~including large corporations, among them Pacif- ic Northwest Bell Telephone and Group ilealth Cooperative of Seattle--have recently opted for total butts on smoking at work (US DHHS 1985a; Ziady 1986). Bans may be preceded over several years bY progressively stricter smoking regulations. Despite these well- 298 publicized st=,:ccssfui examples, smoking bans are rare and not widely supported by public opinion. Only 6 percent of companies with sm,~ki=~l; policies (2 percent of all respondents) in a 1986 survey totally bann,.d smoking (BNA 1986). Only 12 percent ot" adults (4 percent o1" smokers) agreed that "companies should totally ban smoking at work" in a 1985 Gallup poll. Despite this hesitancy, smoking barn* are gaining momentum among large employer~ such as fleeing, wire recently ammunced au upcoming ban that will cover its 90,000 employees (lg~ehart 1986). Smoking bm=s provide the maximum protection for no~smokers, at the cost of greater inconvenience for smokers. They send a clear message thai. nonsmoking is the company norm. They can reduce ventilation needs and maintenance costa due to smoking, but pose potential pr,,blems with enforcement and loss of employees who smoke. 'l'lms, how a bat, is planned, prefaced and introduced, and implemcutt.~l m,d enforced is very important. Through a concern for employee well-being, asslstanco for smokers who wish to quit should be implemented along with bans (Orleans and Pinney 1984). Preferential Hiring of No~smokers The most restrictive workplace smoking policy, preferential hiring of nonsmokers, was not even discussed several years ago. Explicit policies favoring nonsmukers are still uncommon. In the 1986 report of the Burea,, of National Affairs, 1 percent of businesses hire only nonsmokers, 5 percent give nonsmokers preference, and 10 percent permit supervisors to exercise a nonsmoking preference (BNA 1986), The majority either have no policy (43 percent) or do not permit such a preference (39 percent). On the oth6r hand, data from small surveys indicate that personnel managers, the majority of whom are themselves n~msmokers, may preferentially hire nonsmokers (Weis 1981; lglebart 1986). In a unionized setting, selective hiring of nonsmokers may need to be the subject of collective bargaining (Eriksen, in p='ess). Hiring only nonsmokers ensures a smoke-free work environment without conflicts over smoking and makes it clear that nonsmoking is the compa,ty norm. Since the nonsmoking workforce should be healthier, lower health insurance premiums may also result, On the other hand, sncha policy limits the potential pool of new employees, raises the isst,e of what to do about currently employed smokers, and may present problems with verification of smoking status. Employ- era may be reluctant to adopt a policy in which off-the-job activity is a ~ondition o1' employment (Walsh.1984). Assuring c¶~rnpliance of workplace smoking policies is complex, Model poliei~s usually include three enforcement provisions: (1) identifying wire is responsible for policy enforcement, (2) designating penalties for noncompliance, and (3) ensuring the protection of an 299
Page 160: TI07870770
cmployee bringb~g a complniJ~t. These provisions arc often nol; included in practice. Only 23 percent of the policies stipulated penalties for no~tcompliance and only 32 percent specified proce- dures for resolving disputes in the t986 BNA survey (BNA 1986). Approximately half of the policies in two other business surveys had provisions for disciplining viol~ltors (Petersen and Mas.~engill 1986; N ICSH 1980). hnplementation of Smoking Policies Worksites that have adopted smoking policies have differed in tide ease of policy implementation. To aid .employers, tire Anlerican Lung Association and the Office of Disease Prevention and ileaith Promotion of the U.S. Department of Health and FIuman Services have developed guides with specific recommendations on how to adopt and implement wor~ito smoking policies (ALA 198~b; US DlqttS 1985a). These are based on the experience of companies and .can be extremely helpful even though they are not basod on research. The experiences of 12 corlmrationa that considered smoking policies are described in a report of the Bureau of National Affairs (1986). Case reports are also included in a guide from the Office of Disease Prevention and Health Promotion-(US DtlHS 1985a). According to these case .reports, strong suppert from top manage- meat and having an advisory committee composed of a wide variety of employees (including both smokers and nonsmokers, managers, and employee representatlves} are common to succes.~ful policie¢ Surveys of employees can assess distress caused by involuntary smoking and SUpl~rt for policy changes. As a rule, such surveys have generally documented widespr,:ad support for smoking restrictions from employees, tide majority of whom are nonsmokers. Another correlate of succes.q is a well thought out and clearly articulated communication of the policy. A written document should give the rationale for the policy i|nplementation, specify wl~ere smoking will be allowed or prohibited, and define responsibility and procedures for policy enforcement and penalties far violation. Successful policies avoid criticizing smokers or sorting up an antagonistic situation between smokers and nonsmokera. They make it clear that the company is not requiring that emplnyees quit smoking and will help smokers in adjustiDtg to the new regulations. Giving smokers advance notice o~r tire policy and providi~|g help for those who want to quit smoking can help gain their support. Careful plans for implementation are recommended. Allowing several months between the nnnouncement of tide p~,iicy and its effective date gives smokers time to prepare for the chatDge nnd to attend smoking cessation programs if they wish to quit. This provides time for the postiog of adequate numbers of signs and for 300 making any structural alterations that may be necessary. After policy implementation, an advisory committee should monitor its effectiveness and enforcement. A followup survey is helpful to determine wirer, if any, adjustments need to be made. Impact of Pollclea Restrict!ng Smoking In Public Placea and the Workplace Policies that regulate where smoking is permitted in public places may have a number of direct and indirect effects. In the short term, a policy that is adequately implemented and enforced will alter the behavior of smokers in areas where smoking is prohibited and should result in a r,.~hDced concentration of tobacco smoke in that area, Beyond these direct effects, there is the potential for smoking restrictions t~ have broader, indirect effects on smoking behavior and on public attitudes about tobacco use. This section outlines the possible intpects of smoking policies, addresses methodologic consid- erations, and reviews existing data that bear on these hypotheses, Potential lmpacta of Smoking Policies Policy lmpleme~tation and Approual The degree to which a smoking policy or law has been implemen- ted as writtet, is an essential consideration in evaluating its effects on attitudes, behavior, and air quality. Successful implementation involves public awareness of the policy, compliance with its regula- tions, and enl0rcement of violations. Compliance requires not only that smokers refrain from smoking where prohibited from doing so, but also that appropriate decisionmakers develop written policies, designate areas as nonsmoking, and post signs as stipulated, Enforcement requires that policy violations be dealt with, either by peer action or by penalties defined by the policy. Because smoking policies and laws are approved by the majority o.f individuals whose behavior they affect, they are generally held to be self-enforcing, obviating tide need for active policing (Hanauer et al. 1986). When enforcement is =~eeded, smoking policies and legislation rely primari. ly on peers, ~t~sumlng tlmt the nonsmoking majority of the popula- tion will enforce th& policy or statute because it is in their best interest. Nonsmoker, can be expected to favor smoking restrictiol~s, which offer the benel]ts of cleaner air and reduced health risks and require no change in their behavior. The opinions of smokers are expected to be less fay.or,hie because they stand to be inconvenienced. Some smokers may support the policy to assure themselves of having a location where smoking is clearly permitted, because of a desire to quit sm~ki~g, or because of concerns about th~ health hazards of involuntarT ~moking. The degree of smokers' support for a policy 301
Page 161: TI07870771
may also depend on other factors, such as the degree of smoking .restriction or the adequacy of pcdicy itnplementation. Direct Effects: Air Quality and Sm~,king Behavior The evaluation of a specific policy or piece of legislation must address whether the policy achieved its stated goals and must also screen for other effects. The primary goal of policies regulating smoking in public places is the reduction of individuals' ¢xposu~e to environmental tobacco ~moke. Measures of air quality directly assess how well a policy meets this goal. Air quality also indirectly reflects the behavior of smokers and the degree of policy compliance. Smoking policies may have both direct and indirect effects on smoking behavior. The direct effect of adequately implemented smoking restrictions is to limit where smoking is permitted, altering the behavior of smokers in those settings. Smoking policies may have indirect effects on smoking behavior if they influence the behavior of smokers outside these settings. Indirect Effects: Knowledge, Attitudes, Social Norms, and Smoking Behavior Policies that restrict or bau smoking in public places or the worksite convey potentially powerful messages about the role of cigarettes in society and help to reinforce nonsmoking as the normative behavior. Restricting smoking to protect nonsmokers may increase public acceptance of health risks of smoking and 6f involuntary smoking. Smoking restrictions may also alter attitudes about the social desirability of smoking and the acceptability of smoking in public. Changes in the knowledge or acceptam:e of health risks combined with attitude shiP, s contribute to changing social norms about where smoking should and should'not occur, as well as whether it is an acceptable soci:d behavior. Changes in social norms may influence smoking behavior by reducing pressures to smoke and increasing social support for noasmoking and cessation. The comhination of altered atrial norms and reduced opportunities to smoke may encourage smokers to quit and discourage experimentation among nonsmoking youth. Chang- ing social norms may have tbeir greatest impact on t~uagers and young adults, who might be less inclined to experiment with a socially undesirable substance. Current smokers are likely to be prompted by cha.nglng social norms to move further through the stages of self-change that precede cessation (Prochaska et al. 1985). Smoking restrictions may influence smoking behavior