Tobacco Documents Online

~or Medical! /! Hospitals ;oods, Food :, andl Wel- i i tespiratory ,rams, Na- j Bethesd'a,, Pathology,, t of Epide- University,, tneral Hbs- A1 of lYledi- ii ranch, Na- ~ Bethesd'a,, >lic Health, The Johns pi Hospital, le and Bro- h ~ental Pro- Bureau Bureau of. it of Public ian of Im- ssouri. ine, School ~ and Gyne- sd, Division ler, Denver, tal Hiealth ry Disease itah. na1 Medical Gnistratlion, inogenesis; „Bethesda, i ScHUrKAN, LEONARD M., M.D.-Professor andl Head, Division of'Epidemiology,. School, of Public Health, University of Minnesota, Minneapolis, Minnesota. SHCnYKrN, M'iCHAEL B., M.D.-Coordinator and Professor of Community Mtdi- cine and Oncology, Regional' Medical Program, University of' California ( San, DiegQ)., La Jolla, California., S'rA:utER; JExeMiAH,, M.D.-Executive Director, Chicago Heal'th, Research Foundation, Chicago, Illinois VAN DvUxEN, BEN.TAwcrN L., M.D: Professor of' Environmental Medicine,, Institute of Environmental Medicine, New York University Med'tcal Center,. New York, New York.. WYNnEx, ERNesT L., M.D., President, AmericaniHeallth Foundation, New Yark, New York. The chapter on Harrnful~ Constituents of Cigarette Smoke was prepared somewhat differently from the rest of the report, being, the culmination of a one-day conference held in June 1570~t'o review this area of knowledge and to discuss a draft report prepared in, ad- vance by staff 'of the National Institute of Environmental Healthi Sciences and the National Clearinghouse for Smoking and Heal'th Earlier in this section, some of these participants are acknowledged as contributors to other parts of the report, namely,, Dr. Daniel, Horn, who served as Cha2rmanof the meeting, Drs. DanieliP. Asnes, Fred G. Bock, Dietrichi Hoffmann, Albert C. Kolbye, Gardner C. TlIcilTillans Umberto Safl'iotti, Leonard Schuman, Benjamin L. Van Duuren„ and' E'rnest, L. Wynder. In addition, acknowledgments shouldl be made to the, following who were also participants in the, conference :~ Goer, Gio BATTA,, M.D.-Associate Scientific Director for Pragrami Etiology, Nationall Cancer Institute, Natianal, Institutes of Health„Bethesda„Marylandl GR[FFiTH,, RoBExT; Ph. D.-Direct'or; Tobacco and Health Research Institute,, iJ21iversity of'Kentucky, Lexington, Kent'ucky.. G>'~ER[N, MICHAEL, Ph. D.-Senior Chemist, Oak Ridge National Laborat'ory, Oak Ridge, Tennessee. JARUrK,, MURRAY, M.D.-Professor of' Psychiatry and Pharmacology, Albert Einstein College of Medicine of' Yeshiva University,, Bronx,, New York. KENSLER, CaAxzES,, M.D.-Senior Vice President, Life Sciences Division,. Arthur D: Little, I'nc., Cambridge, Massaehusetts. Ko'rIV, PAUL, M.ID: Vice President for Health Sciences, Health Sciences Cen- ter,, Temple University, Philadelphia, Pennsylvania., LIPTON, MoeRis, 1VI.D,,, Ph. D.--Professor and Chairman,, Department of' P'sy- chiat!ry, Univ.ersity of' North Carolina, Chapel! Hill, Nbrth Carolina. REMINGTON, RICHARD, M.D.-Associate Dean for Researchy School of Public Health„ University of' Texas, Houston, Texas., SCHIMELTZ, ERwarry Ph. DL-Head,, Lubricants Investigations, Eastern Utiliza- tion Research and Development Division, U.S! Department of Agriculture, Philadelphia, Pennsylvania. STANTON, MeAaL F., M.D.-Medical Officer, National Cancer Institute, Na- tlional' Institutes of Health, Bethesda, Maryland. Tso;, TtEN C., MLD:-Plant Physiologist andl Leader, Tobacco Quality Investi- gations, Plant Science Researchi Division, ARS, U.S! Department of Agri- culture,, Beltsville, Maryland. 1

The following, professional staff of the National Clearinghouse for Smolting and Health contributed to ~ the preparation of this report : Robert S.. Hutchings, Emil Corwin, Elaine Bratic, Annabel W. Hiecht, Lillian Davis, Richard W'. White, Richard H. Amacher;, Donald R. Shopland, Jennie 1V2. Jennings, Dan Nemzer, Nancy S. ~ Johnstons, and' Gertrude Herrin. ~ Special thanks are dlue Theresa Klotz, Rosalie Levine, andlVlildred ~ Ritchie:.