apart from their inlluence on social norms. By reducing opportunities for smoking, restrictions may decrease a smoker's daily cigarette consumption. By reducing the range of settings where smoking 302 occurs, they reduce the cues had alter the stimulus-response patter,m thai. help to maintain smoking behavior aud that contribute to relap:;e among ex-smokers (Orleans 1986). This could increase the success of quil. a[tempts. Smoking restrictions, especially those at the workplace, may also help smokers to discover alternatives to smoking as a stress reduction tool. Likewise, new entrants into the workforce may not as easily learn to rely on cigarettes to cope with work-related ntressors. This might blunt the increese in smoking prevalence that occurs at the time of workforce entry, especially among I,lue-c~llar workers (O'Malley et el. 1984; [IS DI1HS 1985c), Thus, the wldespread adoption of smoking restrictions may have a profound imlmct on smoking behavior at manY points in its natural history, tiypt~thesized consequences include reduced cigarette con- sumption, increased motivation and progress through the stages of self-change, increased rates of smoking cessatioh, and decreased rates of stuck ing initiation. Smoking p~licies may have additional impacts beyond their effects on attitudes and smoking behavior, such as positive economic effects for employers by reversing the excess costs associated with employ- ess who smoky. It is generally agreed that employees who smoke cost their employers more than nonsmoking employees because of excess absenteeism, increased health care utilization, and reduced produc- tivity (eTA 1986; Fielding 1986; Eriksen, in press). This leads, to greater use of sicknea% disability, and health care benefits and ultimat~;lyl higher health insurance costs to business. Productivity losses to business are attributed not only to the individual smoker's time lost owing to on-the-job smoking, but also to increased maintenance costs due to cigarette-related damage and refus0, Estimates of I.he excess annual cost per smoking employee vary by an order of magnitude, but even conservative estimates are substan. tiai: $300 to $600 (Kristein 1983, 1984; Solomon 1983; Wels 1981). Reductionn in health care costs are partly dependent on whether policies lead smokers to quit smoking. Even if smokers quit, the reduction ia health care costs may not be seen in the short term. Some employer.~ have been concerned that strict smoking bans may unfavo~'ably alter employee turnover patterns or productivity. Smokers' pr~ductivity could decrease if, for example, they are permil.ted to Iztke extra breaks away from their work stations in order t~ sm~ke (eTA 1986; Michigan Tobacco and Candy Distribu- tors and Ve~dor A~sociation 1986). Costs involved in adopting a smoking policy should also be considered. Assessment of the~v endpoints is useful because employers may consider them in deciding whether to i,~plement smoking policies. 303
Page 162: TI07870772
Mcthodologic Conslderutlons in Policy Evaluation Study Design Evaluating a new smoking p~;licy in a defined populal.ion is similar to evaluating a smoking cease! ion intervention, with the addition of noasmokers. Impacts on beliefs and attitudes, as well as on behavior, can be assessed in the population at baseline and at intervals after implementation. Because smoking policies may influence smoking behavior gradually, designs must be able to measure delayed effects. Simultaneous assessment of outcomes in a control population strengthens confidence in the validity of conclusions. With uncon- rio]led pretest/pesttest designs, there is the possibility that changes ~'.~moking behavio.r and attitudes are confounded by outside influences. Worksites, for example, may have concurreut smoking cessation programs that can affect attitudes and behavior. Popula- ttoawide trends in smoking behavior are another source of confoun- ding. In practice, random assignment of whole populations will rarely be feasible, since researchers are rarely in a position to "assign" the intervention and must rely on natural experiments. Quasi-experimental designs, which include natural comparison groups, are the best alternative. Identifying and accessing such appropriate comparison populatious may be difficult in practice. Either longitudinal or cross-sectional campling can be employed. Longitudinal designs, in which the same individuals are interviewed at two or more points in time, provide the best measure of changes in outcome measures, but depend on high rates of followup, which may be practically difficult. Furthermore, individuals' behavior or atti- tudes may be influenced by repeated assessments in such studies. On the other hand, when attitudes and behavior are evaluated by repeated assessn|ents of indepondently chosen cross-st.~tional sam- pies, the possibility exists that smokers and nonsmokers will enter or leave the population at different rates as a consequence of smoking restrictions. Turnover needs to be followed to assure thut changes in bcllavior or attitudes are a result of changes in individual behavior and not changes in the composition of the population. One-time comparivons of populations' with and without policies can provide suggestive but not conclusive data about impact. The validity of differences detected in attitud~ and behavior is depen- dent on the degree 'of similarity 'between the policy group and the control group. Uncontrolled oae-time assessments done before or after policy adoption do not permit conclusions about the policy effects, although they may provide hypotheses for further work. • Poatlmplementation surveys of a population can, however, provide useful information about the degree of policy approval, awareness, compliance, and enforcement. Assessment of the impact of legislation on smoking behavior is more difficult because the unit of study is larger and more diverse. Consequently, de~iled behavioral or attitudinal d'ata and repeated assessmenl~ are more dil'ficult to obtain. Evaluations are ofte~l limited to mtalyses of aggregate measures such as smoking preva- lence and lolmcco consumption, which are collected for other purl~oSes. This approach does not control for potentially confounding inl]uences ,n tebacca use. or smoking behavior, such as price fluctuatioas, hlentifying and asser~aing control groups not subject to smoking lel;islation or regulation can strengthen the confidence in conclusions for the asme reasons as above, but is often difficult to achieve in practice. Assessiug the: Effects of Smoking Policies Ideally, air quality should be measured objectively, but current technology ['or measuring the concentration of tobacco smoke in iudoor air is expensive and cumbersome. There is also uncertainty about which constituent of smoke isbest to measure (See chapters 3 and 4 of this volume). Air quality can also be assessed subjectively, Ratings made by occupants of smoke-free areas can bc compared with those of a control area or to ratings made prior to the ban. Measurement of an individual nonsmoker's actual exposure to secondhand smoke, using biochemical measures, is not a specific measure of the concentration of this smoke in a eingle area because an individmd may have other sources of smoke exposure. Such measures might be useful for assessing the concentration of smoke in areas, like tile worksite, that represeht a primary source of exposure. They cannot be used to measure air quality in other places, like an auditorium, where.an individual spends only a few hours. Many markers of smoking behavior need to be examined in order to understand the multiple effects of smoking restrictions on .behavior. lit a defined population, a new policy may increase smokers' motivation to quit, confidence in their ability to quit, or the number, duration, and success of quit attempts. It may also reduce cigarette consumption among continuing smokers, Workplace poli- cies may Itave different impacts on cigarette consumption at work and outside work. These variables should be separately assessed, A~ in other restmrch in smoking behavior, biochemical verification of self-reperted smoking status is desirable. Public kn~wledge about the health risks of involuntary smoking and attitudes .about smoking can be assessed by surveys, Data on social norms can be construed from survey items such as those measuring the social acceptability of smoking in public places or in the presence of nonsmokers, the rights of nonsmokers to smoke-free air, the perc~:ived prevalence of smoking in the cnvironment~ and the perceived social support for cessation or nonsmoking. The adequacy of a policy's implementation can be assessed by surveys that |neasure individuals' knowledge and compliance with a
Page 163: TI07870773
policy. The degree of noncompliance and enforcement can also be assessed by observations of behavior in public places subject to smoking restrictions. Review of Current Evidence on Impact Workplace 8making Policies In 19B2, Orleans and Shipley concluded that the evaluation of worksite smoking policies was limited to a few public opinion polls. ~lnce th.en, many policies have been adopted, but evaluation remains rare. Most common are baseline surveys done by companies consider- ing smoking policies. The best surveys utilize random or probability samples and achieve high rates of completion; they provide useful one-time data on attitudes and behavior prior to policy implementa- tion. Unl'ortunately, few companies adopting smoking policies have done postimplementation surveys to assess impact. To date, the best evaltmtions of worksite smoking policies have been done in the health care setting. There are two controlled and two uncontrolled studies assessing the effects on employees of adopti~g amnoking policy for a hospital (Rigotti et al. 1986; Biener et ai. 1986; Audrews 1983; Rasenstock et ai. 1986). One uncoatrolled study was reported by Andrews (1983). He described the process by which the New Eng[and Deaconness Hospital in l~oston adopted a restrictive smoking policy in 1977. Patients and employees were surveyed prior to the policy. F.mployees were surveyed again 20 months alter the policy took effect. The survey method and response rate were not specified; presumably it was not a random sample. Policy approval and smoki~g behavior were assessed. The second uncontrolled study (Resenstock etal. 19B6) evaluated the impact of a near-total smoking ban adopted in April ~984 by the Group Health Cooperative o1" Puget Sound, Washington, the fourth largest health maintenance organization in the Nation. Fnur months after the policy was adopted, they surveyed a systematic probability sample of 687 employees, assessing smoking behavior, attitudes toward the policy, and its eff~t on work performance. Employees were asked retrospectively about attitudes and behavior prior to the' poli~y. The response rate was 65 percent. The' two controlled studies oi' tl|e impact of adopting a restrictive hospital smoking policy are similar in design. Both involve prepolicy and postpolicy measurements o!" intervention and control groups and assess similar outcomes. Rigotti and colleagues (1986) studied the impact o{" a total ban on smoking adopted in November 1984 by the pediatric service at Massachusetts General ltospitsi in Boston. All nurses employed by the service were surveyed at baseli~te and at 4 and 12 months. Nurses working on the hospital's medical service, where no policy change occurred, were surveyed concurred|fly as 306 controls. Ile~ponse rates to the surveys ranged from 65 to 75 percentl the prevalence of smoking among respondents and nonrespondent~ did not difl'~,r. Surveys assessed smoking behavior, attitudes about smoking, a~td perceived air quality in both groups. Pediatric nurses answered a~lditional questions.about approval, compliance, and aware|xess ~f the policy. Employment records were reviewed to assess emph~yee turnover before and after the policy. Biener and colleagues (1986) studied employees at two Providence, Rhode Island, hospitals where self-help smoking cessation programs • were being introduced. At one, the Miriam Hospital, there was a concurrent change in smoking policy. Smoking was prohibited hospitalwldc except in three locations as of August 1985. Separate random probability samples of 85 employees at each hospital were surveyed by telephone at baseline (2 to 4 weeks before the policy) and at 1, 6, and 12 months after the policy. Data were collected in both hospitals on smoking behavior, attitudes about smoking, and air quality, lnf~rmation on policy awareness, compliance, and approval was obtained at the intervention hospital. Results o1" these studies are included in the subsequent sections, which address the outcomes of workplace smoking policies, Policy lmpl~,mentation According to case reports, organizations that have adopted smok- ing cm~trol policies generally develop careful plans to introduce the policy, but rarely evaluate how effectively the policy has been implement~l. The findings of Rosensteck and colleagues (1986) indicate that even careful implementation plans may fall short of their goals. In their survey of the Group Health Cooperative employees, ~mly half of the respondents knew of the existence of the advisory group whose role was to provide information to employees, Only 36 percent of the smokers and 76 percent of the nonsmokers felt that th,:y had had an adequate opportunity to express their views. Not ~11 smokers knew that the decision to prohibit smoking was an irrevocable one. Rigotti a~,,l colleagues (1986) found that awareness of the smoking ban on the pediatric service was high; at 4- and 12.month followups, over 90 perx'ent of employees knew where smoking was not permit. ted. Employees noted smoky air or smoking in restricted areas on approximal.~,ly 20 percent of days worked. Two-thlrds of the employ- ees who sm,~kvd admitted at least one personal episode of noncompli- ance during the year after the policy took effect. Although nonsmok- ers perceivc,l themselves to be more assertive in enforcing smoking rules after the smoking ban, many were reluctant to confront a smoker, esl*~:cially if the smoker was a coworker. Biener a~d colleagues (1986) found a similar high level of policy awarenes.~ ~*nd better compliance among the employees of Miriam 307
Page 164: TI07870774
Hospital in Providence. Six months after the adoption1 ,f a policy prohibiting smoking in all but three areas, 95 pelcent of the employees were aware of the I~dicy and half had noted no evidence of noncompliance. There was no evidence that smokers perceived more pressure to abstain in the form of increased assertiveness by nonsmokers; the policy may have reduced the need ~or assertive behavior. Rigotti and colleagues (1986) reported that ,torsos in the centre[ group described themselves us having to be mere assertive about asking people not to smoke than nurses in the i~licy group. Dawley and colleagues (Dawley et al. 1980; Dawley, Carroll et el. 1981; Dnwley, Mortises et aL 1981; Dawley and Baldwin 1983; Dawley and Burton 1985) addressed the question of compliance with smoking restrictions at the New Orleans Veterans Administration Medical Center. Their technique was to unobtrusively observe smoking behavior of individuals occupying areas designated as smoking or nonsmoking. In a series of lO-minuta periods, an observer noted the proportion of people mucking among all individuals occupying a nonsmoking area, which served as the measure of noncompliance. Posting no-smoking signs in a hospital lobby reduced the prevalence of smoking to one-third of its previous level (29 percent to 5 to 11 percent, p~0.01). There was a nonsignificant trend for better compliance with positively worded signs (e.g., "Please do not smoke") compared with negatively worded signs (e.g., "No smoking--Offenders subject to line") (Dawley0 Morrison et el. 19811. Posting signs designating a nonsmoklng area in a cafeteri, results in a similar decline in smoking p,'evalonce in the area. The combina- tion of signs and enforcement Q~dite reminders from staff to noncompliant patients) achieved greater reductions in smoking prevalence than were achiew:d with signs alone; however, the incremental value of enforcement was not directly as,,~essed in the study (Dawiey and Baldwin 1983). Following a change to a more restrictive smoking policy (smoking prohibited except in designated areas, with provisions for enforcement), the noncompliance rate dropped to under 2 percent (Dawley and Burton 19B5). Another study demonstrated that smoking models reduce compliance with smoking restrictions. The noncompliance rate doubled when a smoker was experimentally introduced into the nons,noking area (Dawley, Carroll et el. 198D. These studies i;*dicate that there has been good employee camp|i- ance wltb smoki,g policies in health care facilitie~, even though there may be some reluctance by employees to enforce restrictions. The implementalion of smoking policies in other types of worksites has not been systematically evaluated. Descriptions of the adoption of policies in a number of worksites do not report major problems with compliance (BNA 1986). 308 Air Qu,li(~ Three studios assessed air quality bel'ore and after hospitals adopted rcst|'ictive smoking policies. Both Rigotti and colleagues (1986) and lliener and colleagues (1986) used a subjective measure, the frequency that an employee was bothered by smoke at work. In the Rigotti group's study, perceived air quality was similar in the intervention group and the" control group at baseline. It improved significantly ~lt 4 and 12 months' followup on floors where smoking was beaned ;rod did not change on control floors. At 12 months, 79 percent of the nurses on floors with the smoking ban reported noticing less smoke, and none noted an increase; in contrast, 87 percent of control nurses noted no change in air quality. Biener and colleag,es fo,nd a similar pattern; there was a significant difference in perct,.ived air quality between employee assessments from hospi- tals witl~ and without a smoking policy. At the New England Baptist Hospital in Boston, the distribution of r~pirato;T particulates (liSP) was measured before and one year after the ad.ption of a restrictive smoking policy (Bearg 1984). At followup, ]~1' were lower in many hospital areas where smoking was restricted, most notably in patient care areas and an employee lounge, but remained high in the cafeteria. Because same-day measurements of outside air revealed low ambient RSP levels, Bearg concluded that the higll levels inside the building were a~tributable to smoking rather than air pollution. These studies suggest that hospital policies result in less smoking in work areas designated nonsmokiug, but that nonsmoking areas in cafeterias may provide little protection from secondhand smoke exposure I~c~,u,e of ventlh,tion problems and the increased smoking in the few snmking-permitted areas. Policy Appr~,~,al A number .f private and public sector organizations considering a, smoking i~,liry have asse~ed employee atLitudes prior to implemen- tation. Pncilic Northwest Bell, Pacific Telephone, New England Telepbo,~e, Texas Instruments, and StrideRite are among businesses that have done employee surveys (R. Addison. personal communi~a- ties, July 21, 1986; Pacific Telephone 1983; Robert FJnnegan Associates 1985; BNA 1986; Ziady 1986). Public sector employers include the Hawaii aud Massachasetts Departments of Publi~ llealth (Mnrvit 1980; Naimark 19861. The findings of these surveys are remarkahly similar. Over 60 percent of employees repor~ being at least occasionally bothered by smoke at work (Robert Finnegan Associates 1985; Pacific Telephone 1983; Ziady 1986; R. Addison, personal communication, July 21, 1986). There is broad support for adopting a smoking policy, even among smokers (Pacific Telephone 309
Page 165: TI07870775
1983; Robert Finnegan Associates 1U85; Marvit 1980, Sorensen and Pechacek 1986). A~sessment of employees' approval of policies after implementa- tion have been done primarily in health care settings, High rates of approval are the uniform finding, with smoker-nonsmoker differ- ences. In the Rlgotti group's study (1986), the overall approval of a smoking ban increased from 72 percent at baseline to 8,5 percent at 4 and 12 months. Most of the increase was a result of the improved opinions of the smokers. Only 35 percent of smokers supported the ban at baseline, but by 1 year this nearly doubled, t~ 67 percent. High rates of policy approval aL followup by both smokers and nonsmokers were also reported by biener and colleagues (1986) (69 percent smokers, 89 percent nonsmokers~ bnd Andrews (1983) (83 percent smokers, 93 percent nousmokers). Resenstock and colleagues (1986) found high overall policy approval at 4 months (85 percent), but less support by smokers (36 percent). These data indicate that smoking policies in hospitals are well accepted by employees, and that smokers' initial reluctance diminishes as they gain experience with the policy. Generalization front these studies is ]imlted by the nature of the population studied--health car~ workers. Followup surveys in industrial setting would bq valuable. Sorensen and Pechacek (19861 bare examined correlates of smok- ers' approval of smoking restrictions. They surveyed smokers in eight 'Minnesota businesses without smoking policies, sampling a broad cross-section of employees, from blue-collar workers to profes- sionals. Over three-fourths o1" the 378 respondents agreed that employers should establish separate smoking and nons=noking a=:eas at work. Smokers who favored worksite smoking policies bad greater interest in quitting and more concern for the health risks o~'smoking and saw their social environment as supportive of nonsmoking, as measured by a higher perceived coworker support for quitting and a greater perceived prevalence of nos=smokers. ~,moking Behavior Many smokers anticipate that their smoking behavior will change after a smoking policy is adopted at their worksite. At Pacific Telephone, 51 percent of the smoker~ exp~ted that the policy would lead them to alter their smoking habits, either by cutting down (38 percent) or quitting (13 percent) (Pacific Telephone 1983). In the Rigotti group's study (1986) of u hospital smoking ban, 72 percent of the smokers expected the policy to change their habits. All expected to smoke less at work and most to smoke less outside work. A successfully implemented smoking pelicy will provide a smoker fewer opportunities to smoke. Of course, the smoker may cumpen- lsate for reduced smoking opportunities at work by more intense smoking (number of cigarette,s,,, inhalation, puff topography) on breaks or wil.l~ increased smoking ou~ide work to maintain a constunt ow,rall daily c,nsumption. This is consistent with the addictive uv~dt:l of smoking behavior (Gritz 1980; US DE][~W 1979), But if comi.:,~.