i ~use for report: ibel W. ~acher,, wncx S. dildred CHAPTER 1i I ntroduction and Summary

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INTRODUCTION AND SUMMARY Cigarette: smoking continues to be a major health problem in the: Unitedi States today. It is still too early to tell whether the increas- ing rate of'giving; up smoking by adults during the years 19'67; 1968„ 1969; and early 1970 and the plateauing, of this effect during the past year have had any: measurable effect, on the morbidity: and' rnortalit'y associated with smoking. At the same time that the majorr health professions, voluntary health agencies, and public service agencies concernedl have joined with governmentagencies to reduce the magnitude of this problem through education,, research efforts devoted to understanding, how cigarette smoking affects biological function to produce disease continue at a high levell. This report is largely concerned with reviewing, the research re- ports which have become availablie in the past year. In this chapter; brief summary statements are presented of the state of'knowledg.e in severall areas. These are followed,, where appropriate, by a"high, light" statement of significant ad'ditions to knowledge made as a result of the new research presented in greater detail in the~ body of the report. The state of knowledge! in three areas;, whichi have not been re+ viewed previously, is also presented in the report. These areas are:. Allergy, Public Exposure to Ai'r Pollution from Tobaceo Smoke, and'the Harmful Constituents of Cigarette Sinoke: SUMMARY : CORONARY HEART DISEASE. Cigarette smokers have higher death, rates from coronary heart disease (CHD) than nonsmokers.. This relationship is stronger for men than women. Cigarette smoking markedly increases ani individ- ual's susceptibility to earlier death from CHD'. Cigarette smoking,, hypertension, and elevated serum cholesterol are major risk factors contributing to the development of CHD ; cigarette smoking acts both independently and conjointly with these other factors to in- crease the risk of' developing CHD. Cigarette smoking may con- tribute both to the development of CHD and to the exacerbation of preexistent CHD ;, both nicotine and carbon monoxide are thought to~ contribute to these abnormal processes. Cigarette smoking is associated with a significant increase in atherosclerosis of the aorta. i

and' coronary arteries. Cessation of smoking is associated with a decreased risk of death from CHiD. The risk of CHD~ incurred by pipe and cigar smokers is appreciably less than that incurred by cigarette smokers. FilTighl'2ghtsof' 1~972 ' Report: Coronarg, Heart Disease 1. Recent epidemiological! studies from severall countries confirm that cigarette smoking, is one of' the major risk factors con- tributing,tothe!developmentof'CHD: Avoidance of cigarettesmoking is of importance iln the primary prevention of CHiD. 2: Studies in man and animals have shown a greater myocardial arteriole walli thickness in smokers than nonsmokers: 3. Experimental and epidemiological investigations implicate the elevationi of carboxyhemoglobin levels in smokers as a contributor to the develbpment of CHD and arteriosclerotic peripheral vascular disease., 4: Cigarette smoking, is considered to be the major cause of' pul- monary heart disease (cor pulmonale) in the United States in that it is the most important cause of chronic non-neoplastic bronchopulmonary diseases. Avoidance of cigarette smoking, is of importance in the primary prevention of pu'1i.nonary heart disease. SUIVIIVIARY : CEREBROVASCULAR DISEASE' Cigarette smokers have higher death rates from cerebrovascular disease than nonsmokers. SUMIVIARY : NONSYPHILITIC AORTI.C' ANIEURYSM* Cigarette smokers have higher death rates from nonsyphilitic aortic aneurysm than nonsmokers. SUMIVTARY: PERIPHERAL VASCULAR DISEASE Cigarette smoking is a likely risk factor in the development of peripheral vascular disease. Cigarette smoking appears to aggravate preexistent peripheral vascular'disease. •Thissummarysdatement~ is the samee as that.appearing.inprevious.t reports,, because neww studies adding,to the understanding of'this.area.have not'appearedi.Consequently, the Iiteraturein this area is not reviewedland the statementl is only, included to complete this summary chapter. 10 ~. 21 ~ ob 0