~ation does not occur, the smoker's lower rate at work would reduro overall daily smoking. Studies at present differ on which of tlwse alternutive.s occurs. The results reported below are entirely sell'-rt, perfa; thus, they suffer from a lack of biochemical validation o1' smoking status as well as from an inability to detect compeusatio~t through altered smoking topography (US DHHS 1985). Compensation did not appear to occur in the. Biener group's hospital study (1986). Among smokers in the "policy" hospital, the number of cigarettes smoked daily while at work fell from a baseline of 8.1 to 4.5 at 1 month and 4.0 at 6 months. Over the same time period, the at-work cigarette consumption in the control ,hospital rose slightly (7.6 to 8.1 cigarettes). The difference in smoking rates between baseline and t-month followup in the "policy" group was significant (p=0.02). At 6 months, rite difference in smoking rates at work between hospitals (8.2 vs. 4.0) was also significant (p--0.01), There were no significant change~ in the smoking rate outside work, Smokers in the hospital study by Resenstock and colleagues (1986) reported sm,~king a mean of 15.6 cigarettes daily, 2 fewer than be/ors the policy (p<0.003). These data suggest that smokers did compensate for reduced smoking opportunities at work by increasing their smoking at home. Rigotti m~d colleagues (1986) found indirect evidence for compen- sation. The nurses' self-reported cigarette consumption at work decreased i~= the policy group, but did not change in the control group. However, overall cigarette consumption in the policy group did not chm~ge. Both the degree d change and the number. O( smokers in I.he study were small. In aft earlier study, Meade and Wold (1977) compared the smoking behavior of three British employee groups. Smoking was prohibited at work in two groups. Smokers who were allowed to smoke at work had a somewitat higher self-reported average daily cigarette con- sumption. The maximum rate of smoking obcurred at work in' the afternuon, but for workers prohibited from smoking at work, the maximum r~tte occurred in the interval between leaving work and retiring'at night. There htm been much speculation that. smoking policies will increase the,, smoker's motivation and success in quitting. In the study by Bib:net and colleagues (1986), the percentage of smokers considering quitting in the next 6 months increased from 71 percent at baseline t.o 91 percent at (ollowup, but there was no change in motivation i,i the control hospital group. Two-thirds of the smokers in Roaenutt,ck and colleagues' uncontrolled study (1986) had a 311
Page 166: TI07870776
definite desire to quit. Howew~r, Rigotti and collcaguc,~ (1986) found no difference in the motivatio, of nurses between the control group and the policy g~'oup. Smokers' use of worksite smoking cessation programs before and after policies go into effect have been used as an index of their motivation to quit smoking. The results are ~nixed, In the 6 months after Pacific Northwest Bell adopted a smoking ban in October 1985, 1,044 employees, representing 21~ percent of all smokers, enrolled in programs reimbursed by the company. This compared with 331 who attended free onaite programs in the previous 26 montlts. The cost to thi~ company, per smoker w~ $142 (Martin 1986; K. Rowland, memorandum for Lea Bell, April 25, 1986). At Texas Instruments (R. Addison. personal communication, July 21, 1986}, 486 smokers enrolled in cessation classes during less than I year alter the announcement of a smoking policy; this co~npares with only 11 in 1982, the last year for which statistics were kept. In both cases, this enthusiastic response may i. part be due to the employers' new willingness to pay for the classes, as well as to the lace.tire provided by a new policy. For example, only 8 of 148 smokers at the New England Denconness Hospital who said they were interested in a smoking cessation program on their own time actually showed up (Andrews 1983). Even company sponsorship is not a guarantee of popularity. At the Group Health Cooperative, only two smokers aware of the company-sponsored censation programs had participat- ed Within 4 months of policy .doption (Itosenatock et el. 19B6). The signup rate for worksite-basod self-help smoking cessati(m programs was no greater nta Rhode Island h~pital with a ~!ew smoking policy than at one without {Biener et el. 1986~. It is not known whether the cessation rate of smokers wh. enroll in worksite programs is affected hy the presence of a am.king policy at the worksite. Only uncontr~dled studies with 8olf-rel~rt measures are currently available. At Texas Instruments (R. Addison, personal communication, July 21, 1986~, 34 lmrcent of 354 emplt~yees enrolled the first round of company-sponsored cessation clae~es quit by the end of the program; in the second round df clas~es, 17 percent of 132 enrollees quit. At Pacific Northwest Bell, 44 percent of 639 respon- dents quit smoking in a survey of the 1,200 participants in a company-sponsored program. If nonresponde.Lq art: included as smokers, the cessation rate was 23 imrcent (Shannon 1!186). There is as yet no conclusive evidence that smokiog policies are associated'with increases in smoking cessation attempts or reduc- tions in smoking prevalence. All reports are based on self-reported smoking behavior. There are anecdotal reports of smokers quitting in case reports of company policies (StrideRite, cited in BNA 1986) and in uncontrolled surveys (l~osenstock et el. 1986; Andrews 1983~. Supporting evidence comes from the New England Deaconness 312 Hospital° where a t'~vo-part survey, before and 20 months after the , adoption of o strict smoking policy, demonstrated a reduction in the prevale.ce el' smoking among employees from 32 to 24 percent, along with an i~tcrv.ase in the prevalence of ex-smokers ~27 to 34 percent) {Andrews 1983~. However, metbodologic problems prevent an equivocal co.clusion. The t~rst survey included beth employees and patients, but the followup covered only employees; smoking rates for employees o.ly are not provided. The survey method w,as not specified, hut it did not appear to be a probability sample, thereb~ limiting gen~,ralizability of the finding to the entire grou~. Finally, because the same group of employees was not surveyed aS followup, analternate interpretation for the change in smoking prevalence is that the i.mli~:y influenced employee turnover rates so that smokers left and were replaced by ex-smokers. The study did not assess employee turnover. Controlled studies by Biener and colleagues (1986) and Rigotti and colleagues 0!}86) did not detect an increase in smoking cessation by employees of hospitals that adopted smoking policies. In the study by Rigotti and c~lleagues, nm~es in the policy group did not differ from controls in their motivation to quit, or their expectation of doing so, or in the number or success 6f quit attempts. The prevalence of smoking i. the polic~ group and in the control group was similar at baseline anti did not change 'in the year after policy adoption, Similarly, employees in a Rhode Island hospital with a smoking policy were uo more likely to try to quit or to succeed in quitting than were employees b~ a control hospital (Biener et el. 1986~. The number of smokers in these two studies was.small, and it is possible that the at.dies lacked adequate power to detec~ changes in behavior. Followup periods of greater than 1 year amy also be required. Attitudes Alnmt Smoking • There has laden little assessment of the impact of work.site smoking policies on ~tttitudes about smoking. The two controlled studies hsspitol smelting policies assessed attitudes about the health risks of smoking and shout involuntary smoking (Biener et el. 1988; Rigotti et el. I!~86l. There was no significant change in the smokers' beliefs about the health risks of smoking or about environmental tobacco smo.ke expos.re. Managt:ment Issues There is truly sketchy evidence about the impact of workslto smoking policies on absen.teeism, health care co~ts, productivity, or employee tu~ never. No systematic analysis of economic impact has been done. There is an anecdotal report of cost saving by the Merle 313
Page 167: TI07870777
Norman Cosmetic~ Company, which reported lower absenteeism and i'~oasekeeping costs and incre~sed preductivity in the year after it adopted a ban on smoking (ALA of San Diego 1984). In the 6 months after Pacific Northwest Bell adopted a total smoking bnn, no employees left because of it (Martin 1986). Rigotti a~d colleagues (1986) reported no change in employee turnover in the year after the adoption of a hospital smoking ban. Rosenstock and colleagues (1986) found that self-reported work performance was unaffected in 75 percent of employees and improved in 21 percent. Costs involved in implementing a smoking policy have not been systematically mea- sured, but appear from case reports ta have been small (BNA 1986). Adverse impacts of worksite s~noking policies have not been report- ed. Legislation Restricting 8moking in Public Places Legislation restricting smoking in public places has been less well 'evaluated than worksite smoking policies. Opinion polls in States al~d communities that have passed smoking control regulations provide some information on attitudes about smoking and smoking policies. There are no controlled studies of the impact of legislation on smoking behavior or attitudes. Policy Implementation and Ettforcement Evaluation of the implementation of State or local smoking control statutes has been limited. In general, enforcement is delegated to a State or local agency, such as the department of public health. Enforcement is handled passively rather than actively; the responsi- ble agency responds to complaints, but does not actively monitor policy compliance by surveying worksites, restaurants, or public places. Nonsmokers rights groups and individual activists are a major force for informing the. public and aiding carol-cement by bringing complaints (Sandeli 1984). The experience of cities like San Francisco and States like Minnesota contradicts tobacco industry estimates of the expense and intrusiveness required to enforce a smoking law {Martin 1986, New York Timefi 4/13/86; Sandell 1984). In the first year after San Francisco implemented a strict workplace smoking law in March' 1984, only 124 complaints were processed and 1 citation was issued; there were no legal actions. No new employees were hired and no additional funds were required for enforcemen't. Policy enforcement required progressively less of a single employee's time over a 1-year period (Martin 1986). Minnesota en/brces its 1975 S~ato smoking law in u fashion similar to San Francisco's. State public health depart- ment officials estimate that they handle 1,200 to 1,4(~0 complaints per year, with costs of enforcement estimated to be under $5,000 per 314 year (Sa~tdell 1~84). A survey of 10 California cities with workplace smoking I~w:~ docume~ted that complaint rates were low and enforceme~tt ¢,f these lz~ws was a low priority for all city govern- ments. Ol1~ci~ds indical.ed that they would spend any additional funds ovaliable for enforcement on a public education campaign to increase aw~'eness of the law rotifer than initiate active surveil- lance (Linsolt 1986). Because ~etive monitoring of policy compliance is not done, a low complaint rate is often taken as evidence of a high compliance rate. Data from Mim~esota suggest that this is not always true.' In 1976, 1 year after the comprehensive Clean Indoor Air Act was enacted, 43 percent of respondents to a statewide poll felt that the law was not very effective in reducing smoking in public places; 38 percent found it somewhat e!fective and 12 percent very effective (Minneapolis Tribune 197~i). Six years after the law took effect, a survey of Minnes~ta bnsi~tesses with 200 or more employees docu~.nented that. only 46 percent of businesses had such a policy. Restauran.ts, however, had nearly uniformiy conformed to the law within a year of implementati~m (Sandell 1984). A statewide opinion poll in 1978 demonstrated that over 70 percent of both smokers and nonsmokers felt that the., Clean Indoor Air Act should be strictly enforced (Minneapolis Tribune 1978). Two years later, Minnesotans were of mixed npini~m about the law's enforcement: fewer than half (43 percent) considered it very well enforced, 42 percent felt it was not so well enforced, and 10 percent said it was not enforced at'all (Minnealmlis Tribune 1980). Randolpls (1982) studied factors a~ociated with c~mpliance and enforcement of local o|'dinances regulating smoking. She assessed the implemcnt~ttion of a recently enacted San Rafael, California, smoking ordinmtce by interviewing proprietors of randomly selected buslne~es. I,~ss than 1 year after the ordinance went into effect, 68 percent of 25 proprieters were awa~e of the policy, but only 44 percent of 3~! businesses had complied with the'requirement to post no-smoking signs. The major variable associated with compliance by basiness,nen w~ts the type of business; restaurants, retail food stores, drug stores, banks, and movie theaters were generally posting signs as required, but department stores and small retail stores were not. City resident~ were less well informed. Fewer than half(41~ percent) of 200 rn~d~mly selech.~d .residents surveyed by telephone were aware of the ordinance, and only 11 percent could describe its provlslo~. IL~nd~lph's sl.udy (1982) of implementation also included a 1980 telephone st~rvey of 600 rando~dy selected residents of three northern CaliFornia cities, two with smoking ordinances and one without. Shrinkers were classified as compilers or noncompliers according to whether they refrained from smoking in supermarkets, 315
Page 168: TI07870778
which was required by State law. Clmracteristics o£ smokers who complied were (1) lower daily clgnrette consumption, (2) less per- ceived need to smoke, (3) greater perception of others' disapproval for tobacco smoking in public, (4) and greater support for policies restricting smoking in public places. Smokers' perception of pres- sures to refrain from smoking in public, awareness of the presence of a local smoking law, and the duration of the ordinance were not associated with compliance. Enforcement of smoking laws wan studied in nonmnokers. The best predictor of enforcement behavior was a nonsmoker's degree of nnnoyance with tobacco smoke. Other characteristics associated with enforcement behavior were more negative attitudes about ~mo.king in public places, greater intoler- ance of noncompliance, and higher educational level. • Policy Approval National and regional polls have surveyed public opinion about where smoking should be restricted or banned. Regional polls ha~,e often been taken when legislation is being considered. There are little data obout public opinion on legislation aRer its enactment. Nationwide public opinion about smoking in public places was assessed by Roper polls in 1976 and 1978 (]978), two Gallop polls (1978, 1983), and the 1985 Harris Poll-Prevention Index (Harris Organization 1985). The Roper polls asked separate questions about preferences for a smoking restriction or a total ban; the Gallop and Harris polls offered a choice between the two in the same question. In both Roper polls, a majority of respondents favored restricting smoking in all plraces mentionc~h transportation vehicles (airp[anes, buses, and trains), restaurants, workplaces, and indoor arenas. By 1978 three-fourths of the respondents favored restrictions in all places except the worksite. Total smoking bans were less popular but still the choice of at least one-fourth of the respondents. The 1983 Gallop poll docmnented increased public support for smoking restrictions, particularly in restaurants. More than 80 percent of smokers and 90 percent of nonsmokers favored either banning or restricting smoking in airplanes, buses, and traius and restaurants. Over half of beth smokers and nonsmokers favored restrictions in motels and at the workslte. Although bans were less popular than restrictions, they were twice as popular with nonsmok- ers as with smokers. In 1985, 80 percent of the respondents to a llarris poll supp~rted restrictions or bans in public places in general. Regional polls generally suplmrt the conclusions of natinnwide surveys. Minnesota is one State where pablic opinion of existing legislation has been measured. Five years after enactment, pub|Jr opinion Of Minnesota's 1975 Clean Indoor Air Act remained high. Ninety-two percent of the 1,200 respondents to a statawide poll favm'ed the act, including it7 percent of heavy smokers (two packs per day) and a larger fracl.imt of lighter smokers (Minneapolis Tribune 1980), . During th,: first year of the San Rafael, California, smoking ordinance, n~.arly 70 percent of 200 randomly selected residents agreed that there should be laws shout smoking in public places and 77 percent m,id they would base veiled for the ordinance had they had the olq~wLunity (ltandblph 1982). The reaction of local basle sasses was less favorable. Over half (52 percent) did not like the ordinance, but on!y 41 percent favored rescinding it, The most common reason for support was concern for smoking-related damugo to property. {~ncerns about invading personal rights and fear ol~ losing business were the major reasons for opposition. Attitudes aml .5ocial Norm~ It has been suggested that smoking restrictions will alter public attitudes anti norms about smoking behavior. Tl~ere are few data addressing this hypothesis. Randolph (1982) reported on attitudinal difference~ between residents of California communities with and without smoking ordinances. Smokers iu two cities with laws had more negative attitudes about smoking in public places and were more likely to feel that there should be laws regarding tobacco smoking in public. However, there was no difference in smokers' perceptions of social pressures to refrain from smoking. Nonsmokers in cities with laws were more likely to believe that tobacco smoke should be regulated in public, but they were no more annoyed by tobacco smoke~ intolerant of noncompliance, or disapproving of smoking in public places than residents of the city without a law, Although residents of communities with and without smoking ordinances did not differ in their persennl support of smoking laws, residents of communities with laws perceived greater support for these laws by other residents of their communities. This cross-sectional study cannot differentiate whether the~e attitudinal variations were a cause or consequence of differences in community smoking ordinances. Data from opinion polls demonstrate that negative attitudes about smoking generally preceded rather than followed legislation to restrict stashing in public places. The four Adult Use of Tobacco Surveys, a series of nationwide surveys conducted between 1964 and 1975, measured attitudes in the decade after the health hazards of smoking were first widely appreciated (US DHEW 1969, 1973, 1976), As early as the first survey in 1964, a majority of nonsmokers agreed with these statements: "It is annoying to be near a person who is smoking cigarettes" and "Smoking should be allowed in fewer places than it is now." By 1970, a majority of all respondents agreed with these statem,:nts. By 1975, a majori*oy of smokers agreed with the idea of furtht:r restricting smoking, suggesting that there was wide 317
Page 169: TI07870779
public support for restricting smoking well before thq first compre- hensive Clean Indoor Air Act was passed in Minnesota in 1975. As early as 1973, 73 percent of the nonsmokers in a Mim~esota poll felt that they had the right to a smoke-free environment, and 65 percent wanted to ask ethers not to smoke (Minneapolis Tribune 1973). More recent opinion polls document that negative attitudes about smoking in public continue to grow. in a 1985 Gallop poll, 75 percent of the respondents (including 62 percent of the smokersl felt that smokers should refrain from smoking in the presence of nonsm,=kers. However, nonsmokers' attitudes do net trm~slate directly into action. A smaller proportion of nonsmokers are willing to confront a smoker whose amoke is bothersome. In three successive Roper polls between 1974 and 1978, fewer than 10 percent of the nonsmokers indicated that they would ask an i=tdividual smoking indoors to stop (Roper 1978). Only 32 percent of the nonsmokers in a 1974 Minnesota poll would complnln when bothered by another person's smoking, although an additioual 31 percent would take nonconfron- tational action such as moving away or opening windows (Minneapo- lis Tribune 1974). These data suggest that in the mid-1970s, despite strong preferences, many nonsmokers did not perceive that asking a smoker to stop was socially sanctioned behavior. Smokers, on the other haml, report an awarenes~ of uonsmokers' concerns and a wiiJingness to comply with restrictions. " Over 90 percent of the smokers in a 1981 Iowa poll (Des Moines Register 1981) extinguished "tobacco wizen they saw a no-smoking sign. Sixty percent of the smokers in a 1973 Minzzesota poll (Minneapolis Tribune 1973) bad at least some misgivings about smoking in the presence el" nonsmokers; and 