fated with a incurred' by ,incurred'by tease j ries confirm factors con- of cigarette ion of CHD.. h myocardial ers: ? is implicate nokers as a eriosclerotic ;ause of pul- ~ed States in p-neoplastic jtte smoking ! pulmonary brovascular SUMIVIARY :: NON-NEOPLASTIC BRONCHiOPUIl.IVIONARY DISEASES Cigarette smoking is.the most important cause of'chronic obstruc- tive bronchopulmonary disease (COPD) in the United States. Ciga- rette smokers have higher death rates from pulmonary emphysema and chronic bronchitis and more frequently have impaired pul- monary function and pulmonary symptoms than nonsmokers:, Ex- cigarette smokers have lower death rates from, COPD, than do con- tinuing smokers. Cessation of smoking is associat'ed! with improved ventilatory function and decreased pulmonary symptom prevalence.. For most of the Unitedi States population, cigarette smoking is a more important cause of COPD1 than, air pollution or occupational exposure; cigarette smoking may also act conjointly with occupa, tional or environmental exposure to produce greater COPD mor- bidity and mortality. An infrequent genetic: error,, homozygous alpha,-antitrypsin, deficiency,, has beeni commonly associ~atedl with the early development of severe, panacinar emphysema. Whether or, not cigarette smoking acts together with the i- -1mozygous or hetero- zygous deficiency states to increase the risk, of developing either panacinar emphysema or the more common forms af COPD, has not been adequately studied. Cigarettie smoking, exerts an, adverset effect on the pulmonary clearance mechanism. Respiratory infec- tions are more prevalent and severe, among cigarette smokers,, par- ticuIarly among heavy smokers; than among nonsmokers. The risk of developing or dying from COPD among pipe or cigar smokers is probably higher than that among, nonsmokers: but is clearly less& than that among cigarette smokers. Flighl'ights of'the 1972' Reportr 1'Non-rueoplicstic Bronchopulmonary Diseases L. Recent epidemiological and clinical studies, from several CRYSiVI* nonsyphilitic 2. EASE relopment of 3'. to aggravate 4. rts, because new tly,, the literature . ummary cHapter., countries confirmt'hat rnen~and women cigarette smokers have an increased prevalence of respiratory symptoms and have diminished pulmonary function compared~ to~ nonsrnokers.. Investigations of high school students have demonstrated that abnorrnaii pulmonary function and pulmonary symptorns are more common in smokers than nonsmokers., Recent occupationall studies confirm that cigarette smoking is an important cause of, COPD; acting both~ independently andd in: combination with occupationali exposure.. Recent experimentall studies confirm t'hat cigarette smoking exerts an adverse effect, on pulmonary clearance and macro- phage function. 3 4 b

5, Pulmonary macrophages obtained frorn cigarette smokers ex- hibit characteristic rnorphologic differences when compared to those obtainedi from nonsmokers: SUMIVIARY : CANCER ~ II Cigarette smoking,i's the major cause of lung cancer in men andla6 significant cause of lung, cancer inwomen. The risk of developing f lung cancer in both men and women is directly related to an individ- ual's exposure as measured by: the number of cigarettes smoked, ' duration of smoking, earlier initiation, depth, of'inhalat'ion, and the i` amount of "tar" produced by the cigarette. The risk of developing !i lung, cancer diminishes with cessation of srnoking., Smokers of pipes ': or cigars have a lower risk of developing lung cancer than cigarette i' smokers. Certain occupations are associated' with an increased risk of developing lung cancer. In these occupatianal settings cigarette smoking, appears& to exert an effect that produces much higher lung cancer rates than those resulting, either fromi the occupational ex- , posure alone or from smoking alone. Factors associated with urban living result in an, increase in the risk of' developing lung cancer;~ this effect, however, is minor compared to, the overriding effect of cigarette srnoking,The smoking of cigarettes, pipes, and cigars is a significant factor in the development of cancers of'the larynx andl oral cavity., Pipe smoking, is causally relatledl to cancer of the lip. The significant asso- ciatilon between smoking and the development of cancer of the esophagus i'ssornewhat stronger for ci'gar.ettes than forpipe& oreigars andl the combined~ exposure to alcohol and cigarettes is asso- ciated with especially high rates of cancer of the esophagus. Ciga- rette smoking, is associated with cancer of the urinary bladder in menL There is also an association between cigarette smoking andd cancer of the pancreas. Hiyhlights of'the 1972 Report: Cancer 1. Preliminary result's from a major prospective epidemioJogicall study in Japan demonstrate a st'rong,association between, cig- arette smoking and lung cancer.A dose-response relationship, was demonstrated for the number of cigarettes smoked. These findings in an Asian population withi distinct genetic and cul- tural characteristics confirm the: major importance of' ciga- rette smoking in the causation of lung cancer, ai conclusion which up to now has been based largely on studies of Cauca-0 siani populations in the United States, Canada„ and! Europe. I , 4 r~ WR ~ ~ ~

2.Ex-srnokers have significantly lower death rates for lung can- cer than continuing smokers. The decline in risk following cessation appears to be rapid both for those who have smoked for long, periods of time andl for those with a shorter smoking hsstory,, withi the sharpest reductions taking place after the 3. en andla Ueloping individ smoked, , ; and thee veloping, . of pipes ;igarett'e lsed risk °igarette her lung 'lonal ex- Gh urban cancer; . effect of it factor 6. iy. Pipe unt asso- r of the 1pesoris asso- . s. Ciga- dder inn ting and iiolbgical Veen cig- t,tionship 4 These and cul of ciga- clusion Cauca- urope. first two years of cessation. The risk of developing, lung, cancer appears to be, higher for smokers who have chronic bronchitis. Though both conditions are directly related to the: amount and duration of smoking, an additional risk: for lung cancer appears to exist for ciga- rette smokers with chronic bronchitis which is independent of' age and'r number of cigarettes consumed. Experimental stud'ies on animals have demonstratedl that the particulate phase of tobacco smoke contains certain chemical compounds which can act as complete earcinogens, tumor initiators, or tumor promot'ers.Recently, other compounds have been described that have no i'ndependent activity in two- stage carcinogenesis but accelerate the carcinogenic effects of polynuclear aromatic hydrocarbons in the initiator-promoter system. Additionall epidemiological evidence confirms a significant as- sociation between the combined use of cigarettes andl alcohol, and cancer of the esophagus. Epidemiological studies,have demonstrated a significant asso- ciation between cigarette smoking and cancer of the urinary bladdsr, in both men and women. These studies demonstrate that the risk of developing: bladder cancer increases with in- halat'ion~ and the number of' cigarettes smoked. Epidemiological evidence demonstrates a significant associa- tion between cigarette smoking , and cancer of the paner.eas., S'UMiMARY : PREGNANCY Maternal smoking during pregnancy exerts a retarding influence on fetal growth as manifested by decreased infant birth weight andd an increased incidence of prematurity, defined by weight.. There isi increasing evidence to support, the view that women who smoke. during pregnancy have a significantly greater risk of an unsuccess- ful pregnancy than those who db not. SUiIIMARY~: GASTROINTESTINAL D~ISGRDE~~R& Cigarette smoking males have an increased prevalence of peptic ulcer disease as compared to nonsmoking rnales and a greater peptic

ulcer mortallity ratio. These relationships are stronger for gastric ulcer than for duodenal ulcer. Smoking appears to reduce the effec- tiveness of standard peptic ulcer treatment and to slbw the rate of ulcer healing. Highlights of the 1972' Report: Ga,strointestinr,cl Disorders 1. A possible link between cigarette smoking, and peptic ulcer has been demonstrated in dbgs in which nicotine was found to inhibit pancreatic and hepatic bicarbonate secretion. This could lead to peptic disease by depriving the duodenum of sufficient alkaline secretion to neutralize gastric acidity. 2. Ani investigation in human volunteers has suggested that cig= arette smoking decreases the effectiveness of the lower- esophageal sphincter as a barrier against gastro-esophageal reflux.. SUIVIMARY : TOBACCO AMBLYOPIA* Tobacco amblyopia is presently a, rare disorder in the United. States. The evidence suggests that this disorder, iis related to nutri- tional or idiopathic deficiencies in certain detoxification mecha- nisms, particularly in the rnetabolism, of the cyanide component of tobacco smoke. SUMMARY: NON-NEOPLASTIC ORAL DISEASE* Ulceromembranous gingivitis, alveolar bone loss, and stomatitis nicotina are more commonly found among smokers than among nonsmokers, The influence of smoking, on periodontal disease andd gingivitis probably operates ini conjunction with poor oral hygiene.. In addition, there is evidence that smoking may be associated with edentulismi and delayed socket healing. While further experimental and clinical studies are indicated, it wouldl appear that nonsmokers have an advantage over smokers in terms of't'heir oral health. The information contained in the follo2cing three summarg state_ ments: Allergy, Public Exposure to Air Pollution from Tobacco Smoke, and Harmful Constituents o f Cigarette Smoke, is ne2v and appears for the first time. • This summaryy statementt is the samease that appearingg in previous reports, because new stNdies.addingtotheunderstandingofthis;area have not appeared. Consequently;.ttieliterature, in this area.is.not reviewed and the statement.isonlyincludedto~complete this summarychapter.y b F 4..~