90 percent would not have been offended if asked not to smoke. Only 29 to 36 percent of smokers in three Roper polls (1974-1978) lit a cigarette without looking around, asking others, or refraining from smoking (Roper 1978). There may be, therefore, an interactio|l between attitudes and policy development. These survey data suggest that altitudes about smoking in public preceded and may have contributed to the development of a public policy (Breslow 1982). At the same time, publicity surrounding campaigns for legislation =nay increase public awareness of an issue such as the hazards of involu,~tary amoking and therefore contribute to further changing attitudes. Smoking Behauior The impact of legislation on smoking behavior has received little formal attention. There are no controlled studies in which smoking behavior has been tracked over time in the States or communities that have enacted smoking legislation. In Randoiph's one-time assessment (1982) of smoking behavior in California communities with and without smoking control ordinances, there was no differ- 318 ence in s~neki=xg prevalence or mean daily cigarette consumption between the residents of a city with a recent ordinance and one without. A I.wer prevalence of smoking in one commualty with a longstanding; ordinance was probably explained by demographi~ differences I,:tween that community and the other areas. Uncontrolled reports of declining smoking prevalence or cigarette consumption in a State or cam.reunify with a smoking law cannot establish a c~msal relationship. This was particularly the case during the 1970s, when both smoking prevalence and per capita cigarette consumption were declining nationally. Warner (1981a; Warner and Mutt 1982] conducted a series of analyses of this decline. In separ.ate analyses, he estimated the levels of smoking prevalence and ciga- rette consumption that would have been achieved if previous trends in these indicators had continued unabated through the 1960s and 1970s, Cigarette consumption in 1978, for example, would have been 36 to 41 percent higher had previous pattern8 continued. He ascribed the difference between observed and modeled values to the impact oF the so-called antismoking campaign, defined as the combination o~' public evenls, legislative activity, and Federal regulations that affected cigarette price, counter-advertising, and the circumstances in which sm~,king was allowed. To assess the relative contributions of components of the anti, smoking campaign to the decline in adult per capita cigarette consumption, Warner (1981a) developed a multivariate analysis that included imlependent variables to account for price fluctuations, adverse publicity about smoking, antismoking act{rifles, and the effectiveness of the nonsmokers' rights movement. The percentage of adults residing in States restricting smoking ,in public places was used as an index of the strength of the nonsmokers' rights movement. This variable was strongly associated (p<0.0001) with decreases in consumption from 1973 to 1978. In Warner's view, the temporal relationship between the growth in legislation restricting smoking in public places and the decline in cigarette cm~sumption is so close that a causal relationship is unlikely. Ile attributed the decline in consumption to the changes in attitudes nn~l social norms about smoking that were.an earlier consequence o1" the entire antismoking campaign. He regarded the legislation ~,,~ another reflection of changing social norms rather than the creator of them (Warner 1981b). Recommendations for Research Policies restricting the ci'rcumstances wh.ere smoking is permitted have been ad,pted by a broad range ot" institutions, mostly in the last decade. Smoki~g regulations affect the daily lives of a large and growinl; number of Americans. Consequently, these policies are of 319
Page 170: TI07870780
interest to many individuals and groups. For instance, public health officials are concerned about the health effects of b~th active and involuntary smoking; they are most interested in whether these policies actually reduce a population's exposure to environmental tobacco smoke and whether they will alter the prevalence of smoking, Behavioral scientists, primarily concerned with smoking behavior and attitudes, are chiefly interested in how smoking policies alter these variables and how this knowledge can increase our understanding of the dynamics of smoking behavior. Businesses, unions, and govermnent policymakers have different perspectives. They are faced with deciding whether to adopt smoking restrictions and how to improve the imple,nentation and acceptability of existing ones. Information about the determinants of policy approval and compliance will be of most interest to them. Businesses may also be concerned about the economic and managerial impacts of smoking restrictions.' Understanding the effeot of policies on smoking behavior is of widest interest and deserves attention. Policies may affect the natural history of smoking behavior at several points, ~md detailed behavioral information should be collected to distinguish among effects on rates of initiation, cessation, and relapse, Studying how smokers cope with enforced abstinence may provide additional insights into the maintenance of smoking behavior, Dvladled studies of the influence of policy may advance the state of knowledge about the determinants of smoking behavior in general. The relationship between interventions at the social and individual levels is also of interest. Researchers should consider whether the effectiveness of individual treatment is enhanced by the presence of a smoking policy, and whether the impact of a policy is enhanced by the ayailability of individual treatment. Concurrent collection of infor- mation on attitudes about smoking may help to clarify the nature of the relationships among attitudes, smoking behavior, and smoking policies. In addition to considering a variety of outcome measures, re- searchers should address the determinants of these outcomes. Characteristics of the policy, the institution, and the population should be considered. The components of a smoking policy and its implementation (such as restrictiveness, degree of advance notice, degree of support for the policy by affected groulm, access to smoking cessation programs) that contribute to its effect--be it on behavior, attitudes, air quality, acceptability, or compliance--have generally not been analyzed. Because smoking policies vary widely in their provisions and implementation, they cannot be evaluated as a unitary interrelation; i.e., better oporationalization of "policy" inter- ventions is needed. The relative strength of policy c~m~pone,~ts on each outcome measure should be assessed in order to make informed 320 policy re~'.ommendations. For example, the degree of protection from involuntary smoke exposure afforded by policies of different degrees of stringen~T in not empirically known. To a~ui~v this knowledge, researchers will need to develop and validate me~ures of auvh concep~ as restrictivenem. The index descried in this chapter is a preliminary at~mpt to do that. The com~nen~ of a policy that are most I~werl'ul in r~ucing'eigaret~ consumption, inducing ce~ation at~mp~, preventing relate, or reducing smoking initiation need ~ identified. Similarly, the comimnen~ of a ~licy a~ia~d with maximal a~eptabilil.y and ~mpliance have ~en addr~ed only cur~rily, Dawley and colleagues (Dawley, Morrison etal. 1981; Dawley and Bur~n 19B5), for example, have examin~ variabi~ such ~ the wording of signs or the pr~nce of active enforcement. Ouidelin~ for the implementation of smoking ~licies have not ~n men~lly d~rived. Research ~uld empiri~lly sup~rt or refu~ r~ommendutions on the b~is of extricate. ~n~entions suoh the training of managem ~ handle implemen~tion problems might then ~ develo~ ~ incr~ ~licy a~p~bility and compliant, Diflbrent ty~s of organi~tions have printed different climate for th~ adopti~m of smoking regulations. In ~ing ~licy impact, there may also ~ essential in~ractions ~tween the ~licy and ty~ of facility in which it is adop~. Even within a single ty~ of facility, there may ~ ~nsiderable variability in ~ial norms, s~ial sup~r~, and characteristi~ of the ~p~lation using it. ~ren~n and colleagues (1986~ have ~int~ out thee differenc~ among worksi~. Policy evaluations should ~nsider thee variabl~. B~u~ smoking ~lici~ repr~ent a r~ent s~ial phenomenon, there is at p~ent relatively little information a~ut their impact, New imlicics are ~ing adop~ at a growing rate, providing r~earchers with the op~rtunity to study natural ex~rimen~ that, up ~ now, have largely gone unevaluated. ~e'variety of ~ntial ou~omes, mimer of in~r~t~ partly, and current lack of informs. tiou make eflbr~ ~ coIl~t sys~matie da~ on new public and private sectar smoking ~iiei~ a high priority for r~earch, ~n- trolled studies are d~irable and ~rmit the firmer conclusion, but with the cm'rent knowledge b~, even limit~ effor~ may yield valuable inl~rmafion, Uncontrolled c~e studio, for vxample~ can provide sugg~tive data and generate hy~theses for further ~sting. In some canes, da~ are already partially collected. For example, many Imsiai,~ considering smoking ~licies sudsy employees at baseline, but I~w re.at ~he survey after policy adoption. At the aggregate I.vel, it may ~ p~ible to estima~ the impact l~islation .n smoki]~g prevalence or cigarette consumption by relating aa~.ional sudsy da~ on smoking ~havior ~ smoking r~trictions in g~graphic are~. 321
Page 171: TI07870781
i,Conclusions 1. Beginning in the 1970s, an increasing number of public and private sector institutions have adopted policies to protect individuals from environmental tobacco smoke exposure by restrictlag the circumstm~ces under which smoking is permit- ted. 2. Smoking in public places has been regulated primarily by government actions, which have occurred at F~.~ierai, State, and local levels. All but nine States have enacted laws regulating smoking in at least one public place. Since the mid- 1970s, there has been an increase in the rate o[ eztactment and izi the comprehensiveness of State legislation. ]~al govern- meats have enacted smoking ordinances at an increasing rate since 1980; more than 80 cities and countie~ have smoking laws in effect. 3. Smoking at the workplace is regulated by a cbmbination of government action and private initiative. Legislation in 12 States regulates smoking by government employees, and 9 States and over 70 communities regulate smoking in the private sector workplace. Approximately 35 percent or busi- nesses have adopted smoking policies. The increase in work- place smoking policies has beezz a trend or the 1980s. 4. Smoking policies may |rove multiple eft'acts. ]~ addition to reducing environmental tobacco smoke exposure, they may alter smoking behavior and public attitudes about tobacco use. Over time, this may contribute to a reduction of smoking in the United States. To the present, there has been relatively little systematic evaluation of Policies restricting smoking in public places or at the workplace. ~. On the basis of case reports and a small number of systematic studies, it appears that workplace smoking policies improve air quality, are met with go~i compliance, and are well accepted by both smokers and nonsmokers. Policies appear to be /'ollowed by a decrease in smokers' cigarette consump~.ion at work and an increase in enrollment in company-sponsored smoking cessation programs. 6. Laws resLrlcting smoking in public places have been imple- mented with few problems nnd at Jittle cost to State and local government. Their impact on smoking behavior m~d attitudes ~as not yet been e~aluated. 7. Public opinion polls document strong and growil~g support for restricting or banning smoking in a wid~ range of public places. Changes in attitudes about smoking in public appear to have preceded legislation, but the interrelationship of mnoking attitudes, behavior, and legislation are co.mplex. 322 APPENDIX
Page 172: TI07870782
APPENDIX The Comprehensiveness Index of State Laws To I~rmit comparisons over time, an index' of the comprehen- sivenes~ oJ' each State'8 "smoking law was created, Laws were classified on the basis of the number and nature of places where smoking was restricted or prohibited. The overall principle was that stronger zm.asure~ are those that reduce exposure to ETS to the greatest del;ree. More comprehensive laws were considered t9 be those that i'estrict snzoking in a larger number of public places, extend to privately owned facilities, and cover places where individu- als speud a large amouut of time. Laws regulating smoking in private worksites were considered to be the the most comprehensive, and States with such laws were assigned the extensive category. Because individuals spend more time at work than in any other place out~ide the home, workslte legislation Ires the potential for marked reductions in public exposure to involuntary smoking. Worksite law~ also represent an extension or legislatiozz to the private sector, considered a further evidence of I.heir comprehensiveness. Nine States are categorized as having exteltsive restrictions; the average number of public places covered by their legislation was 11.0. The zzext most strizzgent category, moderate, was assigned to States that regulated smoking in restaurants. Restaurants were chosen because they represent privately owned public places and because, laws covering them have been controversial to enact. It was felt that Stal.~ regulating restaurants but not the private workplace had moderately comprehensive restrictions. The I0 States in thi~ category also regulated smoking in a large number of public places (9.~). The last two categories, nominal and basic, were defined I'or States that did not regulate smoking in restaurants or in the private workphzce. 'l'hey differed in the number of public places covered. States restricting smoking in one to three public places were considered to have nominal restrictions. Those restricting smoking in four or mo;'e public places were classified as. basic. 325
Page 173: TI07870783
This aumber of public places covered by smoking restrictions ihereases with increasing comprehensiveness of categories. Mean number of Number of public place8 Cate_~ States covered Extensive . 9 11.0 Moderate 10 9.5 Basic 15 6.6 Nmninal 8 1.4 No policy 9 0 For the calculation of the comprehensiveness index, categories were weighted as follows: C~ategory Weig~_ht Extensive 1.00 Moderate .75 Basic .50 Nominal .25 No policy .OO 326 References ACTION ON SMOKING AND HEALTtl. Slatewide No Smohlng Law~ Enat'led by State Lcgislatures. Washington, D.C., Action on Smoking and Health, 1986. ADDISON, R. New England Baptist Hospital i~ject, 1983.1984. Report of the Clean Indoor Air I~ucotianal Foundation, Boston, Mommchusetts, September 1984. AMA C~)UNCIL ON SCIENTIFIC AFFAIitS. Nonsmoking in hospitals. Connecticut Medicine 4~151:2~7-305, May 1984, AMERICAN ACADEMY (IF P[~DIATRICS, COMMITrEE ON ENVIRONMENTAL IIAZARDS. h~voluutary smoking: A Imzard to children. Pcdiatri~ May 19B~. AMERICAN ~DLLEGE OF PiIYSICIANS. Cigarette Abuse Epidemic. Unpublished poelllou pnper, January 28, 1986. AMERICAN I IOSPITAL ASSOCIATION. A Re~ouree to A~ist Hospitals in Develop, ing Policies an Smoking. Chicago, American ltospltal A~sociatlon, 1982, AMERICAN I.UNO ASSOCIATION. Creating Your Company Policy. New York, American I.ung Association, 1985a. AMERICAN I,UNG ASSOCIATION. Taking Executive Action, New York, American Lung Association, 1985b. AMERICAN I,UNG ASSOCIATION OF SAN DIEGO. Why Smoking Doesn't Work for Business. 77~e Facts. American Lung Aa~ocl~ttion of San Diego, 1984. AMERICANS FOR NONSMOKERS' RIGIITS FOUNDATION. Collfornla city and county ordinances. In: Appendix of LegiMative Approachel to a Smoke Free,Society, Berkeley, ~.'nlifornta, Americans for Nonsmokers' Rlghte Foundation, 19116, ANDREWS, J.L.. Jr. Reducing smoking In the hospltah An effective model program. Chest 84(21:296-209, August 1983. BAILEY, A. I,'e.wer Connecticut high ~choclo allowing smoking, Connecticut Health Bulb.tin 9714):280-281, 1983. BARR0 S.II., I,AMBERT, C.A. Smoking regulation In re~taurant~ and health-care facilities. Iletler). New England Journal of Medicine 306113):812, April 1, 1982. BEARG, D.W. 1984 Follow.up Study of Measurements of Respirable Particalaie~ Gem.rated l"~,m Tobaccu 8make at the New England Baptist Hospital. Report of Life Energy As~oclate~, Augtmt 1984. BENNETP, D., LEVY, B.S. Smoking pollcle~ and smoking co, alien progranm of large employers in Ma~aehu~etts. American Journal of Public Health 7016~:629-631, June 1980. BERMAN, E.J., ItlCNARDS, J.W. Jr., FISCHER, P.M,, CR~YrEN, D.A. Tobacco In hospitals. Iletter). Journal of the Amerimn Medical A~ociation 254(24):3420, December 27, 1985. BERTEI.SEN, ,I., STOLBERG, C. The h~pital's role in smoking preventlpn: A survey, Massach*tsetts Journal of Communily Health 20-21, Spring 1981. BIENEII, L., ABRAMS D.B., FOLLICK M.J., McANULTY D., DEAN L. Effects of a Restrictive ,~moking Policy on Hospital Employee~. Presentation to the Society of Belmvioral Medicine, Sat= Francisco, March 1986. BRESLOW, L. Control of smoking from a public policy perspective. Annual Review of Public Health. 3:129-151,1982. BUREAU OF NATIONAL AFFAIRS, INC. Where There's Smoke: Problem~ and Policies ~mcernlng Smoking in the Workplac~ Washington, D.C., Bureau of National Alfuirs, Inc., 1986. DARTNELL'S BUSINESS. Smoking still not policy Issue In most offices. Dartnell~# Basiness 19110 I(4~:37-40, June 19~0. DAWLEYo II.II., Jr., BALDWIN, J. The control of smoking: Smoking rate In designatod smoking and no-smoking area~. International Journal of the Addictions 1817):103,3-1038, 1983. DAWLEY, ii.11., BURTON, M.C. Smnklng control in a hospital netting, Addictive Behaoiws I~K4):351-355. 1985. 327
Page 174: TI07870784
DAWLEY, li,ll., Jr., CARROL, S,F,. MOItRISObl, J.~. The di.~.ouragement ol smoking in a hospital setting: The importance of modeled behavior, lnternatiwlal Jrm rnai of the Addictions 16(5):905-91 O, 1981. DAWLEY, it.H., Jr., MORRISON, J., CARREL, S, Compliance behavior in a hospital setting: Employee and patient~' reactions to no-s~noking sign~. Addictive Behauior~ 5{4 h329-33 I, 1980, DAWLEY, H.H., Jr., MORRISON J., CARREL S. The effect of differently worded no- smoking signs oa amoking behavior. International Journal of the Addiction~ 16~8l:1467-1471, 1981. DES MOINES REGISTER. Mint lowans won't challenge amoker~: Poll. Dez Moin~ Sunday Register, July 26, 1981. DILLOW, C. Thank you for not smoking: The hundred year war agaiust the clgarett¢. American Heritage 32(2):99--IO7, 1991. DOYLE, N.C. State and municilmllties regulate smoking in work, public plnce~. Busine=~ and Health 2(1):12, November 1984. ERIKSEN, M. Workplac~ smoking eoatroh l~attonale sad ~pproaches, Advances in Health Education and Promotion, VoL i, In press. ERNSTER, V.L,, WILNER, S.I. Nonsmoking polkles In hasp|tel|. Jrmrnal of Publi~ Health Policy 642):197-203, June 1995. FBLDMAN, J., IIUANG, S., LYMAN0 J.0 SOIIECK, E. The Legal Asl~Ctl of Smoklng Regnlntion, Stanford, Stanford Envlronmentol L~w Society, Mey 1978, FIELDING, J.E. Banning work~lto |moklng. American Jom*~al of Publi~ Health 7648~:957-958, August 1986. [" F,I,DING, J.E. Effectiveness of empl.yee health improvement programa. Journal of Occupational Medicine 24(11):907-916, November 198~. GALLUP ORGANIZATION. Monthly Report on Eating Out, Princeton, Gallup Organization, January, 1984. GALLUP ORGANIZATION, Smoking in America: Public ettltadcs and beha.ior. Gallup Opinion index 155:1--30, June !978. GALLUP ORGANIZATION. Survey of At~itud~ Toward Smelting. Survey c~nduct~d for the American Lung A~soclation, Pri.ceton, Gellup Organlu~tion, July 1985. GALLUP ORGANIZATION. Survey of A~titudes Toward Smoking. l'rinceton, Gallup , Organization, April 1983. GRITZ, E.R. Smokies behavior and tobacco abuse. In: Mello N.K. (ed~. Advanc~ in Sub, lance Abase: Behauiornl and Biological Rest.arch, A R¢~mrch Annual. Vol. 1, Greenwich, Connecticut, JAI Press, 1980, lip. 91-158. GROUP AGAINST SMOKING POLLUTION. Guide to o Smok~.Free Workplace. New York, GASP, 1985. HANAUER, P., BARE G., GLANTZ, S.A.I.egis|alive Approaches to a Smoke.Frt'e Society, Berkeley, Americans [or Nonsmokers Rights Fou.dation, 19ttG. IIARRIS ORGANIZATION. Prevention Index 85: A Report on the Nalion'~ Health. Emmaeus, Pennsylvania, Rodnls P~ ess, 1995. I IOLLANI)ER-COHEN ASSOCIATES. Sun Poll. Baltimore Sun, October 1984. IIUMAN RESOURCES POLICY CORI~)RATION, Smol~i.ng Policies in Large Corpora. lions, unpublished report, 1985. IGLEIIART, J.K. The campaign against |making gains moatentum. New England Journal of Medlcine 314(16):.1059-1tl64, April 1986. JONES, L.D. Advancing the role of hospitals in reducl,g smoking. In: Proceedings of the Nolional Conference on Smoking or Health. New York, American Cancer Society. November 18-20, 1981. KELLY, N.R., COHEN, F.L. Smoking poli~ies in U.S. hospitals: Cnrrent status. Preventive Medicine 8(5):557-561, 1979. KO~I'KE, T.E., KNAPP, J., SILVIS, it., SORENSEN, G. Cl~n Air llealth Care: A Guide to Establish Smol~e.Free Hwlth Care Facilities. Minneapolis, Uni~emlty of Minnesota, 1986. 328 KitISTI,IIN, M.M. ltow much can businex~ expect to profit from smoking ¢easation7 , Prevcolive Medicine 1~2):35~381, March 19~. KRl~'b~lN, M,M, WantS: Smokt.g ~licl~ for tho workplace. Busin¢~ and Health 14-17, Now,ml~r LE~E, N.M., ASHLEY M,J.. I'EDE~N L.L., KEAYS, J.J. The health risks of ~ive sin.king: The g~wing ~ for ~nt~l me~ur~ in encl~ environment, Ch~t ~{ 1):~95, July 1983. LEHMAN, B.A, ~mbrldge may'limit r~urant smoking. ~ton GIo~ April !~4. LICIITENSI'EI N, E., DANAHER, B,G. What ~n the physician do ~ ~lst the patient ~ shq~ smoking? In: Br~sheur, R,E., Rhea, M.L, (~. Ch~nic O~tn~cfi~ Lung ~e: Cibd~l ~ment and Man.meaL ~. ~uis, C.V. M~by~ 1979, pp. 227- 241. LINNEI.L, It.ll. Sudsy: No.smoking ~ here ~ s~y. Hotel and Motel meat ~1~7~ 1-18, May 19, 19~. LINEN, C.J. E~luation of Ten W~pl~ Smoking R~la¢io~ in ~llforni~ ~mhrhlge, M~ch~t~, Iln~ard Univv~lty, instltu~ for the Study of Smok- ing ~havinr and Policy, May ~, 19~. ~ AN(H~L~I TIM~. Hil~n chain a~atlng no~mokv~, ~ A~l~ ~m~ March 2, MARTIN, M.J. The ~n Frsnci~ ¢x~rlen~ with ~ulation of smoking In th~ workplace: The fi~t twelve month~. America Journal of~blic Health 5~, May !1~. MARTIN, M,J., FEllRENIIACII, A., R~NER, R, Ban on smoking in indust~, {let~r). New England J~m~ai of M~iein¢ 31~10):~7~8, ~ptem~r 4, 1~, MARVIT, ILC., RIGNEY, K.B., Y~, F.N, A g~ nelgh~r ~llvy: ~ntmll~ smoking are~m and health department attitud~. Ha~il M~i~! Journal 3~ !0. Jonu.ry 19~. MEADE, T.W,, WALD, N.J. Cig~ret~ smoking pst~rns during the working Bdtbh Journal of ~nti~ and ~ial M~ici~ 31(lk2~, March 1977, MICIIlGAN ~BA~ AND CANDY DlffFRIBU~ AND VENUE A~IA- TION. ~on~ic Im~ct of instituting smoking p~hibltio~ in Michigan, In~ Joffman K,B,, (~). Study: ~n on smoking ~i~ ~ing, Michigan Journal, Febru.ry 4, 1~. MINNEA~LIS TRIBUNK Minn~ ~ll. Minn~l~ ~bun¢, April 15,1973, MINNEA~LIS TRIBUNE. Minn~ ~ll. Minn~l~ ~bune~ Januaff 18, 1~6, MINNEA~LIS TRIBUNE. Minn~ ~]l. Minn~l~ ~ibune, June ~, 1978, MINNEAI~LIS TRIBUNE. Minne~ ~ll. M[nn~l~ ~bun¢, May I 1, 19~, MINN~A ~'gATUT~ ANNUA~ Chapter 211 L,1975, ~tion~ 14~.41-14~.417, " (W~t Supplemvnt) NAIMAItK, R.E. ~b~ a Smo&e.~ Enrichment: $mo~ing ~li~' for se~t~ .~tate bhcilities. {unpubllsh~ manu~ript). ~mbridge~ M~chu~t~, Har- vard Unive~ity, institu~ for the Study of Smoking ~havlot and Policy, April 19~. NATIONAL INTERAGENCY ~UNCIL ON SMOKING AND H~LTII. 8moMng and the Ww ~pl~ce: A National Surly. (unpublish~ man~ript), NATIONAL INTERAGENCY ~UNCIL ON SMOKING AND HEALTH. Smoking and the workph~: A natlon~l sudsy. ~u~tional H~lth and ~fety May NATIONAL RI,~'AURANT A~IATION. ltow ~ume~ Mak~ the ~ion ~t Out. (su~ey~. W~hin~on, D.C., National ~s~urant ~lati~n, Au~ 1982. NATIONAl, RI,~I'AURANT A~IATION. N~ ~ket Fact ~ 1~.1~ W~hington, D.C., National R~urant A~lation, 19~. 329
Page 175: TI07870785
NEW YORK TIMES. Order by Koch lilnlt~ emoklng in city buildings. New York 7~mes, June 26, 1986. NEW YORK TIMES. Plan to rc~trlct ~moki~g in NYC faces consideralJle opposition. NtW York ~mes, July 6, 1986. NEW YORK TIM~. San Fronct~ olflclals ci~ su~ with law. ~¢~ York April 13. 1986. NUEHRINO, E., MARKLE, G.E. Nl~tlne and norms: The r~me~enco of s deviant behavior. ~ial i~ble~ 21(4):513~26, April 1974. OFFICE OF T~HNO~Y A~MENT. Smoki~eg in the Workplace: ~l~t~ l~ue~ U.S. ~ngr~, O~ of T~hnoi~ ~menL May 19~. O~I[ANSKY, S.J. Is smoker/nonsmoker mg~atton eff~ive in r~iucing p~ive inhalation mnong nonsmokers? American Jou~al of ~blic H~lth 7~7~737-7~. July 1982. O'MALLEY, P.M., BACHMAN. J.G., JOHN~N, LD. Peri~, SEe. and ~ho~ on substance use ~mong American youth, 197~2. American Journal ,~f ~blic ltealth 47(7);68~, July ONTARIO R~AORANT AND ~1) SERVIC~ A~iATION. A Guide for ~tabl~hing a No.Smoking ~tio~ On~rio, On~rio I~urant and F~ ~rvices A~iation, 19~. ORLEANS, C~., SHIPLEY, ~H. Wor~i~ smoking ~ation initiative: Review ~d recommendetions. Addicti~ ~hapio~ 711~1-16,1982. ORLEANS, CN., PINNEY, J. ~o~moking in the Workpla~ A Guid~ for Empl~. W~shin~on, D.C., ~nter for ~r~rate Public Involvement, 19~. ORLEANS, C.T. Precaution ~ tl~ National ~r lnstitu~ ~mfe~n~. Evalu- ation research desi~ for worksite n~mnoking ~lici~ sad pr~ra~ April 1986. PACIFIC TELEPHONE. Emph~e 8moklng ~tudy. Pacific Teleph~me, ~r~rate Research Division, Human It~ur~ Admini~tration, Proj~t #82~, January 1983. PARK RE~RI). Study shows park city res~urnn~ are ignoring no smoking e~ laws. Park R~o~, Park City, U~h, June 13. 19~. P~E~EN, D.J., MA~ENGIL[,, D. Smoking r~ulations In the ~rklda~: An u~a~. Pemonnel ~1, May 19~. • PR~IIASKA, J.O., DiCLEMENTE, C.C., VELICER, W.F. Prattling change smoking status for ~lf<hungers. dddivti~ ~havio~ 1~4):39~{~, RAN~LPH, F.L. The Regub,tion of 8making in ~blic Place: ~icto~ of Compliant~ and Volunla~ Enfow,'m¢~,t Behavior. ~ral Di~rhetion, Unlve~i- ty of Califoroiu, I~rkeley, 19t12' ~ RAS}IAK, N.E., O~EN, L.K., SPEAI~, A.K., HAGGERTY, J.M. Smoking imliclse e~ond~ry ~h~ls in Ari~na. Jou~al afghan! H~ith ~):1~1~, May REPACE, J.L., ~WREY A.H. A qunnti~tive ~timate of nonsm~kers' tong ~n~r risk from pa~ive smoking. Envi~ument International 11:3-22, RHOAD~, E.R., FAIRBANKS, L.I,. Smoke-fr~ faciliti~ in tl~e Indian Ile~dth ~rvlce. (later). ~ew England J~mrnal of M~icine 31~24):1~48, ~m~r 12, 1985. RIG~I, N.A., HILL PIKL, B., CLEARY. P., SINGER. D.E., M~I,LEY, A.G. TI,e impact o£ bonning smoking on a I~pi~l ward: Ac~p~nce, ~mpliun~, air quality ned smoking ~havior. (a~tracD. Clinical B~h 34(2):~3A, April 1~. ROBERT FINNEOAN A~IAT~. 8making Poli~ P~fe~ac~ of Emplo)~ of New England ~lephon~: d~ Employee Opinion ~es~h Sun~q. (unpublieb~ re~rt) April 198~, ROPER ORGANIZATION. A Study of ~blic Attitad~ To,~ ~i~a~tte and the To~cce ind~ in 1978. Roar O~ani~tion, May 1978. 330 ROSEN~"I'OCI(. I.M.. STERGACItlS, A., HEANEY, C. Evaluation of smoking prohibitim~ p~licy in a health maintenance organization, American Journal of l'%iblic lle¢dth 76(8):1014-1015, August 1986. SANDEIJ,, S.D. The campaign for clean air indoors. Business and Hcaith 19-2L Now:tuber 1984. SEFFRIN, J.it., BRASIlEAR, R.E., SHIRELE¥, L.A. A stotowide survey of hospital p~lle.y a~ed practice concerning cigarette sale~. Americat~ Review of Rsspirotory Dise~se 111~6): i 105-1107, December 1978. SIIANNON, A.R. Smoking cessution program survey. Pacific ~Vorthwes! l~¢iiBusins~s Research, J t,nc 1986. SlllPLEY, R.I I., ORLEANS, C.S. Treatment of cigarette smoking, In: Boud~wyns, P.A., Keels, I".J. (eds~. Behaoiorai Medicine in C,~nerai Medical Prattle. New York, Addi~,~n Wesley, 1992, pp. 237-268. SHORT. R.E., WILLIAMS, D.C. Normative beliefs abeut tobacco smoking on ~mpus in relation Io ~m exposition of the viewpoint of the nonsmokers' righta movement, Jour~al o[ l'sy,:hology I00:261-274, 1978. SOBEL, R. They Satisfy: The Cigarette in American Lif~ New Ynrkj Anchor Pre~/Doubleday, 1978. SOLOMON, I,.C. The other side o~" the smoking worker ~ontrovemy. Admiaistru#or 2813):72-73, March 1983. SORENSEN, 11., PE~HACEK, T. Support for l¢o~rnoking Poli~ie~ Among Employtd ~mokers. (m~pnblished manuscript). August I, 1986. SORENSEN, (i., I'ECIIACEK, T., PALLONEN, U. O,~'cupat|enal and worksito norms and attitudes about smoking cessation. American Journal of Public Health 7616):544-649, May 1986. TIIOMAS, E.(I. Committee of 600 report: Smoking in the office: A burning Issue, Man,,g#me~t World 914)I 1-12, April 1980. TRI-AGENCY TOBACCO FREE PROJEC'I'. State Legislated Action on Clean Indoor Air Act. N~w York, American Cancer Society, American Lung Associatlon, Ame,'icn,e I b..art Association, February 1986. UNIVERSITY OF CALIFORNIA SURVEY RESEARCH CENTER. California poll, University ~)f California, l~erkeley, duly, September, October |984, U.S. DF, I'ARTMENT OF IIEAI,TH, EDUCATION AND WELFARE. AduR ~]~c of Tobarco, 1970. U.S. Department of Health, Education, and Welfare, Public Health Service, O.,j~ter for Disease Control, National Clearingleouse for Smoking and " Health, Jura, 1973, DHEW IISM Pub. No. 73-8727. U.S. DEPAItTMENT OF IIEALTH, EDUCATION AND WELFARE, Adult Use of Toba,.ce, 197.5. U.S. Department of Health, Education, and Welfare, Public Health Service. lle~dth Servlce~ and Mental lleelth Administration, National Clearing. house for Smoking and Ilcalth, June 1976. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Use of Tobacco, Practices, Attitudes, Knowledge, and Beliefs, United 8tats: Fall 1964 and ~prlag 1966. U.S. l)~:portment of Health, Educatio,~, and Welfare, Public Health Serviced Heallb Services and Mental Health Administration, National Clearinghouse for S~noking [m,l ilealth, July 19~9. U.S. DEI~AIt'I'~IENT OF HEALTH. EDUCATION. AND WELFARE. Kresnegor,'N.A, (Ed). (?il:,trr¢te ~moking as a Bepend~at l~ocess. NIDA Research Monograph 23. U.S. l)~.pm'~ment of Health, F-,ducatioa, and Welfare. Public Health Service, Alcohol, l)r~g Abuse and Mental Health Administration. National Institute on Drug Abut, c, Jauuary 197:). U.S. DEPARTMENT OF HEALTII AND ||I.IMAN SERV|01~;. Guide to ~'J~,cing 8making at the Worksit~ U.S, Department oi" Health and llu,m~,~ See vice.s, Public lle,dth Service, Office on Smoking and Health, 198~a, 331
Page 176: TI07870786
U.S. DEPARTMENT OF HEAL'I'll AND IIUMAN 5ERVICP~% Legi.~hdive Overview. U.S. ~pnrtment of Ilealth and llumaa ~ices, Public ilealth ~*'vi~, Office of the ~Js~nt ~'e~ry for ]J~,allb, O~ ,m Smoking and ! leallb, U,S, DEPARTMENT OF HEAU~II AND ilUMAN SERVICF~. The It~lth ~. quen~a of Smo~i~g: ~ncer and Chronic i~ng ~e in the Workplace. A of the 8u~n General U.S. ~r~vnt of Health sad Ilumnn ~,~i~, Public Health ~ice, Office of the Agl~t ~re~ry for Health, Olfico on Smoking ~nd llenlth, 19~. U,8. DEPARTMENT OF ItEALTH AND HUMAN SERVICe, N.tb,nul 8u~y of lVorA~ite Health ~motion Activili~. U.S. ~pa~,ent of Ile, dth and lluman ~r~i~s, Office o[ D[~ Preventhm ond Health P~omotion, 19~ (i,, U.S, DEPARTMENT OF HEALTH AND II~MAN SEItVIC~, 7'l,e I[ealth qufn~s of Smo~b,g for Women: A lie~ of lbe 8u~n Geneml. U.S. ~partmeat, of llenlth and Iluman ~rvi~, I'ublle Health ~lce, Office of the ~re~ry for ltealth, Offi~ on Smuking and Health, 19~. U.K DEPARTMENT OF H~ALTH AND HUMAN S~VIC~. T?,¢ [[ea~tl, quenc~ of Smo~i~lg: ~io~ulor ~s~ A Re.we of the Sa~t~n Gem.mL U ~. ~partment of Health dad llumaa ~, Pgblic Health ~rvi~, Offi~ A~ls~nt ~re~ry for Health, O~ on Smoking and lleulth, DllllS Pub. No.(PHS~2.~I79, 1982. U.S, DEPARTMENT OF HEALTH AND HUMAN SERVICe. TI~e H~llh quenc~ of Smoki~: ~wni¢ O~ltucli~ ~ng ~e. A Re~ ~f the GenemL U.S. ~lm~ment o[ Health and Human ~i~, ~bllc II~lth ~i~, Office of the Amie~nt ~ for Health, Office on S~klng mad Ilealth, DIIHS Pub. No.(P]IS~4-~, ]984. V~EL, P. The don't butt inn: Ho~ now ~r ~ non~mokers. Chi~ February ~, 1986. WASH, D.C. ~r~ra~ zmoking ~llcl~: A review and an ~nolye~. Jou~ol of ~u~ltonal M~iicine ~!~17-22, Jmma~ WASH, D.C., GOIt~N, N.P, ~nl appr~ch~ ~ zmoking deter~n~. Annual Reoie~ of ~blic Health 7:1~-149, 1~. WARNE~ K.E. Cigaret~ zmoking in the !~0'~: ~te imwzct of the unthinking campaign on consumption. ~i~nce 211(44~7~-731, Februaff 13,1981a. WARNER, K,E, S~te legielatlon on mztoking and bemlth: A ~mpari~n of two ~iicy ~iencez 13:139-152, l~lb, WARNER, K.E. IIegional differen~ in S~ ]~]slntion on ciga~ttv smokh~g. T~ WARNER, K.E., EItN~E~ V,L., ]I(JLflR~K, J.H., LEWIT, KM., PER1~HUK, M., STEINFELD, J.~, WliE~N, E.M. Public ~licy on amoking ~nd h~lth: Toward a emoke-fr~ generation by the year ~, Ci~u/ation 7~2~IA~A, February 1986. WARNER, K.E., MUiIT, I[.A. Impact of the antimnoki,~ campaign on smoking prevalence: A cohort analysis. Journal of ~bli¢ H~lth ~li~ ~4):37~, ~em~r 1982. WEIS~ W.L, Can you affo~ ~ hire smoke~? ~nnel Admin~tm~or 2~6}71-78, May 198L WIN~R, B.A., BARTL~. E.E. Employ~ ~l[-help smoking ~ttion programs: A review of the lilernture. H~lth ~lu~tion Quarterly 11(4~349-359. Wilier 19~, ZIADY, M. A smok~-fr~ workplace: Clearing ~e air nt Pacific Northwest Bell. H~lth, O~ Business (1):1,1986. 332

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size: