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Ets - Environmental Tobacco Smoke Report From A Workshop on Effects and Exposure Levels

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Peterson, Y.
Rylander, R.
Snella, M.C.
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Anderson
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Aviado, D.M.
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Axelsson, G.
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Bake, B.
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Cosentino, A.M.
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Gillis, C.R.
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Grimmer
Guerin, M.R.
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Hawthorne, V.M.
Henriksen
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Higgins, C.E.
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Hoffmann, D.
Hole, D.J.
Holt, P.G.
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Jarvis, M.J.
Jenkins, R.A.
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Kobayashi, D.
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Kreiss, K.
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Rourke, C.
Russell, M.A.
Rylander, R.
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Snella, M.C.
Spears, A.W.
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Sterling, E.M.
Sterling, T.D.
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Wynder, E.
Zober
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Atmospheric Health Sciences
Center for Disease Control
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Epa, Environmental Protection Agency
Equitable Environmental Health
Franklin Inst
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Greater Glasgow Health Board
Harvard School of Public Health
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Simon Fraser Univ
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European Journal of Respiratory Dis
Univ of Geneva Switzerland
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ETS - Environmental Tobacco Smoke Report from a Workshop on Effects and Exposure Levels . Editors : R. Rylander Y. Peterson M.-C. Snella March 15-17 1983 University of Geneva w Switzerland ~ ~ - o . ~ I
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Published simultaneously as European Journal of Respiratory Diseases Supplementum No. 133, vol. 65, 1984. P 0 i ISBN: 87-16-06258-2 ISSN: 0106-4347 Printed in Switzerland Atar S.A., Geneve © 1983 Geneva ] ] 2. 1 .
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Contents PREFACE ..................................... 5 INTRODUCTION ................................ 7 Ragnar Rylattder 1. EXPOSURE LEVELS .............................. 9 1.1. Environmental tobacco smoke measurements: retrospect and prospect . 9 Melvin W. First 1.2. Investigations on the effect of regulating smoking on levels of indoor pollution and on the perception of health and comfort of office workers 17 Theodor D. Sterling and Elia M. Sterling 1.3: Analytical chemical methods for the detection of environmental tobacco smoke constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Roger A, ,Jenklns and Michael R. Guerin 1.4. Carbon monoxide as an index of environmental tobacco smoke expo- sure ................................... Domingo M. Aviado. 1.5. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rapporteurs: Martm J Jaryis and'Cornelius f. Lynch 47 61 2. DOSE-MEASUREMENTS IN HUMANS . . . . . . . . . . . . . . . . . . . . 63 2.1. Half-lives of selected tobacco smoke exposure markers ......... 63 Cornelrus.J. Lynch 2.2. Measurement and estimation ~ of smoke dosage to non-smokers from~envi- ronmental tobacco smoke . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Martin f.. Jarvit and Michael A. H. Russell 2.3. Validitg of questionnaire data on smoking and other exposures, with special reference to environmentali tobacco smoke . . . . . . . . . . . . . . . . 76 Goran Pershagen 15, 2A Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 W' Rapporteurs: Roger A. Jenkins and T/ieodor D. Sterling ~ N C!1 0 ~
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3. EFFECTS IN HUMANS ............................. 85 3.1L Does environmental tobacco smoke affect lung function? ........ 85 Bjorn Bake 3.2. Environmental tobaccco smoke and pulmonary function~ testing .... 88 Anthony M. Cosentrno 3.3. The effects of environmental tobacco smoke exposure and gas stoves on daily, peak flow rates in asthmatic and non- asthmatic families ..... 90 Michael D. Lebouitz 3:4. Acute effects of environmental tobacco smoke . . . . . . . . . . . . . . 98 Annetta IY/eber 3.5. Respiratory symptoms in the children of smokers: an overview ..... 109 Patrick G Halt and Kepen j. Txrner 3.6. The effect of environmental tobacco smoke in two urban communities in the west of Scotland . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Charles R. Gi11u, Dov~id j. Hole, rictor M. Hawthorne and'Peter Boyle 3.7. Environmental tobacco smoke and lung cancer . . . . . . . . . . . . . 127 Ragnar Rylawrder 3.8. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 Rapporteurs: Gdran Pershagen and Anthony M. Cosentino 4. WORK GROUP RESULTS . . . . . . . . . . . . . . . 4.1. Exposure . . . . . . . . . . . . . . . . . . . . . . . Chairman and rapporteur: Melvin [Y~ First 4.2. Effects on health . . . . . . . . . . . . . . . . . . Chairman~: Mrchael A. H. Rur.rell Rapporteur: Mic6ael D. Lebowitz 137 137 140 5. WORKSHOP PERSPECTNES . . . . . . . . . . . . . . . . . . . . . . . . . 143 Ragnar Rylander 6. GENERAL REFERENCES ON STUDIES OF ENVIRONMENTAL TOBACCO SMOKE ......... ......................... 147
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Preface The Second Workshop on Environmental Tobacco Smoke with~ particular reference to effects and exposure levels was held in Geneva, Switzerland, March 15-17, 1983. The workshop was organized by Ragnar Rylander M. D, University of Gothenburg, Sweden, an& University of Geneva, Switzer- land, together with~ Yvonne Peterson and Marie-Claire Snella, research assistants and Isabelle Gourdon. It was supported by a grant from~the Tobacco Institute, Washington D. C., to the University of Geneva. The symbol for the workshop was designed by Ariane Catry. The participants in the Workshop are listed below. Domingo M. Aviado Atmospheric Health Sciences, Inc. P 0 Box 307 Short Hills, New Jersey 07078 - USA Bjorn Bake Department of Clinical Physiology Sahigren's Hospital 413 45 Gothenburg - SWEDEN Anthony ML Cosentino St. Mary's Hospital and Medlcall Center 450 Stanyan Street San Francisco;, California 94117 - USA Melvin W. First Department, of Environmental Health Sciences Harvard University 665 Huntington Avenue Boston, Massachussets 021'15 - USA Charles R. Gillis Greater Glasgow Health Board West of Scotland Cancer Surveillance Unit Ruchill Hospital Glascow, G20 19NB - SCOTLAND Roger Guillerm Centre d'Etudes et de Recherches Techniques sous-marines D.C.A.N! 83800 Toulow Naval - FRANCE Patrick G. Holt Clinical Immunology Research Unit Princess Margaret Children's Medical Research Foundation c/o Princess Margaret Hospital for Children G P O Box 18*D Perthi Western Australia - AUSTRALIA Horst Huckauf Freic Universitat Berlin Universitatsklinikum Steglitz Med Klinik und Poliklinikum Hindenburgdamm 30 1000 Berlin 45 - WEST GERMANY
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, Martin J. Jarvi's Institute of Psychiatry. Addiction Research Unit 101 Denmark Hill London SE5 8AF - ENGLAND Roger A. Jenkins Bio/Organic Analysis Section Analytic Chemistry Division Oak Ridge National Laboratory POBoxX Oak Ridge, Tennessee 37820 - USA Michaell D. Lebowitz Division of Respiratory Sciences The University of Arizona Health Sciences Center 2 College of Medicine Tucson, Arizona 84724 - USA Cornelius J. Lynch Franklin Institute Policy Analysis Center 1320 Fenwick Lane Silver Spring, Maryland 20910 - USA Goran Pershagen National Ihstitute of Environmental Medi- cine Box 60208 104 01 Stockholm - SWEDEN Michael A. H. Russell Institute of Psychiatry. Addiction Research Unit 101 Denmark Hill London SE5 8AF - ENGLAND Theodor D. Sterling, Simon ~ Fraser University Department of Computing Science; 291- 4277 Burnaby, British Colombia - CANADA V5A 1S6 Annetta Weber Department of Hygiene and' Work Physio- logy ETH-Zentrum 8092 Ziirich - SWITZERLAND Andreas Zober Institute for Occupational and Sociall Mede- cine and Policlinic for Occupational Dis- eases University of Erlangen-Ntirnberg Schillerstr. 25/29, 8520 Erlangen - WEST GERMANY ORGANIZING COMMIITEE Ragnar Rylander Department of Environmental Hygiene University of Gothenburg P 0 Box 33031 400 33 Gothenburg - SWEDEN Yvonne Peterson Department of Environmental Hygiene University of Gothenburg P 0 Box 33031' 400 33 Gothenburg - SWEDEN Marie-Claire Snella Environmental Medicine Unit Institute for Social and Preventive Medicine Quai Charles-Page 27 1205 Geneva - SWITZERLAND Tobacco s possible e1 which has years. A rt made by K perception very real. ` stances prc that even The combi the popula tific data c speculatior medical in environme clusions on scientific e It is necc scientific r with a criti elaboratior research. 7 workshop attempt w health effe mental tob On that existing ini ficient to al
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Introduction RAGNAA.RYLANDER' A Tobacco smoke in the environment and its possible effects on non-smokers is a subject which has been widely discussed! over many years. A reference to its irritating effects was made by Kratschmer in 1870 (1). In the public perception of the exposure to tobacco smoke is very real. The odor threshold for severali sub- stances present in tobacco smoke are so low that even minute exposures are recognized. The combination of anxiety in certain parts of the population and the absence of firm scien, tific data on effects has left~ the f eld open for speculation and far reaching, claims on the medical importance of tobacco smoke in the environment have been made. However, con- clusions on the issue mustbe based on available scientific evidence. It is necessary in such situations to perform a scientific review of available scientific data with a cri'tical assessment of their validity and elaborations on suggestions for further research. This was the approach taken by a workshop assembled in 1974 of which an attempt was made to evallrate the possible health effects following exposure to environ- mental tobacco smoke (2): On that occasion it was concluded that existing information on dose levels was insuf- ficient to allow for the evaluation of any health hazards by extrapolating data from reported associations with exposures to tobacco smoke:. It was further concluded that the carbon ~ mon- oxide in the smoke dld' not present a healtL hazard and'that the information ~ was inconclu- sive concerning health effects on children: No scientific evidence was available to suggest that genuine allergic reactions were part of the res- ponse pattern, and there was : no information on the possible risk for lung cancer. The major effect consideredfrom a public health point of view was found to be the subjective feeling of irritation and annoyance. There was insiffu~ cient data to permit an~ estimate of dose-res- ponse relationships or to determine how wide- spread or important this reaction was in~ the general population. Since the time of the 1974 workshop, research relating to environmental' tobacco smoke has continued and a number of reports have been~ publishedi In view of this, another international workshop was held with the goal of evaluating the existing knowledge, formu- lating concliisions regarding the scientific validity of published data and suggesting,areas of future research. The workshop began with formall presenta- tions on recent work presented by active researchers in the area. Work groups were then
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8 established to summarize knowledge im dlf- ferent areas and identify areas for future work. The results from the work groups were dis- cussed in a final plenary session. The term "passive smoking'-is often used to indicate non-smoker exposure to tobacco smoke. From an environmental medicine point of view this is a misnomer; in other cir- cumstances reference is always made to the exposure agent rather than to the means of exposure. In the context of the workshop, reference will thus be made to envinmmeutal tobacco rraak.r (ETS). The impact of the workshop particularly in political terrns is difficult to foresee. Govern- mental authorities frequently request precise answers on scientific issues relating to public health~ However, science may not always be able to provide such absolute answers. This clearly applies to the current state of know- ledge concerning ETS. 1. Kratschmer F. tJber Reflexe von der Nasenschleimhaut auf Atmung und Kreis- lauf Sitzungsberichte der Kai'serlichen Akademie der Wissenschaften zu Wien 1870: 62:147 170. 2. Rylander R. Environmental tobacco smoke effects on the non-smoker -report from a workshop. Scand J Resp Dis 1974: supp191, pp 1-90. Thi'sdisct nature of c ronmental characteri: smoke. THE NAT It is comi mental tot' smoke frac enters the : tion that is The smoke referred to defined in nology (1) system (for the smoke i end of a cig end,throug situation, it part of a ci~ through the smoking, sic end during
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9 1. Exposure levels 1.1. Environmental tobacco smoke measurements: retrospect and prospect MELVIN W. FIRST This discussion will cover three topics: the nature of environmental tobacco smoke, envi- ronmental smoke measurements, and the characterization of environmental tobacco smoke. THENATGtRE OF ENVIRONMENTAL TOBACCO, SMOKE It is commonly accepted that, by environ- mental tobacco smoke (ETS); we mean the smoke fraction of the burning tobacco that enters the atmosphere, in contrast to the frac- tion that is inhaled an&retained by the smoker.. The smoke fraction entering the atmosphere is referred to as "sidestream" and this word is defined in the Dictionary of Tobacco Termi- nology (1) as follows: "In a closed smoking system (for analytical purposes), sidestream is the smoke that does not issue from the mouth end of a cigarette but rather from the burning end,,through the paper, etc. In a free smoking situation, it is all of the smoke issuing from any part of a cigarette except that which is drawn through~the mouth~end during puffing. In free smoking;,sidest'ream may issue from~the mouth end during static burning." The Dictionaryy def nitaon does : not agree precisely with eve- ryday experience as smokers exhale some por- tion of the inhaled smoke, and thereby make an additional contribution of tobacco smoke products into their immediate environment. There is little agreement on the precise nature of tobacco smoke and, hence, on how to quantify its presence in the environment~ Whereas the Dictionary of Tobacco Termino- logy (1) defines "particulate phase" and "total particulate matter" as the portion of the smoke collected on a Cambridge filter pad, it also defines "cigarette smoke condensate" and "whole smoke condensate" as "cigarette smoke that is condensed or trapped by a method' which attempts to collect all the smoke."' It is clear that'~ all four terms refer to the same particle fraction and essentially define it as whatever can be collected with a device that separates particles from aerosols. The remaining combustion products are called "gas phase", defined as the part "which~ passes through a Cambridge filter." The gas phase is further subdivided into "consensable gas phase.,. the fraction of mainstream smoke which passes through a glass-fiber filter disc
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10 and can be trapped' in a glass coil at specific temperatures designed to trap specific chem- icals." The dividing line between condensable and non-condensable gas phase components will'be a function of the condensing tempera- ture. Although there are a number of perma~ nent gases, such as carbon dioxide, carbon monoxide, nitrogen oxides, and ammonia, in the smoke that will not condense at any of the temperatures usually employed to make a sep- aration, there are hundreds, and'perhaps even thousands, of smoke components whose con- densable behavior is markedly influence& by temperature. Below a temperature equivalent to gas- phase saturation, the entire inventory of con- densable smoke components exists partially in the vapor phase and'partially dissolved in a liquid phase composed of aqueous an& tarry fractions of the smoke particles. Higher tem- perature favors the enrichment of the gas phase at the expense of the liquid phase, and' lower temperature causes the reverse. Although the effect of temperature on the liquid-vapor rela- tionship is wel] defined for pure substances, the vapor pressure interrelationships have been studie&for only a few commercially important binary and ternary combinations. The temperature range in the indoor envi- ronment is narrow, i.e. from 15 to 30 °C, meaning that temperature effects on conden- sation are negligible. Of great importance is the enormous dilution that occurs immediately as tobacco smoke is discharged to the atmos- phere, making it unlikely that additional con- densation will occur even if the temperature is lowered substantially. However, as water makes up about 16 °r6 by weight of the total particulate matter of cigarette smoke, and liquid organic components much of the remainder, it is possible for the particulate phase of smoke to dissolve volatile water- and organic-soluble smoke components that would not otherwise be found in the condensed phase of whole cigarette smoke. The vapor phase and the particulate phase of cigarette smoke contain many of the same components but as environmental smoke becomes more and more dilute, the trend is toward transfer of material from the particulate phase to the gaseous phase. When one seeks to measure the concentration of the particulate phase by continuous sampling,methods, some fraction of the water- and tar-soluble compon- ents (as well~as the water, itself) will be lost to the discharged air stream. Therefore, the com- position of smoke particulate matter in the environment may differ from the composition of a sample collected on~a Cambridge filter and both will be different from a sample of ciga- rette smoke collected directly from an analy- tical smoking machine. To evaluate the contribution to ETS made by exhaled smoke, it is necessary to know what fraction of inhaled smoke is retained and whether the composition of exhaled smoke is the same as inhaled' smoke: The fraction of retained smoke has been estimated by a number of investigators to be $2-97 °Ya, making the amount exhaled to the environment appear to be trivial in relation to the relative amounts of sidestream and mainstream smoke produced per cigarette smoked (Table 1). However, more recent measurements (2) show adifferent picture. The new estimates of the percentage of inhaled smoke particles that is later exhale& were based on measurements of the weight of exhaled smoke particles collected on absolute- type filters compared with the weight of inhaled particles collected in the same manner. To avoid interfering with an individual's normal smoking pattern, smoke inhalation rate and quantity were measured by a miniature air-flow measuring transducer contained in a cigarette holder. The data were used' to pro- gram a cigarette smoking machine that repro- I TABLE 1. Compound Tobacco bur; No. particlca_ Tar Nicotine Benzo(a)pyxe Pyrene PhenolS Ammonia Nitrogen Oxi~ Carbon Mono #' Filter cigare duced each using identic: the machine nected to the this method ii amount of ir accuracy and introducing t the subjects, a dies. Exhaled sn the human s handheld exl- smoker's mot stream smoke TABLE 2. Ciga Group All Males Females
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11 )hase ise of same noke nd is ulate .ks to ulate some ipon- ost to com- n the sition :r and ciga- inaly, made what I and :)ke is on of by a aking ppear ounts 3uced vever, ferent age of .-haled ght of olute- ,ht of inner. dual's mrate iature d in a ) pro- repro- TABLE 1. Comjiarrsox of mairatnam and sidestteam smoks constituents (mg/crg) i Compound Mainstream Sidestream Ratio Sidestream/ Mainstream Tobacco burnt 347 (20 sec) 411 (550 sec) 1.2(27) No. particles produced 1012 3.5x1012 3.5 Ta'r' 20.8' 44.1 2.1 10.2 * 34.5 * 3.4 * Nicotine 0.92 1.69 1.8 0.46* 1.27* 2.8* Benzo(a)pyrene 3.5x 10 75' 13.5x10-5 3.7 Pyxene 13x10-s 39x10-5 3.0 Phenols 0.228 0.603 2.6 Ammonia 0.16 7.4 46 Nitrogen Oxides 0.014 0.051 3.6 Carbon Monoxide 19 88 4.7 * Filter cigarette.. duced each subject's smoking pattern while using identical cigarettes. Allismoke inhaled by the machine was passed through a filter con- nected! to the mouthi end of the cigarette. By this method it was possible to measure the total amount of inhaled smoke with considerable accuracy and precision without, in any way, introducing unnatural', smoking restraints on the subjects„as had been, done in all prior stu- dies. Exhaled smoke was captured directly from the human smoker by positioning a small handheld exhaust hood 4,8 cm from the smoker's mouth. To avoid collecting side- stream smoke, the hood was operatedl only during smoke exhalation. All smoke captured by the hood was collected on an absolute-type filter for comparison with the inhaled weight. AnaNysis was conductedl by extracting the' smoke from the filters in methanoli and meas- uring UV absorbance at 400 nm. Prior to, and immediately following the smoking of cigarettes, blood samples were taken and analyzed for carboxyhemoglbbin (COHb) i and nicotine concentration. The results of this study (Table 2) showed that for a group of eleven confirmed smokers, inhaled smoke retention ranged from 22' to 75 %, a three-fold variation among subjects. The average for all subjects, eachiof whomwas TABLE 2. Cigarette smoke depbsitron in confirmed smokers. Deposition % Group Subjects Measurements Range Mean (S:D.)', All 1l1 22 22-75 47 (13) Malps 6 9 33-75 57 (13) Females 5 13 22-49 40 (18) ~,_
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12 studied twice, was 47 %, about one-half pre- viously published averages. Other interesting results were (a) that the correlation coefficients relating particle mass deposited in the lungs to changes in blood! nicotine and carboxyhemo- globin were 0.64 and 0:12, respectively, and (b) the average puff volume of the subjects was 53 ml, 50 qfi greater than the standard puff volume used by the Federal Trade Commission (FTC). As 50 9"0 of inhaled smoke is discharge& to: the air, it is clear that exhaled smoke makes a significant contribution to ETS. The smoke has, however, changed its characteristics because smoke particles grow by absorption of water vapor, and agglomeration during their residence in the warm, saturated respiratory passages and differential lung retention by par- ticle size changes the size spectrum of the expelled particles in comparison to the inhaled smoke. There is also a loss of water-soluble components from the gas phase, as well as from~ the particulate phase. • Studies conducted with an airway simulat'or consisting of variable lengths of glass tubes lined with glass fiber filter paper moistened with physiological saline solution indicated that the respiratory tract is an infinite sink for a large fraction of the volatile smoke products in the gas phase. Gas samples were extracted with a gas-tight syringe from~ numerous sampling locations and analysed' for a number of smoke components by gas chromatography: Saturated hydrocarbons were not decreased by passage through the wetted wall tubes, whereas highly soluble compounds, such as acetone, weree removed promptly from the gas stream. Ana- lytical results for 17 smoke components (according to length of passage through wetted-walli tubing) are shown in Table 3. TABLE 3. Qxontttiss prerent in 1 m1 gat phace smake o, f fotfrth pxff of 1 R i renarrh' cigarette. Compound* Micrograms remaining,after passage through indicated length of wetted! walll tubing 0 cm 30 csr 60 cm 120'cm Methane 1.75 1.80 1.73 1.73' Ethylene 0.72 0.59 0:67 0.6& Ethane 1.24 L29' 1.27 1.31 Ptopylene 0:59 0.62 0.60 0.59 Propane 0.52 0.39 0.50 0:49 Acetaldehyde 1.90 1.48 0.49' 0! 14 Isobutylene 0.48' 0.52 0.47 0.48 n-Butane 0.34 0;38 0.35 0.37 Acetonitrile 0.29 0.041 0.00 0.00 Acrolein 0.28 0.21 0:15 0.10, Acetone 1.53 0.40' 0! 18 0.00 Acrylonitrile 2.00 1 ~98 1.79 2.21 Propionitrile 0:54 0.26 0.16' 0:16 2-Butanone 0.29 0:23 0.19 0 j23 Crotonaldehyde 0.26 0:25 0.23 0.26 2-Pentanone 0.15~ 0!11 0.10 0.09 Toluene 0.29 0.28 0.27 0.32 * Listed in the order in which they penetrated the ehromatographic column. Alth with iga: results tion of stances a gas pl tributed phases - pressure aqueous partide compou, the airw equilibri pounds new equ process, depleted absorbed expelled residencc system, b ferences In sun containir number unstable phases. regarding ETS and pretation relative t( . ENVIR A recent identified measured these corr hydrocarb teen), nic( nitrosamii matter (tc aldehydes,
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13 Although the experiments were conducted; with gas phase alone, it is possible to extend the results to the particulate phase by the applica- tion~ of partial pressure relationships for sub- stances distributed between a liquid phase and a gas phase. Volatile smoke products are dis- tributed initially in the gas and particulate phases according to each component's partial pressure relationship between gas phase and aqueous or non-aqueous phase of the smoke particles. As the gas phase becomes depleted of compounds absorbed into the moist surfaces of the airway simulator, as shown in Table 3, the equilibrium is disturbed and' volatile com- pounds leave the particulate phase to form a new equilibrium with the gas phase. By this process, smoke particlts can become severely depleted of volatile compounds that are readily absorbed by lung and respiratory tissues. Thus, expelled cigarette smoke, after an appreciable residence time in~ the human respiratory system, has marked physical and chemical dif ferences from sidestream~ smoke. In summary, ETS is an ill-defined entity containing variable amounts of an unknown number of compounds distributed in highly unstable ratios between the gas and particle phases. This leads to great uncertainty regarding what should be measured to quantify ETS and even greater uncertainty in the inter- pretation of environmental measurements relative to human responses to ETS. ENVIRONMENTAL SMOKE MEASUREMENT A recent review of ETS measurements (3)' identified all' the substances that have been measured as indicators of ETS: They include these components: acrolein (three); aromatic hydrocarbons (six), carbon monoxide (seven- teen); nicotine (four), nitrogen oxides (three), nitrosamines (three), airborne particulate matter (ten), and others, including phenols, aldehydes, SO2 and sulfates (one each): Most ETS measurements (55 g'o) have been made with portable easy-to-use, direct-reading instruments that estimate CO and suspended particulate matter as surrogates for cigarette smoke. Both substances are widely dispersed in the biosphere from sources other than tobacco combustion and both occur indoors from internal sources as well as by infiltration ~ from the outside. The same comment applies to measurements of acrolein, aromatic hydtocar- bons, nitrogen oxides, nitrosamines, phenols, aldehydes, sulfur dioxide, and sulfate as surro- gates for tobacco smoke. The major defect asso - ciated with using the above-named gases, vapors, and particles as surrogates for ETS is the likely presence of sources other than~ tobacco that produce concentrations suffi- ciently high to confound attempts to distin- guish the amount contributed solely from tobacco smoke. A few examples will serve to illustrate the point. Restaurants, cafes, and bars, favored'& loca- tions for measuring ETS, habitually use gas for cooking and for heating water. Often the gas- using facilities are located4nside public rooms, e.g. gas or charcoal grills, and make a major contribution to the concentration of CO in the room. Many restaurants, cafes, and bars are located on large streets and infiltration~ of CO and particulate matter from motor traffic is another major contributor to indoor air con, tamination. The portable, direct-reading electrochem- ical instruments that are widely used for CO measurements have a serious defect for indoor measurements in restaurants an& bars in that they respond to ethyl alcohol vapors much more stronglp than they do to CO. Therefore, special filters must be used~ at the entrance to the device to avoid spurious reading from ethyl alcohol and similar compounds that may be present in small concentrations, especially as the instrument cannot be relied upon to read
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14 closer than 1-2 ppm CO even under the best of circumstances. Public places of the sort noted above, as well as sports arenas, transportation waiting rooms, hospitali lobbies, and large offices, normally experience a great deal of foot traffic and other activities that generate airborne particulate matter from, flbors, rugs, furniture, clothing, etc. In addition, these types of facilities are likely to be close to busy highways and to expe- rience frequent arrivals and departures that permit constant intrusions ofdust, from outside air. The fallacy in using air dustiness as a sur- rogate for ETS is that the more people that use these kinds of facilities, the more bustle there will be and, hence, the more airborne dust, created. Assuming,that the fraction of smokers and non-smokers is always about the same, the more people presents the larger the numbers of smokers, but also, the greater the amount of internal dust generating activity. This is not to say that tobacco smoking does not make a con- tribution to indoor airborne particulate matter but rather to point out that in public places other sources of airborne particulate matter are iikely to be of sufficient magnitude to con- found measurements of ETS. This comment iss especially pertinent for the TSI piezoelectric portable airborne particle sampling and ana- lysis instrument that has been used frequently for tobacco smoke measurements . This appa- ratus was not designed for this: type of service and lacks the sensitivity and precision needed to sense the small incremental concentrations attributable to tobacco smoking in public places. Similar comments appNy to all the other tobacco smoke surrogates that have beenmen- tioned except nicotine. Nicotine is an unique component of tobacco smoke and aside from some commercial usage of extracted nicotine sulfate as an agricultural insecticide„there is no other source of nicotine in the environment than smoking tobacco. With the exception of watery nicotine is the largest single component of the particulate phase of tobacco smoke. "IThe nicotine concentration is unaffected by the moisture content of the smoke and sensitivee gas chromatographic (GC) analytical methods are available for its measurement. This makes nicotine the ideal indicator for tobacco smoke. Airborne nicotine cam be sampled with a gas-tight syringe and analyzed by a GC method capable of detecting,picograms of nicotine in a 25-50 ml sample (4). Integrated samples of air- borne nicotine can be taken at a rate of 21/min over 10-30 min by passing the air through a Cambridge, or similar glass fiber filter, that has been~ treated with 0.5 ml~ of 0.5 molar potas- sium bisulfate to suppress the volatility of cap- tured nicotine. Although nicotine is the preferred indicator for ETS, it remains difficult to relate the meas- ured nicotine concentration to any other con- stituent of the smoke because of the wide range of nicotine content of present day cigarettes, at least in the United States. It is, however, poss- ible to smoke selected! cigarettes in a test chamber and establish with reasonable cer- tainty the ratio of nicotine to other compon- ents of interest, It is also possible through investigations of consumption habits to com- pile a record of contemporary cigarette usagee in the locality where atmospheric testing will be conducted and! use the data to estimate an average nicotine value for interpreting en« vironmental measurements. To test the concept of nicotine as the best indicator of ETS, a! series of simultaneous measurements was made in realistic, uncon- structured conditions in public places using the three most popular measurement methods: CO by Ecolyzer, suspended particulate matter by model 3500 TSI piezoelectric instrument, and nicot: material e: a nitroge shown in The nu tion betw particulat, ments. Th use of gas had the mc centrations moving a. TABLE 4. , Location Chamber 1 Chamber 2 School cafetc School cafete Tavern li Tavern 2 Tavern 3 Bus terminal Fast food rest Small sitdowi Small sitdowr
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15 a a s ,- r- i- i- ;e tll tn 1- P.' and nicotine by filtration and analysis of the material extracted from the filter by GC, using a nitrogen-sensitive detector. Results are shown in Table 4. The numbers demonstrate a poor correla- tion between the result of simultaneous CO, particulate matter, and! nicotine measure- ments. The proximity of street traffic and the use of gas appliances im restaurants and bars had the most important influence on CO con- centrations, whereas the number of people moving around had the most important influence on particulate matter concentra~ tions. It may be concluded that there is not, at present, a thoroughly satisfactory method for measuring the totality of ETS: At present each investigator of ETS has latched onto a tiny, but distinctive, fragment of the whole aerosol and has sought to reveal the entire universe from it. Humility seems not to be an outstanding char- acteristic of those who measure ETS and then draw sweeping conclusions regarding health effects from a tiny part of the whole exposure spectrum. TABLE 4. Simultaneous mearunmentr oftodacco smoke ron.rtituents: ocation Average CO ppm Average particulate matter mg/m1 Average nicotine µg/m3 Chamber 1 2.0 0.30 ~ 13.9 Chamber 2 1.5 0.29' 13.9 School cafeteria 1 LO 0.02' 5.5 School cafeteria 2 0.5 . 0.04 2.7 Tavern 1 8.0 0.40 6.3 Tavern 2 8.0 0.66 9.4 Tavern 3 7.0 0.57 15.9 Bus terminall 3.5** 0.11 Fast food restaurant 5.0 0.15 30.0 Small sitdown restaurant 1 6.0 0!25 12.0. Smalll sitdown restaurant 2 6.5 0126 16.3 Dumrption One 2R1 cigarette machine smoked - 0.75 ach-1 *' One 2R1 cigarette machine smoked - 0.75 ach-1 * Large open eating area away from kitchen - no smokers Large open eating area away from kitchen - 2-3 smokers within 3-4 m Moderately crowded, small drinking estab- lishment on street corners 1-5 smokers Moderately crowded, small drinking estab- lishment on street cornery 2-3 smokers Moderately crowded, small drinking estab- lishment on street corner, 1-3 smokers, (mostly, just one) Waiting room - 30x10 m. Bus stands on two Ibngs sides,, 50-100 people, 1-5 smokers Kitchen and eating, eombined! into one room 13X23 m. 1-3 smokers throughout sampling period 15 diners - 4 smokers, open1itchen door, side. eating area 23 diners - 1 smokery open kitchen door, side eating area * air changes per hour. ** outside air 2.0-2.5 ppm CO; 0.07 mg/m3 suspended' particulate matter.,
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16 CI3ARACTERIZATION OF ENVIRONMENTAL SMOKE There is no single measurement that can be used to characterize the totality of ETS. No single measurement other than nicotine corre- lates well with~smoking under realistic condi- tions. Even~ nicotine becomes less than ideal whenever there is uncertainty regarding the nicotine content of the cigarettes being use& during the measurement' period. Inasmuch as realistic measurements of ETS are characteristically undertaken to relate the amount found to some impact on human re- sponse, e.g. irritation of mucous membranes, dtcreased lung function, headache or psycho- logical distress, it would seem logical to con- centrate environmental~ smoke measurements on the specific compound, or combination of compounds, that most directly affect that par- ticular physiological response. Thus, if one wishes to study lung function, it seems more logical to seek out an& measure those sub- stances that~ affect lung ftinction directly, rather than to measure CO that affects only red blood cells. Selecting the precise compounds that affect the tissues an& physiological functions under study is not easy and after the selection has been made, performance of the required measurements may be arduous. Nevertheless,, we must, in my opinion, proceed in this direc- tion if we are ever to be ablt to apply respect- able science to the investigation of the effects of ETS on human populations. Finally, more research is needed on the fate of tobacco smoke products as they age and become more dilute in the oxygen- and water vapor-rich indoor atmosphere. More research is also needed on the inter-relationships between tobacco smoke products so that, ulti- mately, it will become possible to resolve the measurement task on a rational basis and, at last make a start on realistic research into the interaction of ETS an& people. REFEAENCES 1. DeBardeleben M.Z (Fd)j Dictionary of'Iiobacco Terminology, Philip Morris Inc. Technical Infor- mation Facility, P 0 Box 26583, Richmond, Va 1980. 2.1 Hinds W, First M.W, Huber G;L., Shea J.W: A method for measuring respiratory deposition of cigarette smoke during smoking. Am ind Hyg Ass J 1983: 44:113-118. 3. Sterling T.D, Dimoch H, Kobayashi. D. Indoor byproduct levels of tobacco smoke: A critical review of the literature. J Air Pollut Control l Ass 1982: 32:250-259: 4. Grubner 0, First M.W, HuberG.L. Gas chroma- tographic determination of nicotine in gases and liquids with suppression of absorption effects. Analyt Chem 1980: 52:1755-1758. Melvin W. First, Sc. D. Harvard School of Public Health Boston, MA 02115, USA C L 0J Since the mic building-assoc and illnesses I America and I health compla: tigations coinc effort to min reducing fres: increasing the acceptable terr conditioned, n ings (1): Healtl headache and systems and' pr, these instances nished buildin ambient air are trolled and ligi lamps. Onlyin a or illnesses tract as carpet shaml O ducting systema C,;, levels of formald ~ N t`? Cn N N
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Ks te :Id er ch PS ti- he at he 17 1.2. 'Investigations on the effect of regulating smoking on levels of indoor pollution and on the perception of health and comfort of office workers THEODOR D. STERLING AND EI:IA M. STERLING A of .ss or .al .ss ,a- ad ts. INTRODUCTION Since the mid-1970s many investigations of building-associated epidemics of complaints and illnesses have been undertaken in North America and Europe in response to occupants' health complaints. The majority of these inves- tigations coincide in time with a concerted effort to minimize building energy use by reducing fresh air ventilation rates and increasing the operational comfort ranges for acceptable temperature and humidity in air conditioned, mechanically ventilated build- ings (1). Health complaints have ranged from headache and eye irritation to reproductive systems an& pregnancy problems. Almost alli these instances have involved new or refur- nished buildings in which conditions of ambient air are completely mechanically con- trolledi and' lighting supplied by fluorescent lamps. Only in a few instances were complaints or illnesses traced back to specific causes such as carpet shampoo residues,, fiberglass from ducting systems, rock wooly and excessive levels of formaldehyde. But~ specific causes for symptoms were not determined for most inves- tigations. The term "Building Illness" has been used to refer to these epidemics of complaints from building occupants about symptoms and'. dis- comforts including headaches, burning eyes,; irritation of the respiratory system, drowsiness, fatigue and general malai'se experienced' over an extended period of time with the cause remaining undetermined but suspected to be related to components of the building, or air supply system (2,3). In modern, energy-effi- eient office buildings tobacco smoke, perhaps because of its visibility, is frequently regarded as an important source of airborne particulates and gases. It is thus only natural that a great deal of attention has been concentrated on smoking as a source of indoor airborne sub- stances and as a possible cause for Building Illness. However, modern buildings tend to generate alargg variety of pollutants as well7as to entrap large numbers of them ~ penetrating from the outside. Evidence from many studies has now demonstrated that buildings indeed entrap and concentrate a large variety of pol- d (.7 N U'1 - N W
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18 lutants found both outside and generated inside andthat, in fact, for many pollutants the levels of concentrations inside buildings, under normal working conditions, exceed those found' on the outside (4, 5, 6). It is the purpose of our review to compare the levels of possible cigarette smoke-related aerosols with the prevalence of health-related complaints in offices with different rules and regulations about permissions, restrictions or prohibitions of smoke. Our information will come from different sources: First from a review of pollutant levels reported for 111 buildings selected for study because of persistent building-related com- plaints and from 32 buildings selected for: study because of absence of complaints. The data from these buildings also make possible a com- parison of pollutant levels in buildings with and without rules restricting or prohibiting smoking. Second, from a study done in collaboration with the Office Professional Employees Inter- national Union, Local 153, in New York City. This study was based on nine buildings in which approximately 1100 members of Local 153 responded to a detailed health an& envi- ronment questionnaire which~made it possible to compare the prevalence of complaints of discomfort or of symptoms related to Building Illness in offices where smoking was per- mitted, restricted or prohibited. POLLUTANT LEVELS, BUILDING ILLNESS COMPLAINTS AND SMOKING RESTRICTIONS Since 1977, there has been a large increase of Health Hazard Evaluations initiated by occur pants of sealed, air conditioned ~ buildings who believe their office (or work environment) too be hazardous and their symptoms to be building-related. Most of these evaluations were done by the US National Institute for Occupational Safety and! Health (NIOSH), the US Center for Disease Control (CDC), by State Departments of Health and Labor in the US, and.by a number of privately sponsored inves- tigations of sealed buildings. A large number of the reports from such investigations are now available in Canada and the United States (in addition to similarly motivated European stu- dies). Many of the studies report results of indlls- trial hygiene investigations of indoor condi- tions including information on a variety of pollutants carefully and repeatedly measured. Also available for most of these studies are detailed health surveys of symptoms and com- plaints, which typically include inforrnation on personal habits and on some of the relevant history of respondents. Reports of 1i11 buildings studied in response to Building Illness complaints were obtained. Seventeen of these buildings restricted smoking. Also, reports of 32 other buildings were obtained of which, 11 restricted smoking. (A list of these reports and information, on where they may be obtained will be furnished on request.) Information oni smoking restric- tions came from individual reports and was further clarified as needed~ by discussion with investigators. If smoking was restricted at some periods but measurements were taken when smokers could have been present, the obtained values were grouped with other measures from buildings without smoking restrictions. POLLUTION'IN BUILDINGS WITH AND WITHOUT COMPLAINTS Most studies of Building Illness complaints measured background levels of pollutants. The types of pollutant selected for measurement depended as inuch on~the investigators' hunch of what might possibly cause problems in the building as on~the measuring and testing facil- ities at their d investigations levels of a lar ured levels c chemicals anc (such~ as noist once. An ade, was available suspected ind related to sm, informatiom ir found in modE cient building plaints have b Not all stuc able units. Le ppm, ppb, mg,. TABLE 1. Medr Pollutant Aldehydes' Amines Aromatic Hydrocarbons Carbon Dioxide Carbon Monoxi( Formaldehyde Hydrocarbons Nitrogen Chcidea Nitrogen Dioxid l Ozone Particulates Sulphur Dioxide Temperature Relative Humidity a: Not includin€ a b: Two values a W ND: Tested but No data IU N ~a
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d. re 3- )n ctt se d. A gs ,g. ,)n ed ic- "as th ne en ed )m its he :nt ch he :il- ities at their disposal. Thus, our review of 143 investigations in buildings reveals measured levels of a large number of substances. Meas- . ured levels of approximately 156 different chemicals and 12 other miscellaneous factors (such as noise or bacteria) are cited' at least once. An'adequate number of measurements was available for subsequent analyses of 12 suspected indoor pollutants, which might be related to smoking. These measures provide information in the pattern of polllttant levels found in modern, sealed, so-called'energy-effi- cient buildings in which health-related com- plaints have been recorded. Not all studies reported results in compar- able units. Levelfr were expressed in counts, ppm, ppb;,mg/m3 or µg/in3. Conversion of the 19 units to a common scale was accomplished for specific chemicals. In many, instances measure- ments were taken but no detectable lei+e!(ND) was found or the results were reported as "trace amounts". Where a range of values was reported for repeated measurements in a building, the average value assigned to that building was the statistical median. By this method, bias was avoided due to too many ND findings or due to isolated unusually high values. The choice of medians also makes the estimate of a typical pollution burden some- what independent of the sensitivity of the measuring procedure as it is possible the pol- lutant was present but in levels below that of the sensitivity of the test procedure. Table 1 gives the averages (median) of the 12 TABLE 1. Median tetrlr of pollutants mearxnd `most frrqxently in bwtldings imrstigated for heattb complaints ollutant Buildings without smoking, restrictions Number of Reports Buildings with smoking restrictions Number of Reports All : buildings Aldehydes' ND 5 - 0 ND Amines ND 10 - 0 ND Aromatic Hydrocarbons Trace 39 56.07 mg/m3 21 ' Trace Carbon Dioxide 354.5 ppm 20 476.5 ppm 2 354.5 ppm Carbon Monoxide 2 ppm 44 4i 12 ppm 7 2.25 ppm Formaldehyde Trace 35 ND 3 Trace Hydrocarbons ND 47 ND 2 ND Nitrogen Oxides ND 21 ND 1 1 ND Nitrogen Dioxide ND 9 - 0 ND Ozone ND 22 0.001 ppm 2 ND Particulates 0.028 mg/m3' 13 0.015 mg/m3 1 0;021 mg/m3 Sulphur Dioxide ND 15 ND 1 ND Temperature 720 F 17 730 F 6 72°'F Relative Humidity 38% ' 20' 23.5% 5 35.1% a: Not including Formaldehyde b: Two values are 8.14 mg/m3 and 104.0 mg/m~ ND: Tested 6ut no detectable levels found - : No data
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20 most freqpently measured pollutants obtained from the 111 buildings with Building Illness reports and Table 2 gives the same information for the 32 buildings studied specifically for pol- lutant levels. Each table gives the number of buildings from which each pollutant level was obtained. Buildings were divide& also byy whether smoking was or was not restricted in the location where measurements were obtained. Because of differences in the way buildings were selected for measurements, we present the data separately in Tables 1 and 2. In most studies, methods for measuring pollutant levels were of no greater sensitivity than were necessary to detect"1'hreshold'Limit Values (TLVs) or other industrial standards. Thus there was a large number of reports in Table 1 with N:D. readings. Values inTable 2 usually were obtained as part of investigations using sensitive state of the art procedure. For the two values thought most relevant to evaluate the contribution of smoking, carbon monoxide (CO) and particulates, values in Tables 1 and 2 do not substantially differ from each other nor do measurements of CO and particulates from smoking-restrictedi areas differ from those of workplaces without such restrictions. Values in both tables can be com- pared also with those available in the literature. Reported' values were no higher and oftem lower than those reviewed in amumber of pub- lications (3, 4, 5, 6)j For instance, a number of studies compared outdoor levels of CO with~ levels in offices where there was smoking. One by Chappell and Parker (7), of 10 offices, TABLE 2. Median ltt.edr of pollutants meaturod mart frequenty in buildings imuertigated for reasons other than bealtb tomplaint.r. Buildings without smoking Pollutants restrictions Number of Reports Buildings with smoking restrictions Number of Reports All Buildings Aldehydes° 0.09 mg/m3 5 0.025 mg/m' 4 0.087 mg/m' Amines 0 - 0 - Aromatic Hydrocarbons 0.09 mg/m3 11 4.5 Mg/M3 3 0.11 Mg/M3 Carbon Dioxide 7293 ppm 2 900: ppm 11 9001ppm Carbon Monoxide 3.5 ppm 10 3.4 ppm 3 3:41 ppm Formaldehyde 0.26 ppm 2 0:024 ppm 2 0.027 ppm Hydrocarbons 0:0275 mg/m3 22 0.18' mg/m~ 2 0.0295 Mg/M3 Nitrogen Oxides 4i116 ppb 7 26 ppb 1 38.8' ppb Nitrogen Dioxide 33.9 ppb 4 - 0 33.9 ppb Ozone 0.005 ppm 1 0.0145 ppm 2 0.012 ppm Particulates 0:037 mg/m3 9 0.036 Mg/M3 1 0.036 mg/m4 Sulphur Dioxide 0.09 ppm 2 0:012 ppm 2 0.012 ppm, Temperature 71 °F 3 - 0 71°F Relktive Humidity 39% 3 - 0 39% a: Not including Formaldehyde -: No data reports average inc be 2.5 ppm. A stu offices found indoc ppm and outside c These figures agree CO level of 2.25 p with Building Illne 3.4 ppm based on, neither table is the ence in CO levels smoking was and a Regarding susp. average (median) fo; for Table 1 and 0.03 Table 2, all of them tions. There were to< what the average dif these buildings and t tions. These values are ~ the average of 0.17 n andiFischer (9) using measure particulatec- apparently at randoi than the average of I ured with a Piezoelec Repace and Lowrey ( smoking was permitt Part of the reaso values in 24 buildings the buildings monit Lowrey were public establishments, sports the values in the revie, to the white-collar wc Another reason for may be related to tec ments taken by Weber Repace andLowrey ( ] Respirable Aerosol Ar in studies reviewed ht used gravimetric mc involving air pumps :
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22 samples taken~ before cleaning the crystal. Weber and Fischer (9), for instance, took an extraordinarily large number of samples and so did Repace and Lowrey (10). The one excep- tion in our series also using a Piezoelectric bal- ance (13) again reports a very large value (2-4 mg/m3) but offers no details of sampling. In contrast, the highest value in our series reported through other than the Piezoelectric method is 0.224 - 0.62 mg/rn3 (14): Thus in the finallanalysis the estimates obtained by the Pie- zobalance of aerosol particulates in the pre- sence of tobacco smoke may be seriously over- estimated. Until these questions are answered, results from the use of Piezoelectric balance need to be interpreted with caution. Also inter- preted with caution need to be anycomparison between measurements of particulates obtained through filtering and electrostatic methods because of the different sizes of par- ticles measured' by each method. In short, this whole issue of how to sample particulates needs clarification. The one large difference between values in areas with and without smoking restrictions is that of aromatic hydrocarbons. The measure- ments of aromatic hydrocarbons in smoking, restricted environments were made in hospi- talfi where hydrocarbons are normally present inthe air. Aromatic hydrocarbons measured in workplaces without smoking restrictions did not include hospitals. Nevertheless aromatic hydrocarbons were measured in a large number of offices (and are included'.inXables 1i and 2 for this reason) where theywere found in "trace amounts". It appears, then, that there are no differences on the average values of the kind of pollutants measured in these studies in buildings with and without~ smoking restrictions. Also, the levels of pollutants that were measured in buildings with health-related complaints were no larger than those reported! in the literature from buildings without such complaints. The cause of complaints probably does not lie in the levels of individual pollutants measured in the studies evaluated here. Nevertheless, Building Illness might still be related to other substances in the indoor air or combinations that have not been measured directly (15).. HEALTH AND COMFORT IN NINE OFFICE BUILDINGS A computer-readable, self-administered work environment questionnaire was given to mem- bers of the Office Professionat Employees International Uhion, Local 153, New York City. The questionnaire was constructed so as to document perceived environmental condi- tions, symptoms and complaints related to Building Illness among occupants of nine such~ buildings. The buildings chosen had no prior histories of complaints. Among others, the Health and Work Envi- ronment Survey questionnaire contained! detailed information about: 1. Environmental conditions (such as air movement, lighting, odors, etc.): 2. Lighting conditions (ranging from ques- tions on fluorescent lighting to window lighting). 3. Health-related symptoms (such as head- aches, dizziness, fatigue, sleepiness, and others which have been very ofren reported in buildings with health and comfort com- plaints): 4. Life-style factors andl personal factors (including, smoking). 5. Stress factors (such as job security).. There were other questions as well about equipment use, employment history, types of appliances used! at home, and others not reported here. Answers on other conditions scale : 1 for "Nev times"; 3 for "C werephrased'so t. indicated a favora a 3 an unfavorabl, there too little air ever experienced' Using this scoring struct indices basec assign a subject a , her average ratir. • included in each then be related to including those indices of interest define them are gi Each respondeni how he or she fel mentaf or stress cc symptoms (as me mental, stress and I "average" or "poo and "high"' for eae: better separate "gc ("`high") conditions favorable condition~ when all questions. were answered as fa ponse that was unt making up the ind, subjects rating as ` "good" (or "low") average of "'1", a "1 cation an average of average scores classi on a particular envi i nd'ex. The major findinz published in detail e tistically significant indices of health and
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cause. a the in the ilding tances ve not I work ) mem- )lbyees r York :d so as condi- ated to ne such io prior k Envi- ,ntained as air m ques- window as head- ess, and reported ort com- l factors ),4 ell' about , types of -hers not Answers on health, environmentali and! other conditions were scored on a three-point scale: 1 for "Never or Rarely"; 2 for "Some- times"; 3 for "Often or Always". Questions were phrased'so that "Never or Rarely" or a 1 indicated a favorable and "Often or Always" or a 3 an unfavorable response. For example, "Is there too little air movement?" or "Have you ever experienced headaches while at work?". Using this scoring scheme it is possible to con- struct indices based on related questions, and assign a subject a score corresponding to his or her average rating or the individual item included in each index. These indices could then be related to various sets of conditions,n including those relating to smoking. The indices of interest here and the questions that define them are given in~ Table 3: Each respondent was classifiedi according to how he or she felt that the overall environ- mental or stress conditions or health-related' symptoms (as measured by each environ- mental, stress and health index) were "good",, "average" or "poor" (and "low", "average" and "high" for each stress index). In~order to better separate "good"' ("low")' and "poor" ("high") conditions, a "good" ("low")j that is a favorable condition was assumed to exist only when alll questions making up any one index were answeredias favorable (i.e. "1i"). Any res- ponse that was unfavorable to any question making up the index (i.e "3") classified thee subjects rating as "poor" ("high"). Thus a "good"' (or "low") classification required an average of "1", a "poor" (or "highi") cl'assifi, cation an average of greater than "2". AlDother average scores classifiedla subject as "average" on a particular environment, stress or health index. The major findings in this study, which is published in detail elsewhere(15), were a sta- tistically significant association between all indices of health and disease and conditions of 23 ventilation, lighting, Video Display Terminals (VDTs) or Cathode Ray Tubes (CRTs)~use and stress (possibly in that order). Analyses of envi- ronment, health and stress indices in relation to smoking were made. There were different types of smoking restrictions: In one set of buildings, smoking was prohibited. Usually a special area was set aside for smokers. In another, smoking was prohibited during specific usually busy timeperiods,,for instance between~ 1O am and 9 pm, but permitted during others (16). Apparently smokers comply gen- erally with regulations. Also, compliance tends to be reinforced by non-smokers' insistence of adherence to regulations. Regarding smokers and smoking, restric- tions, the following groups were identified: Non-smokers working in places where smoking was permittedi Non-smokers working in places wheree smoking was restricted. Non-smokers working in places where smoking was prohibited. Smokers working in places where smoking was permitted. Smokers working in places where smoking was restricted. Smokers working in places where smoking was prohibited. As responses to questions were almost id'en- tical for places where smoking was restricted and where ii was prohibited; we also combined the workplaces where smoking was restricted or prohibited into a single category. The next series of tables show these relation- ships for non-smokers (Tables for smokers, not shown here, are similar). Rather than giving individ'uall cell frequen- cies, we elect to present the outcome of the cross tabulations as percentages in such a way that direct comparisons can be examined: Each column gives the proportion of individuals
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24 TABLE 3. Group,r af rrrporue,r ured to canstruct "health" and "rtrr.a" related indices. Health Related Building Illness - headache - fatigue - nose irritation - eye irritation - sore throat or cold symptoms Cardiorespiratory - nose irritation - breathing difficulty - chest pain or tightness - racing heart Musculoskeletal - neck ache - sore arms, hands or wrists - backache Neurophysiological ~ - headache - dizziness - fatigue - sleepiness, - moodiness - depression - lightheadbdness. - confusion Somatic Stress Related ' Decision Making - In your job are you able to make decisions on your own? - are you free to determine how you do your job? - Can you set the speed at which you work? - Are you able to influence company policies,that affect your job? Job security - Is your job security good? During the past year, were you facediwith possible job loss or layoff? (exclude actualljob loss or layoff). Physical - Does your job require you to work very fast? - Does your job require you to exert a lot of phy- sical effort? - Are you required to use awkward work motions? Relationships - Are co-workers helpffil in getting your job done? - Is your supervi'sor helpful in getting your job done? - Are you faced withabuse or hostility from: cus- tomers or clients, supervisors or co-workers? nausea - skin rashes - ringing in ears sore throat or cold symptoms. - frequent urination Visual - blurred vision - eye irritation - split or dbuble vision - trouble focusing eyes who rate their environment, health or stress conditions asgood, average, orpoor. Thus Table 4 shows that of the 1128 non-smokers working in places where smoking was permitted, 11.7 % rated their ventilation conditions (as measured by the VentilationIndex) asgood, while 11.4 %, 10:0 96 and 10.8 % of non-smokers working inn places where smoking was restricted,, prohi- bited, and either restricted or prohibited, did so. Of the 128' non-smokers working wheree smoking was permitted, 32:0 % rated their building ventilation (as measured by the Ven- tilation Ihdex) asp'oor, while 28.6 °Yo, 23:3 % and 26.2 % of non-smokers did so who worked' where smoking was restricted,,prohibited; an& either restricted or prollibitedi The hypothesi between the freq Chi Square stati smokers separate. for Table 4 is 1.1 freedom, falls fai cance. (For d.f. _ be 9.488 or larger to or larger than ~ rejection of the nu It should be noted this series. We drr TABLE 4. Pemnttage rrttritted, Non-tmokerr working n Ventilation Index Good Average Poor Nb of cases x2=111718p< .8 TABLE 5. Peresatage permitted, Non -smokrrr vorkrng wt Temperature Index Good Average Poor ~ No of cases W U1 X2=8:0637p< .0S ~ ' Ignoring rounding e ~ N CO
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25 .on ~our that yeary voff? ast? - phy- work ir job ur job i c cus- :ers? ed; did ; where d their ie Ven- 3 tYo and worked ted„and The hypothesis of statistical indcpendence between the frequencies was computed using, Chi' Square statistics for non-smokers and smokers separateNy: For instance, Chi' Square for Table 4 is 1.1718 which, for 4 degrees of freedom, fa115 far short of statistical signifi- cance. (For d.f. = 4, Chi Square would have to be 9.488 or larger for a one-tailedtest and'equal to or larger than~ 7.779 for a two-tailed test for rejection of the null hypothesis with p<0105). It should be noted that d f= 4 for all tables in this series. We draw attention to the fact that the column labelled "PROHIBITED OR RESTRICTED" is not included in the calcu- lation of Chi Square values. That column serves as a summary, combining frequencies observed in workplaces where smoking was "RESTRICTED" with where it was "PROHI- BITED". The distribution of responses to questions assessing the quality, of environmental condi- tions of Ventilation (Tablt 4), Temperature (Table 5),,Humidity (Table 6), Lighting(Table 7), and Odor (Table 8) do not differ statisticalHy TABLE 4. Percentage distribxtion fpr nsporxns to "Ventilation lndex"for non-smokers working wherre smoking uwaspermitted, nsttrcted,, probibited, and restricted or profiibrted. Non-smokers working where smoking is: Ventilation Index Permitted Restricted Prohibited! Prohibitedl or Restricted Good 11.7 11.4 10.0 10.8 Average 56.3 60.0 66.7 63.1 Poor 32.0 28.6 23.3 26.2 100.0 100.0 100.0 100.0 No of cases 128 35 301 65 x2=1.1718p5.88 TABLE 5, Percentage distribution for responses to "Temperature Indtx" for non-smokers nvorking where smoking mas permitted, restricted,' prohibited and restricted or probibited. Non-smokers working where smoking is: Temperature Ihdex Permitted Restricted' Prohibited Prohibited or Restricted' Good 13.1 5.9 3.4 4.8 Average 69.2' 79.4 93.1 85.7 Poor 17.7 14.7 3.4 9.5 100.0 : 100.0: 100.0 * 100.0. No of cases 130 34 29 63 x2=8.0637p_< .09 * Ignoring rounding errors
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26 TABLE' 6. Ptrcentagq disttibution for ruponses to ' h(xmidity Index " for non-rmokerr working mbere smoking was permitted, restricted, , probibited; and rastricted or prohibited. Non-smokers working ivbera smoking is: Humidity - Index Permitted' Prohibited or Restricted Prohibited Restricted Good 30.2 Average 63.6 Poor 6.2 100.0 No of cases 129 x2=3A025p< .42 * Ignoring rounding errors 42.9 34.5 39.1 57.1 62.1 59:41 0.0 3.4 1.6 100.0 100.0 100.0 * 35 29 64 TABLE 7: , Percentage distribution for rrsponser to ' Envimnmental Ligbting Index" for non-smokers working mhere smoking was permitted, nstricted probibited, and restricted or prohibited. Non-smokers working,mbere smoking is: Environmental Lighting Index Permitted Good 38.0 Average 47.3 Poor 14.7 100.0 No of cases 129 Ptohibited or Restricted Prohibited Restricted 28.6 27.6 28.1 60.0 62.1 60.9 11.4 10.3 10.9 100.0 100.0 100.0 * 35 29 64 x2' = 3.2241 p _- .52' *Ignoring rounding errors between environments with and without smoking regulations. Inspection of the distri- bution appears to reveall a tendency for the largest proportion of "good" as well as "poor" ratings to be given by those respondents working in areas where smoking,is permitted (Tables 4, 5 and 7). Also interesting, and con- trary to expectation, is that non-smokers who work where smoking is permitted give more favorable (good) and fewer unfavorable (poor)) ratings than non-smokers working where smoking is prohibited: However, the best con- clusion from these distributions, based on the statistical test, is that the ratings of workplaces as "good"„"average" or "poor" areindepen- dent of smoking regulations. TABLE 8. Pemnta rutrlcted, Non-lmokers working _ Odor Index Good Average Poor No of eases x2=5.8"T17p< .- TABLE 9. Pemntaga permitted,' Non-smokers working a Building Illness Index Good Average Poor No of cases 7L2 = 6.494i1' p _- .1 Indices of he ("Buildings I11nes: "Absenteeism") ar, nificant (Tables 9, for a high percenta where smoking is ; Illness symptoms a where smoking is dency is found for health: On the othe;
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27 TABLE 8. Percentage distribution for responses to "Odor Index" fir non-smokerr working where smoking was permitted,, restricted, prohibited, and restriited or prohibited. Non-smokerrivorking mlien smokixg is: Odor Index Permitted Restricted Prohibited Prohibited or Restricted Good 37.9 26.5 31.0 28.6 Average 47.7 67.6 48.3 58.7 Poor 14.4 5.9 20.7 12.7 100.0 100.0 100.0 100.0 No of cases 132 34 29 63 x2=5.8717p;.21 TABLE 9. Percentage distributivn for resp,oMses to "Building Illness Index" for non-smokers working wberr smoking was permitted, restricted, , p'rohibited, and restricted or prohibited' Non-smokers iaork.4rg where smoking is: Building Illness Index Permitted Restricted Prohibited Prohibited or Restricted Good 43:1 28.6 48.4 37.9 Average 38:7 60;0 41.9 51.5 Poor 18.2 11.4 9.7, 10.6 100.0. 100.0: 100.0: 100.0. No of cases 137 35 31, 66 x2' = 6.4941 p --1- .16 Indices of health related complaints ("Buildings Illhess", "Visual Health",, aad "Absenteeism") are again not statistically sig- nificant, (Tab1t s 9, 10; 11)~ There is a tendenry for a high percentage of non-smokers im areas where smoking is permitted to rank Building Illness symptoms as poor compared to places where smoking is prohibited. A similar ten- dency is foun& for responses related to visual health: On the other hand; there is less "Absen- teeism" among non-smokers where smoking is permitted than where it is prohibited. Again,, our conclusions, reinforced by the results of statistical test, are that health related com- plaints and smoking regulations are indepen- dent of each other. Tables 12 to 14 show the relationship of smoking to perceived stress. Employees working in places where smoking is permitted report substantially less stress than employees.
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28 TABL.E 10: Percentage dittribation fpr responses to "Yisxal Healtb"for.nm-smokirs morking;wJiere smoking was permitted, restricted, prohibited, and restricted or prohibited. Non-smokers working where smoking is:. Visual Health Index Permitted Good 68.6 Average 16.1 Poor 15.3 100.0 No of cases 137 Prohibited or Restricted' Prohibited Restricted 62.9 71i0 66.7 31.4 16.1 24.2 5.7 12.9 9.1 100.0 100.0 100.0 35 31 66. x2 = 5.77%p < .22 TABLE 11. Percentoge dirttibution fo'r n*onses ta `Absenteeism Inde.x" fopr non-smokirs working where smok,ing was permitted, restricted, prohibited, and'nstricted'orprab'ibited: Non-smokers working where smaking is: Absenteeism Index Permitted Good 88:8 Average 10:4 Poor 0:7 100.0 *' No of cases 134 Prohibited or Restricted Prohibited Restricted ~ 84.8 80:6 82.8 15,2 19:41 17:2 0.0 0.0 0:0 100!0 100!0 100A 33 31 64 x2=2.471i1p< .65 * Ignoring rounding errors in smoking restricted or prohibited work- places. It is likely that this relationship simply reflccts a more permissive and tolcrant attitude by the employers. This can be seen also from the relative lack of relationship between smoking status and stress in employee to employee relationships (Table 15), which~falls short of statistical' significance (although showing the same trends as do the other stress/smoking relationships): Finally we return to the review of buildings with Building Illness complaints which made up the first part of our discussion. The analiysis also explored the possibility that Building Illness complaints were related to the absence of smoking regulations. Table. 16 shows the relative frequency of symptoms of "eye strain and irritation", "nose and throat irritatiod", and "fatigue" and "headache" reported' as major problems in buildings with TABL: Non-smc Job Securit) Index Good Averagc Poor No of c x2=2' * Ignorii TABLE Non-smoh Physical Stress Index Good Average Poor No of ca: x2 = 12. and witl trend he throat ir smoking ever, tht tical sign ference i studies ir: resttictec symptom
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29' -itted,, TABLE; 12. Percentage distribution forresponses to `fob Securiy Index" for non-smokerr working where smoking was permitted, restricted, probibittd,, and restricted or probibited Non-smoksrs working where smoking in ted' Job Security Index ermitted estricted rohibited Prohibited or Restricted ted Good 66.4 44.1 26.7 35.9 7 Average 32.8 47.1 60.0 53.1 2 Poor 0.7 8.8 13.3 10.9 1 100.0 * 100.0 100.0 100.D * 0 No of cases 1341 34: 30 64 x2'= 25.1117p< .001, * Ignoring rounding errors 7kixg was bited r icted 2.8 7:2 0.0 0.0 64 :)uildings !ch made ,ossibility •e related ns. Table Iptoms of nd'throat :eadache" ings with TABLE 13. Percentage distribution for responses to "Physical Stress~ Index" fvr non-smoken aorking where smoking was permitted, restricted, prohibited, and restricted or pro/iibitid: Non-smokers morking mbere smoking is: Physical Stress Index Permitted Restricted Prohibited Prohibited or Restricted Good 9.6 8.8 0.0 4.6 Average 80.1 70.6 67.7 69.2' Poor 10.3 20.6 32.3 26.2' 100.01 100.01 100.01 100.0' Nb of cases 136 34 31 65 x2=12:2418p< .02 and without smoking restrictions. There is a trend here of fewer reports of eye, nose and throat irritation as a major complaint when smoking is restricted than whenit is not. How- ever, these differences falli far short of statis- tical significance and, anyway, the largest dif- ference is for headaches, for which~ 50 % more studies in smoking-restricted than smoking not restricte& environments report as a major symptom. DISCUSSI©N The available data do not support a conclusion that increased reports of Building Illness symp- toms are associated with smoking. Pollution levels in buildings without smoking restric- tions are no greater than those observed in buildings with smoking restrictions or in build~ ings that were not studied for illness com• plaints. Inother words, neither pollution levels
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30' TABLE 14. Percentage dist ributioR for n*onses to ' Stnsr Decision Index" far non-smokers working where smoking was permitted, nstricted; prohibited, and restricted or pmbibited. Non-smokers working where smoking is: Stress Prohibited Decision or Index Permitted Restricted Prohibited Restricted Good' 0.7 0:0 3.3 1.6 Average 66.2 46.9 43:3 452 Poor 33:1i 53:1i 53.3 53.2 100.0 100.0 100:0 * 100.0 No of cases 136 32 30 62 x2=9.6003--< pA5 *' Ignoring rounding errors TABLE 15. Pereentage distribution fnr rerponres to "Interersona/ Strrfr Index " fo'r non-smok.en working where smok.ing wa.r penmitted, nestricted,' pmbibited, and restricted or pro6ibited. Non-smokers working mhen smoking is: Interpersonal Prohibited Stress or Index Permitted Restricted' Prohibited Restricted Good 16.3 13.3 3.7 8.8 Average 71.5 80.0 88.9 84.2 Poor 12.3 6.7 7.4, 7.0 100.0 * 10U 10U 100.0 No of cases 123 30 27 57 x2=4.4935p< .34 * Ignoring rounding errors TABLE 16. Percentage of incidentt of most proreinent Building Illness-Retated ryrnptomt in 95 buiJdings without, and 16 buildings with smokJng restrictions. S.ymptomr Eye Nose/Throat Smoking Fatigue Irritation Irritation Headache C Not restricte& 31.9 55.8' 56:8 51.6 tj Restricted1 37.5 50:0 43.8 75.0 ~ N C!t W Cn nor patt ings wi While = inquirec veye& F smokin, (Nonec with act the inv,possible related • Salisbur in a buil (17). N reportec collar w the inte violet er the prc When replacec increase icantly : tilation (18). Re by31% The r vide ani tion 1ev plaints u location Modern pollutarr inadequ created irrespec mitted. Acknoml~ The au Kreiss - invalual
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,king mar )i'ted cted .6 i2 ,.2 1.0 2 roking war, ibited ,r -icted 8.8' 4.2 7.0 0:0 57 'at, and' 16 dache 1.6 5.0 nor patterns of symptoms differ between build- ings with or without smoking restrictions. While almost all investigations reviewed here inquired about the smoking habits of the sur- veyed population, only eight suggested that smoking might be the cause of the problem. (None of these eight studies supports its claims with actual data.) On the other hand, some of the investigations did! a careful review of the possible effects smoking might have on health- related complaints. For instance, one study by Salisbury compared smoking density by floors in a building to frequency of health complaints (17). No association was found: We have reported elsewhere that complaints of white- collar workers in these buildings may be due to the interaction of low ventilation and ultra• violet emitting fluorescent lamps which lead to the production of photochemical oxidants. When high ultraviolet emitting lamps are replaced' or when ventilation rates arec increasedi reports of symptoms decline signif- icantly and do so dramatically when both ven- tilation and lighting conditions are changed (18). Reports of eye irritation alone decreased by 31 %. The review of available studies does not pro- vide any objective evidence that either pollu- tion levels or patterns of health-related com- plaints differ in some remarkable way between locations with or without smoking restrictions. Modern buildings tend to generate and entrap pollutants from numerous sources. Under inadequate ventilation, conditions may be created where discomfort and illness result irrespective of whether or not smoking is per- mitted. Acknowledgement The authors are indebted to Dr Kathleen Kreiss and Dr Richard Keenlyside for their invaluable assistance in providing data for the 31, project; in addition we wouldilike to thank the investigators whose results we included in our study and who made their reports available and answered questions about their data: We owe a debt of gratitude to our associate, Helen Dimich-Ward for valuable help in data prepa- ration and analysis. We also appreciate the colr- laboration and support by Local 153 of the Office and Professional Employees Interna- tional Union of New York City: We thank the many members of our staff who helped sort out and deal with these data, especially Mr Chris Collett, Ms Carol Rourke and Ms Diana Kobayashi. REFERENCES 1l American Society of Heating, Refrigeration and Airconditioning Engineers, ASHRAE. Stan- dard 90-75, Energy conservation on new building, design, ASHRAE Inc.,, Atlanta, Georgia, 1975. 2. Baxter P. J, Paper on biological substances and indoor air quality. Prepared for the Subgroup for Health Effects of Indoor Pollution„Proceedings US'Government Inter-agency Research Group on Indoor Air Quality: Workshop of Indoor Air Quality Research Needs, Leesburg, Virginia, Dec 3-5, 1980. 3. National Research~Couneil, National Academy of Science, Indoor Pollutants;, National Academy Press, Washington DC, 1981. 4. Sterling T. D, Kobayashi D. Exposure to pollu- tants in enclosed living spaces. Environ Res 1977: 13:1-35. 5. Sterling T. D, Dimich H, Kobayashi D. Indoor byproduct levels of tobacco smoke: A critical review of theiiterature. J Air Pollut Control Ass 1982:32:250:259: 6. Yocum J,E: Indoor-outdoor air quality relation. ships. J Air Pollut Control Ass 1982: 32:500- 520: 7. Chappell S. B, Parker R. J. Smoking and carbon monoxide levels in enclosed public places in New Brunswick: Can J pubLHlth 1977: 68!:159- 161. 8. Szadkowski' D, Harke H! P,, Angerer J. Body burden of carbon monoxide from passive smoking in offices. Iht Med 1976: 3':310-313.
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32. 9. Weber A, Fischer T. Passive smoking at work. Int Arch~ occup Environ Hlth 1980t 47:209- 221. 10. Repace J. L, Lowrey A: H. Indoor air pollution, tobacco smoke and public health. Science 1980: 208:464-472. ' 11. Sem G. J, Tsurubayashi K, Homnia K. Perfor- mance of the piezoelectric microbalance respir- able aerosol sensor. Am ind' Hyg Ass J 1977: 38:580-586. 12. Daley P.,S„Lundgren D. A. The performance of piezoelectric crystal sensors used to determinee aerosol mean concentrations. Am ind Hyg Ass J 1975: 36:518-524. 13. Pimm P, Silverman F, Shephard' R. J. Physio- logical effects of acute passive exposure to cigar- ette smoke. Archs envir Hlth 1978: 33:201- 213. 14. Elliot L. P, Rowe D. R. Air quality during public meetings. J Air Pollut Control Ass 1975: 27:635-636. 15. Sterling E. M, Sterling T. D, Kobayashi-Hartell D, McIntyre E. D: Health and' comfort in, modern office buildings: Results of a work envi- ronment survey. Report to the Office and~ Pro- fessional Employees Ihternational Union; New York, N Y. 1983. 16. Salisbury S. A. Health Hazard Evaluation and Technical Assistance Reporti No. TA 78-39. Midwest Stock Exchange, Chicago,, Illinois, National Institute for Occupational Safety and Healthj Cincinnati, Ohio, 1979. 17. Salisbury S. A, Kelter A, Miller B, Roper P. TA 80-122-1117. 101 Marietta Tower Building, Atlanta, Georgia, US National, Institute for Occupational Safety and Health, Health Hazard' Evaluation,,Cincinnati, Ohio, 1982. 18. Sterling E. M, Sterling T. D. The impact of different ventilation and lighting levels on Building Illness: An experimentall study, Pro- ceedings International'' Symposium on Indoor Air Pollution, Health and Energy Conservationj October 13-16, University of Massachusetts, Amherst, Massachusetts, 1981 Can J publ Hlth 1983 (in press). Theod'or D: Sterling. Ph. D: Simon Fraser University Department of Computing Science; 291-4277 Burnaby, British Colombia CANADA V5A 11S6 Detert tobacc sary to ronme smoke sands~ liquid chemi< of its c lyze. 1 the ch exhale ETS- pling a ization trover: of cert not rel. errone, is to re stituen the gr, metho( infreqt of a m( acteriz the sul
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33 iation and CA 78-39. ), Illinois,. Safety and )per P. TA Building, stitutc for Ith Hazard' impact of levels on ;tudy, Pro- on Indoor aservation~ sachusetts, publ Hlth 291-4277 1.3. Analytical chemical methods for the detection of environmental tobacco smoke constituents ROGER A. JENKINS AND MICHAEL R. GUERIN INTRODUCTION Determination of levels of constituents in tobacco smoke polluted! atmospheres is neces- sary to characterizing human exposure to envi- ronmental l tobacco, smoke (ETS). Tobacco, smoke is a highly complex mixture of thou~ sands of compounds. The smoke exists in both liquid and gaseous phases, and can change chemically and physically with time. Because of its complexity, the smoke is difficult to ana- lyze. Additionally, the relationship between the chemicali composition, of sidestream and exhaled mainstream smoke-the precursors of ETS-and that of ETS itself, is unclear. Sam- pling and analytical methods for the character- ization of ETS have been the subject of con- troversy themselves (1), because the presence of certain, interfering substances, whether or not related to tobacco combustion, can lead to erroneous results (2): The purpose of this paper is to review analyticali methods for those con- stituents of ETS which have been the subject of the greatest interest. In addition, analyticall methods will be described which have been, infrequently used, but which offer the promise of a more economical or more thorough char- acterization of ETS. Because of the breadth of the subjects, not all of the work employing, specific methods is referenced. The reader is referred'to the review by Sterling e1 al.' (3) for a more thorough coverage of the results obtained in various studies. DETERMINATION OF INDIVIDUAL COMPONENTS Carbon monoxide Carbon monoxide (CO) is probably the most widely monitored constituent of ETS (4-8)j . CO is a major constituent' of tobacco smoke. It is chemically stable, present solely in the gas phase, and only relatively simple analytical instrumentation is require& to perform the analysis. However, CO emitted from othery non-tobacco combustion sources (such as vehi- cular traffic) can frequently confound interpre- tation of results. The two most common methods of analysis involve electrochemical oxidation and non-dispersive itlfrared'& detec- tion. In the first method, a small air pump draws a sample of the atmosphere (filtered of particu- lates) through an electrochemical cell. The cell contains an electrode, the surface of which is constructed from a proprietary, material. This material acts as a catalyst to lower the electro- chemical potential at which CO in the sample
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i 34 is oxidized' to carbon~ dioxide. The amount of current flowing in the cell is proportional to the concentration of CO in the sample stream. Many commercial varieties of this system~ are currently marketed. These instruments are relatively inexpensive, portable, and! simple to operate. The chief disadvantage of the system is that any substance which ~ can be oxidized at the same electrochemicalipotential as the CO can contribute to the response. Ethanol vapors are a particularproblem„especially when, such measurements are made in taverns, etc. (1): Commercially available traps, placed in the sampling line, can alleviate the problem some- what. In studies in our laboratory with rela- tively concentrated diesel fuel smokes, we have found'that the petroleum vapors also result in a positive response. For short sampling times, we have found that small amounts of Tenax- GC, backed with activated charcoal, can remove the interference. At longer times, these traps become saturated. In addition, we have found at least one analyzer system which is three times as sensitive to oxides of nitrogen (NO.) as to CO. Under normal conditions, this should not pose a problem for accurate CO analyses, since the amount of NOa in cigarette smoke is only a few percent of that of CO. However, in cases where higher than normal NOg levels are encountered, a correction for NOX response may be necessary. Non-dispersive infrared' (NDIR) measure- ment of FtTS carbon monoxide levels (9, 10) seems, to have received much less attention, perhaps because the instrumentation is some- what less portable. In~this technique (11), a gas cell containing,the sample is irradiated at one end' of the cell with a polychromatic infrared source. A detector, a chamber containing smalll amounts of the compound to be analyzed, is located at the other end of the cell! Depending on the amount of analyte in the sample to absorb the infrared radiation, the gas in the detector absorbs of the remaining, radiationi The resulting, change in pressure im the detector is taken as the response of the ana- lyzer. NDIR analyzers for CO tend to be more specific than the electrochemical analyzers and as such„less susceptible to interferences. How- ever, they are much~ heavier and bulky,, and somewhat more expensive. Particulate matter Particulate matter from evaporation-conden- sation~aerosois such as wood or tobacco smoke is usually defined operationally e.g. the part of the aerosol which is retained on a specified filter. However, since tobacco smoke particu- late matter is a mixture of compounds pos - sessing a very large range of volatilities, the conditions under which the particles are col- lected can affect the amount and chemical composition of the materiall collectedi For example, work done in our laboratory (12) has indicated that collecting tobacco smoke oni a standard Cambridge filter (13) i at flows of 1-2 liters per minute results in a weight loss of 30-40 % of the material which otherwise would have been collected under standard Federal' Trade Commission conditions (14) of one 35 ml-2 second duration draw every minute. Gas chromatographic analysis of the particulate matter collected at the higher flow rate indicates that some of the more volatile constituents are present in greatly diminished quantities on the f lter pad. Presumably, the higher flow rate caused'them to be evaporated from the pad'! following initial deposition. While the problem of evaporation of collecte& particulate constituents may be less serious when sampling more dilute and more homo- geneous smokes, the concentration per unit volume of collected'material will increase with samplingtime. Drawing even relatively smoky atmospheres through the filter may result in unavoidable evaporation of some collected "VAQW&I.: const loader Dc, assay • for a: facilit; factor, tempe specif Th for th from F sample where charge trostat. whose ponse acknoN much tobaccc reports in this the balh measur Mea! light sc greatest nique r Measur notass side sr sponse and sid optical and rec: scatterir one con affordin have ha( ting dic backscat determi
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35 idiation. in the the ana- be more zers and s. How- !ky, and :onden- ~ smoke : part of xcified )articu- ds pos- ies, the ire col- iemical dJ For 12) has .eona of 1-2 loss of erwise indard ;14) of every of the r flow olatile lished ~y, the :)rated ;ition. lected' =rious .omo- unit : with moky ilt in ected1 constituents as the filter becomes more heavily loaded. Despite the technical problems, gravimetric assay of collected smoke is still commonly used for assessing particulate levels (4, 9, 15). To facilitate inter-experiment comparisons, such factors as filter medium, flow rate, ambient temperature and relative humidly should be specified. The piezoelectric balance has also been used for the determination ambient particle levels from ETS (6, 16). In this system (17; 18), an air sample is drawn by a small pump through a cell where the smoke particles are electrically charged. Then, the smoke droplets are elec- trostatically precipitated on to a quartz crystal, whose vibrational frequency changes in res- ponse to mass loading. The device has beem acknowledged by the manufacturer to be as much as 15 % inaccurate when measuring tobacco smoke particles (18). However, recent reports (3) have alluded to additional problems in this particular application, and as a result, the balance is no longer recommended for ETSS measurements: Measurement of particle concentrations by light scattering, techniques probably has the greatest inherent appeal (19), since the tech- niqpe relates closely to personal observation. Measurement of back scattered light-while not as sensitive as measurement of forward! or side scattering, offers the advantage of re- sponse stability and'simplicity: While forward and side scattering techniques rely on precise optical alignment of two probes (transmitter and receiver) for reproducible response, back- scattering probes have both systems built into one component. Relative orientation is fixedi affording a very reproducible response. We have had considerable success using light emit- ting diode/photo transistor combinations as backscattering probes for the quantitative determination of particulate concentrations (20, 21). While most of these measurements have been made at relatively high smoke con, centrations, extrapolation of response rates suggests that these systems could be useful for quantitative measurements at typical ETS par- ticulate levels. All of the light scattering approaches have the drawback of calibration at dilute smoke concentrations. First, response calibration is usually performed by gravimetric analysis of filter samples of the smoke cloud, with all of the inherent difficulties of gravimetric ana- lysis. Secondly, experiments performed' in our laboratory have indicated that the backscatter response per unit smoke collecte& of various smokes can be consid'erably different (factors of 2-3) (22). Small apparent differences (10- 20'gb) among various types of tobacco smoke have also been noted. However, with careful calibration techniqpes, such light scattering approaches should be useful for semi-quantita- tive determination of ETS particulate levels. All of the above described methods suffer from a lack of specificity: There are many other sources of particulates in any environment,, both~ from combustion and other activities. Accurate determinations of ETS contributions to ambient particle levels should include cor- rection for other sources by determination of background levels. If short term measurementss are made, diurnal variations should be taken into account. Nicotine Use of environmental levels of nicotine as an indicator of ETS levels has a particular appeal (6; 9„23), since nicotine is the only compound present im significant quantities which is unique to tobacco. The typicali approach to nicotine analysis first involves obtaining a large sample of airborne particle matter on a filter. The filter is extracted~ with a polar sol~ vent, after which the volume of solvent is reduced in, order to boost, nicotine concentra-
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36 tion in the extract. Usually gas/liquid chroma- tographic analysis with a relativeby polar sta- tionary phase is performed~on the concentrated extract to determine the quantity of nicotine present (6). Because of nicotine's relat2vely, high vola- tility, two stages in this procedure -collection of particulates and concentration of the extract-can induce significant losses of col- lected nicotine. Although~the authors are una- ware of any references to such in the literature, it would seem that use of a'''C-labeled nicotine spike of the filter, prior to the beginning of sampling, would help to correct for nicotine losses incurred in sampling and later analysis. This approach requires access to liquid scintil- lation counting equipment. In the absence of such recovery corrections, quantities of nico- tine determined in smoky atmospheres should probably be taken~ as lower limits, rather than exact levels. Oxides of nitragem Chemiluminescence monitoring is about the only currently used!procedure for the measure- ment of ambient levels of oxides of nitrogen (NOa) (5-7, 9). Chemiluminescent monitoring, is extremely sensitive (direct measurement down to the part per billion range is possible), and, in most cases, very accurate. The analy- tical procedure is relatively straightforward! (24). An air sample is drawn into a reactiom chamber. The nitric oxide (NO) in the sample is reacted witL ozone which is generated con- tinuously by the analyzer. About 10 % of the reaction product is nitrogen dioxide (NOZ)~ which is in an electronically excited quantum state (NO2 *)J In order to return to its ground state, the NO2 * emits a photon, which is meas- ured by a photomultiplier tube. Thus, the light emitted is a function of the NO concentration. In order to measure ambient levels of nitrogen dioxide, the air sample is first routed through~a converter assembly. The assembly catalytically reduces NO~ to NO. The air sample, con- taining both endogenous NO plus that from the reduced NO2 is routed back through the ozone reaction chamben There are a number of potential interfer- ences which can confound the interpretation of results. Carbon dioxide (CO2), can quench the chemiluminescent reaction (25), but this is not usually a problem at ambient CO2 levels. Hydrogen cyanide (HCN), and some primary amines,and nitro compounds can be converted into NO or NO2 by the stainless steel reducing catalyts used in some analyzer's NOZ to NO converter assemblies (26). Also, HCN has been shown to be a positive interference when ana- lyzing concentrated smokes using carbon- base&converter assemblies (27). The extent of the interference at ambient smoke levels iss unknown, In contrast to the electrochemical CO ana- lyzer, the weight and size of the NOY analyzer preclude single handed portability. In addi- tion~ the system requires tanks of gas standards for calibration. However, the equipment can be mounted in a moveable rack. The accuracy and sensitivity, of the chemiluminescent ana- lysis make it the method of choice for deter- mination of NOa levels. Aldebydea Because of their high reactivity, formaldehyde and acrolein tendl not to be found at high con- centrations under ambient conditions. They have received considerable attention from an occupational exposure standpoint, since both of these compounds are use& frequently in industry. Because of this attentionj there exist a number of analy,ticall chemical methods for monitoring ambient levels of these com- pounds. The methods have been employed by a number of ETS investigators for characteriza- tion and health effects studies (5, 7, 10, 28- 32). Basic: an air .. trappin~ The for soluble i wash or For forr tropic a( cinol is analyzed colored tometric trations. The c is that tl lutely sp This ma itoring i compoui tobacco eonstitue dye. Tak iline (P. While P, hyde ov probably at leasr ~ maldehy formalde be due t usedl A mor dinitropl ping/det rcact wit form the vatit•.e. 7- separatec graphic i ehromate chicf dis: more so f is rcquin
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r sample, con- plus that from ck through the ;ential interfer- ~t interpretation )2) can quench (25), but this is ent CO2 levels. i some primary an be converted' ,s steel reducing r's NO2 to NO , HCN'has beem ence when ana- using carbon- ). The extent of :moke levels is -mical CO ana- .e NOa anaHyzer bility. In addi- of gas standards equipment can k. The accuracy minescent ana- '1oice for deter- -, formaldehyde nd at high con- mditions. They ention from am )int, since bo& I frequently in, on, there exist a tl methodfr for :)f these com- ilemployed by a or characteriza- ; (5, 7, 10, 28- Basically, these methods' involve bubbling an air sample through water or some other trapping medium, such as molecular sieves. The formaldehyde and acrolein are highNy soluble in water. Next, an aliquot of the sieve . wash or water solution is reacted with a dye.. For formaldehyde, the dye is often chromo- tropic acid or para-rosaniline. 4-hexyl resor~ cinol is usually employed if acrolein is being analyzed. The absorbance of the resulting colored complex is determined spectropho- tometrically, and' related to ambient concen- trations. The chief drawback of this type of approach is that the dyes which are used are not abso- lutely specific for the compound in question. This may be of little consequence when mon• itoring industrial atmospheres, where a single compound may predominate. Howevers tobacco smoke is comprised of thousands of constituents, manyof which may react with the dye. Take, for example, the use of para-rosan- iline (PA) for formaldehyde measurements. While PA has a 100: 1 selectivity of formalde- hyde over acetaldehyde (33), mainsteam (and probably sidestream) tobacco smoke contains at least 30 times as much acetaldehyde as for- maldehyde (34), Thus, as much as 25 9/0' of the formaldehyde measured in ETS could in fact be due to acetaldehyde, if the PA reaction is used. A more specific approach involves the use of dinitrophenyl hydrazine (DNPH) as a trap- ping/derivatizing, reagent (35). DNPH will react with virtually all carbonyl compounds to form the yellow dinitrophenyl hydrazine deri- vative. The individual derivatives can then be separated and visualized using gas chromoto- graphic (36, 37) or high performance liquid chromatographic (38139) procedures. The chief disadvantage with this approach~ is that more sophisticatedlanalytical instrumentation is required. Nevertheless,,given the potential 37' interferences in cigarette smoke, DNPH deriv- atization and analysis would seem to be the method' of choice. Benzo (a) ' pyrene (BaP) BaP is a five ring polynuclear aromatic hydro- carbon which is an experimentally confirmed' carcinogen (40). It is a product of most incom- plete combustion processes, including the smoldering,of tobacco. There are only a few references to the quantitative determination of BaP in ETS (41, 42), This is probably due to the laborious analytical procedure required to unambiguously determine BaP by classical methods (see below). This situation will prob- ably change as instrumental methods improve. Classically, BaP determinations have been performed by initially collecting a: high- volume sample of air particulates. The filter is extracted' and the extract subjected to repeated solvent partition. The isolate is then purified by column chromatography (usually on alu- mina or Florisil) and subjected to fluorescence spectrometry for final determination. The pro- cedure is quite lengthy, usually requiring one or two person-days per analysis and is prone to interferences. The advantage of this aproach is thatsophisticated analytical instrumentation is not required. Recently, many improvements have been made in procedures for the determination of BaP in complex organic matrices, such as syn- thetic crude oils (43, 44) and fly ash: extracts (45, 46): One of the more promising approaches, which exhibits the potentiali for application to ETS samples, involves sequen- tial, or, multidimensional, chromatography,,In this approach, the sample extract, (first spiked with a radiolabeled 14C BaP tracer)~is first, sub- jected to a semi-preparative scale normal phase high performance liquid chromatographic sep- aration (HPLC). The eluted'fraction (detected by UV absorbance), containing BaP (along with
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severaliother similar constituents) is collected, concentrated and subjected to analysis by re- verse phase HPLC, which acts to separate the BaP from the other similar constituents. The BaP is visualized by fluorescence detection. Recovery determinations are made by deter, mining the amount, of radiolabel remaining in the analyzed solution This procedure is much less laborious than the solvent partition method and should yield a very accurate value for the BaP present in the sample. Volatile nitraramims The determination of volatile N-nitrosamines (VNA's), in tobaccco smoke polluted atmos- pheres has been pioneere& by Hoffmann's group (47, 48), The concern over VNA's stems from their suspected carcinogenicity in many animal models (and thus, by inference, humans) (49) and the fact that the production of VNA's in sidestream cigarette smoke-per unit tobacco combusted-is many times greater than that in mainstream cigarette smoke (48, 50), This latter fact is probably a result of the higher concentrations of oxides of nitrogen and secondary amines -precursors of VNA's-in sidestream smoke. The analysis of VNA's in ETS is fairly com- plicated (48), First, an air sample is bubbled through a citrate buffer to which has been adde& 14C-dimethyl nitrosamine (for recovery measurement). Next, the buffer is subjected to liquid:liquid extraction, followedby a clean.up on basic alumina. The latter step serves to sep- arate the: VNA's from volatile nitro alkanes,, which would' interfere in subsequent steps. Finally, an aliquot is subjected to gas/iiqui& chromatography with a Thermal Energy Ana- lyzer (TEA) used as a nitrosamine specific detector. The TEA is, in essence, a pyrolysis unit which cleaves the N-N bond'in~the VNA's backed by a sub-ambient pressure chemilumi- nescent analyzer (see above) to detect the resulting nitric oxide. Recoveries are deter- mined on an aliquot of the pre-GCITEA iso- late using liquid scintillation counting. Clearly, the procedure is both labor and equipment intensive. However, it appears to be the only, method for obtaining accurate values on these constituents which are present at levels on the order of tens of nanograms per cubic meter in ETS. PASSIVE SAMPLERS Passive samplers differ from ~ active samplers in that with the former, the chief transport mechanism to the collection point is diffusion. In contrast, active samplers employ convec- tion-usually with the aid of pumps-as the primary form of mass transport. Passive samplers have been employed in industrial hygiene monitoring situations for several years. Passive systems are relatively inexpen- sive and simple, and require no elaborate port - able pumping apparatus to achieve quantita= tive results. Typically, passive samplers have been used at ambient concentrations which are greater than those usuailk- observed in tobacco ~ smokepolllrted atmospheres. However, recent improvements in the final analvsis procedures, coupled with longer sampling times, sugges that passive samplers could offer significan utility for monitoring of ETS constituent 'levels. Below is a brief discussion of the theory of operation of passive samplers, followed b; two specific examples of such scstems andlthe use. The reader is referred to a review article (51) ~for more details on the theory of operatiofl of passive samplers. The two types of passive samplers r d'1fT'it,- sion and permeation-are schematically por' trayed in Figurc 1. Each consists of two m¢iQ components: the barrier to diffusion and the trapping or adsorbent medium The latter ead consist of almost anything a-hich has a stron$ ' affinity for the anah-te, including water On l '- OPEN . IN C 4:Yf'Kllt 'la' ..».;r~t. ttu . r.! . e::c l u;. `.•.f ` ..;3SSuK .+`.r :,tc rh: .ar r .:.,nt: .- R .,d ..
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/TEA iso- ig. Clearly, equipment )e the only es on these vels on the ic meter in .amplers in transport s diffusion. )y convec- ps-as the t. Passive industrial x several v inexpen- orate port- : quantita- plers have : which are in tobacco ver, recent Tocedures, :.s, suggest significant onstituent the theory )llowed! by s and their iew article operation ,rs-diffu- ically por- two main. ,n an& the latter can, Ls a strong water andl 39 PASSIVE SAMPLERS SAMPLING TUBE DIFFUSION SAMPLER SAMPLER BODY PERMEATION SAMPLER Figure 1: Schematic diagram of diffusion and per- meationitype passive samplers. adsorbent paper or resin. In the diffusion sampler, the barrier is distance. That is; one end of the tube is open. This permits the ana- lyte to diffuse toward the adsorbent medium at some rate which depends, in part„on the size of the opening,,the distancezothe adsorbent„and the size of the molecule: In the permeation sampler, the primary barrier to mass transport is a permeable membrane. Many permeation samplers now employ poHydimethyl siloxane membranes, whose permeability is not depen- dent on anaHyte concentrations. The mem- brane has the additional effect of improving the selectivity of the sampler. The chief driving force in both these systems is the depletion of the constituent in question at the surface of the adsorbent. Each sy,stem1as some minor draw- backs. Diffusional samplers arc more affected by ambient humidity, whereas membrane ANALYTE TRAPPING MEDIUM samplers require calibrationdn standard atmo- spheres :of the analyte in questioni In a study being condiicted by Oak Ridge National Laboratory, passive membrane samplers (52) are being employed to moni'tor formaldehyde levels in residential indoor atmospheres. The sampler consists of a few milliliters of deionized water im a small cup. The open end is covered with a polydimethyl siloxane membrane. Airborne formaldehyde diffuses through the membrane and remains dissolbed in the water. Upon return of the sampler to the laboratory, an aliquot of the water is reacted with~ pararosaniline (see above) and the resulting colored complex is read spectrophotometrically. Initial results (:52) indicate that about 50 % of the homes have formaldehyde concentrations which, on one or more occasions, exceeded 100 parts per billion.
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40 There appears to be many sources of foi dehyde in the residential env,ironment, mainly glues used in processed wood products and' it was impossible to relate-at least in this stud'y-elevated formaldehyde levels to tobacco smoking. Another type of passive sampler is just starting to be used for the determination of BaP and other polynuclear aromatic hydtocarbons in polluted atmospheres (53, 54): In this case, a small diffusional' sampler uses filter paper impregni with a heavy atom-containing salt (lead or thallium acetate) as the adsorbent medium: The heavy atom enhances the phos- phorescence of the BaP to the point where direct measurements on the filter paper can be made at room temperature, rather than under cryothermali conditions. Thus, for BaP deter- minations, the filter paper is simply exposed to light of a 395 nm wavelength, and phosphor- escent emission is measured at 695 nm. These passive diffusional samplers have been used in the lightly polluted' atmospheres of synthetic fossil fueliplants, and have been shown to have detection limits of 1x10-I0g (i.e. 0:1 nanogram) BaP (54): These types of samplers offer consid- erable promise for the convenient monitoring of BaP in, atmospheres containing,ETS. MULTICOMPONENT CHROMATOGRAPHIC CHARACTERIZA'TION' One of the disadvantages of single component analytical methods for ETS characterization is that only a very tiny fraction of the smoke in question is described; i.e: one of thousands of components. In addition, specific constituent analysis pre-supposes a knowledge of the con- stituents of interest. As such, it does not len& itself to addressing broader questions, as to, for example, changes with~ time in the relative composition of the smoke. An effective approach~ to this problem can be the use of multicomponent chromatographic profiling techniques, by which a number of individual components can be visualized on a given chro- matogram. The chromatogram can be likened to "fingerprint" of the smoke in that~ a compo- sitional pattern of the major constituents can be obtained without knowing their individual identities. Tentax-GCR„ a porous polymer resin, has received extensive use for the trapping of vola- tile organic compounds in complex matrices (55, 56). In our laboratory, it has been usedfor the sampling of the vapor phase of cigarette smoke (57), stack emi'ssion from goal gasifiers (58), urinary volatiles (59), and the vapor phase of military obscurants (12): Recently, we have applied it to the sampling and characterization of residential indoor atmospheres. Detailed descriptions of its use can be found elsewhere (57). Briefly; a sample of the atmosphere in question is filtered and drawn through a car- tridge filled with Tenax. Volatile organic com- pounds are adsorbed on the resin, Following, sampling; a portion of the resin is removed, and ithermally desorbed inside the heated injec- tion port of a high resolution gas/liquid chro- matograph; , which separates the individiial constituents according to their degree of inter- action with the liquid stationary phase in the chromatographic column. To illustrate the utility of this approach~for characterizing com- piex atmospheres sich as ETS, some pilot stu- dies performed in~our laboratory are described below. The experimental arrangement is schemati- cally depicted in Figure 2. For mainstream smoke experiments, low tar, commercial ciga- rettes were smoked under standard conditions (35 ml, 2'sec duration) (14) ion anADL/II (60), smoking machine modified to smoke at li puff per minute. The resulting smoke was expelled into a 0.5 m3 chamber in which a fan gently circulated the smoke. Sidestream cigarette smoke was generated by allowing a cigarette to FLO MONIT smoulder insi ticle concent. the infrared above. CO ~ with ani elec 61): The atm< min-1 throug filter (13) anc mately 20 m replacing tha was first passe coali filter. In studies, CO o rise to as muc pling times tc minutes. In, a CO concentr; 10-20 ppm, i sampling timc collect a coml Tenaz. Then
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individual ;iwen chro- be likened t a compo- ents can be individual resin, has ng of vola- :x matrices en used for )f cigarette )al gasifiers -apor phase ly, we have icterization s. Detailed i elsewhere losphere in ough a car- -ganic com- Following s removed, .eated4njrc- '.iquid chro- individual ree of inter- ,hase in the ustrate the :rizing com- ie pilot stu- re described is schemati- mainstream iercial ciga- I conditions ,DL/II (60) )ke at l puff vas expelled r fan gently n cigarette cigarette to 41 ADL/II SMOKING MACHINE Frgun 2. Schematic diagram of experimental assembly for sampling and'characterization of highly diluted tobacco smoke. smoulder inside the chamber. The smoke par- ticle concentration was monitored by two of the infrared' backscattering sensors described above. CO concentration were determined with an electrochemical analyzer (Ecolyzer- 61). The atmosphere was sampled at about 2 1 min-t through a standard 45 mm~ Cambridge filter (1i3) and a cartridge containing approxi- mately 20 mg of Tenax (35-60 mesh). Air replacing that withdrawn from the chamber was first passed through a large activated char- coal filter. In order to facilitate smoke aging studies, CO concentrations were permitted to rise to as much as 80:ppm. This enabled sam- pling times to be reduced! to approximately 2 minutes. In actual ETS environments, where CO concentrations wouldibe expected to be 10-20 ppm, it would suffice to increase the sampling times to 15 or 20 ~minutes in order to collect a comparabllr amount of materialion the Tenaz. Then the Tenax was analyzed by high resolution gas/liquid chromatography (analy- tical details are found in the Figure captions,, see belbw): In Figure 3 are compared! the high resolution, chromatograms of the vapor phase of the main- stream cigarette smoke with that of the side- stream smoke from the same brand of ciga- rettes. Clearly, a large number of individual constituents is visualized. There are two obvious differences between the two chroma- tograms. First, there is considerably more total material ini the gas phase of the sidestream smoke. This is probably due to the greater amount of tobacco combusted during stnoul- dering. Secondly, the gas phase of the sides- tream smoke contains a disproportionately larger amount of the less volatile constituents (those that elute at a higher temperature). ImFrgure 4 are compared chromatograms of the sidestream smoke collected immediatelyy after generation, with~that of the same smoke
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42 MAINSTREAM GAS PHASE w I SIDESTREAM GAS PHASE ;i i q;~ I I' ~I~ TIME (min) 0 20 40 60 80 100 120 140 ° -LIQ N2 -30 3 0 70 110 150 190 230 TEMPERATURE (°C) Figure 3. Comparison of high resolution gas chroma- tograms; fresh filtered gas phase from mainstream, cigarette smoke vs. fresh filtered gas phase from sidestream cigarette smoke. Cigarette: 85 mm filter U. S. commercial,,8 mg "Tar": delivery as per Ui S. FTC standard smoking conditions (reference 14). Sampling conditions: 5.4 1 drawn through Cam- after standing one hour. Close examinatiom reveals very few differences in the composi- tional profiles. The exceptions to this are the components eluting near 65 and 95 minutes, where a few peaks have been greatly dimin- ished in~the aged smoke. This suggests that for short durations, few changes would occur in the relative composition of the smoke constit- bridge filter and 200 mg of 30/60 mesh Tenac GCR. Chromatographic conditions: column: 60 m X 0.31 mm i.dL DB-5 coated (1.0 µm film thickness) fused silica capillary column. Desorb Tenax at 250 °C for 19 min ar5 ml/min. Carrier gas: He at 1.2 ml/min at 30 °C. uents which are visualized by this procedure. The data serves to illustrate the wealth of chemical, information which can be obtained' during relatively short sampling sessions. CONCLUSIONS Because of the chemical complexity of ETS, fairly sophisticated! analytical chemical 0 ~LiQ FiBure 4. tograms . vs. aged method uremen method and pa chemic: render i curate. the are ~ chroma compol ~, more a4 N ~ W;b Q
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;TREAM AS ASE rREAM aS 4SE 140 ;h Tenac GCR. :GOmX0.31 iickness) fused : at 250 °C for 1.2 mlymin at s procedure. e wealth of be obtained' ;essions: <ity of ETS, chemical 43 - - FRESH SIDESTREAM GAS PHASE ; ~ AG ED SIDESTREAM GAS PHASE 120 140 L 10. N 2 30 70 110 150 190 230 TEMPERATURE (°C) i Vi ~ TIME (min) 0 20 40 60 80 100 30° Figun 4. Comparison of high resolution gas chroma- Cigarette sampling, andl chromatographic condi- tograms: fresh filtered sidestream cigarette smoke tions: same as Figure 3: vs. aged (1 hour) filtered sidestream cigarette smoke. methods are required to perform reliable meas+ urements. Even relatively straightforward methods, such as those for carbon monoxide and particulates, are subject to significant chemical or physical interferences which can render the results obtained misleading or inac- curate. Severall procedures, relatively new to the area of ETS' analysis, such as sequential chromatography, passive sampling, andlmulti'- component profiling, offer the promise of more accurate characterization of this complex matrix. Even with these methods the results obtained must always be assessed for the poten- tial inflizence of confounding factors from other, non-tobacco smoke sources. Acknowledgemerrl We express our appreciation to Cecil E Higgins for the high resoltition chromatographic ana- lysis of the chamber smoke samples. Research~ was sponsored by the National Cancer Institute
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44 under Interagency Agreement No. YOI-CP- 60206 under Union Carbide Corporation con- tract W-7405-eng-2G with the U.S. Depart- ment of Energy: REFERENCES 1. FirstM. W, Hinds W.C. Ambient tobacco smoke measurements. Am ind'HygAss J 1976: 37:655- 657 2. Molhave L. Indoor air pollution due to organic gases and vapours of solvents in building mate- rials. Environ Int 1982: 8 t 117-127. 3. Sterling T. D, Dimich H, Kobayashi D. M. Indoor Byproduct Levels of Tobacco Smoke : A critical review of the literature. J Air Pollut Control Ass 1982: 32:250-259. 4. Cuddeback Jl E, Donovan J. R, Burg W. R. Occupational aspects of passive smoking. Am ind Hyg Ass J 1976: May, 263-267. 5. Fischer T, Weber A, Grandjean1 E. Luftverun- reinigung durch Tabakrauch in Gaststattem Int Arch occup Enviton Hlth 1978: 41:267=280:. 6. Weber A, Fischer T, Grand)ean E. Passive smoking in experimental and field conditions. Environ Res 1979: 20,205-216. 7. Weber A, Fischer T, Grandjean E. Passive smoking: iiritating, effects of the total smoke and the gas phase. Int Arch occup Environ Hlth 1979: 43:183-193: 8. Weber A„Fischer T. Passive smoking at work. Int Arch occup Environ Hlth 1980 : : 47:209- 221. 9. Hugod C;, Hawkins L, Astrup P. Exposure of passive smokers to tobacco smoke constituents. Int Arch occup Environ Hlth 1978: 42:21- 29: 10. Harke H. P, Baars A, Frahm, B, Peters H, Schultz Ch. Relation between smoke consti- tuents and number of smoked cigarettes, time and room volume (in German). Iht Arch~ Arbeitsmed 1972: 29:323-3391 11. Willard H. H, Merritt L. IL. Jr, Dean J. A. Instru- mental methods of analysis. D. Van Nordstrand & Co Inc, Princeton, NJ. 1965, pp 134-136: 12. Jenkins R. A, Gayle T. Ms WikeJ. S, ManningD. L. Sampling, and chemical characterization of concentrated smokes. In Toxic Materials in the Atmosphere, ASTM STP 786, American Sociery, for Testing and Material, 1982;,pp 153•166: 13. Wartman W. B. Jr, Cogbill E. C, Harlow E. S: Determination of particulate matter in concen- trated'aerosols. Application to tar, and nicotine in~cigarette smoke. J Ass Off Anal Chem 1959: 31:1 i705-1709. 14. Pillsbury H. C, BrightC. C; O'Connor K. J. Irish. F. W. Tar and nicotine in cigarette smoke. j Ass Off Anal Chem 1969: 52:458-462. 15. Hoegg V. R. Cigarette smoke in closed spaces. Environ~Hlth Perspect 1972: 1:117-128. 16. Quanr F. R, Nelson P. A.: Sem G. J. Experi- mental measurements,of aerosol concentrations inloffices, Environ Int 1982: 8:223-227. 17. Scm G. J, Tsurubayaski K A new sensor for respirable dust measurements. Am ind Hyg Ass J 1977: 36:791~800. 18. Sem G. J, Tsurubayaski K, Katsumori H. Per- formance of the piezoeltctric microbalance res- pizable aerosol isenson Am ind Hyg Ass J' 1977: 38:580 -588: 19' Johansson C. R. Tobacco smoke in room air- an experimental investigation of odour percep- tion and irritating effects. Building Services Engineer 1976: 43:254-262. 20. Higgins C. E, Gayle T. M, StokelyJ. R. Sensor for the determination of tobacco smoke partic- ulates in inhalation exposure system. Beitr Tabakfors Int 1978': 9:185-189. 21. Jenkins R'. A„ Gayle T. M.: An instrumentali inhaled -smoke dosimeter for the quantitative characterization of aerosol exposure. In Pu!- monary Toxicity of Respirable Particles, Pro- ceedings 19th Annual Hanford Life Sciences Symposium, 22-24 Oct 1979, Richland, Wash. US Department of Energy, CONF 791002, pp 68-86 : 22. Homberg,R. W. Personal communication. 23'. Hinds W. C; First M. W. Concentrations of nicotine and'tobacco smoke in publicplaces. N Eng J Med 1975: 292:844-845. 24. Stevens R. K, Hodgeson J, A. Applications off chemiluminescent reactions to the measure- ment of airpollutants. Analyt Chem 1973: 45:443A-449A.. 25. Matthew R. D, Sawyer R. F, Schefer R. W. tainil 8:11 27. Jenki of ni ilumi 59t9: 28. Web kun_ Int : 218. 29. Matt Metc selec in dc 8:14' 30. Geisl Miks, pling indoc 31. Ayer smok 1285. 32. Webe Expe auf c Hlth 33. Matt' 34. Grie: R. A, exper condd In G: Cigar ettes. Wel£ tutes Smok Marc 35. Kuw: tion c luted by h J Chi 36. Hosl Interferences in chemiluminescent' measure- ment of NO and NO2 emissions from combus- tflon systems. Environ~ Sci Technol 1977: 11:11092-1096. 7. 26. Winer A. M, Peters J. W, Smith J. P,,Pitts J. N. Response of commercial chemiluminescent NO-NO2 analyzers to other nitrogen>con- O W parai dinit colui Papa min. dinii grap
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E: C, Harlow E. S. ; matter in concen. ro tar, and nicotine -Anal Chem 1959: )'Connor K. J. Irish arette smoke. J Ass 8-462: in closed spaces. : 1:117-128. ;em G: J. Experi- sol concentrations 8:223-227: 9 new sensor for . Am ind Hyg Ass :atsumori' H. Per- microbalance res- d Hyg Ass J 1977: ,ke in room air- of odour percep- luilding Services >kely J. R. Sensor so smoke partic- re system. Beitr 9. An instrumental - the quantitative eposure. In Pul- e Particles, Pro- rd'. Life Sciences Richland, Wash. )NF 791002,, pp munication. incentrations of public places. N Applications of o the measure- t Chem 1973: Schefer R. W. seent measure- s from combus- technol 1977: , J. P, Pitts J. N. ~miluminescent nitrogen-con- taining compounds. Environ Sci Technol 19741: 8':1118-1121. 27. Jenkins R. A,Gi1lIB, E. Determination of oxides of nitrogen (NO.) in cigarette smoke by chem- iluminescent analysis Analyt, Chem 1980: 59:925-928. 28, Weber A, Fischer T, Grandjean E. Reizwir- kungen des Formaldehyds auf den Menschen. Int Arch occup Environ Hlth 1977: 39:207- 218. 29: Matthews T. G, Hawthorne A. R, Howell T. C;. Metcalfe C. E,,Gammage R. B. Evaluation of selected monitoring methods for formaldehyde in domestic environments. Environ Int 1982: 8:143-1511 30. Geisling K. L,, Tashimm M. K, Girman J. R, Miksch, R. R, Rappaport S. M. A passive sam- pling device for determining formaldehyde in indoor air. Environ Int 1982: 8:153-158. 31. Ayer H. E;,Yeager D. W. Irritants in cigarette smoke plumes. Am J publiHlth 1982: 72:1283'- 1285. 32. Weber A, Fischer T, Gierer R, Grandjean E. Experimentelle Reizwirkungen von Akrolein auf den, Menschen. Intl Arch occup Environ Hlth1 1977: 40:1i17-130: 33. Matthews T. G. Personal Communication. 34. Griest W. H„Guerin M. R, Quincy R. B, Jenkins R. A, Kubota H. Chemicall characterization of experimentall cigarettes and cigarette smoke condensates in the fourth cigarette experiment, In Gori, G. B. (Ed), Toward Less Hazardous Cigarettes. In Fourth Set oflExperimental Cigar- ettes: US Department of Health, Education„and Welfare, Public Health Service, National Insti': tutes of Health, National Cancer Institute, Smoking and Healthl Program, Report No. 4, March 1980. 35. Kuwata K, Vebori M, Yamasaki Y. Determina- tion of aliphatic and aromatic aldehydes in pol~ luted airs as their, 2;4-dinitrophenylhydrazones by high, performance liqpid chromatography. J, Chromatogr Sci 117, 264-268 (1979):. 36. Hoshika Y,,Takata Y. Gas chromatographic se- paration of carbonyl compounds as their 2,4- dinitrophenyihydrazones using glass capillaryy columns. j Chromatogr 120, 379-389 (1976). 37. Papa L. J,,'hurner L. P. Chromatographic deter- mination of carbonyl compounds as their 2,4- dinitrophenylhydrazones 1. Gas chromato- graphy. J Chromatogr Sci 10, 744-747 (1972): 45 38. Fung K, Grosjean D. Determination of nano- gram amounts of carbonyls as 2,4 dinitrophenyl- hydrazones by high performance liquid chroma- tography. Anal Chem 53; 169' 168'-171 (1981). 39. Manning D. L, Masarinec M. P, Jenkins R. A, Marshall A. H. High performance liquid chro- matographic determinationl of selected gas phase carbonyls in tobacco smoke. J Assoc Off Anal Chem 66, 8-12 (1983). 40. Dipple a in chemical carcinogens. Searle C. E editor. American Chemical Society: Washington D.C. 1976, pp. 245-314. 41. Grimmer G, Bohnke H, Harke H; P. Passive smoking: measuring concentration o€polycyclic aromatic hydrocarbons inlrooms after machine smoking of cigarettes. Int Arch occup Environ Hlthj 40;, 83-92 (1977): 42. Caluskinova V. 3,4-benzpyrene determination in the smoky atmosphere of social metting rooms and restaurants: a contribution to the problem of the noxiousness of so-called'passive smoking. Neoplasma 11, 465-468 (1964). 43. Tomkins B. A, Kubota H, Griest W. H, Caton J. E,,Clark B. R, Guerinl M: R. Determination of benzo(a)pyrene in petroleum substitutes. Anal Chem 52, 1331-1334 (1980): 44. Tomkins B. A, Reagan R. R, Caton J. E, Griest W. H. Liquid'chromatographic determination of benzo(a)py,rene in natural synthetic, and refined crudes. Anal Chem 53, 1213-121i7 (1981). 45. Tomkins B. A. Griest W: H, Caton J. E, Reagan R. R. Multicomponent isolation, and analysis of polynuclear aromatics. In Cooke M., Dennis A. J. and Fischer G. L(Eds). Polynuclear Aromatic Hydrocarbons: Physical and Biological Chem- istry, Columbus, OH, Battelle Press, 1982, pp 813-8241 46. Tomkins B. A. Reagan R. R, Maskarinec M. P, Harmon S. H„Griest W. H, Caton J. E: Analy- tical chemistry of polycyclic aromatic hydrocar- bons present in coal-fired power plant fly ash. Ih Cooke Mi,, Dennis A. J(Eds) Polynuclear Aro- matic Hydrocarbons: Formation, Metabolism, and Measurements, Columbus, OH, Battelle Press, 1983, pp 1173-11187. 47. Brunnemann K. D, Hoffmann D. Chemical lstu- dies on tobacco smoke LIX. Analysis of volatile nitrosamines in tobacco smoke and'polluted
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46 indbor environments. IARC Sci Publi 1978: 19 :343-356. 48. Brunnemann K. D, Fink W; Moser F. Analysis of volatile N-nitrosamines in mainstream and sidestream smoke from cigarettes by GLC-TEA. Oncology, 1980 : 37 :217-222. 49. Magee P. N, Montesano R, Preussmann R. NL nitroso compounds and'related carcinogens. In Searle C. E. (Ed). Chemical Carcinogens, Amer- ican Chemical Society Monograph 173 1976, pp 491-625. 50. Brunnemann K. D, Yu L, Hoffmann D. Assess- mentof carcinogenic volatile N-nitrosamines in tobacco and' in mainstream and' sidestream smoke from cigarettes. Cancer Research 1977: 37:3218-3222. 51. Fowler W: K. Fundamentals of passive vapor sampling. American Laboratory 1982: 14:80- 87. 52. Hawthorne A. R, Gammage R. B, Dudney C. S. Womack D. R, Morris S. A, Westley R. R, Gupta K. C. Preliminary results of a forty-home indoor air pollutant monitoring study. Proceedings of Air Pollutiom Control Association Specialty Conference on Measurement and Montoringom Non-Criteria (Toxic) Contaminants, Chicago,. IL, March 23-24, 1983, pp 514-526, APCA,. Pittsburgh, PA, 1983: 53. Vo-Dinh T, Gammagg R. B, Martinez P. R. Analysis of a workplace air particulate sample by synchronous luminescence and room tempera- ture phosphorescence. Analyt Chem 1981: 53:253-25& 54. Vo-Dinh T. A personnel or area dosimeter for polynuclear aromatic vapors. Proceedings of the National Symposium on~ Recent Advances in Pollutant Monitoring of Ambient Air and Sta- tionary, Sources, May 4-7;, 1982, Raleigh, NC, EPA-600-983-007, pp 289-300. 55„ Bellar T. A, Lichtenberg J. J. Determining vola- tile organics at microgram-per-litre levels by Gas Chromatography, J AWWA 19741: 66:739- 744. 56. Pellizzari E. D. Analysis for organic vapor emis- sions near industrial and chemical waste dis- posal sites. Environ~Sci Technol 1982: 16:781- 785. 57. Higgins C: E„Griest W. H, Olerich G. Applioa- tion of tenax trappingto the analysis ofgas phase organic compounds in ultra-low tar cigarette smoke. J, Ass Off Anal Chemi 1983: 66:1074- 1083. 58. Bombaugh K. J, Page G. C,, Williams C. H,. Edwards L. 0, Balfous W. D, Lewis D. S, Lee K.. W: Aerosol characterization of ambient air near a commercial lurgi coal gasification plant. Kosovo Region, Yugoslavia, EPA 600/7-80- 177, US Environmental Protection Agency, Research Triangle Park, NC. 1980, pp 32-35, 59. Brazell R. S, Jpnkins R. A„Bayne C K. Profile analysis of organic volatiles in urine and tobacco smoke exposed beagles. Analytica chim Acta. 1982: 139:247-256. 60. Arthur D. , Little, Inc„ Acorn Park, Cambridge, MA 02140. 61. Energetics Science,, Inc, Hawthorne, NY 19532. Roger A., Jenkins Bin/Organic Analysis Section Analytic Chemistry Division Oak Ridge National Laboratory POBoxX Oak Ridge, Tennessee 37820;, USA Carbo chemi ment: was re Envir Non: the su by Ste numb measu other emph: explai measu well : mono levels pobyc' mines retent ally a• levels other as ext4 globir Th oxide globii
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47 J. Determining vola- -n-per-litre levels by WWA 1974: 66:739- r organic vapor emis- chemical waste dis- chnol 1982: 16:781- Olerich G. Applica- analysis analysis of gas phase tra-low tar cigarette em, 1983; 66:1074- C, Williams C. H; 3, Lewis D. S, Lee K. n of ambient air near gasification plant. -ia, EPA 600/7-80- Protection Agency, C. 1980, pp 32-35. Bayne C. K Profile in urine and tobacco nalj•tica chim Acta. rn Park, Cambridge, Hawthorne, NY JSA 1.4. Carbon monoxide as an index of environmental tobacco smoke exposure DOMINGO M. AVIADO INTRODUCTION. Carbom monoxide is the most widely used chemical marker for monitoring environ- mental tobacco smoke (ETS) ~ exposure. This was recognized during the 1974 Workshop on~ Environmental Tobacco Smoke Effects on the Non-smoker (1) and in subsequent reviews om the subject~ The 1981 summary of the literature by Sterling et al. (2) clearNy shows that: the number of publications on carbon: monoxide measurements far exceeds those relating,to all other constituents of tobacco smoke. The emphasis on carbon monoxide can be explained by the availability of techniques for measurements of both the exposure levels as well as the uptake or absorption or carbon monoxide. On the other hand, only exposure levels have been measured for particulates, polycyclic aromatic hydrocarbons, nitrosa- mines, aldehydes and acrolein, and pulmonary retention or absorption values are not gener- ally available. Nicotine and thiocyanate blbod levels have been reported but for technical and other reasons, the available information is not as extensive as measurements of carboxyhemo- globin. The current methodology on carbon mon- oxide in the inspired air and carboxyhemo- globin in the blbod evolved~ from the need to protect miners who were exposed to carbon monoxide in tunnels, and factory workers in contaminated areas. The general population can be exposed to high~levels of carbon mon- oxide in households with gas burning stoves and combustion heaters, and carbon monoxide deaths occur among fire victims. In recent years, the more extensive exposure of the gen- eral population to atmospheric carbon mon- oxide from vehicular and industrial sources has attracted considerable attention which had led to the development of instruments that are more sensitive and accurate, and& simpler to operate than those in use in most of the pub- lications considered during the 1974! Work- shop. The purpose of my presentation is to review the usefulness and limitations of the use of carbon monoxide as an index of ETS exposure. This review starts with a consideration of con- trolled experimental situations, then proceedfi to a discussion of uncontrolled~ but realistic sit- uations, and concludes with a brief considera- tion of health effects and some suggestions for future research. At each stage, I will attempt to discuss the application of measured levels of carbon monoxide and carrboxyhemoglobim to the overall question of their use to measure ETS exposure. ..
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48 EXPERIMENTAL JUSTIFICATION During the 11974 Workshop (1), Corn reviewed the characteristics of cigarette sidestream smoke and the factors inEluencing,its concen- trationland distribution in occupied spaces (see below): While one earlier study showed'! that total carbon monoxide in sidestream smoke was less than, that'~ in mainstream smoke (ratio less than 1)j Corn relied on the results from his laboratory that showed sidestream smoke con- tained 4.7 times more than mainstream smoke. This,often cited figure may no longer be reli- able because there have been other subsequent studies showing different ratios. That reported, sidestream/mainstream carbon, monoxide relationships are variable seems clear based on early and recent studies on combustion of tobacco leaf and' collection of cigarette main- stream smoke. The presence of carbon monoxide in ciga- rette smoke was demonstrated for the first time in 1899 by Wahl (3) who mixedia few drops of blood in a flask with 2 or 3 mouthfuls of tobacco smoke, and showed the formation of carboxyhemoglobin. During the next fifty years, there was verification by collection and measurements of carbon monoxide resulting from combustion of tobacco leaf (4-10): The results ranged from 4:5 to 90 ml carbon mon- oxide per gram of tobacco (Table 1): The great differences in yield were presumably due to different methods of obtaining the tobacco smoke, availability of oxygem in the combus- tiomchambery variety of tobacco leafs and form of tobacco product, i.e. cigar, cigarettes or pipe tobacco. TABLE 1. Carbon monoxide yrelds fmm tobrrcro tombwstiom. Investigators (reference number) ml COyg tobacco mean or range mg CO/cigarette mean or range (4) Lee 1908 4.8 (5) Lehmann 1909 17:1i to 26.8 (6) Armstrong 1922 0:8 to 1.24 (7) Baumberger 1923 9:5 (8) Ehrismann & Abel 1934 19.7 to 39.9 (9)', Saruta 1937 71.5 (10) ! Kohn-Abrest 1949 45.6 (11) Philippe & Hobbs 1956 2:8 to 5.7 (12) Osborne et al. 1956 3.3 to 5:7 (13) Mumpower et ali 1962 5.1 (14) Newsome & Keith 1965 5.0 to 1'1.01 (15) Jarrell 1965 0.5 to 1.0 (16) Harke & Drews 1968 3,4'to 7.7 (17) Kruszynski & Henriksen 1969 3.5 to 8A (18) Otsuka et al. 1970. L6 to 5.6 (Q9) Horton & Guerin 1974 4.4 (20) Btunnemann~& Hoffmann 1974 3.3 to 5.4 (21) Joigny 1976 17:6 (22) Browner et ali 1977 5.0 to 22.4, (23) Fairweather et al. 1981 1.0 to 28.0. (24) Hoffmann & Wynder 1982 0.5 to 26.0 Mailrstrnan Studies oo cigarette varied re, carbon rr addition monoxide there are namely, t used, porc cigarette ff cigarettes even thouo to collect rican ciga oxid%ig mg (Table Sidestrram/. The studic stream sm (25-30). T. 3.4 to 148 tream sm highest va the lowest has been s value is dL oxide anal for carbor TABLE 2. Investigatoi (reference i (25) Sforzo (26) Spean (27) Hoffm (28) Johns, (29) Klosti w (30) Hoeg ~ ~ ~ V W
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49 n monoxide in ciga- ated for the first time mixed a few drops of or 3 mouthftils of -ed the formation of ring the next fifty on by collection and' monoxide resulting cco leaf (4-10). The 90 ml carbon mon- (Table 1). The great presumably due to aining the tobacco gen in the combus- bacco leaf, and form tr, cigarettes or pipe mg CO/cigarette mean or range Mainstream Carbon Monoxide per Cigarette Studies om the carbon mqnoxide content of cigarette mainstream smoke have shown varied results ranging from 0.5 to 22.41 mg carbon monoxide per cigarette (11-22). In addition to the factors influencing carbon monoxide yield of tobacco leaf listed above, there are additional ones relating to cigarettes, namely,, type of cigarette smoking machine usedi porosity of cigarette paper and! nature of cigarette filter. Available commercial brands of cigarettes show even a wider range of yield, even though the same smoking machine is used to collect mainstream smoke (23, 24) r Ame- rican cigarettes 0.5 to 26 mg carbon mon- oxide/cigarette; and British cigarettes 11 to 28 mg (Table 1).. Sidestream/Mamttream Carbon Monoxide Ratio The studies on collection and analysis of side- stream smoke have been limited' in number (25•30). The published~reports show a range of 3:4 to 148 mg carbon monoxide in total sides- tream~ smoke per cigarette (Table 2). The highest value was reported by Hoegg (30) an& the lowest by Sforzolinin and Savino (25). It has been suggested by their critics that the low value is due to the technique for carbon mon- oxide analysis but since the mainstream level for carbon monoxide is comparable to the results of others, the method cannot be seri- ously questioned. The sidestream/mainstream ratios range from 0.18 to 4.17. Additional research is necessary to narrow this range (Table 2), It is of course possible that future measurements cannot limit the range of the ratio since mainstream carbon monoxide yields vary as much as 54 times (Table 1). Eguatronr for Predieting Carbon Monoxide Levelr It is not possible to adequately discuss environ- mental exposure to tobacco smoke without reviewing the mathematical equations that have been developed by ventilation scientists. In 1963, Turk (31) derived an equation for predicting the concentration of odorous gases in a room as a function of time. In 1969; Turk's equation was employed by Owens and Rossano (32) to estimate the gas concentration of ciga- rette smoke in an occupied space (Fig. 1). It should be noted that of the nine variables in the equation the "quantity rate of generation within the room" or sidestream smoke, is the variable that cannot be predicted from avail- able information (Table 2). The reported levelk of carbon monoxide vary by a factor of 44 so that it is presently infeasable to predict tobacco smoke exposure in an occupied space as Bridge and Corn di& in 1972, using three modified equations (33). There have been few attempts 2.8 to 5 7 . 3:3 to 5.7 5.11 5.0 to 11.0 TABLE 2. Cardon monaxide conttntr of cigantte mainstnam and sidestream smoke. 0.5 to 1.0 3.4 to 7.7 Investigators CO mg/cigarette Ratio 3.5 to 8.1 (reference number) mainstream sidestream Side/Main 1.6 to 5.6 4.4 (25) ~ Sforzolini & Savino 1968 19.3 3.4 0.18 3.3' to 5, 4, (26) Spears 1975 22 56 2.5 17.6 (27) HofEinann et aU 1979 1to20 ? 2.5 5.0 to 22.4 (28) Johnson et ali 1973 14I 46 3.3 1.0 to 28.0 (29) Klosterkotter 1977 15 52 3.5 0.5 to 26.0 (30) Hoegg 1972' 31.4 148 4.7
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50 to substitute theoretical equations for actual measurements of tobacco smoke exposure (34): Recent efforts" to estimate ventilatory require- ments based' on predictable amounts of side- stream carbon monoxide levels (35-39), would seem therefore to be questionable for the rea- sons stated above. For the same reasons, expression of cigarette eqµivatents that non- smokers are likely to inhale, based on a fixed sidestream/mainstream ratio shoul& not be considered valid. CONTROLLED TOBACCO SMOKE EXPOS[PRE EXPERIMENTS Following the 1974 Workshop, additional chamber exposure experiments have been con- d'ucted'so that there are at least fifteen, pub- lished reports (40-54) which is more than twice the number available to the earlier workshop participants. The reported' experiments have one common feature: a known number of cigarettes were lighted, sidestream smoke was generated either by human or machine smoking, and humam exposure levels were measured by: a) carbon monoxide analysis inside the chamber or occupied room; or b) carboxyhemoglobin analysis of blood of exposed subjects; or c) both. The results sum- marized in Table 3 are arranged according to increasing carbon monoxide levels in the expo- sure chamber, a room with windows and doors sealed; or a poorly ventilated room. T. In (r: (4 (4 (4' (4 (4 (4 (4 (4' (4, (4! (5t (5 (5: (5: (5 C =Coe-(Qi+EQ,)t/'Y+Ci'+G [1_e-(Qi+EQ,)t/v] Qi+ EQv = volume or room (ft~) V t = time (minutes). C= concentration of vapor in room at any time (mg/fO) Cb, = initiat concentration of vapor in room (mg/ft3) Ci = concentration of vapor in the infiltration air (tng/ft3) E = efficiency of the filter Qi = volume rate of infiltration or ventilation (cfm) Qv = volume rate of air through filter (cfm) G = quantityy rate of generation within the room (mg/min) Figurc 1: Equation proposed~ by Owens and Rosano (32)~to calculate concentration of cigarette smoke i~ occupied space. (~ (Jl ~ N 19 ni( an mi rei ox C~ m m sa Cft
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- at least fifteen pub- ;i&is more than twice the earlier workshop ed experiments have a known number of idestream smoke was iuman or machine xposure levels were i monoxide analysis ccupicd room; or b) dysis of blbod of )-th. The results sum- rranged according to de levels in the expo- i windows and doors ated room. 51 TABLE 3. Carhm monaxide and carbox>Jxmoglobin leatiG in controlkd ebamberr or arntilated rooms. Investigators (reftrence number) (40) ~ Anderson & Dalhamn 1973 (41) 1 Seppanen 1970 (42), Grimmer et al. 1977 (43) Lawther & Commins 1970, (44) Hugod et al. 1978 :45) Hurschman et al. 1978 %46) Polak 1977 47) Pimm et aL 1978 48) Weber 1976 49) Klbsterkotter, & Gono 1976 50) Harke 1970 51) Russell et al. 1973 'i2) Harmsen & Effenberger 1957 53) Dahms et al. 1981 (54) Aronow 1978 No. Carboxyhemo- Cigarettes/ CO globin % hour/10 cm3 ppm Control Change Carbon Monoxide Levels. Of the 15 published stu- dies two had no measurements of carbon mon- oxide levels and 12 studies showed mean carbon monoxide levels of 4.5 to 38 ppm. Harmsen and Effenberger (52) reported a level of 80 ppm in a room with exposure of 3.2 cigarettes/hour/10 m3, which~is not excessive since most other investigators have more than doubled this amount of cigarette combustion, with following carbon monoxide values: Polak (46) 6.7 cigarettes/hour 10 m3 = 23 ppm,. Russell etaL (51) 18.6 cigarettes/hour/10 m~ = 38 ppm. Since the 80 ppm was reported in 1957, prior to the introduction of modern tech- niques, it is reasonable to exclude this study and generalize that in all controlle& experi- ments with combustion, of up to 18.6 ciga- rettes/hour/10 m3; the maximal carbon mon- oxide level is about 40 ppm. Carboxyfiemoglobin Levels. The uptake of environ- mental carbom monoxide was estimated by measuring carboxyhemoglobin levels in blood samples collected' from non-smoking subjects 3.1 4.5 0.3 0 3.8' 16 116 +0.4 1.4 17 ... ... 4.7 20 ... ... 2.5 20 0.7 -H 0:9 ? 20, ? +1.4 6.7 23 2.0 -I' 0.3 2.4 24 0.5 +0.3. 6.7 24 ... ... 13.3 28 ? +1.4 3.1 30 ... .•. 18:6 38 1.6 +ll0 12 80 ... ... ? ... 0.72 +0.4 2.4 ... 5.92 -f-3:9 in 10 of the 15 experiments (Table 3): In spite of the wide range of carbon monoxide levels in the enclosed space (4.5 to 38 ppm), the expo- sure related change in carboxyhemoglobin levels ranged from +0.3 to +1'.41 percent. There is no direct relationship betvveen both measurements because the duratjon of expo- sure (one to three hours) may not be sufficient to achieve alveolar air-pulmonary capillary blood equilibrium. Furthermore, the subjects did not have comparable pre-exposure levels; they ranged from 0.3 to 2.0 percent carboxy- hemoglobin. Although there are eqpations predicting car- boxyhemoglobin levels from known inspired carbon monoxide levels, they are applicable only to experimental inhalation of carbon monoxide gas mixture and not to fluctuating carbon monoxide concentrations associate& with ETS exposure. The two studies report carboxyhemoglobin levels after exposure to ETS in patients suf- fering from either bronchial asthma (53) or
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52 angina pectoris (54), The shortcomings of these studies are not only limited to, a lack of exposure levels of carbon ~ monoxide, a routine measurement for almost alli investigations in this field. There are other criticisms relating to the significance of the tests used to evaluate health hazards of ETS exposure. Although there was a reduction in ventilatory measure- ments for the chronic asthmatics, the effect was reversible and' none of the patients actually developed an acute asthmatic attack. For the anginal patients, the earlier appearance of sub- jective chest pain during bicycle ergometry after exposure to cigarette smoke, compared to that prior to exposure, does: not necessarily indicate a worsening of the disease process. That the carboxyhernoglobin levels of anginal patients rose by 3.9 percent after two hours of exposure suggests that the carbon monoxide level in the exposure room must have exceeded 38 ppm, which is the highest level reported in a study with combined' measurements of expo- sure and uptake levels (51). TOBACCO SMOKE EXPOSURE INDOORS Severalipublications on the use of carbon mon- oxide as an index of tobacco smoke exposure relate to realistic situations : indoors, such as offices, restaurants, bar, taverns, nightclubs, public enclosures, workplaces and moving vehicles. Most of this information was derived following the 1974 Workshop to determine if tobacco smoking,in public places can generate levels of carbon monoxide that are hazardous to the health of non-smokers. Offices and Conference Rooms. There are nine pub- lications:on carbon monoxide levels in offices and conference rooms (55-63) One of the early studies on, carbon monoxide levels associated with tobacco smoke was conducted by Harke (56) who examined'two air conditioned build- ings in Hamburg. Although smoking was,per- mitted, values exceeding 5 ppm carbon mon- oxide were rarely observed. There were brief periods where carbon monoxide levels reached 7 to 15.6 ppm, and in one case,,the high1evels were attributed to a lighted cigarette held close to the inlet of the measuring device. Since out- door carbon monoxide levels were not meas- uredi it is not possible to determine if indoor levels of less than 5 ppm were due entirely to cigarette smoke. A significant portion of indoor carbon monoxide is most l`tkely derived'.. from outdoors! because other investigators reported that indoor carbon monoxide levels are either equal to or slightly greater than out- door levels. The peak indoor to outdoor differ- ential reported can be as much as 10 ppm whereas the minimaLdifferential as low as 0!2 ppm. The peak carbon monoxide levels reported inside offices and' conference rooms are 20'ppm in France (58), and 32.5 ppm in the United States (Table 4): These levels are not exclusively generated by cigarette smoking. Rertaurantr, Bars, Taverns and Nighttlub'r. The carbon monoxide levels in eating,, drinking and entertainment establishments are generally less than 10'ppm with exceptions (64-71): The reported levels are as high as 15 ppm in a tavern in Finland (66), and, as high as 30 ppm in a tavern in Ohio (69). There is no direct evidence that cigarette smoke is the sole source of the carbon monoxide inside restaurants since various sources (cooking stoves, tableside food' preparations, etc.). have not been excluded. The indoor levels of carbon mon- oxide can originate im part from outdoors and the highest indoor-outdoor differential reported is 3.0 ppm (68). The publications liste& in Table 5 refer not only to restaurants but also to supermarkets and hospitat lobbies (65); hotel lobbies and bus terminals (71). One study relating to restaurants and theater, lobbies (72) has been excluded from the Table 5 because carbon monoxide levels were stated'as TABL Count. investi Germaa (55) F (56) 1=. Canada (57), C Francr (58) ~ F flurtria (59) St United . (60) C (61) L (62) Sl (63) A TABLI Countr investi, Canada (64) Cl (65) Se Finland (66) Sc France (67) B Smitzer, (68) F Ux;ted (69) C (70) E (71) r
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)pm carbon mon- There were brief ide levels reached! se, the high levels igarette held close dtvice. Since out- s were not meas- termine if indoor re due entirely to cant portion of iostlikeNy derived her investigators monoxide levels greater than out- to outdoor differ- auch as 10 ppm itial as low as 0.2 nonoxide levels onference rooms d 32.5 ppm in the :se levels are not irette smoking. I Nrghtclubr. The ing, drinking and ts are generally tons (64-71), The as 15 ppm in a s high as 30 ppm here is no direct is the solp source iside restaurants ; stoves, tableside iave not been of carbon mon, from outdoors loor differential -he publications ly to restaurants hospital lobbies ninals (71): One d.theater lobbies m the Table 5 .Is were stated as TABLE 4': Indoor carbon monnaxidt /tuelf of o~'icet and conference roomt. Country and' investigators CO/ppm indoors Germany (55) Portheine 1971 5 to 25 (56) Harke 19741 <5 to 9 Canada (57) ~ Chappell & Parker 1975 2.5 ± 1ff France (58), Beaucent et al. 1982 10to20 Austria (59) Stehlik et al! 1982 8 to 16 United States (60) Coburn et al. 1965 4 to 9 ~61) Dublin 1972 32.5 (62) Slavin & Hertz,1975 8to10 (63) Allen & Wadden 1982' 4.5 to 13:0 TABLE 5. Ixdoor carbon monoxide /evek of restaurants, bars, tatxrns and nigbtcJubr. Country and investigators CO/ppm indoors Canada (64) Chappell & Parker 1977 4.0 ± 2.5 13:0 ± 7.0 (65) Sebben et al. 1977 13.4 Finland . (66) Seppanen & Uusitalo 1977 2.5 to 15 France (67) Badre et al. 1978 2 to 23 Smitz<rland (68) Fischer et al. 1978 0:5 to 5.1 United States (69), Cuddeback et all 1976 3 to 30 (70) Equitable Environmental Health Inc. 1976 6.2 (71) Nylander 1978' 2 to 20 Mean or rangee outdoors 2.5 ± 1,0. 8 to 10 1 to 2 4.2 to 13.3 Mean or range outdoors 2:5 ± 1.5. 2:5 ± 1.5. 9.3 Oto15 0A to 4.8' 6:45 1 to 15 53'
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54. less than 10 ppm, rather than in specific num- bers. consideredi Machinery and production of industrial chemicals can, contribute to meas- ured carbon monoxide levels. TABL. Occupational Indoor Exposura. The last group of studies on ind'oor exposure to cigarette smoke relate to workers without any description of nature of their occupation (Table 6). The study conducted in Germany characterizes them as "office workers" with~ a subgroup of "passive smokers" working in, the same room ass smokers (73). In spite of the 8-hour exposure in the offices with smokers, the non-smokers had a reduction in mean carboxyhemoglobin levels from 0.82 percent to 0.63 percent. In the study of workers from Switzerland, there is a reported indoor-outdoor differential of 1.1 ppm carbon monoxide (74-76): Although car- boxyhemoglobin levels were not measured, it is safe to assume that there would' not have been any significant change. In the Ameriaan~ study, some of the workers carried a portable carbon monoxide analyzer and hourly mean differences from 0.1 to 4.7 ppm were reported between areas where smokers were allowed' and those otherwise (77). In, all of these reports, since the work environment is not specified, the contribution of carbon monoxide sources other than cigarette smoke has to be TABLE 6: Indoor carbon monoxide lesxla' of'work ploces. Country and investigators Germany (73) Siadkowski et al. 1976 Swiszerland (74), Weber & Fischer 1980 (75) i Fischer & Weber 1980 (76) Welier 1981 United Stater IN'PRAVEIIICULAR TOBACCO SMOIGE EXPOSURE AND OUTDOOR SOURCES OF CARBON MONOXIDE Excessive smoking in a poorly ventilated car has resulted in levels as high as 80 to 110 ppm (78, 79): Any contribution from vehicular emission was not measured' although it was clearlydemonstrated that intravehicular levels of carbon monoxide were significantly reduced as soon as air vents were opened (79, 80). The carbon monoxide levels associated with cigarette smoking have been measuredin buses (81), airplanes (82), ferryboats (83), submar- ines, and train, compartments (52, 67). The reported~levels were less than 40 ppm and were dependent on the number of smokers, extent of ventilation of occupied vehicles and outdoor levels of carbon monoxide (Table 7). The con- tribution of vehicular emissions to intravehi- cular levels of carbon monoxide has been reviewed' by Harke (85). Like most American cities, recent studies in Geneva show that heavy vehicular traffic can cause carbon mon- oxide levels as high~ as 25 ppm (86). CO/ppm Mean or, range indoors outdoors 2,78 ± 1.42 1.07 to 6:33 2.8 L7 Vehicl investi Axtonm (78) Si (79) H (80) H (67) B- Intrrcity (81) Se AirpAasr, (82) U. Firryboo (83) G Submarri (84) C: Trarns (52) H, (67) Bs TABLE Tobacco _ Experir Offices Restaur: Work e Movin Air grral Tlireshc Submar nutdoo Carbmxy Genera Vatien HE, LEVE (77) White & Froeb 1980 (smoking, permitted). 3. 11 to 29.4 W 'rhe p (smoking not permitted) 3.3 to 13.8 U1 carbor
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TABLE 7: Leuds' of carbon monoxide in Wicle'r. )oorly ventilated car gh as 80 to 110 ppm ion from vehicular -ed although it was intravehicular levels. ,ignificantly reduced opened (79, 80). vels associated'with n measured in buses )oats (83), submar- ents (52, 67). The kn 40 ppm and were f smokers, extent of hicles and outdoor ;Table 7~ The con- sions to intravehi- 3noxide has been ke most American ~eneva show that 'ause carbon mon- pm (86). Vehicles and investigators CO ppm Mean or range indoors outdoors 55 4Ntomobiler '8) Srch 1967 90 ... '9) Harke & Bleichert 1974 80 to 110 ... 0) Harke & Peters 1974 12'to 24 ... ') Badre et al. 1978 14 0 ercio BNrer1) Seiff 1973 18 to 33 ... •alanes ) i U.S. Department of Transportation 1971 2 to 5 ... yboarr ~ Godin et al. 1972 18.4 ± 8.7 - 3:0 ± 24 '7rtrt.0er Cano et al. 970 <40 "s er 1957 0 to 40 Harmsen & Effenber g Badre et al~ 1978 4 to 5 !A'BLE' 8. Summary of indoor litvli of carbon monoxide, air quality standards, and carbaxybemaglobm lc-a1 of rafety: %obucco smoke exposure f:xperimental chambers an&semi-ventilated rooms CO ppm 45 to 38 ()ffices and conference rooms 2.5 to 32.5 Restaurants, bars, taverns and'nightchibs 0.5 to 30 Work environments 2.8 to 29.4 Moving vehicles 10 to 30 Air quaGty rtandardn CO ppm Threshold limit value (TL'V: 8 hours) 50' Submarines (continuous for 90 days) 25 Outdoor primary standard (1 hour), 35 (8 hours) 9 C-rdoxybemoglobm letKLt of rafety Gcneral population Patients % COHb 5 (?) 1.8 to 3.0 HEALTH EFFECTS OF CARBON MONOxIDE sure necessitates a brief discussion on~potentiali LEVELSDURING TOBACCO SMOKE EXPOSURE health hazards. The reported indoor carbon monoxide levels can be regarded as an index of The preceding review of reported levels of ETS exposure provided that other sources of carbon monoxide associated' witb, ETS expo- carbon monoxide are recognized, measured
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56 and deducted to arrive at a net value from tobacco smoke exposure. It should be noted that although most reported indoor levels are less than 10 ppm, there are isolated instances exceeding 10 ppm and reaching as high as 38 ppm. These include situations of excessive smoking in poorly ventilated rooms and'those in which the outdoor levels of carbon mon~ oxide contribute& to the measured carbon monoxide indoor (Tables 3, 4 and 5). Air Quality Standardr, Almost alli published levels of carbon monoxide derived' from tobacco smoke are below. the outdoor primary standards of 35 ppmfor1 hour and9 ppm for 8 hours under realistic conditions. There is, therefore, little reason to suspect any adverse effect on human health, from reporte& indoor carbon monoxide li:vels normally associated with~ ETS exposure.. Carboxyhemogiobm I:evelr of Safey. The general population should definitely be protected from exposure to carbon monoxide that would result in, carboxyhemoglobin levels of 5 percent, or more. This recommendation is based on the review of the results of animal experiments and human observations on carbom monoxide exposure (87-90). The biological implications of results showing that in patients with car- diovascular disease, carboxyhemoglobin levels as low as 1.8 to 3.0 percent can reduce the patient's ability to pedal, a! bicycle ergometer are currently a matter of controversy: One of these studies related to tobacco smoke expo- sure and has been discussed above. The nine other reports oni bicycle ergometry involve inlialationi of carbon monoxide mixtures. That carboxyhemoglobin levels as low as 1.8 to 3.0' percent can subjectively reduce a patient's ability to pedal a bicycle_ ergometer has been characterized by the National Academy of Sciences.-National Research Councill Review Panel as follows: "There is no evidence from these results that the exposure to carbon mon~ oxide increases the frequency and severity of chest pain, or the development of other com- plications, or that it shortens life expectancy among patients with angina pectoris or other clinical manifestations of heart disease" (90). Although levels between 1.8 and 3.0 percent have been questioned as pathological, no con- firmatory evidence is present in the form of electrocardiographic signs of myocardial ischema appearing in exercising patients during inhalation of such low levels of carbon monoxide. Future Research. The above discussion implies that additional studies are necessary before it can be determined if carboxyhemoglobin lcvels from 1.8 to 3.0 percent are harmful to certain segments of the population. In recent years, interpolation of personal carbon mon- oxide exposure from daily outdoor average levels has been criticized (91-93): Carbon mon- oxide analyzers carried by individuals showed exposure levelfi that were different from those reported'from, area monitoring,stations. If this instrument is further reduced in, size, it can be strapped to the individual for extended periods of time. Such a devise would assist in the design of epidemiologic studies to include day and night, indoors as well as outdoors. REFERENCES 1. Rylander R(Ed): Environmental tobacco smoke effects on the non-smoker. Report from a workshop. Scand J Resp Dis 1974: Suppi 91:1- 90. 2. Sterling T. D, Dimich H, Kobayashi' D. M. Indoor Byproduct Levels of Tobacco Smoke: A critical' review of the Literature. J Air Pollut Control Ass 1982: 32:250-259: 3. Wahl F. Ueber den Gehalt des Tabaksrauchen and Kohlenoxyd Pfliigers Arch Physiol. 1899: 78:262-285. 11 1 1: th t .-~.-,~---T-,---
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58 spaces. Environ Res 1972: 5:192-209. 34. Corn M. Characteristics of tobacco sidestream smoke and factors influencing its concentration and distribution in occupied spaces. Scand J. Resp Dis 1974: Suppl 91, pp 21-36. 35. Jones R. M, Fagan R. Application of mathemat. ioal, model for the buildup of carbon monoxide from cigarette smoking im rooms and houses. ASHRAE Ji 1974: pp 49-53. 36: McNall P. E. Jr, Practical methods of reducing airborne contaminants in, interior spaces. Archs envir Hlth 1975: 30:552-556. 37. Penkala S. J;, De Oliveira G. The simultaneous analysis of carbon monoxide and suspended'par- ticulate matter produced by cigarette smoking., Environ Res 1975 : 9 :99-114. 38. Wang T. C. Air quality in a conference room. Chemtech 1978; pp 154-158. 39: Leaderer B. P, Cains W. S, Isseroff R. Bergitrnd' L. G. Ventilation requirements in occupied spaces for control of total suspended particulates and carbon monoxide generated from tobacco smoke. Paper presented arInternational Sympo- sium on Indoor Air Pollution; Health Energy and Conservation, University of Massachusetts. 19811: pp 1-4. 40. Anderson G; Dalhamn T. Health risks due to passive smoking (in Swedish). Lakartidningen 1973 : 70:2833-2836. 41l Seppanen~A. Smoking in closed'space and its effect on carboxyhemoglobin, saturation of smoking and nonsmoking subjects. Ann clin Res 1977: 9:281-283. 42. Grimmer G. Bohnke H. Harke H. P. Zum Problem, des Passivrauchens: Aufnahme von polycyclischen aromatischen Kohlenwasser- stoffen durch Einatmen von zigarettenrauch- haltiger Luft. Int Arch occup Environ Hith 1977:40t39'-99: 43: Lawhter P. J, Commins B: T. Cigarette smoking and exposure to carbon monoxide. Ann NY Acad Sci 1970: 174:135.147: 44. Hugod,C, Hawkins L, Astrup P. Exposure of passive smokers to tobacco smoke constituents. Int Arch occup Environ Hlth 1978: 32':21- 29. 45. Hurshman~L. G, Brown~B: S, Guyton R. S. The implications of sidestream cigarette smoke for cardiovascular health. J Environ, Hlth 1978: 41:145-149. 46. Polak E. Le papier a cigarette. Son role dans la pollution des lieux habites. Tabagisme passif: notion nouvelle precisee. Bruxelles Mcd 1977: 57:335-340. 47. Pimm P, Shephard R J] Silverman, F. Physio- logicalleffects of acute passive exposure to ciga- rette smoke. Archs envir Hlth 1978: 33:201- 213. 48. Weber, A. Luftverunreinigung unde Belastigung durch Zigarettenrauch: Zum Problem des Pas- siverauchens. Z Krankenpfl 1976: 69:11~- 118. 49. Klosterkotter W; Gono E: Zum Problem des Passivrauchens. Zbl Bakt Hyg 1976: 162:51- 69: 50: Harke H. P. The problem of "Passive smoking". Mnnch med Wschr 1970: 51:2328-2334. 51. Russell M. A. H, Cole P. V; Brown E. Passive smoking: Absorption by non-smokers of carbon monoxide from room-air polluted by tobacco smoke. Postgraduate Med,J 1973: 49:688 692. 52. Harmsen H. Effenberger E. Tabakrauch in Ver- kehrsmitteln, Wohn- und Arbeitsraumen. Arch Hyg Bakt 1957: 141-383-400. 53. Dahms T. E, Bolin J. F, Slavin R. G. Passive smoking; effects on bronchial asthma. Chest 1981: 80:530-534. 54. Aronow W. S. Effect of passive smoking on angina pectoris. N Eng J Med 1978': 299:21- 24. 55. Portheine F. Zum Problem des Passiver- auchens. Munch Med Wschr 1971: 18':707. 56. Harke H, P.,The problem of passive smoking I. The influence of smoking of the CO concentra- tions in, office rooms. Int Arch Arbeitsmed 1974: 33:199-204. 57, Chappell S, Parker R. A study of carbon mon- oxide levels in enclosed public spaces. New Brunswick Council on Smoking and Health, Fredericton, New Brunswick, Canada. 1975, 16 PP• 58. Beaucent C, Grunewald, A, Brygoo-Butor F, Cornet A, Philbert M. Pollution atmospheriqµe dans un bureau du centre de Paris ventile par gaines d'aeration. Risques pour la santE du per- sonnel. Arch Mal Prof Med Trav Secur Soc 1982: 43 r126-128: 59. Stehlik G, Richter 0, Altmann H. Concentra- tion of Dimethylnitrosamine in the air of smoke-fllled rooms. Eeotoxicol Environ Safety 1982: 6:495 -500. 60. Coburn R. F, Forster R. E; Kane P. B: Consid: erations of the physiological variables that determine the blood carboxyhemoglobin con- centration in man. J clin Invest 1965: 4 61. I t 2 62. S F ~ 4 63. r' ' r if 2 64. C n r 65~ S, S I 66. S, g 1' 67, B G 4 68. F rt A 69. C 0 in 70. E rec di D 71. N C+. '2. 2. Pt ai 3( 73. S7 bi sr 3 74: w ~ 75. F F 76. 1
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e. Bruxelles Med 1977 i f, SilvermI Physio- assive exposure to ciga- ir Hlth 1978: 33:201- igung unde Belastigung Zum Problem des Pas- npfl 1976: 69:11-118. E: Zum Problem des kt Hyg 1976: 162:51i- i of "Passive smoking". Y: 51:2328-2334. '. V„ Brown E. Passive non-smokers of carbon ir polluted by tobacco d J 1973: 49:688-692. E. Tabakrauch in Ver- 1'Arbeitsraumen, Arch -400. Slavin R. G. Passive mchial asthma. Chest f passive smoking on, J Med 1978: 299:21- )blem des Passiver- ;chr 1971: 18':707. of passive smoking I. ; of the CO coneentra- int Arch Arbeitsmed study of carbon mon. public spaces. New ~moking and Healthj ick, Canada. 1975, 16 A, Brygoo-Butor F, lution atmospherique de Paris ventile par pour la sante du per~ ~fed "I1rav Secur Soc mann H': Concentra- nine in the air of ,xicol Environ Safety , Kane P. B. Consid'- gical variables that :)xyhemoglobin con- clin Invest 1965: 44:1899. 61. Dublin W. B. Secondary smoking. A problem that deserves attentiori, Pathologist 1972:. 26:244-245. >2. Slavin R. G, Hertz M. Indoor, air pollution. Paper presented at the American Academy of Allergy Annual Meeting, San Diego, CA: 1975, 4 pp. Aller! R. J, Wadden R. A. Analysis of indoor concentrations of carbommonoxide and ozone in an, urban hospitaL Environ Res 1982. 27:136-149. ChappelliS. B, Parker R. J. Smoking and carbon monoxide levels in enclosed public places in New Brunswick. Can Jpubl Hlth 1977: 68:159- 161. Sebben J, Pimm P, Shephard R. J. Cigarette Smoke in enclosed public facilities. Archs envir Hlth 1977: 32:53-58. Seppanen A, Uusitalo A. J. Carboxyhaemo- glbbin saturation in relation to smoking, and various occupational conditions. Ann clin Res 1977: 9:261-268., Badre R. Guillerm R, Abran N, Bourdin M, Dumas C. Atmospheric pollution by smoking, (im French). Annls pharm, fr 1978: 36:443- 452. 66. Fischer T, Weber A, Grandjean E. Luftverun- reinigung durch Tabakrauch in Gaststatten. Int Arch occup Environ Hlth 1978: 41:267-280. 6'). Cuddeback J. E, Donovan, J. R, Burg, W. R. Occupational aspects of passive smoking. Am ind Hyg Ass J, 1976: May,, 263'-267: 70. Equitable Environmental Health Inc. The results of a preliminary survey of indoor/out- door carbon, monoxide levels in Washington, DC. 1976: 10 pp: 71. Nylander L. R. Statement to the Chicago City Council. 1978c 5 pp. Perry J. A study onithe hazard of tobacco smoke air pollution to health. B'C Med J,1973: 15:304- 305. '3: Szadkowski D, Harke H. P, Angerer J. Body burden of carbon monoxide from passive smoking in offices (in German). Inn Med 1976: 3:310-313. '4. V6'eber A, Fischer T. Passive smoking at work. !nt Arch occup Environ Hlth 1980:, 47:209- 221 Fischer T. VG'eber A. Passivraucheniam Arbeits- platz, Soz Praventivmed 1980: 25:401-4016. '6: Wcber A. Passivrauchen Luftqualitat, Mass- 59 nahmen. Soz Praventivmed 1981: 26:182- 184. 77: White J. Froeb H. Small-airways dysfunction in nonsmokers chronically exposed to tobacco smoke. New Engl J, Med 1980: 302:720-723: 78. Srch M. Ueber die Bedeutung des Kohltnoxyds beim Zigarettenrauchen im Personenkraftwa- geninnern. Dt Gesamte Gerichtl 1967: 60:80- 89. 79. Harke H. P, Bleichert A. Zum Problem des Pas- siverauchens. II. Untersuchungen Ueber den Kohlenmonoxidhalt der Luft im Kraftfahrzeug durch das Rauchen von Zigaretten. Int Arch Arbeitsmed 1974: 33:207-220. 80. Harke H. P, Peters H. Zum Problem~des Passiv- erauchens. III. Ueber den Einfluss des Rauchens auf die CO-Konzentration in Kraft- fahrzeug bei Fahrten im Stadtgebiet. Int Arch Arbeitsmed 1974: 33:221-229. 81L Sciff H. E. Carbon monoxide as an indicator of cigarette-caused pollution levels in intercity buses. US DD ept of Transportation 1973: 11 PP• 82. US Department of Transportation: Health aspects of smoking in transport aircraft. NIOSH 19:71: 85 pp. 83. Godin G, Wiight, G, Shephard R. J. Urban exposure to carbon~monoxidb. Archs envir Hlth 1972: 25 :305-313. 84: Cano J. P, Catalin Jl Badte R, DumasC,,Viala A, Guillerme R. Determination de la nicotine par chromatographie en phase gazeuse. II. Applica- tions. Annls pharm fr 1970: 28:633-640. 85, Harke H. P. Passiverauchen im Auto.,Rep Annu Conf Get Soc Ind Med 1074: pp 164-174. 86. Snella Mi C, Rylander, R, L,andry J.,C. Pollution due au CO, un risque pour la sante a Geneve.> Soz Praventivmed 1980: 25 :199-200. 87. US Environmental Protection Agency: Air quality criteria for carbon monoxide. 1979: EPA 600/8-79-022. 88. Rylanden R, Vesterlund J1 Carbon monoxidt cri- teria,Scand J. Work Environ Hlth. 1981: Suppll 1, 7:39 pp. 89: World Health Organization and the United Nations Environment Programme: Environ- mental Health Criteria 13: Carbon Monoxide. 1979: 125 PP• 90. National Academy of Sciences-National Research Council: Medical and biologic effects of environmental pollutants. Carbon Monoxide. 1979: 239 pp.
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60 91. Gilmore T. M, Hanna T. R. The need for repre- sentative anibient air carbon monoxide sam- pling., J Air Pollut Control Ass 1976: 26:965- 967: 92. Cortese A. D, Spengler J. D. Ability of fixed monitoring stations to represent personal carbon monoxide exposure. J Air Pollut Control Ass 1976: 26:1144-1150. 93. Morgan M. G, Morris S, C: Needed'c A national R & D effort to develop individual air pollution monitor instrumentation. J Air Pollut Control Ass 1977: 27:670-673. Domingo M. Aviado Atmospheric Health Science, Inc. P.O. Box 307 Short Hills, New Jersey 07078, USA. In a post the a Iac was like' ited slou P dcn lonl that wer Ilc Spc; won~ smrn tlon rcrl' fc rc Part, cha: late, ti+ tlon that cml mdt
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Veeded: A national vidual air pollution Air Pollut Control c: USA. 1.5 Discussion RAPPORTEURS MARTIN J. JARVIS AND CORNELIUS J. LYNCH comment to Firat'r paper the question was ,,d why ambient nicotine concentrations in study were higher in a non-smoking,area of arge room than in the area where smoking ::as permitted First replied that he thought it iikely that nicotine is relatively rapidly depos- ited on surfaces and subsequently evaporates sdowly into the emvironment~ Pershagen commented that from~ the epi'- dcmiological' standpoint, interest is more on long term~ exposure levels of tobacco smoke ttian~in the relatively short term values which were recorded inithe studies presented by First. lie drew attention to long term, studies by Spengler (1) which, indicated that there were good correlations between the number of smokers in private homes and the concentra• tion of suspended particles found! in them. In reply First, stressed that private homes are dif-fcrent from the public places he had studied, partly because of the very low rates of air change seen in houses which are well insu- lated. Sterling,suggested that the levels of pollu- tion found by Spengler might reflect the fact that workers may bring dust from their place of employment into their homes, rather than indicating an effect of smoking in the home itself Occupation was a confounding factor not controlled for in Spengler's studies. Regarding Sterling's paper, Zober queried whether the buildings being compared were really comparable. For example, some might be next to motorways and' others in the country. Simple factors like these might account for differing,pollirtant levels. Russell suggested that buildings should be character~ ized not by smoking but by levels of specific components, e.g. nicotine in order to select the material for the testing of the hypothesis. Further points that were raised were that compliance with smoking restrictions may not always have been ensured,and, that in the absence of a specific indicator of tobacco smoke, it was difficult to evaluate the effects of smoke exposure per se. After Jenkin's paper, Gillis wondered whether inhalation of nitrosamines might be associated with,cancer of the alimentary tract, and asked how confident Jenkins was of the methodi: employed to measure nitrosamine levels. Jenkins replied that the technology for measuring nitrosamines was stillisimilar to that reported by Hoffmann et al. (2) and said' that one could have "moderate confidence" in1 thee measurements of nitrosamines in sidestream smoke.
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Russell expressed, the hope that new data might be forthcoming on ratios for various smoke constituents in sidestrearn and, main- stream smoke, not, only in machine generated' smoke, but also for ETS. Jenkins said that no such data were presently forthcoming and it was suggested that in that case the Workgroup should consid'er whether the figures presented in the 1970 Surgeon General's (3) report should be relied on prn tem. Concerning Aviado's paper Lebowitz asked whether there might be a major contamination effect due to other sources (e.g. gas stoves), many of which emit more CO and which have not been accounted for in the studies pre- sented. Aviado replied that there may well be such problems in using CO. REFERENCES 1. Spengler J. D, Dockery D. W, Turner W. A, Wolfson J. M, Ferris B. G. Long term measure- ments of respirable sulfates and particles inside and outside homes. Athmospheric Environ 1981: 15:23-30. 2. Hoffmann D, Adams J. D,, Brunnemann K. D, Hechr S. S. Assessment of tobacco-speci6c N- nitrosamines in tobacco products. Cancer Res 1979: 39:2505 -2509. 3. U: S. Department of Health; Education and Wel- fare. Smoking and' Health: A report of the Sur- geon~ General. Washington D. C:' U. S. Public Health Service 1979. 2. Many smc of termin, associated Plasma co carbon m. used as m: Cotinin( as a markc (ETS) bec, levels of pl minal hah nicotine. t over nicoti well, becat There is in the liter biological age, sex, v passive sm there is a variation i active sme (5-1'1). In ordei groups vo: rc-cval'uat plasma an C~dmokers. ~ Group N IU~
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W, Turner W. A, .ong term measure- and particles inside nospheric Environ Brunncmann K. D, tobacco-specific 1*i- Aucts. Cancer Res Education and Wel~ 1 report of the Sur- D. C: U. S. Public 2. Dose-measurements in humans 2.1. Half-lives of selected tobacco smoke exposure markers CORNELIUS J. LYNCH smoking-related studies involve the use rminal half-lives of biological markers iated with exposure to tobacco smoke. rna cotinine and nicotine, and expired air )on monoxide, in particular, have been ,,:,l as markers of exposure (1-4): c;cxinine has some advantages over nicotine :, a marker of environmental, tobacco smoke ;1:1'S) because smokers usually have very low Icvels of plasma nicotine, and the cotinine ter- niinal' half-life is much longer than that of nicotine. Cotinine is occasionally, preferred over nicotine as a marker of active smoking, as well, because of this difference in half-lives: There is a wide range of half-lives reported in the literature, and the halE life of a specific biological marker can differ as a function of age, sex, whether the subject in an active or passive smoker, and other factors. In addition; there is a considerable amount of individual variation involved due to metabolism and, for active smokers, also due to inhalation practices (S•11). In order to address these issues further, two groups volunteered to participate in a study to re-eval6ate the terminal half-life of cotinine in plurna and of CO as measured in expired air of smokers. Group 1 (47 men, 41 women) consisted of smokers from~ a larger research project beingg conducted by the Franklin Institute, and Group 2 (8 men, 11 women) consisted of par- ticipants ima smoking cessation program spon- sored by the Atlanta, Georgia, Lung Associa- tion (12). No one of these volunteers had engaged in any smoking-related practice, other than ciga- rette smoking, for at least one year (pipes; cigars, snuff, chewing tobacco, marijuana), Since neither group was recruited originally for an investigation of biological half-lives the protocol had to fit into the pre-arranged' schedule and environment specified for other purposes. A fee was offered!to the volunteers to encourage compliance with the protocol. Volunteers in the first group agreed to abstain from smoking for a 24-hour period for the purpose of this study. Ten milliliters of venous blood were drawn when the volunteers reported to the test center to begin~ their smoking abstinence period. Samples were taken in the late afternoon~ or early evening, when the smokers had reached their daily peak cotinine levels: Blood samples were drawn again when the volunteers reported to the test center 24 hours later. Volunteers in the second group alli quit smoking on a Tuesday evening, after which a
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64'. sample of 10 milliliters of venous bloodl was drawn. Additional samples were drawn from each volunteer at 24-hour intervals-that is, on the following three evenings -for a total of four samplcsper volunteer. All blood samples were centrifuged and frozen within~ 15 minutes of being drawn, and subseqpently assayed for cotinine concentra- tion (1i3). The cotinine terminal half-life, in hours, for each subject in the first group was estimated from, the expression: C24 = Co (0.5) 24/F% where Cp and C24 denote the cotinine levels in nanograms : per milliliter from the initial and 24-hour plasma samples, respectively. Ty'i denotes the cotinine terminal half-life value, in hours. For Group 2, four cotinine values were available for each volunteer. The terminal half-life was estimated'using simple regression of the logarithms of cotinine values vs. time. For both groups, the half-life estimates were averaged separately by sex of the subjects. Results are summarized in Table li for male subjects. The 47 men in the first group smoked an average of 35.2 cigarettes per day (CPD), with a range of 20 to 70 CPD: The associated'stan- dard error of the mean (SEM) was 1.6, This group averaged 36.8'years of age, 70.2 inches in height, and' 77.8 kg in weight. The initial, or baseline, plasma cotinine concentrations aver- aged 281 ng/ml, with a range of 132 to 514 ng/ml. Baseline samples were taken approxi- mately 20'minutes after smoking the last cigar- ette. All subjects had been smoking in their customary manner up until this time. The average plasma cotinine terminal half- life for these 47 subjects was 14.6 hours, with a range of 7.1 to 28.0 hours. This is considerably shorter than values reported' in the litera- ture. The eight male subjects in Group 2 smoked significantly fewer„CPD than did the subjects in Group t This difference in consumption reflects a difference in recruiting criteria for the two groups. Group 1 subjects were recruited from a larger, ongoing study of smokers of at least 20 CPD. No such restriction had beemimposed on participants in Group 2, the smoking cessation program volunteers: The Group 2 subjects also had a significantly TABLE 1 L Seketed statistics for male smbjectl. Age Height Weight Baseline plasma cotL Th CPD (years) (inches) (kg) (ngLml) (hours). Groxp 1 (TFI) 47 subjects, average 35.2 36.8 70:2 77:8 281 14.6 range 20-70 21-60 66-75 59.1-95.5 132=514 7.1-28:0 SEM 1.6 1.5 0.3 1.5 25.11 0.7 Gmup 2 (ass:) 8 subjects average 28.1 38A 71.6 77,5 418 15.4 range 15-40 21~.55 68-75 61.4-86-4 225-775 11.2-29.6 SEM 3.3 2.6 0.8 3.0 64.5 2.8' Groups 1 er 2 55 subjects average 34.2 37.0 70.4 77.5 301 14.7 higher nglml, 1). The Group : Group The w cotinine was 14. Fema tion grc than dic (once a- inal rec slightly plasma ~ hours fo. with a a TABLE : Group 1 ( 47 subject Groxp2( 8 subject Growpf 1 E 55 subject For G was 42.2 ppm. 24 was 11.• a hours. G W' rouF
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65 group smoked an. :r day (CPD), with he associated stan- ?M) was 1.6: Thiss age, 70.2 inches in ;ht. The initial, or mcentrations aver- nge of 132 to 514 ere taken approxi, >king the last cigar- smoking in~ their this time. iine terminal half- 14.6 hours, with a 'his is considerably red in the litera- i Group 2 smoked' in did the subjects e in consumption -uiting criteria for I subjects were -)ngoing study of ,io such restriction ipants in Group 2, ram volunteers. had a significantly higher average baseline cotinine value (418 ng/ml, as compared to 281 ng/ml' for Group 1): The average plasma cotinine half-life for sroup 2, however, was comparable to that of Troup 1(15.4 and 14.6 hours respectively). Che weighted average combined plasma -3tinine terminal half-life for the two groups as 14.7 hours. Female participants in the smoking cessa- )M group smoked signifdcantly fewer CPD 1n, did the female participants in Group 1 -ice again, because of the difference in orig- a1 recruitment criteria), They, were also ghtly older and somewhat thinner. The 4sma cotinine terminal half-lives were 15.1 ,urs for Group 1 and 15.7 hours for Group 2, -:th a weighted average of 15.2 hours. These i:1BLE 2. Carbon monoxide for mak' .arbjects. values are slightly higher than those for the male participants, but the differences are not statistically significant (at the 5°/a level). Along with the plasma samples for cotinine, expired air was sampled for estimating the carbon monoxide half~life and as partial veri- fication of smoking abstinence. Each subject inhaled deeply, retained' the breath for 5 seconds, and exhaled most of the breath to eliminate dead-space air. The remaining end tidal air was then used to filli a 1-liter polye- thylene sample bag, which was immediately attached to an Ecolyzer (Energetics Science, Elmsford, NY) to yield a CO value. The CO half-lives,were estimated using,the same exponential procedures that were used to estimate the cotinine half-lives. Data for the male subjects are summarized in Table 2. Groxp 1 (TFI) 47'subjects average 42.4 9.4 1i1.4 range 26-73 6-15 7.9-19.3 SEM 1.6 0.4 0.5 Grorp 2 (tzrt:) 8' subjects average 42.9 9.0 10.6 range 27-52 6-15 9:6-13:4 SEM 2.4 L2 0.6 Grorrp.r 1 e'r 2 55 subjects average 42.5 9.3 11.3 range 26-73 6-15 7.9-19.3 SEM 1.4 0.4 0.4 For Group 1,,the average baseline CO level was 42:2 ppm. This decreased on average to 9,4 ppm. 241 hours later. The average CO: half-life was 11.4 hours,, ranging from 7:9 to 19.3 hours. Group 2 male subjects had comparable results, but the average half-life was slightly lower (10.6 hours); and the range was much shorter-fr6m 9.6 to 13.41 hours. Combining these two groups, the average CO half-live was 11.3 hours. Although there is consistency between these two groups, the CO half-life estimates are considerably longer than values reported in the literature:.
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66 Corresponding, data were obtained for the female subjects. Baseline CO for the first group was higher than for the second group, and the average 24-hour value was lower. The resulting average CO half-life was also signifi- cantly shorter-10:5 hours compared to 15.6 hours. The small sample size of Group 2, and the fact that the average CO half-life is so much greater than reported in the literature, suggests that-at least for CO-this second'group may be highly selective. The weighted average expired air CO half- life for the two groups of female subjects com- bined is 11.6 hours, with a range of 6.0 to 20:5 hours: A summary of the average estimated half- lives for plasma cotinine and expired! air CO is given in Table 3, for both male and~ female respondents. of cardioc smoking I Res 1981: 6. Benowitz J. Interind and cardio Pharmac e 7: Holland R oxide and I 174:154-1' & Landaw S. on total b carbon mc TABLE 3. Snntmary oJmrra& balf-litrs Gygroxp and b,y sex. 235. 9. Matsukura Matsuyama Average Cotinine Sample Size Half-Life (hours) Average Expired Air CO Hkff-Life (hours) i and daily smokers. C 561. Group Male Female Male Female 1 47 41 14.6 15.1 Male Female 11.4 10.5 10. Peterson J. elimination young men 2 8 11 15.4 15.7 10.6 15.6 171. 1i& 2 combined! 55 52' 14.7 15.2 11.3 11.6 It is to be recalled that neither of the voltrn- teer groups was formed solely for the purpose of providing,the types of data shown; the pro- tocol had to fit into a pre-arranged' schedule and environment. Consequently, there were restrictions on obtaining additional applicable data (such as the types of cigarettes smoked), particularly from participants in the smoking cessation program. The sponsor did not want to distract the participants from the principali objfctive-which was to quit smoking. How- ever, the results are quite different from what had been anticipated: the average plasma cotinine half-life is shorter and the average expired air CO half-life is longer than what have been reported in the literature. The con~ sistency by group and sex suggest, however, that previously reported half-lives should be re-examined. REFERENCES 1. Ashton H, Stepney,,R, Thompson J. W. Should intake of carbon monoxide be used as a guide to intake of other smoke constituents? Br Med J 19811: 282. 2. Russell M. A. H, Wilson C, Pate11U. A„Cole P. V, Feyerabend C. Comparison of the effects on tobacco consumption and carbon monoxide absorptionlof changing to high and low ciga- rettes. Br Med J. 1973: 4:512-6. 3. Stewart R. D. The effects of low concentrations of carbon monoxide in man. In Environmental Tobacco Smoke Effects on the Non-Smoker, R.. Rylander (Ed). Report from a Workshop. Scand' J' Resp Dis. 1974: suppl 91 pp 56~62. 4: Wald ~N, Howard'S; Smith P. G, Bailey A. Use of carboxyhemoglobin levels to predict the deve- lopment of disease associated with cigarette smoking. Thorax 1975: 30:133-1401 5. Benowitz N: L, Kutt F, Jacob P. Circadian study
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red air CO half- ,le subjects com- ge of 6.0 to 20.5 estimated half-xpired air CO is We and female son J. W. Should .ised as a guide to aents? Br Med J tel U. A, Cole P. of the effects on rbon monoxide :h and low ciga- i v vconcentrations Environmental Non-Smoker, R. Vorkshop: Scand 56-62. Bailey A. Use of redict the deve- with cigarette -140:. of cardiovascular and hormonal responses to smoking high or low nicotine cigarettes. Clin Res 1981: 29:269A. Benowitz N. L, Peyton J, Jones R. T, Rosenberg J. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. JI Pharmac exp Ther 1982: 221:2. Holland R. A. B. Reaction rates of'carbon mon- oxide and hemoglobin. Ann NY Acad Sci 1970: 1 i74:154-17 L Landaw S. A. The effects of cigarette smoking )n total body burden and excretion rates of -arbon monoxide. J occup Med 1973: 15:231- :35. `datsukura S. Sakamoto N, Seino Y, Tamada T,, latsuyama T, Muranaka H! Cotinine excretion nd daily cigarette smoking in habituate& nokers. Clin Pharmacol Ther 1979: 25:555- zterson J. E, Stewart R. D. Absorptiom and limination of carbon monoxide by inactive oung men. Archs envir. Hlth. 1970: 21:165- ,1L 67 11L Processes that influence the body carbon mon- oxide stores. Part 1. In Biological Effects of Carbon Monoxide, R. F. Coburn (Ed). Ann N Y Acad!Sei 1970t 174:5-75. 12. Gori G. B, Lynch C. J. Smoker intake from cigarettes in the 1 mg FCT tar class. Respiratory Toxicology and' Pharmacology 1983: 3.2:110- 120. 13. Jacob P, Wilson M. Benowitz N. L. Improved gas chromatographic method for the do-termina- tion of nicotine and cotinine in biologic fluids. J Chromatogr biomed Appl 1981: 222 :61-70: Cornelius J. Lynch, Ph, D: Franklin Institute Policy Analysis Center 1320' Fenwick Lane Silver Spring, Maryland 20910, USA
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2.2. Measurement and estimation of smoke ,dosage to non-smokers from environmental tobacco smoke MARTIN J. JARVIS AND MICHAEL A. H. RUSSELL INTRODUCTION. Recent increased! public awareness and con- cern about envi'ronmentali tobacco smoke (ETS) has derived from a number of epidem- iological studies which have suggested signifi- cant risks to the health of the exposed non. smoker. Some studies have found! that young, children with smoking parents have an increased' risk of bronchitis and pneumonia,, especially in the first year of life (1, 2): Adults chronically exposed to ETS have been reported to have impaired lung function (3) and an increased risk of lung cancer (4-6). The issue has provoked'intense debate (7-9), and it is fair to say, that the reality of the risks is not as yet generally accepted by the scientific commu- nity. One of the weaknesses of the studies so far performed is that they have not attempted to quantify the actual dose of ETS received by the non-smoker„although, as one critic has argued; this is fundamental to evaluation of the evi- dence (10).. Epidemiological investigation of the risks of ETS exposure would benefit from both a reli- able non-invasive marker and a validated ques- tionnaire for assessing the degree of exposure. While blood carboxyhaemoglobin (COHb) has been found to be of use in short-term studies, it is not specific to tobacco smoke and may not be sufficiently sensitive to reflect the totality of exposure across the whole range of situations occurring in daily life. Thiocyanate (SCN) may likewise suffer from a lack of specificity and sensitivity. Nicotine is specific to tobacco but has a short half life in plasma, and! its major metabolite, cotinine, may provide a better guide. The present paper addresses several issues on estimating the human dose of'ETS, In the first section we present data relating to the validity of self-reports of ETS exposure and to the choice of biochemical marker for use in~ epidemiological surveys. We then document the smoke dose received from a short-term natural exposure, and in the final section relate this to blood' and urinary nicotine levels resulting from slow intravenous infusion of small known doses of nicotine. This enables us to reach some conclusions about the dose received from ETS, as opposed to that received from smoking. These studies will be published in greater detailielsewhere. Validity of te#'-reportr A sample of 121 self-reported non-smokers attending,outpatient clinics: at St. Mary's Hos- pital, London, filled in a smoking question- naire and providec air, saliva and urii defined as those a cigarettes, pipes ot plasma cotinine a latter requirement 21 self-reported n biochemical mar: found in self-reF therefore incomp non-smoking stat exclusion of thes, u•ith respect to between measure vclf-reported E" "deceivers" typic exposure to ETS. 1'A{3LE 1. Duerall, se f srpor f`.zprred! Air CO (1 r .()l ib (percent) P!3sma nicotine (r ",liv2 nicotine (n} I nnc nicotine (n} I".,sma cotinine (i •.Irv, cotinine (nt ' runc cotinine (ns, It'.,rn°.t J(.N (Pm, .:,, , M:\ (mmc . r:nc 1,(::\(hmo r h-cnall mear :,x•: but it can I : +o~nic markr rciatcid,toexpos -nccntration ( - plasma, saliv
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,ke and may not be ect the totality of ange of situations yanate (SCN) may of specificity and! fie to tobacco but ma, and its major provide a better sses several issues )se of ETS: In the ta relating to the 'S exposure and to marker for use im e then document rom a short-term~ final section relate y nicotine levels 2nous infusion of ie. This enables us > about the dose ed to that received' will be published -ted non-smokers it St. Mary's Hos - noking question- naire and provided samples of blood, expired ir, saliva and' urine. True non-smokers were efined as those who reported no smoking of garettes, pipes or cigars and whose levels of asma cotinine were below 20 ng/ml. The ter requirement resulted in the exclusion of self-reported non-smokers whose levels of chemical markers were similar to those nd in self-reported smokers, and were efore incompatible with their claimed -smoking status. It should be noted that ision of these subjects was conservative respect to establishing a relationship .~een measures of smoke absorptiom and rcported ETS exposure, since the _eivers" typically reported high levels of )sure to ETS. 69 Exposure to ETS was indexed by the re- sponse to the questionnaire item: "Have you been exposed to tobacco smoke from someone cke in the past three days?" The response catego- ries were "Yes, a lot", "Yes, some", "Yes, a little", and "None at all". Only 7 of 100 sub- jects reported "yes, a lot" and almost one half (46) reported no exposure at all in the past three days. This was not unexpected in a group composed mainly of elderly people, many of whom were chronic invalids and'led restricted lives. A number of markers were measured by standard'i methods in samples of various body fluids and in expired air. The data are pre- sented in Table 1. iSLE 1. Overall average leulr of bioahemleal marker.c of smoke ab'torp'tron in non-smokers and'aueragc koe/r by degne of lelf-rejiorted E'TS exp'oruro: Total sample Level by degree of self-reported exposure to ETS \umber of persons Mean (SD)', 100 None at all 46 A little 27 Some 20 A lot, 7 P value Lxpired Air CO (ppm)i 5.61 (2.70) 5.7 5.6 5,6 5.0 NS COh'1b (percent) 0:87 (0.67) 0.94 0.81 0:80 0.80 NS Plasma nicotine (ng/ml): 0:90 (1.24) 1.04 0.76 0.72 0.90 NS Saliva nicotine (ng/ml) 4.80 (5.76) 3.81 4.80 4.44 12.12 <. 0 5 Urine nicotine (ng/ml) 8:31i ('15.13) 3.87 12:22 11.92 12.22 =.06 Plasma cotinine (ng/ml)', 1.46 (2.28) 0.82 1.811 2.52 1.81 <.005 Saliva cotinine (ng/ml): 1.69 (2.27) 0.73 2.20 2.80 2.63 <.001 l rine eotinine (ng/ml) 4.96 (8.39) 1.55 6.50 8.65 9.36 <.001 Plasma SCN (µmol/1) 50.76 (24.3) 48.1 55.5 51.7 47.4 NS' Saliva SCN (mmol%1)', 1.30 (0;93) 1.27 1.50 1,03 1'.51 NS L'rine SCN (µmol/1) 74184 (40:6) 72:8 80.3 74.2 73.1 NS Overall mean levels of each marker were low, but it can be seen that the concentrations of some markers were nevertheless clearly relaredito exposure, while others were not. The concentration of cotinine, whether measured in~plasma, saliva, or urine varied systematically with exposure. In those reporting the two highest levels of exposure it was at ltast three times greater than in those who reported no exposure at all. By way of example, the distri- bution of individual levels of urinary cotinine is shown in Figure 1. It can be seen that only 12 ~ ~
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70 40 35 30 E ~ c 10 5 , 0 NONE A LITTLE AT ALL per cent of subjects had undetectable levels, despite nearly 50 per cent reporting no expo- sure. Thiocyanate and' carbon monoxide CO levels were unrelated to exposure, as was also the concentration of nicotine in plasma. How- ever, there was a linear increase in salivary nicotine with exposure, and! urinary nicotinee was significantly higher in those who reported any degree of exposure than in those who: reported "none at all" (12.1 v 3.9 ng/ml,,p< .005). Analysis by time of day of attendance at the clinic showed that while cotinine measuress were relatively insensitive to this variable, sal- 25 t r Figure 1. SOME A LOT Distribution of individual concentrations of urinary cotinine by degree of self- reported exposure to ETS. Horizontal bars indicate median values. ivary nicotine concentration was markedly higher in afternoon (n=64) than in morning (n =36) attenders (5.65 v 3.35 ng/ml„p< .01). Indeed, only in afternoon attenders did sali- vary nicotine level relate to self-reported expo- sure. These data; gathered in a stringently defined group of non-smokers, demonstrate that bio- chemical markers can provide a sensitive guide to the extent of recent daily life exposure to ETS. Of particular significance from an epi• demiological standpoint is that non-invasive samples of urine and saliva conveyed essen, tially the same informatiom about exposure as did invasive and less easily gathered blood samples. preferabli they pro,. three ds useful as testing, = differenc metaboli their hal hours re; different nate varr and hen tifying c The validity guides fashion. utility C the util concluc or urins ever pc give v: I?TS. Short-tc; The da ryday smoke specifi menta (11),'1 om thc l: ndcr tmokc an ho no>n-s: 1?cr ct thc in tar ci; +clf-r~ acutc w•crc
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Figure 1. ion of individual ttions of urinary by degree of self- exposure to ETS.M il bars indicate alues. was markedly han in morning ng/ml, p < .01): enders did sali- f reporte&expo- ngently defined! istrate that bio- i sensitive guide ife exposure to .e from an epi~: it non-invasive onveyed essen- out exposure as ;athered blood samples. Measures of cotinine are likely to be ,referable for epidemiological surveys since hey provided a good guide to exposure over a !lree day period, while nicotine was only ;eful as marker of exposure on the day of sting, and even then not im plasma. These 'ferences between nicotine and its major :.tabolite are no doubt due to differences in .ir half lives in blood (about 2 hours and 12 irs respectively) i and in their disposition in 'erent bodty fluids. Neither CO nor thiocya- varied varied with the reported exposure to ETS hence are unlikely to be of value in quan- ng chronic exposure to ETS. lie data also provide evidence for the lity of responses to questionnaire items as es to ETS exposure, albeit in circular .ion. Biochemical markers validate the ;ty of self-report, and self-reports validatee utility of biochemical markers. We can 1nclude that while measures such as salivary ~r urinary cotinine should be employedlwher- vcr possible, self-report by questionnaire can give valuable informatiom about exposure to 1:7'S. 57r'ort-ternr natural exporure The data above suggest that under normal eve- ryday conditions, the majority of urban non- smokers have measurable amounts of tobacco specific substances in their bodies. Experi, mental exposures are also well documented (11). The amount absorbed obviously depends on the severity and duration of the exposure. l;nder extreme conditions in an unventilated smoke-filled' room (38 ppm CO) for just over an hour we found that the COHb levels of non-smokers increased by an average of one pcr cent (12); which is roughly equivalent to the increase produced by, smoking one middle- gu cigarette. CO, then, whilee not sensitive to self-report of daily life exposure, reflects an Acute extreme experimental exposure. We 'a'erc interested to document the absorption,of 71 nicotine and CO from a more natural experi- mental exposure and to obtain data for esti- mating dosage in "cigarette-equivalents". We studied seven urban non-smokers who provided samples of blood, expired air, urine and saliva at 11.30 in the morning of a normal working day and again in the evening fol- lowing 2 hours exposure to ETS in a public house (13 ppm CO). This study has been reported fully elsewhere (13). The mean values of each measure of smoke intake before and after the exposure are shown in Table 2. All subjects had measurable level5 of both ~ nicotine and cotinine on the morning of the study day. Following the work day and pub exposure there were significant increases in the levels of all compounds measured. Expired air CO levels rose by an average of 5.9 ppm, equi- valent approximately to the smoking of one cigarette, while plasma nicotine increased by only 1.7 ng/ml. This represents a smalli frac- tion of the typical increase in plasma nicotine from smoking a cigarette, and points to an apparent discrepancy between CO and nico- tine in estimating the acute dose from ETS in cigarette-equiivalents. Nicotine and CO differ both in their half lives in blood and in their behaviour in ambient air. Nicotine is contained mainly in the smoke particles which, unlike CO would tend to settle gradually. Furthermore, it is probable that nicotine evaporates gradually from ageing smoke particles. Data on half-lives of various smoke components in ageing smoke are not available. In order to reach a better estimate of the dose of nicotine received by our subjects, we undertook a laboratory study where known smalli doses of nicotine were administered to subjects to compare the resulting blood levels. Estimation of nicotine intake We measured! the plasma nicotine concentra- tions in six subjects before, during and after O W M
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intravenous infusion of 1.0 mg nicotine base at „ a steady rate overr, one hour. The experiment was repeated in two of the subjects with a dose of 0:5 mg nicotine base. Average plateau levels of plasma nicotine reached 6.6 ng/mL and 4.2 ng/ml respectively. These values are consider, ably higher tham we found in~ our short-term exposure. They are also higher than those reported even under extreme conditions of exposure (14). The areas under the mean con- centration-time curves (AUCs) after the two infusion doses were comparedwith the mean~ AUC of three subjects in another study (15) who smoked one middle-tar cigarette. The 1.0 mg and' 0:5 mg nicotine infusion AUCs were about 50 per cent' and' 35 per cent respectively of that produced by one cigarette. The slow infusion of nicotine over one hour was designed to simulate the intake from short- term exposure to ETS. The average plasma nicotine concentration after exposure in the public house was 2.5 ng/m1(Table 2), which is 0.38 of the 6.6 ng/mll produced by the 1 mg nicotine infusion. But, the 1 mg infusion was equivalent to only 0.50 of the cigarette dose, suggesting that the nicotine intake from the exposure in the pub was equivalent to only 0.38 X 0.50 = 0.19 of a cigarette. Similar calculations with 0.5 mg nicotine infusion data give an equivalent for the exposure in the pub of 0:21 of a cigarette. In summary, if it is assumed that the plasma nicotine concentration of 2.5 ng/ml was mainly determined by nicotine intake during rather than prior to entering the pub (which is not unreasonable in view of the short half-life of nicotine in plasma), the estimated nicotine intake during the 2 hour exposure was roughly equivaient~ to 0;2 of a cigarette, while the CO intake was equivalent to one cigarette. Normal daily expoture Estimates of intake during brief exposures of 1-2 hours provide little information about exposure throughout a normaP day. Owing to its short half-life, plasma nicotine is unsuitable as an index of nicotine intake over the past few hours. This is apparent from the data in table 3. Urinary nicotine concentration is probably a better marker of intake over several hours. Data on urinary, nicotine concentrations in non-smokers are available from previous and the present studies (Table 3) and one way to determine their dose equivalent is to relate TABLE 2. Aarrage ler.el,r of intake mearares in .retxia nom-.rmokerr before and a, fler exporure te emvimtrmental tobacco smoke im Q public boun. Nicotine concentrations (ng/ml) Plasma Saliva Urine Cotinine concentrations (ng/ml) Plasma Saliva Urine Expired air CO (ppm)', Before After Statistical significance 0.76 2.49' t= 5:5, p<:005 1.90 43.63 t= 7.2; p,<.001, 10:51'1 92;63 t= 3.8, p <.01 1.07 7.33 t=12.3;,p <.001' 1.50 8.04 t= 8.6, p<.001 4.80 12.94 r= 3.1, p<:025 4:71 10.57 t= 9.9; p<.001' TABLl Numbe: Natural , ("non-ex 26 46 Natural < i"cxposec *3G "54 Attcr exl- i2(Amht (Amht !licna to l 2H) ng lnr. "Cx1'. ,1n:)kc;rs '!'u IcVe l hese a.+utnpt 4 urtna Iruake i! m,n F.m~ the .am u11nC C\
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73. PABLE 3. Summary of data on plasma and urinary nicotine concentratiour in non-rmokerr umder variour conditiottr of e.xpo.run to ETS. hat the plasma 3 ng/ml was intake during : pub (which is short half-life nated nicotine re was roughly while the CO garette. f exposures of mation about iky. Owing to e is unsuitable -r the past few 3ata in table 3: is probably a :everal hours. :entrations in previous and d one way to tt is to relate atistical'; nificance nben of persons ral l conditions -: on-smokers)' 27 12 7 i6 t0 6 I conditions ,~xposcd" non-smokers) '6 46 11 conditions ;ed" non.smokers) ;0 •54 •. , - experimental exposure lmbient CO 28 ppm for 70 min) ~ '+ lmbient CO 13 ppm for 2 hrs): Mean nicotine concentrations (ng/ml) ., Plasma Urine Reference - 10.7 Russell & Feyerabend (1975)14 0!7 - Russell & Feyerabend (1975) 0:8 11.0 Public house study - 15. 11 Feyerabend! et al. (1982)16 0.9 8.3 St. Mary's outpatients study 0.2 3.6 IV nicotine study (before infusion). 7.5 Feyerabend et al. (1982)16 1l0 3:9 StL Mary's outpatients study - • 21.6 Feyerabend et all (1982)16 0.8 12.1 St. Mary's outpatients study 0.9 80 Russell et al. (1973)12 2.5 93 Public house study A-.:e (.ategorisation of "non-exposed" vs "exposed" non-smokers under naturali conditions was based' on self-reports. Urinary nicotine concentrations im a sample of 100~smokers from Russell & Feyerabend (1975)'^ and Feyerabend et al. (1982)'6 averaged 1289 ng/ml:, ' l:xposure on the day of the sampling. '' Some exposure in the past three days. them to the average levels found in smokers (1289'nglml); When this is done, the averages for "exposed", "non-exposed" and! all non- smokers are roughly 1/80, 1/250 and 1/125 of the Ic.•els found in smokers. These estimates depend on a number of usumptions. The main one is that the relation Of urinary nicotine concentrations to nicotine tntike is linear. Another is that smokers and nnn_smokers excrete as unchanged nicotine thc same proportion of a given d'ose. There is *"tTtc et'idence that this is so (17): It is likely that the influence of urine pH and! urine flow om nicotine concentration wouldl be balanced in large samples and there is no reasom to expect systematic differences between smokers and non-smokers in these factors. The five-fold discrepancy betweemCO and nicotine intake in the short-term study suggests that CO'intake from normal daily exposure to ETS would be proportionally higher, i.e. roughly 1/15, 1/50 and 1/20 of the intake of smokers for "exposed", "non-exposed" and all non-smokers respectively;,
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74 Intake of other amoke coa.ttituentr and implicatianr, for health The fact that iin cigarette-equivalent terms non-smokers appear to absorb different pro- portions of nicotine and' CO when exposed to ETS suggests that caution is needed in, extra- polating the dose of any particular smoke con- stituent in the absence of a direct measure. The tar fraction is of particular concern since it is likely to be implicated in any ri'sk of ETS expo- sure affecting the respiratory system. We simply note that nicotine, like tary is in the particulate phase and that nicotine concentra- tions are likely to provide a better guide than CO to the amount of tar absorbed. Our estimates of the doses of nicotine and CO received by non-smokers in their daily lives are both low, and might therefore be con- sidered to pose minimal risks to health. How- ever, two considerations militate againstt this conclusion. First, since we haveshown, a dose- response relationship between~ exposure and intake, there is a likelihood that some heavily exposed individuals may receive a larger, and possibly clinically significant, dose. Secondly, and as pointed' out above, our data strictly apply only to those smoke constituents that we have measured. Non-smokers may receive a larger proportion of the smoking dose of cer- tain other smoke components. One possibility is that the risk to non-smokers derives from qpalitatives differences between sidestream~ and mainstream smoke. The sidestream/main- stream ratios are particularly high, up to ten, in the case of various carcinogenic nitrosamines (li1). Finally, it is worth noting that the persons most heavily exposed to ETS are those who smoke actively as well, and hence are exposed to their own mainstream and sidestream smoke. The U.S. Surgeon General (11) recently concluded that "Pipe and cigar smokers expe- rience overall mortality rates that are slightly higher than non-smokers... Coronary heart disease, lung cancer, emphysema and chronic bronchitis clearly are associated with cigarette smoking; but for cigar and pipe smoking, death rates for these diseases are not greatly elevated above the rates of non-smokers." Pipe and cigar smokers, particularly in the classical' epi- demiological' studies, comprised mostly indi- viduals who had never smoked cigarettes, and who were therefore likely to be noninhalers. They would then be "passive inhalers" of both sidestream and mainstream smoke, and to the extent that their numbers included some who actively inhaled, any observed risks of mor- bidity and' mortality can only be an overesti- mate of the risks of ETS exposure per se. AcknoJUledgement We thank the Medical Research Council for financial support. REFERENCES 1. Harlap S, Davies A. M, Infant admissions to hospital and maternal smoking. The Lancet 1974: 529-532. 2. Colley J. R. T, Holland W. W, Corkhill R. T. Influence of passive smoking and parental phlegm on, pneumonia and bronchitis im early childhood. The Lancet, 1974!: 2:1031-1034: 3. White J. Froeb H. Small+airways dysfunction in nonsmokers chronically exposed to tobacco smoke. New Engl Ji Med 1980: 302:720-723: 4. Hirayama T. Nbn-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan. Br Med J 1981: 282:183- 185:. 5, Trichop4ulos D, Kalandidi A, Sparros L, McMahon B. Lung Cancer and Passive Smoking. Int J, Cancer 1981: 27:1-4. 6. Garfinkel' L. Time trends in lung cancer mor- tality among non-smokers and a note on passive smoking. J natn Cancer Inst 1981: 66:1061- 1076. 7. Editorial. Passive smoking: Forest, Gasp, and facts. The Lancet 1982: 1:548-549: 8. 9: 10. 12. -
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75 .. Coronary heart .,sema and chronic itcd with cigarette pe smoking, death ot greatly elevated :okers." Pipe and i~the classical~epi- -ise& mostly indi- :ed cigarettes,, and o be noninhalers. inhalers"'of both ;moke, and ~ to the cluded some who -ed risks of mor- y be an overesti'~ )osure per sa. :arch Council for 8. Rossiter C. E. Passive smoking. The Lancet 1982: 1:1356. 9. U S Department of Health and Human Services. The Health consequences of smoking: Cancer: A report of the Surgeon Generalj Washington, DC: US Public Health Service;,1982. ' 0: Lee P. N. Passive smoking: FdI Chem Toxic 1982: 20:223-29. i. US Department of Health, Education and Wel- fare. Smoking and Health: A report of the Sur- geon General; Washington DC: US Public Health Service, 1979:. Russell M. A. H, Cole P. V, Brown E. Absorp- tion by non-smokers of carbon monoxide from room-air polluted by tobacco smoke., The Lancet 1973: 11:576-579. Jarvis M. J, Russell M. A. H, Feyerabend C. Absorption of nicotine and carbon monoxide from passive smoking under natural conditions of exposure. Thorax 1983: 38: 829-833. RusselllIvf. A. H, Feyerabend'M.,Blood and uri- nary nicotine in non-smokers. The Lancen 1975 : 11:179-181. 15. Russelll M. A. H, Jarvis M. J. Feyerabend C, Ferno O. Nasal'nicotine solution : a potential aid to giving up smoking?'Br Med J 1983: 286 :683- 684. 16. Feyerabend C, Higenbottam T, Russell M. A. H. Nicotine concentrations in urine and saliva of smokers and non-smokers. Br Med J 1982: 284:1002-1004. 176 Kyerematen G. A, Damiano M. D, Dvorchik B. H, Vesell E. S. Smoking-induced changes in nicotine disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin ~ Pharmacol Ther 198~ :, 32 t 769-780. Martin J. Jarvis Institute of Psychiatry Addiction Research Unit 101 Denmark Hill London ~ SE5 8AF ENGLAND Lnt admissions to ing. The Lancet V, Corkhill R. T: ng and parental ronchitis in early : 2:1031-1034. ys dysfunction in 3sed to tobacco ): 302t720-721 wives of heavy f lung cancer: a 1981: 282:183- A, Sparros L, r and Passive 7:1-4. .g cancer mor- note on passive 1981: 66:1061~-
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2.3. Validity of questionnaire data on smoking and other exposures, with special reference to environmental tobacco smoke CitSRAN PERSHAGEN INTRODUCTION In epidemiological studies of etiological nature, the quality of the exposure information, is of fund'amentall importance. In many situa- tions this information is obtained via question- naires, e.g. because data from other sources are not available: Obviously, the information in questionnaires may be biased and the precision may sometimes be low due to difficulties, and recall. Special problems arise in retrospective studies of diseases with a long latency and a short clinical course,,e.g, lung cancer. In such cases exposures have often assessed via ques- tionnaires or interviews with relatives. A vali- dation of such data against other sources is necessary. Information on several types of exposures is needed in epidemiological studies on health effects due to environmental tobacco smoke (ETS): Perhaps the single most important factor is to get accurate information on smoking habits of the subject under study. For instance, the findings of increased'lungtancerd risks among non-smoking women, married to smokers may be invalidated if some these women actually smoked and if'this was more common than among,women in the compar- ison group, i.e. who were married to non- smokers (1, 2)., The same reasoning may be used for respiratory symptoms in children; is there a bias in the reporting of smoking habits for children to smokers in~ comparison with similar data for children to non«smokers? Assessment of ETS exposure in the house- hold may be based on questionnaire data on smoking habits of relatives. Several studies have evaluated the validity of such informa- tion; On the other hand, no data are available on the quality of questionnaire information on long term exposure to ETS in other situations, e.g, in the workplace. The following discussion~ will initially deal with the quality of questionnaire information on smoking habits of the respondents. A sub- sequent section will discuss the validity of smoking information~ for relatives: Finally, a brief evaluation will be made of questionnaire information on occupational exposures and other factors which may be of importance as confounders in a study of health effects due to ETS. Ivartdity of questionnarre iirformation on tmoking habi# of the respondent There are several l objective measurements on tobacco smoke exposure, which can be used to test questionnaire validity.. Serum thiocyanate (SCN) and two of the al. (3) fou could best non-smoki men there ures and i 90% in a smokers. smokers, smoking I later study smoking f of the bio time elaps time peric rettes in mates of, amount of filters, di+ multiple i beyond tl smoking ; When c dctermina smoking 1'ctitti et,. `)J % in ( non-smo' that the c tHc stand measures yucstiont ttvuv of trnl,+uishi, ancl S(;\ lr,w scnsi~ j~nmaril~. rrtmtnatt +mokcd erxn et ... I ;)xcho,
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ang : to g may be tildren; is ing habits ison with :)kers? he house- e data on al studies informa- available available rnation on situations, tially deal formation its. A sub- •alidity of FinalHy, a stionnaire sures and 3rtance as :cts due to Aing habits ments on oe used to ;iocyanate SCN) and1 expired carbon monoxide (CO) are vo of the most widely used measures. Vogt et (3) found that a combination of the two uld best discriminate between smokers and n-smokers. In a group of 123 middle-aged n there was agreement between these meas- s and information given in interviews for "o' in a classification of smokers and non- kers. After exclusion of "atypical" kers, i.e. subjects with unusually light king habits, the agreement was 99 9a. In a study, Vogt et'al.(4)showed that cigarette :ing frequency was the strongest predictor le biochemical measures followed by the elapsed since last smoking and the longest period that the smoker had been off ciga- :.s in the past. Other questionnaire esti- ..sres of dosage, e.g. depth of inhalation, the ,--ount of each cigarette smoked and the use of tilters, did not contribute significantly in a multiple regression evaluation of CO or SCN, bevond that alteady available from reported smoking frequency. When comparing the results of CO and SCN determinations with questionnaire data on smoking, habits in 267 subjects, agedl 18-72, Petitti et al. (5), found an overalll agreement of 91!g'o in distinguishing between smokers and non-smokers. In fact, the authors concluded that the questionnaire information should! be the standard against which the physiologic measures should be judged. Assuming that the questionnaire is accurate, there was a sensi~ tivity of 72 % and a specificity of 99 % for dls- tinguishing non.smokers from~ smokers by CO and SCN measurements. The comparatively low sensioivityof the physiologic measures was primarily due to tbeir limited ability to dis- eriminate non-smokers from those who unokcd less than 10 cigarettes per day. Ped- etScn et al (6) measured! CO in expired air of 130 School children an&concluded thatat most 77 5.5 % had given false information about their smoking habits in a questionnaire. A good indicator of the reliability of data in questionnaires may be given by assessing their reproducibilty. In some studies the informa- tion on smoking habits has been compare& with questionnaires answered at different occasions or between self administrated! ques- tionnaires and interviews (5, 7, 819). As a rule, a very high reproducibility has been obtained, sometimes as high as 99 %. U'alidity of qxestionnain info~ rmation on smoking babits of relatives Causal factors for lung cancer have been inves- tigated in a number of retrospective studies. The information on smoking habits in these studies was often~ obtained via interviews or qpestionnaires to relatives. A validation of the data was sometimes also performed and such studies provide the best source of information about the quality of questionnaire data on smoking habits of relatives. Table 1 summarizes the results of some stu• dies where data on smoking habits from sub- jects have been compared with the same infor- mation from a next-of-kin. Besides investiga- tions on lung cancer cases an& controls, the table contains some other studies from which relevant information can be extracted. The next-of-kin data was obtained via postal ques- tionnaires or in interviews. The data for the subjects were collected in a similar way or indi- rectly from~medicalifiies. The table shows that the agreement is 90-100 % ' between the two sources of information, in a crude classification of smokers and non-smokers. The validity doess not seem to be affected by the living status of the subject under investigation. The table also shows that' the overall agree- ment is somewhat lower when data on detailed smoking habits, are compared, i.e. about 80 %. As can be expected, the precision becomes poorer, when the information is more detailed. R
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78 TA.BLE 1. Yalidity of data from retatirxs on smokrng habits of living or dtceared subjects in diffennt sttrdies. . Complpte agreement (%) Number of subjects Smoker/ Detailed Living , Dead non-smoker smoking habits Reference 338 ^r100°_ Haenszellet aL' 1962. 1953 92 74b' Rogot & Reid, 1975 300 96 Kolonel ct a1. 1977 166 786' Kolonel et a1. 1977 83° 92 88 d Higgins et at.,1981i 14 100 Pershagen & Axelson, 1982 83 99 Dambers 1983 61 79 d Dambers 1983 37 846 Dambery 1983 • "Virtually all". b Number of cigarettes per day: In studies by Kolonel at a1.' and Damber, agreement within ± 10 and 6 cig/day, respectively. `Not stated whether subjects of the interview were dead'or alive. d Use or not of cigarettes,,pipe tobacco or cigars. In the study by Kolonel et al. (10), including mostlyhusbands and wives, there was an exact agreement for number of cigarettes smoked per day by the husbands in 36 Wof the couples, within ± 5 cig/day in 54 % and within ± 10 cig/day in 78 %. This study also indicated! a high validity in the information by the relative on age at start of smoking, i.e. 84 % agreement within ± 4 years. No major biases were noted in the reporting of smoking habits by the subjects or their rela- tives. However, in two of the studies there was a tendency for the relatives to report a, higher cigarette consumption thani the subjects them- selbes (10;, 1i1). In this situation it cannot be excluded that the relatives provided the more accurate information For most of the studies in Table 1, the infor- mation was gathered from relatives with a recent knowledge of the subjects. The studies by Pershagen and Axelson (12) and Damber (13), show that accurate data on smoking habits may be obtained from relatives also for subjects who have been dead for several years. Validity ofquertronnaire informatlon on occup'atron and other factors Some studies have compared questionnaire information on occupation and different expo- sure factors with similar information~ in the study subjects from relatives. ObviousNy such a comparison provides information both' about the validity of the subjects' own responses and the responses of the relatives. Using, a classification of occupation into broad categories Rogot and Reid (11) found! a complete agreement in 77 % between next,of- kin and personal questionnaire for 600 sub- jects. Pershagen and Axelson (12) compared occupational exposure information obtained via a questionnaire to relatives of 160 deceased smelter workers with~data from employee reg- isters. The questionnaire data regarding employment or not at the smelter, had a very high validity, i;e. a sensitivity of 98 %and a specifacityof 99' exposures the se the specificity a Kolonel et'alt on personal hab subjects, predon Without a poss members were ii husband, e.g. alc beverages and sj, .rbout 75 % of icceptable limit: lear associatio, vithin couples c 'tics, e.g. levc cuome. \n analysis of a •:onnaires can c Md non-smokei -.rcv: This is tru( "1:rhits of respon r.,cY is somewh. ~rnoking habits rion could a15o ,tudies. Some n naires may prov cxposures of intt . lmtional factors. It should be n -m the validity c t;rlincd in a stu •'ctir{;n where : •.rnoking habits,atcdl one may , 'r thc reporting : thrs ty.pe of e: • "qPic for futu, Ilirxvama T:
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ttxdiet. , 1982 ithin ± 10 and 6 ad for several r on otcwpation and I questionnaire I different expo- ,rmation in the )bviously such a tion both about n responses and )ccupation into :id (11) found a -tween next-of- -e for 600 sub- (12) compared ,ation obtained of 160 deceased nemployee reg- iata regarding Iter, had a very of 98 46 and a_ )ecificity of 99 °lo. For specific occupational :posures the sensitivity was lower (40 %) but _ specificity was over 90 4''0: {olonel i et al.(10) examined interview data personal habits in a sample of 300 pairs of ects, predominantly husbands and wives. 1outi a possibility to communicate both ;bers were interviewed! about habits of the md, e.g. alcohol use, and consumption of rages and~ specific food items. In general, - 75 % of the couples agreed within, :able limits for most items. There was no association of the degree of accuracy -1 couples with socioeconomic character- e.g. level, of education and family c. CONCLUSIONS :alysis of available data shows that ques- ...tires can discriminate between smokers non-smokers with a high d'egree of accu- This This is true both with regard to smoking l.1hits of respondents and relatives. The accu- racY is somewhat lower for data on detailed smnking habits of relatives, but the informa- tuon could also be of use in epidemiological studies:. Some reports indicate that ques'tion- naires may provide valid'information on other exposures of interest in ETS studies, e.g: occu- p2tional factors. It should be notedithat no data are available on thc validity of smoke exposure information obtained in a study on effects of ETS. In a stud'y destgn where health effects of ETS from unoking habits of the respondents are investi- Rucd one may well imagine systematic errors in the reporting of smoking habits. The quality Of thts type of exposure information should be a topic for future research. REFERENCES: t• fliravama T. Non-smoking wives of heavy smnkcrs have a higher, risk of lung cancer: a 79 study from Japan. Brit Med J 1981: 282:183- 185. 2. Trichopoulos D, Kalandidi' A, Sparros L, Mac- Mahon B. Lung cancer and passive smoking. Int J, Cancer, 1981: 27:1-4. 3. Vogt T., Selvin S;, Widdowson G, Hulley S. Expired air carbon monoxide and serum thio- cyanate as objective measures of cigarette expo- sure. Am J. publ. Hlth 1977: 67:545-549. 4. Vogt T; Selvin S, Hulley S. Comparison oflbio- chemical and questionnaire estimates o€tobacco exposure. Ptev Med 1979: 8:23-33. 5. Petitti D, Friedman G,, Kahn W Accuracy of information on smoking habits provided on self-administered research questionnaire. Am J publ. Hlth 1981: 71:308-3111 6. Pedersen L, Sidney K. Lefcoc N: Am objective measure of the validity of children's responses to a questionnaire on health and smoking. Can J publ. Hlth 1977,: 68:497-498. 7. Enterline P, Capt K. A validation of informa- tion provided by household respondents in health surveys. Am Jlpubl. Hlth 1959: 49:205- 212: 8: Lebowita M, Burrows B. Comparison of ques- tionnaires: The BMRC and NHLD respiratory questionnaires and! a new self completion ques- tionnaire. Am Rev resp Dis 1976: 113:627- 635. 9. Samet J. Speizer, F, Gaensler E. Questionnaire reliability and' validity in asbestos exposed workers. Bull Europ Physiopath Resp 1978: 14:177-178. 10. Kolonel L„Horohata T,,Nomura A. Adeqpacy of survey data collected from substitute respon- dents. Am J Epidemiol 197,7: 106:476-484. 11. Rogot E; Reid D. The validity, of data from next-oE kin in studies of mortality among migrants. Int J Epidem 1975: 4:51-51. 12. Pershagen G, Axelson O. A validation of ques- tionnaire information on occupational exposure and smoking., Scand J Work Environ Hlth 1982: 8':24-28; , 13. Damber L. How reliable are data on smoking habits obtained via questionnaires to relatives? (in Swedish). Preliminary report by the Centre of Oncology, Dept.,of Oncology Umea, Univer- sity,, Umea, Sweden. 14. Haenszel W. Loveland D, Sirken M. Lung- cancer mortality as related to residence and smoking histories. I White males J Nat Cancer Inst 1962~ 28:947-1001.,
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80! 15. Higgins L, Welch K, Oh M, Bond G,,Hurwitz P. Goran Pershagen Influence of arsenic and smoking on lung cancer National Institute of Environmental Medicine among smelter workers: A pilbt "study: Am J Ind Box 60208 Med 1981: 2:33-41. S-10401 STOCKHOL.M SWEDEN The discussion c the accuracy ot amount of smol dies. Sterling dr study, (1) showi products consun and' on telephoc less than the offi stamps which h: sold in the US. Another poin reports of the ai multiples of "fi• or one pack, 2 estimate more : how much pe< could questionr amount of smo by the actions - in his experie smoked were i replied that in agreement bet relatives. Lebo studies of man reliability of : study of smelte of type and let of his experier
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2.4 Discussion RAPPORTEURS ROGER A. JENKINS AND THEODOR D. STERLING ® c discussion on Pmbagen i paper dealt with accuracy of estimating prevalence and ,)unt of smoking from questionnaire stu- .I:s. Sterling drew attentiom to the Warner dy (1) showing that estimates of tobacco ;> aducts consumed in US based on personal .rnd on telephone interview, were 40 percent Icss than the official count based on sale of tax stamps which have to be attached to every pack sold in the US. Another point of view brought up was that reports of the amount smoked were mostly in multiples of "f'ave" or "packs" (i.e. 10, 20, etc. Or one pack, 2 packs, etc.). Not being able to estimate more accurately from qµestionnaires how much people smoked, how accurately could questionnaire methods help estimate the amount of smoke to which they were exposed by the actions of others? Zober mentioned that in his experience, reports of the amount Smoked were in multiples of five. Pershagem rcplied that in his study, there had been good' agreement between self reports and that of relatives. Lebowitzadded'that epidemiological Studies of many populations showed very high rcliability of smoking questions, and that a ttudy of smelter workers has shown good recall °f type and length of exposure the worker had Of his experience (2). Rylander concluded that all this showed how difficult it might be to study the relation betnveem lung cancer and exposure to environmental tobacco smoke (ETS) exposure in view of the difficulties to obtaimgood exposure data. In comments to Ru.rrcll'f presentation, Jen- kins contributed that Russell's findings in humans patterned what Jenkins had observed with smoke exposed beagle dogs, namely that only 1-2 % of the nicotine retained by the indi, vidual can be accounted for at any given~time be measurement of plasma nicotine. First inquired if Russell's subjects were smokers or non-smokers. They were mostly non-smokers although some had smoked. He suggested'~that Russell's approach could be used to study poss- ible difference in metabolism of nicotine betroveen smokers and non-smokers. Russell further thought that the problem might be dif- ferences in potency between mainstream and sidestream smoke. If it can;be shown that expo- sure to ETS is relate& to an increased risk for lung cancer even though the exposure level is very low, then perhaps what caused lung cancer in the smoker was nor: the mainstream inhaled actively but the sidestream taken pas- sively. On the paper by Lyxcb; First inquired why plasma cotinine was chosen as a marker, rather
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82 than plasma nicotine. Lynch indicated that the primary reason involved the suspected rates of nicotine and cotinine decay in the plasma. The study reported was part of a larger smoking cessation experiment and thus had to work withinthe constrictionof that experimentt The design of the main experiment involved obtaining blood and breath samples 24 hourss apart, Thus nicotine, with a suspected' half life of less than one houry would nearly completely disappear from the blood after 24' hours. Plasma nicotine's utility as a long lived indi- cator of smoke exposure is minimal. ~ Aviado indicated that the differences observedl between the CO half lives of the. Group I and Group II females may be due to differences in the way in which those values were determined. The former was a two point determinationy the latter, an exponential decay curve fittedl to four points. Jarvis was puzzled by the magnitude of the observed CO half time value compared to other findings of 3-6 hours, and wondered' if ambient CO levels were obtained during the studyy and if ethanolfilters were employed with the Ecolyzer used to assay the breath samples. Lynch answered in the affirmative to both questions, but indicated that only ambient CO levels were measured in the room in which blood and breath samples were takem Cosentino queried if the breath samples were true alveolar air. Lynch replied in the affirmative and described the procedure for sampling and analysis of the expired air for CO levels. Bake suggested that there may be another more accurate approach to obtaining CO half life, which involved making detailed measure- ments of COHb after controlled exposure con- ditions. Consideration should also be given~to the possible differences in COHb half lives fol- lowing acute and chronic exposure, due to dif- ferent equilibrium compartments. Actually,, some of the differences in the literature may be accounted for on this basis. Lynch agreed, but indicated that he had been interested in obtaining half life values under real life condi- tions, a half life which represented the average of values which could be obtained for thee various activities that an individual might undergo in a given day. Cosentino indicate& that different average CO half time values might be obtained for dif- ferent individuals. Lynch agreed. Regarding Jmvis" presentation, First started by asking if cotinine levels were observed in the physiological fluids of smokers which were one hundred times larger than those found in non-smokers exposed to ETS, would it be reasonable to conclude that the latter received about 1/100!of the dose of an active smoker? Jarvisthought that that would be a reasonable estimate of exposure level differences:. Pershagen wondered about the sensitivity and specificity of the biochemical markers to distinguish between non-smokers and smokers with usually light smoking habits, e.g. those who had not smoked a day or two before the measurements. Jarvis responded that no bio- chemical marker is completely specific in dis- criminating between smokers and non- smokers, firstly because of ETS exposure of non-smokers, and! secondly, because some smokers may smoke only infrequently. Nev- ertheless, of the available markers, cotinine discriminates best, and is sufficiently sensitive to d'etect the majority of even very light smokers. Rylander asked what levels of plasma cotinine might be expected in smokers. Jarviss felt that 300-500 ng/tnl plasma would be a reasonable estimate. REFERENCES 1. Warner K E. Possible increases in underre-
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83 tture may be I agreed, but iterested in al life condi'- I the average ,ned for the -idual might rent average ained for dif- First started observed in s which were lose found in would it be itter received ~tive smoker? : a reasonable ences. he sensitivity al markers too s and smokers its, e.g. those wo before the I that no bio- pecific in dis- s and non- 5 exposure of xcause some quently. Nev- -kers, cotinine ently sensitive en very light porting of cigarette consumption. J, Am Stat Influence of arsenic and smoking on lung cancer Assoc 1978: 73:314-318. ' among smelter workers: A pilot study: Am J Ind 2 Higgins I, Welch K, Oh M, Bond G, Hurwitz P. Med 1981: 2:33-41.
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In the horr. environmen heavy when ventilation i~ children whc may therefor conceivably , a way thatt impaired. The first stu, studyby Schi: authors conc:' studies on 81 had no effect. restricted to had never sm ratory flow r (MEF50) a'a' among childr tunately, the s subsample no As pointed c possible that chance and ii
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3.1. Does environmental tobacco smoke affect lung function? BJt3RN BAKE INTRODUCTION in the home environment the exposure to 'nvironmental tobacco smoke (ETS) may be ieavywhen members smoke a lot at home and' %~entilktion is poor (1). Particularly the younger children who spend most of their time at home may therefore be heavily exposed which could conceivably affect the developing lung in such a way that the lung function~ becomes impaired. REVIEwOF STUDIES The first study in this area appears : to be the study by Schilling and coworkers (2), where the authors conclude on the basis of lung functiom studies on 816 children that parental smoking had no effect. However, when the analysis was restricted' to the subsample of children who had never smoked themselves, maximal expi- ratory flow rate at 50% of the vitall capacity (MEF50) was significantly (p<0.05)~ lower among children with smoking parents. Unfor- tunately, the authors do not give the size of the subsample nor the magnitude of the difference. As pointed out by the authors, it is entirely possible that the difference was significant by chance and! in any case the effect was small. Two years later Tager et a1. (3) published a report on children's lung function and parental smoking based on measurement of 261 children 5 to 9 years of age, who had never smoked and where adequate smoking history was obtained from both parents. They found no statistically significant difference in forced expired volume in one second (FEVI) and the maximum mean expiratory flow rate between 25 and 75% of the forced vital capacity (MEF25-75) in groups of children with different parental smoking habits. Howevery a signifi- cant trend~ consistent with decreasing level of MEF25-75 with~ increasing parental smoking was found. Because the authors used a method for standardization of MEF25-75 into standard deviation scores, these results cannot be inter- preted in terms of magnitude of flow rate. In a recent abstract (4) these authors show results from~ a longitudinal study confirming the deteriorating effect of ETS on children's lung function. 16;689 children with adequate spirometric recordings and completed questionnaires from both parents formed the basis for an analysis carried out be Hasselblad et al. (5): For tech- nical reasons only forced expired volume in 0.75 s(FEVo;75) was obtained-a somewhat unusual spirometric variable. A multiple
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86 regression analysis revealed that parentali smoking significantly accounted for 0.1% of the variance, i.e. minutely, but because of the large number of children involved also minute effects become significant. Unfortunately, no information was obtained on the childrens own, smoking habits. To minimize possible bias in this respect, an analysis was carried out on, those children only who were 6 to 9 years of age. Then FEVp_75 was significantly lower among children where the mother was a smoker, whereas the father's smoking habits had no effect. However, the difference between those children where none of the par~ ents smoked' and those where the mother smoked more than 20 cigarettes per day,, was on average only 21 ml for the boys and 16 mli for the girls. This reduction corresponds to 1.6 and 1.3g'o'. Dodge reported 1982 (6), spirometric meas- urements of 558 children in a longitudinal study over four years. Children exposedlto ETS did, however, not show lower FEVI or FVC and furthermore, no effects on: lung growth were found. Lebowitz et al. (7),similarly found no effect of parental smoking habits on children's FEVI, MEF5p, and MEF25 (max- imum expiratory flow rate when 25 per cent of the vital capacity remains) in 3441 house- holds. Thus, there is still uncertainty as to the harmful effects of parental smoking on lung function in children. If at all there is an effect on children's lung function, the available information certainly indicates that it is very small and probably biologically unimportant~ Adults may of course have been exposed! to ETS as children and as adults either in the home or in the workplace environment or both. The exposure time maybe many decades. Unfortunately, no study has considered the combined effect of at least two of these three circumstances, mainly because the studies pub- lished so far have not primarily been designed to investigate possible effects of ETS on lung function. i Imthe work by Schilling et al. (2) referredito above, there were no demonstrable effects on one parent's smoking on the other parent's lung function among 114 pairs but,, on the other hand, exposure outside the home was not considered nor possible confounding effects of ex-smoking. White andFroeb (8) published a study which has attracte& much attention because the results appeared to show that exposure to ETS at the workplace clearly had an effect on lung function-the magnitude of which was com- parable to active smoking of about 1 to 10 cigarettes per day. However, there are impor- tantt unanswered questions regarding, e.g. se- lection of subjects and occurrence of ex- smokers and therefore the interpretation of the results is an open question. Comstock et'al.' (9) analysed possible effects of household tobacco smoke on FEVi and FEV,/FVC (the ratio of FEVy to the forced vital capacity) of 418: never-smokers 20 years of age or more. 325 were not exposed, whereas 93 were exposed to ETS. They foundla nonsignif-icant tendency for persons with another smoker in the household to have impairedlven- tilatory lung function, Finally, Kauffmann~ et al. (10), have utilized data from a large French survey to study pos- sible effects of passive smoking in the home environment on lung,function: In the overall analysis comprising over 3000 neversmokers, 25~to 59 years of age about half of which were exposed to ETS, there were no significant dif- ferences. However, when only those subjects were considered who were 40 years of age or older presumably corresponding to at least 15 years of exposure, persons exposed to ETS (n=530) had significantly lower MEF25-75 than true non-smokers (n= ,'b0): For females also FEVI x more, wher persons we: pai& work a- avoid interf exposure) a to the amou band was ev per day the 0.4 1/s and i Does then I results in chi: there is an ef the study by I an associatior home enviro. ventilatory lu have been e: years. Other ; do nor appear magnitude of however, yet dered the con~ cumstances of As ETS pe! harmful pollu least that if all sure to this a: function in ch question is raru tion is not yet
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87 referred to e effects on ter parent's )ut, on the )me was not -ig effects of study which )ecause the sure to ETS tect on lung h was com- -)ut 1 to 10 = arc impor- ling e.g. se- nce of ex- tation of the ssible effects r FEVy and o the forced rs 20 years of t, whereas 93 _ a nonsignif ,ith another npaired ven- have utilized to study, pos- in the home n the overall eversmokers, f which were gnificant dif= hose subjects :ars of age or to at least 15 osed to ETS also FEV1 was significantly reduced. Further- more, when only those female ETS exposed persons were considered who were without paid work at the time of the study (in order to avoid interference with~possible occupational exposure) a dose-effect relationship according to the amount of tobacco smoked by the hus- band was evident. If the husband smoked 20 g per day the reduction im MEF25-75 was about 0:4lys and in FEV1 about 0.1 1.. CONCLUSIONS Does then ETS' affect lung, function? The results in children are inconsistent but if at all there is an effect it appears minute. In~ adults, the study, by Kauffmann (10), strongly suggests .In association between exposure to ETS in the home environment and a small reduction in ventilatory lung function im the subjects who have been exposed for more than 15 to 20 years. Other published' results in adults (2,, 9) do not appear to be inconsistent. The potential magnitude of the effect of ETS exposure is, however, yet uncertain as no study has consi- dered the combined effects of the various cir- cumstances of ETS exposure. As ETS per se is likely to be a potentially harmful pollutant, it seems probable to me at least that if all other factors were equal, expo- sure to this agent would indeed affect lung function in children as well as in adults-the qµestion is rather how much-and this ques- tion is not yet fully answered. REFERENCES 1. Repaee J. L, Lowrey A. H.,Indoor air pollution, tobacco smoke„and public health. Science 1980: 208:464-472. 2. Schilling R. S. F, Letai A. D, HuiiS. L, Beck G, Schoenberg J. B, Bouhuys A. Lung function~ respiratory disease and smoking in families. Am J Epidem, 1977: 106:274-283. 3. Tager I. B, Weiss S. T, Rosnen B, Speizer F. E: Effect of parental cigarette smoking on the pul- monary function of children. Am J Epidem 1979: 110:15-26'. 4. Tager I. B, Weiss S. T, Rosner B. Longitudinali assessment of the relationship of parents' ciga- rette smoking and level of pulmonary function, in children, Am Rev resp Dis 1982~ 125:145. 5. Hasselblad V, Humble C: G, Graham M. G, Andersson H! S. Indoor environmental deter- minants of lung function in children, Am Rev resp Dis 1981: 132t4',9-485. 6. Dodge R. R. The effects of indoor air pollution on Arizona: children. Arch envi Hlth~ 1982: 37:151~155. 7. Lebowitz M. D, Armet D. B, Knudson R. The effect of passive smoking on pulmonary func- tion in children. Environ Int 1982: 8:371- 374. 8. White J. R, Froeb H. F. Small-airways dysfunc- tion in nonsmokers chronically exposed' to tobacco smoke. N Engl JI Med 1980: 3302:720- 723. 9. Comstock G, Meyer M. B, Helsing K. J, Tockman M. S. Respiratory effects of household exposures to tobacco smoke and! gas cooking. Am Rev resp ~ Dis 1981: 124 :143-148. 10. Kauffmann F, Tessier J. F, Oriol P. Adult pas- sive smoking in the home environment: a risk factor for chronic airflow limitation. Am J Epidem. 1983 : 1 i17:269-280: Bjorn Bake, Mi D. DD epartment of Clinical Physiology Sahlgrenska Hospital University of Gothenburg S-413 45 GOTHENBURG, SWEDEN
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TABL after ex 3.2. Environmental tobacco smoke and pulmonary function testing ANTHONY M. COSENTINO INTRODUCTION The question to be answered! is whether envi- ronmental tobacco smoke (ETS) causes an alteration in lung function and whether there is a subset of individuals uniquely susceptiblee to this exposure. I shall discuss the lung function tests com- monly employed to study this problem and also suggest other studies to be utilized' in future studies. The discussion shall not deal with acute infectious processes, diseases in children or lung cancer. METHODS FOR MEASUREMENTS Spirometry is most commonly employed for lung function measurements. The most repro- ducible measurements are those with the least variability in~a normal population and include the FVC, FEVI and FEVt;/FVC ratio (1) Measurements made from the terminal portion of the flow-volume curve suffer from very sig- nificant intra-subject; and inter-subject varia- tion (1, 2). Also,,although smallicktanges only in the terminal portion of the flow-vohlme curve without associated changes in the FEV I, may be a sensitive way to identify asympto- matic smokers, the significance of such an iso- lated! finding in other populations remains spe- culative. The FEVI correlates well with func- tional disability. Airways resistance measurements are best utilized to assess acute effects of inhalational challenge. The subjects serve as their own con- trol. EFFECTS OF ENVIRONMENTAL TOBACCO SMOKE Studies, to date, of the long term effect of ETS on lung function have revealed minimal, if any, abnormalities (3,,4): The statisticalsignif-' icance of these findings is questionable and the clinical significance even less certain Studies, to date, of the effects of acute expo- sure to ETS have been essentially negative though symptoms of cough and wheezing have occurred, A recent paper by IDahms et al. (5)1 showed significant decline in function in asth- matics. Exercise studies during exposure to ETS have been essentially negative (6,7): but the studies are probably inadequate. In general, it appears that individuals with normal lungs react minimally if at all to ETS, either acutely or chronically. A subset of patients with~ hyperreactive airways, i.e. asthma, may react adversely to ETS. It is sug- I- Spiro (-) gest' subj invc aw
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89 and ions remains spe- s well with func- -ements are best s of inhalational as their own con- :MENTAr. ,CE =rm effect of ETS :aled' minimal, if - statistical signif- :stionable and the s certain. cts of acute expo- :entially negative nd wheezing have Dahms et'al. (5), : function in asth- ring exposure to icgative (6j7) but iequate. individuals with y if at all to ETS,. Ily. A subset of ~-e airways, i.e.. to ETS: It is sug- TABLE 1. Suggeited procedure to intrttigate lung function after expoure to envimnmerual tobacco tmoke Acute _F.xparun Spirometry and Raw,, etc. who are symptomatic but with "normal" spi- rometry should be subjected to exercisee testing. Exercise studies should include an effort to reach maximum level of exercise with moni- toring of EKG, fs VE, Vco2, Vo2; R and post exercise spirometry. Table 1 presents suggested investigational approach. I -1 ~ Normal i Abnormal REFERENCES - ~ Symptoms Symptoms ~ 1. Cochrane G. M, Prieto F, Clark T. J. H. Intra- Exercise subject variability of maximal expiratory flow- volume curve. Thorax 1977, 32:171-176. Exercise Chronic Exposure ~ gested that an effort, be made to identify these subjects and that they be targetedl for further investigations. RECOMMENDA'PIONS I emphasize the value of history taking and/orr a' well designed questionnaire (8): Individuals 2 Knudaon R. J, Slatin R, Lebowit¢ M. D, Burrows B. The maximum expiratory flow volume curve.. Am Rev resp Dis 1976; 113:587 600. 3. White J, Froeb H. Small-airways dysfunction in non-smokers chronically exposed to tobacco smoke. New Engl J, Med 1980: 302:720-723. 4: Schilling R. S. F, Letai A. D, Hui S. L, Beck G, Schoenberg J. B, Bouhuys A. Lung function, res- piratory disease and~ smoking in families. Am J Epidem 1977: 106:274-283. 5, Dahms T. E, Bolin J, F, Slavin R. G. "Passive smoking"; effects on bronchiall asthma.. Chest 1981: 80:530-534. 6: Shephard'.R. J. Collins R, Silverman F:,,"Passive" exposure of asthmatic subjects to cigarette smoke. Environ Res 1979: 20:392-402. 7. Shephard R. J~ Colling R, Silverman F. Responses of exercising subjects to acute "passive" cigarette smoke exposure. Environ Res 1979: 19:279- 291 i 8. Shephard R. J, Cox M. Physical fitness, respira- tory symptoms and lung, function. Respiration 1980: 39:193-205. Anthony M. Cosentino St Mary's Hospital 450 Stanyan Street Department of Pulmonary Disease San Francisco, Califbrnia 94117, USA
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3.3. The effects of environmental tobacco smoke exposure and gas stoves on daily peak flow rates in asthmatic and non-asthmatic families MICHAEL D. LEBOWITZ INTRODUCTION There is substantial agreement that environ- mental tobacco smoke (ETS) produces annoyance and sensory irritant effects (1). There is a potential for cardiovascular and'res- piratory diseases as we11'(1): Certainly, govern- mental agencies are concerned about the inter- actions of ETS with other gases in~ the work place, especially carbon monoxides and oxides with nitrogen (2). However, the specific con- tributions of sidestream smoke to personal exposures have not been documented. Several studies have shown that the levels of carbon monoxide and! other sidestieam smoke constituents in indoor areas are high in many instances (1, 3). Deposition~ of sidestream cigarette smoke in the human respiratory, tract has been shown to be only about 11 94i; this dosage is similar to other aerosols and much less than mainstream smoke (4). The impact of ETS on indoor concentrations of NO2 is usualNy small compared to the impact of gas stoves (5). Therefore, blood carbon monoxide (CO) levels may be higher in those exposed to ETS (6, 7)„ but are probably lower than the carboxyhemoglobin levels associated with~ exposures to unvented gas stoves (1). Some of the same respiratory diseases may occur in indoor situations in which high~levels of respi- ratory particles and gases are due to wood' burning, not to ETS' (8, 9). Effects of ETS on respiratory illnesses may occur in some settings (1). Most studies of children's illnesses have been influenced by parental reporting bias (1i0; 11, 12) and by problems associated with retrospective obser- vation. Several studies have examined the effects of smoking on children's lung function,, without controlling for gas stoves,, and have found' significant relationships (13, 14): How- ever, in these studies there were no actual',con- centration measurements indoors: On the other hand, studies by Binder et ul.' (15) and Schilling et al.(16) utilizing, indoor measure- ments showed that indoor levels of respirable particles were higher in homes with smokers, but that there was no effect on children's symp- toms or lung function. Also, Lebowitz et al. (17), d'emonstrated! that controlling, for genetic influences in body size and lung function elim- inated the influences of parental smoking on children's lung function. Recently, prospective studies of the effects of ETS, controlling gas, stove emissions, have been~ performed by severall groups (18, 19, 20, 21, 22, 23). The results have been quite con- tradictory. Speizer et al. (21, 22) demonstrated the effects c significant r, in the samc slightly dift appears to _ might, be at 1, (24). Hasse maternal sm variance in Volume (FE from previoi trend when t same time (2 such effect function, crf though self exposed chi examined I cooking anc effect of gas physiologica in healthy st both have b effects (27,, effects of ET demonstrate, (29) showed or controls,, demonstrate, asthmatics: This pape peak flows in association v relevant poll We studiedl Tucson, whi, sample of fan representati-, study (31). ~ tially all mid with and wit
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91 vels of respi- ue to wood lnesses may t studies of fluenced by 12) and by ctive obser- amined the ng function, s,, and have , 14), How- r actual l con- rs: On the al. (15) and or measure- )f respirable ith, smokers, lren's symp- ~itzetal.(17)for genetic ]ctlon ehm- imoking on = the effects ;sions; have (Y8, 19, 20, i quite con- :monstrated the effects of gas stoves, but not of ETS (a significant reverse trend was seen). However,, in the same project with more data, using slightly different methods of anaHyses, it appears to indicate that the effects of ETS might be at least as critical as those of gas stoves (24). Hasselblad et a1. (20) showed that maternal smoking habits explain 0.1 % of the variance in children's Forced Expiratory Volume (FEV.75). However, they utilized data from previous studies that had'shown no such trend when examining other risk factors at the same time (25, 26). Dodge (19) did not find any such effect when examining children's lung function, cross sectionally or longitudinally, though self reported cough was higher in exposed children. In adults, Comstock (18)) examined ETS effects controlling for gas cooking and vice versa. They found some effect of gas cooking, but not of smoking. Two physiological studies of effects of ETS exposure in healthy subjects have been~ conducted, and both have been negative in regards to such effects (27;, 28). Two similar studies of the effects of ETS on asthmatics and controls have demonstrated conflicting findings. One study (29) showed no important effect in asthmatics or controls, whereas the other study (30) demonstrated a broncho-constrictor effect in asthmatics. This paper will report, on a study on daily peak flows in asthmatics and non-asthmatics in association with exposures to ETS and other relevant pollutants. METF3ODS ~~ We studied 117 families (229 subjects)i ini Tucson; which were derived from a stratifiedl sample of families in geographic clusters from a representative community population under study (31):, The families studied were essen- tially all middle class and'represented familiess with and'without reported asthma. They have been monitored over a: two-year period, using daily diaries for symptom information and peak flows. Peak flows were performed between 1500:1900 hours each day using a mini-Wright peak flow meter (117). Diary re- sponse rates were acceptable for a majority of days in all seasons. The subjects were trained in the use of the peak flows and symptom diaries by trained nurses. Monthly checks by phone and seasonali checks by visit were made to insure proper usage, and'the mini-Wright peak flow meters were calibrated. All families pro- vided information as to household characteris- tics. Micro-indoor and', outdoor monitoring have been conducted in, a random cluster sample representative of all study households (n = 41) for temperature, humidity, air pollutants, pollen, bacilli, fungi and algae, for 72 hours eachi (32). Indoor samples were measured in living rooms and! kitchens, and micro-outdoor samples were taken in front andl back (TSP, RSP, CO, 03, pollen). Macromonitoring for air pollutants (by the County Health Dept.) and pollen was conducted simultaneously in the center of each cluster. Regional daily weather data were provided by the U. S Weather Bureau. Symptoms rates per 100 person days were calculated from daily diary data for asthmatics and non-asthmatics within exposure groups,, for comparative purposes. Peak flows were transformed to standard normal deviates (Z scores) to remove effects of height, age, sex and season, Statistical techniques used were fre- quency distributions contingency tables and multivariate analysis of variance, using SPSS programs on a DEC 10=Cy,ber 175 computer system RESULTS Exposures : Total suspended particulate (TSP) indoors
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92 TABLE 1. TSP, RSP and CO by enmmnmentat tabatm smake adga.r .rtor.ti rrsagr. No smaFsrs Snro.ke.i " Sanaksng Stnut Gas Gas stove Electric stove Electric No Yes Gas Eleetric TSP x ' 19.3+ 14.9*** 30.6+ 36.3*** 17:7*** 33.0 25.5 28:0 5 11.2 8.9 20.0 14.9' 10.7 18.2 17.6 16.6 n 9 5 11 8 14 19 20 13 RSP x 8.7 4.2** 8.3 19:6** 7.2+ 13.1 8.5 13.7 s 8.9 4.6 7.5 15,9 8.0 13.1 8:2 14.8 n 10 5 11 8' 15 19 21 13 CO x 1.4 0.9* 1.4' 1.0 1.2 1.2 1.41** 0.97 s 0.6 0.4 0.6 0.6 0.6 0.6 0.56 0.54' n 9 5 6 6 14 12 15 11 * significant by 2 tailed t-test, p <.05. ** p <.025. ***:p <.005. + borderline significant (2 tailed t-test),.05 <p <.010. ranged from 5.7 to 68.5 µg/m3 and micro- outdoor TSP ranged from 2.1 to 169.6 µg/m3: • Cyclone measurements of respiratory particu- late (RSP), were often below readable levels; the maximum was 49':7 µg/m3 indoors and 124.5 µg/m3 outdoors. Scanning electron microscopy y,ielded'~ little identifying informa- tion on the type of dust found on the floors of homes, except to show it was not similar to outdoor TSP (80 % silica quartz, about 5 µmg). Total micro-outdoor pollen counts were approximately 5 % of the macro-polltm counts (max = 15117), and micro-indoor pollen counts were only 5 % of the micro-outdoor pollen counts (minimum MMAD around 10- 15 µm): Averages,of the two spot CO readings were lower than 2.4 ppm: micro-outdoor readings were 18 ppm. Indoor 03, was measured between 0 land 0.035 ppm. Temperature and humidity varied by season, but the former did not vary very much indoors over the year and the latter did not differ much between indoors and outdoors over the year. Correlations of indoor pollxtants: Indoor CO correlatedlsignificantly with micro- outdoor CO (r =.60; p <.003)but not with regional CO measurements (1.5 - 4.9 ppm on days of indoor monitoring). Indoor CO was significantly associated with gas stove usage, but not with ETS (Table 1), nor with gas burning, furnaces, hot water heaters or washers-(dryers) (i.e, vented appliances). Thus, though low, it was used as the indicator pollutanr measure of combustion, emission from the gas stoves. Both TSP and RSP were significantly associated'with ETS, but not with gas stove usage (Table 1). Attempts to estimate concent'rations of CO,'I1SP, and RSP in houses not, monitored, by cluster and season, essen- tially yielded a classification based on gas stove usage and smoking in the houses. Neither ETS nor gas stove usage was associated with, social status. There were 24 normal children (ages 4-24)i who had daily peak flows (Vmax) over an 11- month period. After age and height correction, no inter-subjgct differences in baseline data C.~ ~ were seen; all Their Z-score examined in r meteorological Differences in child were adju covariate. Me related to Vma perature, relati tion (P), baro: bined indoor children's Vm: with outdoor , hourly 03, sel (Table 2), and • sions; the lat removing all oi to Vmax in thc those exposed ! icantly higher outdoor envin Vmax is relate outdoors and c Vmax in a, mental conditi and previous] TABLE 2. Aae, 03 (ppm) .038 .038 -.051 .052 -.079 .08 -.12 All
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93 ;as Electric .5 28.0 .6 16.6 13 .5 13.7 .2 14.8 13 .41** 0.97 .56 034 11 -antly with micro- 103) but not with 1.5 - 4.9 ppm on Indoor CO was gas stove usage, 1), nor with gas ater heaters or ited appllances): d as the indicator bustion emissibn SP and RSP were ETS, but not with tempts to estimate tnd RSP in houses nd season, essen- based on gas stovee uses. Neither ETS,ciated with social ildren (ages 4-24), 'max) over an l li- height correction, in baseline data were seen; all were within the normal range. Their Z-score transformed peak flows were examined in relation to indoor and outdoor meteorological and air pollution variables. Differences in the number of observations per child were adjusted by using these numbers as a covariate. Meteorological data significantly related to Vmax were used as covariates (tem- perature, relative humidity (RH) or precipita- tion (P), barometric pressure). In this com- bined indoor-outdoor pollutant analysis, children's Vmax were significantly associated with outdoor daily TSP an& daily maximum hourly 03, separately and as an interaction (Table 2), and'with exposure to gas stove emis- sions; the latter relations were only after removing all other variation. 03 had a relation to Vmax in those not exposed to indoor ETS; those exposed to indoor ETS had'a non-signif- icantly higher average Vmax. The effect of outdoor environmental factors on children's Vmax is related to the amount of time spent outdoors and exercise (33): Vmax in adults was related to environ- mental conditions, as were symptoms. Active and previously active smoking negatively affected Vmax in all groups. The multivariate analyses of variance yielded associations of Vmax with: i) gas stove usage in asthmatics, normali and allergics, ii) outdoor NO2 in the same groups iii) outdoor CO in asthmatics and allergics, iv) outdoor 03 in those with symp- toms of non-asthmatic airways obstructiom (AOD); v) temperature in asthmatics, and high relative humidity in AOD. Seasonal effects on various groups (related to interactions of envi- ronmental conditions) were removed. There was an independent interactive effect of out~ door NOZ and gas stove usage on Vmax in asthmatics, as well as an independent effect of gas stove usage, probably related to the corre- lation of indoor and outdoor NO2, as pre- viously reported by others (1). In asthmatics in one cluster (all asthmatic families); there were additional independent associations with Vmax: high relative humidity, micro-pollen, active smoking, and indoor TSP (as seen in Table 3). Neither ETS, RSP, or fungi had any significant effects om Vmax in this group or other groups. Low temperature was most important for "asthma attacks". 03 had significant negative TABLE 2. Acn•age Z tcorr la'max * in ebrldrtn in nlatian to daily outdoor 0 j and 'TSP. TSP (µg/m3) 03 (ppm) <56 56-77 77 + All .038 +.108 +.239 +.156 .069 .038 -.051 +.042 -.162 -.061 .024 .052 -.079' +.242 -.021 ~ -.474 -.115 .08 -.12 -.088 -.196 -.804 -.310 All .115 -.027 -.227 Analysis of variance (ANOVA): p <.0001. * Expressed as standard normal deviates (mean = 0, s.d. = 1, units are s.d:, units). k- B I
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94 TABLE 3. Aisociationr of smoking and irtdoor TSP with averagt Z score Vmax* in adirlt' arthmatics (in asthma clxsttt). TSP (µg/m3) Smoking <25 25-68.5 Current Ex Never x -1.17 -1.92 -2.41 -2.18 -1.25 s, .99 1.83 2.08 1.86 1.44' Person days 1205 1334 857 687 1574 ANOVA: p <0.001 p <0.001 * Expressed as standard normal deviates (mean = 0, s.d. = 1, units are s.d: units): n association with. Vmax in low temperatures, but the effect was not striking. (Asthma symp- toms were not day-of-week dependent), ETS was not associated with any daily symptom, prevalence rates in adults. However, indoor TSP and'RSP (but not outdoor TSP) were asso- ciated with several' symptoms in asthmatics and non-asthmatics. Both were associated with increased "asthma" symptoms in asthmatics, and' with increased rhinitis in asthmatics and non-asthmatics. Indoor TSP was associated also with eye irritation in alli adults and increased'productive cough in non,asthmatics. On the other hand, gas stove usage was asso- ciated also with increased rhinitis in all adults (as was indoor CO), increased productive cough in asthmatics an& allergics, and increased sore throat prevalence rates in non- asthmatics. Indoor CO was associatediwi'th eye irritation. Micro-pollen was associated with "asthma attacks", as well as eye irritation, and rhinitis (in summer). There DISCUSSION were no effects of ETS on~ Vmax or symptoms in children or adults, asthmatics or others. This parallels the negative findings for children's lung function in a: stud'y, of the 344 nuclear families (n = 344) and in the 700 + children and 3 100 adults in the larger: commu- nity population (34, 1I7), from which this study sample was drawn The study did show more symptoms, including infection,type, in parents with symptoms, especially smokers. Further- more, there were no effects of parental occu- pational exposure, and' these did not affect indoor pollution concentrations. Indoor TSP didy however, have an effecton adult's daily symptoms and on asthmatics' Vmax, which must be associated with other characteristics of the indoor TSP (the part not correlated with ETS). Uhfortunately, because of sample size and the number of confounding factors, precise exposure-effect could not be determined. This would' appear to ~ be a major methodologicaliproblem, for these types of stu~ dies, as one must account for co-variables (age, sex, smoking), symptoms (asthma; allergy, AOD), indoor and outdoor meteorological; pollutant and pollen, differences. The effect of gas stove emissions seems more pronounced and may hide minor perturbations that could be due to the same gaseous pollu- tants. One could estimate that, effects would'be seen from ETS if it were 3-5 times greater (the approximate degree that stove emissions exceed sidestream smoke (1)', or if it were 9 times greater, based onidose estimates of sides- tream smoke (4);, to see the same effects of active srnoking. Children, asthmatics, and! those with prior chronic AOD symptoms, seem more sensitive TAB Curre Past : Artac: Not a No sy. * 53 c Sourct to the positi, seen affect that sI our q seen a base& unkno acute/ challer reacti% toms ; interm It may represe chial rt Appi warran: greater able qt objectic tionof! 8°°d in priate t( be remc history so (e.g. will be
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95 TABLE 4. Metbochadim rerpoxre (FEhIPD20 as cumulatiar breath unitt)J Data nported as per cent of examined group. lid show more vpe, in parents •kers. Further- parental occu- iid not affect ; e an effect on m asthmatics' ed with other ' (the part not ately, because f confounding could not be to be a major ,e types of stu- variables (age, hma, allergy, eteorological, is seems more perturbations ;aseous pollu- ects would be _s greater (the e emissions if it were 9 iates of sides- ne effects of ;e witL prior iore sensitive Persons * Marked (<25 CMU): Moderate (25-199 CMU)~ Non-reactor (2004 CMU) Current asthma 4, 100 0 0 Past Asthma Attacks SOBWZ or FEVI 2.01 13' 46 54 0 Not above, other symptomes 33 3 45 52 No symptoms 11 0~ 45 55 * 53 of the 61 adults were subjects in this study. Source: Coaker et'al.,,1982;,Burrows, Cline,,Coaker, 1983 (unpublished data): to the effects of various pollutants. These sup- positions were demonstrated by associations seen in this study. Even indoor conditions affect some at these groups, especially those that spend more time outdoors (as indicatedby our questions). Even effects that have been seen are probably more acute, reversible types, based on levels of exposures. However, it is unknown how frequent or severe such~ acute/reversible effects are. Methacholine challenges in asthmatics and intermediated reactivity in mostwith "asthmatic-type" symp- toms; some without symptoms also showed intermediate reactivity (35) as seen in Table 4. It may be that these acute reversible effects represent sub-clinical or predisposing bron- chial reactivity or obstruction. Appropriate populatiom selection is always warranted, probably with better sampling in greater numbers than foundin this study: Reli- able qµestionnaires and daily diaries, good! objective testing, an& criteria for characteriza- tion of susceptibles are necessary. They rely on good interviewers an&technicians andlappro- priate testing,(36). Parental reporting bias must be removed as well'if one is to examine medical history (12; 19, 36), Some studies still fail to do so (e.g. 37). We hope that longitudinal studies will be useful, as do other (14, 22, 23, 38). The ability to examine effects of various indoor and outdoor environmental conditions was of great benefit. Proper integrated'quanti'. tative exposure estimates would be of even greater benefit (39)1 Peak exposure informa- tion would! be useful' also. Uhfortunately, the present study did not have this type of infor- mation. Acknmvledgemertt Supported by EPA Grant #R805318 and NIH SCOR Grant #HL14136. "Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through contract or grant #R805318 to Michael D. Lebowitz, Ph, D., it has not been subjected to the Agency's required peer and& policy review and therefore does not neces- sarily reflect the views of the Agency and no official endorsement should be inferred". REFERENCES 1. National Research Councill(NCR). Indoor Pol~ lutants. Washington, D: C. National Academy of Sciences. 1981. lI!
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96 2. National Institute of Occupational Safety and Health (NIOSH). Adverse health effects of smo- king and the occupational environment. Cincin- nati. US Dept Health Educ Welfare Publ No. 79-112. pp 1-11. 1979. 3. Repace J. L, Lowrey A. H. Indoor air pollution{ tobacco smoke, and public health. Science 1980: 208: 464-472. 4. Hiller F. C, MeCusker K. T, Mazumdcr M. K, Wilson J. D, Bone R.: C. Deposition of sides- tream cigarette smoke in the human respiratory tract. Am Rev resp Dis 1982: 125:406-408. 5. Yocom J. E. Indoor-outdoor air quality rela- tionships: A critical review. J Air Pollut Control Ass 1982: 32:406-408. 6. Olshansky S. J. Is smoker/non-smoker segrega- tion effective in reducing passive inhalation among non-smokers? Am J publ Hlth 1982: 72:737 739. 7. Radford E. P', Drizd T. A. Blood carbon monoxide levels in persons 3-74 years of age: United States„ 1976-80. NCHS' Advance Data 1982: 76:1-24. 8. Anderson H. R. Respiratory abnormalities, smoking habits, and ventilatory capacity in a high ~ land community in Papua, New Guinea: Prevalence and effect on mortality. InrJ Epide- miol 1979: 8:127-135. 9. Sofoluwe G. O. Smoke pollution in dwellings of infants with broncho-pneumonia: Archs envir Hlth 1968: 16:670=672. 10. Cederlof R. Colley J. Epidemiological investiga- tions on environmental tobacco smoke. Scand J resp Dis 1974::91:47-49. 11. Lebowitz M~ D, Burrows B. Respiratory symp- toms related to smoking habits of family adults. Chest 1976: 69:48-50: 12. Weiss S. T, Tager I. B, Speizcr F. E; Rosner B. Persistent wheeze. Its relation to respiratory, ill- ness, cigarette smoking, andlevel of pulmonary function in population sample of children. Am Rev resp Dis 1980: 1i22:697-707: 13. Tager I. B, Weiss S. T, Rosner B, Speizer F. E: Effecrof parental cigarette smoking on the pul- monary function of children. Am J Epidem 1979: 110:15-26. 14: Tager I. B;, Weiss,S. T, Rosner B. Longitudinal assessment of the relationship of parents' ciga- rette smoking and level of pulmonary function in children. Am Rev resp Dis 1982: 125:145. 15. Binder R. E, Mitchell,,C. A, Hosein H. R, Bou- buys A. Itnportance of the indoor environment in air pollution exposure. Archs envir Hlth 1976: 31:277-279. 16. Schilling R. S. F, Letai A D„Hui~S. L, Beck G, Schoenberg J. B, Bouhuys A. Lung function, respiratory disease and smoking in families. Am J Epidem 1977': 106:274-283. 17: Lebowitz M. D, Armet D. B,,Knudson R. The effect of passive smoking on pultnonary func- tion in children., Environ Int 1982~ 8:371- 374. 18: Comstock G. Meyer M. B, Helsing K. J, Tockman M. S. Respiratory effects of household exposures to tobacco smoke and gas cooking. Am Rev resp Dis 1981: 124:143-148, 19. Dodge R. R. The effects of indoor air pollution on Arizona children. Archs envir Hlth 1982: 37:151-155. 20. Hasselblad V, Humble C. G, Graham M. G, Andersson H. S. Indoor environmental, deter- minants of lung function in children. Am Rev resp Dis 1981: 132:479 -485, 21. Speizer F. E; Ferris B. G. Jr, Bishop Y. M. M, Spengler J. Health effects,of indoor NO2 expo- sures: Preliminary results. In nitrogen Oxides and their effects on health. S. D. Lee (Ed) Ann Arbor: Ann Arbor Press 1980: pp 343-359. 22. Speizer F. E, Ferris,B. G. Jr, Bishop Y. M. M, Spengler J. Respiratory disease rates and pulmo- nary function in children associated with NOZ exposure. Am Rev resp Dis 1980: 121:3-10! 23. Melia R. J. W, Florey C. du V, Altman D. G, Swan A. V. The Association between respira- tory illness and NOy,temperature and relative humidity. Int J Epidemiol11982: 11:164-169. 24. Dockery D. W, Ware Ji H, Speizer F. E, Ferris B. G. Jr. Preliminary, longitudinal analysis of pul- monary function in school children in the six cities study: Am Rev resp Dis 1982 ~ 125:145. 25. Chapman R. S. Hasselblad V, Hayes C: G, Wil- liams J. V., R, Hammer D. I. Air pollution and childhood ventilary function. I. Exposure to particul'ates matter in two southeastern cities, 1971-1972. In Clinical Implications of Air Pol- lution Research ~ A. J. Finkel, W. C. Duel (Eds) Acton, Mass: Publ S6 Group 1976: pp 285- 303. 26. Hammer D. I, Miller F. J, SteadA. G; Hayes C. G. Air pollution and childhood ventilatory function. I. Exposure to particulates matter in two southeastern cities, 1971-1972. In Clinical Implications of Air Pollution Research A. J. N 27, Pimm P. gical! eff, rette sm 213. 28. Shephar, ponses o cigarette 19:279-:: 29. Shephar, Exposur Smoke. 30: Dahms " smoking 1981: 8( 31. Burrows Knudsoi king anc to airwa 32. Lebowit Tucson tructive valence 102:13". 33. Lebowii berg C. ) Barbee effects c indoor asthmat 34. Lebowi kovita I
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is envir Hlth S. L, Beck G, ung function, ifamilies. Am udson R. The monary func- 1982: 8:371- [elsing K. J, of household gas cooking. -148. r air pollution ir Hlth 1982: lop Y. M. M,. 3r NO2 expo- rogen Oxides ;i.ee (Ed) Ann p 343-359. lop Y. M. M, :s and pulmo- ed with NOZ : 121:3-10. 1'ltman D. G, .veen respira- and and relativc 11:164-169. F. E, Ferris B. ialysis of pul- en in the six 32: 125:145. es C. G, Wil- 3o[hition and Exposure to astern cities, is of Air Pol- Duel Duel (Eds) 176: pp 285- . G, Hayes C. I ventilatory res matter in 2. In Clinical :search A. J. 27. Pimm P, Shephard R. J, Silverman F. Physiolo- gical'effects of acute passive exposure to ciga- rette smoke. Archs envir Hlth 1978: 33:201- 213. 28, Shephard R. J, Collins R,, Silverman F. Res- ponses of exercising subjects to acute "passive" cigarette smoke exposure. Environ Res 1979: 19:279-291. 29. Shephard R. J. Collins R, Silverman F. "Passive" Exposure of Asthmatic Subject to Cigarettes Smoke. Environ Res 1979: 20t392-402. 30. Dahms T. E, Bolin J. F, Slavin R. G. Passive smoking; effects on bronchial' asthma. Chest 1981: 80:530-534. 31. Burrows B, Lebowitz M. D, Barbee R. A, Knudson R. J, Halonen M. Interactions of smo- king and immunologicalifactors in relationship to airways obstruction, Chest (in press). 32. Lebowitz M. D, Knudson, R. J, Burrows B. The Tucson epidemiological study of chronic obs- tructive lung disease. I. Methodology, and pre- valence of disease. Am J Epidem 1975: 102:137-152. 31 Lebowitz M. D, O'Rourke M. K, Dodge R, Hol- berg C. J, Corman G, Hoshaw R. W, Pinnas J. L,, Barbee R. A, Sneller M. R. The adverse health effects of biological aerosols, other aerosols, and indoor microclimate on asthmatics and nonr asthmatics. Environ4nt 1982: 8:375-380. 34. Lebowitz M. D, Bendheim P, Cristea G, Mar- kovitz D;,Misiaszek J; Staniec M. Van Wyck D. 97 The effect of air pollution and'weather on lung function in exercising children and adolescents. Am Rev resp Dis 1974: 109:262-273. 35~ Coaker L, Lebowitz M. D, Abraham T, Garfield M. Sugihara S, Burrows B. Methocholine chal- lengc: The correlation of smoking with airway response in symptomatic and'asymptomatic sub- jects. Am Rev resp Dis 1982: 125:253., 36. World'HealthCrganization (WHO)i Guidelines for epidemiological studies in environmental health. Environmental Health Criteria Series. Geneva: World Health Organization/UNEP. 1983: 37. Gortmarker S. L, Klein Walker D, Jacobs F. H, Ruch-Ross H1 Parental smoking and the risk of childhood asthma. Am J publ Hlth 1982: 72:574-578. 38. Dodge R. R. The respiratory health and lung function~ of Anglo-American children~ in a smelter town. Am Rev resp Dis 1983: 127:158- 161. 39. World Health Organization (WHO). Estimating, humam exposure to air pollutants. Copen- hagen/Geneva: WHO. 1982: Michael D. Lebowitz Division of Respiratory Sciences University of Arizona Health Sciences Center Tucson{ Arizona 85724, USA
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3.4. Acute effects of environmental tobacco smoke ANNE'TTA WEBEA INTRODUCTION The aim of our studies was to investigate envi- ronmental tobacco smoke (ETS),and its acute effects on humans. We also investigated dose- response relationship on the concentration of ETS particularly with regard to levels that can be considered tolerable for humans. For that purpose laboratory and field studies were made on: the degree of air pollution due to ETS by measuring the concentrations of some pol- lutants in the air (CO, NO; formaldehyde, acrolein, particles and nicotine); the degree of acute irritating and annoying effects of ETS. These effects were analyzed by means of questionnaires, and by means of measurements of eye blink rate, heart rate and respiratory frequency. Furthermore, we tried to find' out whether any of the individual chemical components measured could be used as an indicator for evaluating the degree of ETS contaminatiom and its acute effects. Laboratory Experiments The experiments were carried out in a chamber of 30 m3,,with an air temperature of 20-24° and the relative humidity (RH) i between 40 and 60 %. The ventilation rate could be varied between 0.1 and 16 air changes/h. Cigarette smoke was produced by a Borg- wald smoking machine under standardized conditions. The smoke in the chamber con- sisted of the sidestream smoke, the mainstream smoke having been let out of the chamber. Healthy students were exposed in groups of 2 to 3 in the chamber. They also participated in an experiment with identical, conditions, except that there was no smoke. In a first experiment (1) 33 subjects were exposed to continuously increasing concentra- tions of smoke. The main results are summa- rized in, Figure 1.. The figure shows that the concentrations of CO, NO, HCHO and acrolein in exposure chamber increased linearly with the number of cigarettes smoked. Both mean subjective eye irritation and mean eye blink rate increased in an almost linear fashion with increasing smoke concentration. Subjective nose and throat irritation were also determined. The effects on the nose were less pronounced than those on the eyes, and those on the throat were the smallest. Thus, the eyes are the most sensitive orgam to irritation due to ETS. Frgure eye b1E lutant an un In mcnts relatic. of exli corres 32-43 tratio,
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aCCO :ween 40 and ild be varied /h. A by a Borg- standardized :.hamber con~ it mainstream ic chamber. d in groups of iarticipated in 1 conditions, subjects were ng concentra- -s are summa, centrations of i in exposure the number of ,ubjective eye e increased in teasing smoke -ritation were -he nose were the eyes, and lest. Thus, the a to irritation 99 1 11 22 32 42 43 ppm 0.08 0.42 0.77 1.11 1.45 1.50 ppm 0.03 -0.18 0.32 0.47 0.62 0.64 ppm 0 0.05 0.11 0.16 0.20 0.20 ppm 0 10 20 eye irritation index ••••••••• eye blink rate Figure 1. Mean subjective eye irritation, mean eye blink rate and concentrations of some pol~ lutants during continuous smoke production in an unventilated climatic chamber. In the second series of laboratory experi- ments (2, 3) the acute effects were analyzed in~ relation to smoke concentration and duration of exposure: The smoke concentrations used corresponded to 1.3, 2.5, 5 and' 10 ppm CO. 32-43 subjects were exposed to these concen- trations during 1 hour,, each smoke concentra- eye Irritation eye blink rate/min very strong 5-1 r- 80 33 subjects. Ventilation rate 0.01 h'1. Eye irri- tation index calculated from the answers to 4 questions concerning eye irritation. 0 min : measurement before smoke production. tion increasing linearly during the first 5 to 10 min and then remaining constant at the desired level for the remaining part of the hour. The part of the CO due to tobacco smoke was obtained' by subtracting the background level in the chamber before smoke generation from the CO concentration present during
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100 3 2 1-' eye irritation index 10 ppm 5 ppm .... .................... control ,1 ,%~-__.- .......... .... - 0 20 Figure 2. Subjective eye irritation due to envi- ronmental tobacco smoke, related to smoke concentration and duration of exposure. CO valuerare levels during smoke production~ smoke generation, This difference value was used as an indicator to evaluate the degree of air pollution due to tobacco smoke. Figure 2 and 3'illustratethe results obtained for subjective eye irritation and eye blink rate considered'as an objective measure for eye irri- tation.. The figures demonstrate that: - the mean eye irritating effect increased with~ increasing smoke concentration - the mean eye irritation increased with the duration of exposure in spite of a constant smoke concentration. The same,,but less pronounced result have 40 60 exposure min minus background level, before smpke pro- duction. 32 to 43 subjects. 0 min: measure- ments before smoke production. also been observed for nose and throat irrita- tion. The results presented until now were all mean values from all subjects. We have shown, however, in these laboratory studies, as well as in field studies (7, 8), that some individuals, such~as people reporting sensitive eyes as welli as persons with allergic troubles and non- smokers, suffer significantNy more from irrita- tions and annoyance due to ETS than the others: For that reason the percentage of sub- jects with strong impairments of well-being must be taken into consideration. The mean incidences of people with "strong" and "very strong" subjective eye irritation are reported in Figure 4. Figurr smoke CO vab The marked irritatio pondinf Anno was alsc naire-s tionship annoyan gcnerati, remaine, rest of th sure had annoyan Accor these resi
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101 40-, v were all ive shown, ;, as well as ndividuals, yes as well and non- rom irrita- than than the sge of sub- well-being The mean and "very reported in 35 -~ 30-1 25 -~ ~ 20 " eye blink rate/min ~~\ / 10 ppm :~ ~-5ppm ~ 2.5 ppm ~ 1.3 ppm . f.. .............. •• controi ~ . _ . 0 20 Figure 3. Effects of environmental tobacco smoke on eye blink rate. CO values are levels during smoke production The figure demonstrates that there is a marked increase in the incidence of strong eye irritation between the smoke levels corres- ponding to 1.3 and 2.5 ppm CO: Annoyance due to ETS exposure-which was also determined by using the question- naire-shows a different dose-response rela- tionship compared to irritation. The annoyance increased rapidly as soon as smokee generation started and, after 10 to 15 min., it remained' approximately constant during the rest of the exposure. Thus the duration of expo- sure had' nearly no influence on the degree of annoyance. According, to our opinion, and' based on these results, a possible limit to protect healthy I i.4'-~ , v.e I1 1 40 60 exposure min minus background! level before smoke pro- duction. 32 to 43 subjects. 0 min: measure- ments before smoke production. people in their everyday environment against impairment of well-being by environmental tobacco smoke should lie in this range, i.e. between 1.5 and 2.0 ppm CO, since a marked" increase from about 3 to over 10 % of strongly impaired subjects appears therein. In a third series of laboratory experiments (4, 5; 6) we wanted to find out which compon- ents of tobacco smoke were mainlyresponsible for irritation and annoyance. By comparing the degree of irritation and annoyance of acrolein alone, of formaldehyde alone, and of the gas phase alone to that of the whole sidestream smoke, it coul& be shown that - acrolein and formaldehyde were only to a
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102 % with "very strong" or "strong° • 60 min exposure eye irritation A 40 min exposure 20n 15-~ 10-~ 5-1 0 smoke concentration Figxre 4. Percentage of persons with strong or minus background level before smoke pro- very strong eye irritating,reactions related to duction. 32 to 43 subjects: 0 min: measure- the degree and duration of exposure. ments before smoke production. CO values are levels during smoke production TABLE 1. Air pollution due to tobacco smokt in 44 workrooms-valuet are indoor concentration during work minus indoor concentration befpre work. Component Number of samples Mean value Standard deviation Maximum CO (ppm) 353 1.1 1.3 6.5 NO (ppb) 348 32 60, 280. PM (µg/m') 429 133 130~ 962 (z Nicotine (µgLm3) 140 0:9 1.9 13.8 ~ N N m O 3 2-I *, 1-i
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total sidestream smoke gas phase control * p< 0.05 ** p<0.01 Figure 5. Annoying effects of the total side- stream ~ smoke of cigarettes and of its gas phase alone, both exposures corresponding to an environmentat tobacco smoke induced CO level of 10 ppm. 32' subjects. 0 min = measurement before smoke production. minor extent responsible for the irritation caused by the sidestream smoke of ciga~ rettes other compounds in the gas phase were to a large extent responsible for the annoyance due to the sidestream smoke of cigarettes (see Figure 5) the particulate phase is to a large extent 103 responsible for the irritating effects of the sidestream smoke, since objective and sub- jective eye irritation were much lower with the gas phase alone than with the total sidestream smoke (see Figure 6). Field rtudy at workplaces In a field study (8) air pollution due to tobacco smoke was measured in 441 workrooms. For that purpose, the concentrations of CO, NO, nicotine and particulate matter were deter- mined~ in each~ rooms during 2 successive days (12 one-hour mean values per workroom). During these 2 days„the employees have been interviewed individually on the presence of irritation and annoyance as well as on their opinion about smoke in the environment. Table 1 summarizes some results of the chemicall measurements. The concentrationss of the measured pollutants increased as a con, sequence of smoking. The standard' deviation values show that the variance of the measured values was very large, sometimes exceeding 100 %. This means that the degree of air pol- lution varies markedly from one workroom to the others but also in one and the same work- room. Figure 7 reports some results from the inter- view, separated into groups of smokers and non-smokers. It can~ be deduced that: - approximately one third of the employees qualified the air where ETS is present at work as "bad" - forty per cent were disturbed by the smoke one quarter of the persons reported eye irritation at work non-smokers reacted significantly more to ETS than~ smokers.
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104 I 30-~ 20-~ 10_~ 0-i eye blink rate/min _.~ ..' ~* _ - - - - - ..~*4 _. ~**.....,,,_,...,,,.._.._ . 0 20 40 60 *. ** exposure min total sidestream smoke gas phase control p<0.05 p<0.01 Figun 6. The effects of the total! sidestream smoke of cigarettes and of its gas phase on eye blink rate. Both~ exposures correspond to a tobacco smoke induced CO level of 10 ppm. 32 subjects. 0~ min = measurement before smoke production. Furthermore, the employees suffering from hay fever reported~ significantly more eye irri- tation at work than those without hay fever, Chemical indicator and do.re-n.rpon,re nlatlonrbip These studies investigated whether there is a chemical substance which could be used as indicator of ETS and its acute effects. It seems that CO or nicotine could be appropriate, CO because it is inert and! easily measurable nico - tine because it is specific to tobacco smoke. In order to get an answer to this question, dif- ferent correlations were considered. Comlations between the chemical components The Pearson correlation coefficients between the different pollutant concentrations meas- ured in the workplace study are indicated in Table 2. Whereas there is a relatively high correlation between the gas phase components CO and NO, the correlation with the particulate phase (nicotine and the particulate matter) is low: The low correlation with nicotine may par- tially be explained by the fact that most values were in the range of the lower detection limit of our method of measurement by gas chroma- tography. The low correlation of the gaseous components with the particulate matter is most probably due to the different physical prop- erties (sedimentation, adkorption and desorp- tion of the particles) and to the fact that the PM-values include particles from other sources than tobacco smoke, Therefore, carbon mon- oxide can be considered as a useful indicator for nitrogen oxides, but not for the particulate matter nor for nicotine. Correlation between the chemical components and the effectr on men: dore-rrspbnre relationship In the laboratory experiments, CO has shown to be a good indicator to evaluate the effects of air pollution due to ETS. There was a nearly linear relationship between CO and the degree d G7 EJ'~ O J Figue due pres, TAB CO NO NO1, PM
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n/ationtbrp her there is a :d be used as fects. It seems propriate, CO asurable nico- cco smoke. In question, dif- .red. gh correlation ients CO and ticulate phase iatter) is low. -ine may par- at most values letection limit ~y gas chroma- )f the gaseous matter is most )hysical prop- a and desorp- - fact that the i other sources carbon mon- :eful indicator -he particulate ponents and the :O has shown : the effects of was a nearly .nd the degree Interviewed persons 0 20 40 60 80 % Ouestion Answer I I I I ~ Air quality good with regard to smoke bad never Disturbed by smoke sometimesl often Eye irrita- tion at work never 0 ts iiiiiiiiiiiiiiiiiiiiiililifilillif ® 5e ** 42 sometimes/~~ 3s ** often IIWIIW ~ g 73** [] Non-smokers+ex-smokers (N=237) ® Smokers (N=235) Figure 7. Evaluation of air quality and effects Results from 472 employees in 44 work- due to environmental tobacco smoke at the rooms. present workplace. TABLE 2. Cornlatiion coefficients between diffmeut pallutant concentrations due to tobacca smoke. 44 nrorkroomt Va/ues are indoor concentration durirtg mork mrnws indoor concentration befom mork. Number of correlated pairr= 345 for CO, NO, NOZ, AM and f 10 for nicotirre. NO NOZ PM Nicotine CO 0.73 0.55 0.33 NO 0.66 0:12 NOt 0.23 PM 21 0.01 0.01 0.36 039 11 II
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Air quality with regard to smoke: 'bad' 0 20 40 % I I I I I j CO 51.4 (ppm) >1.4 Nicotine so. (Ng/m3) >o. PM s15 (pg/m3) >15 18 20 42 ** ~ 0 22 3 ** Disturbed by smoke: 'sometimes'/'often' 0 20 40 % I i I I I I fifilllllLlllllll 35 iII ® Figure 8. Results of the interview related to rooms with low and high CO, nicotine, PM levels. of irritation. In the field: study, however, thiss dose-response relationship was much less obvious. The results of the interviews from the study at the workplace-divided into rooms with a low and a high CO, PM an& nicotine level-are represented in Figure 8. In the rooms with~high levels of CO, nico- tine and PM concentrations, more people evaluate air quality with regard to smoke as "bad". Analogously, the percentage of people with eye irritatiom and disturbances was also Eye irritation at work: 'sometimes'/'often' 0 20 40 % t i 1 i ij N 25 181 111111111111 1Ut11~ 28 244. Total: 472 employees in 44 workrooms. N= number of persons per group. * p<0.05; **' p<0.01, (X2-test). increased. Hence, it follows that there is a rela- tionship between air pollution due to ETS (measured by the parameters CO, nicotine and PM) and the reported annoyance and eye irri- tation. Thus, the observed effects can be explainedi at least to some extent, by ETS. However, this relationship is only applicable if mean values of large groups are considered. In fact, if we take each room into consideration and calculate the individual correlations between the meam pollutant concentrations of TABLE 3. Correlation coefficierrtr ixtwsn mean pollmtant concentratlon in each room and cornrpondrng nsultr fmm tb intervirm. Number of'comlattd pairs= 35 "* p <0.01. Air quality: Annoyed: ubad' "sometimes"/"often"' CO 0:10 0.46* * Nicotine 0:22 0.10 : PM - 0.02 0:10 Eye irritation: "sometimes"/"often' 0.21 -0.08 0.08. eac roo. Tat relo uret can ind ET` ind gasL ma: sarr F shii,. cou I
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e is a rela- etoETS -otine and d eye irri- s can be ,y ETS. ipplicable )nsidered. >ideration rrelations rations of !tr from tbe ition c '/"often" each room and the reporte& effects in this room, we obtainl a very poor relationship. Table 3 shows the corresponding Pearson cor- relation coefficients for these relations. The data demonstrate that from the meas- ured CO values in an individual room, one cannot easily draw conclusions on the extent of individual irritation and annoyance due to ETS. Therefore CO can only be used as an indicator to evaluate the degree of some gaseous components due to ETS and to esti- mate roughly the acute effects onl a large sample of persons. Regarding the weak dose-response relation- ship in the field studies, the following facts could be responsible: 1. The measuring method used is only repre- sentative in a limited way for the exposure of individual persons. In real conditions, the smoke is not distributed in a homoge- nous way (as it was in the climatic chamber), and it can vary a lot over time at one place. The short-term accumulationl of irritants : and particles in the cloud exhaled by a smoker is probably, to a large extent, responsible for the irritations and annoyance. These short concentration peaks are, howevery masked in our mean values over 1 hour in the field studies. In fact, a recent investigation (9) has shown that the highest peak values can be 100 time higher for the particulates, and 30 time higher for NO thanl the mean room concen- trations after one cigarette has beenl smoked. The amount of particulates may reach 100 mg/m~, NO 750 ppb in the exhaled smoke, at a distance of I m from the smoker. 2. The calculated values of various com- pounds correspond only approximately to the air pollution due to ETS: In our field' study at workplaces, the control measure- 107 ments have been made in the unoccupied room before work began (between 04.00 and 06.00). It was assumed that the condi- tions in the unoccupied room at the time were the same as during work over the day. This assumption is, however, not quite accurate: during the day the level of pollu- tants: coming froml the outside traffic is higher than early in the morning, when there is nearly no traffic. Therefore, the ca1= culated values give slightly too high levels for the air pollution due to ETS. 3. Inl field studies, individual psychological factors (relationship with smoking coworkers, general job satisfaction, attitude towards smoking) may considerably influence the individual evaluation of irri- tation and annoyance. Thus there is a considerable variance both in chemical measurements as in subjective per- ception in field studies. Perhaps an ameliora- tion could be reached on the chemical side by using a man-monitoring system which gives better information on the individual's expo- sure to ETS and other pollutants. REFERENCES 1. Weber A, Fischer T; Grandjean E. Objektive and subjektive physiologische Wirkungen des Passiv- rauchens. Int Arch occup Environ Hlth 1976: 37:277-288. 2. Weber A, Fischer T, Grandjeanl E. Passive smoking in experimental and' field conditions.. Environ Res 1979: 20:205-216,. 3. Muramatsu T, Weber A, Muramatsu S, Aker, mann F. Eicperiinental study on i irritations and annoyance due to passive smoking. Int Arch occup Environ Hlth 1983: 51:305-317. 4. Weber A, Fischer T, Grandjean E, Reizwir- kungen des Formaldehyd9 auf den Menschen. Int Archloccup Environ Hlth 1977: 39<207-218. 5. Weber A, Fischer T, Gierer R, Grandjean E.. Experimentelle Reizwirkungen von Akrolein auf den Menschen, Int Arch occup Environ Hlth 1977: 40! 117=130.
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108 6. Weber A, Fischer T, Grandjean E. Passive smoking; irritating effects of total'smoke and gas phase. Int Arch occup Environ Hlth 1979: 43:183-193. 7. Fischer T, Weber A, Grandjean E. Luftverun- reinigung durch Tabakrauch in Gaststatten. Int Arch occup Environ Hlth 1978: 43e267 280. 8. Weber A, Fischer T. Passive smoking at work. Int Arch oceup Environ Hlth 1980: 47:209-221. 9. Weber A, Fischer T. SchadstofEkonzentrationen im Blasfeld von, Rauchern. Sozial4 und' Praven- tivmedizin (in press). Annetta Weber Swiss Federal Institute of Technology. Department of Hygiene and Work Physiology ETH-Zentrum CH-8092 Zi7RICH-SWITZERLAND Surve- smoki amon lowin mariz, a) inc tio tra h) thi beii Iift ml Cj, cx ha rci p, . :t r~
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ntrationen d'PrIven- ology 3.5. Respiratory symptoms in the children of smokers: an overview PATRICK G. HOLT AND KEVEN J. TURNER EPIDEMIOLOGICAL FINDINGS Surveys on the association between parental smoking habits and' respiratory symptoms amongst their offspring have produced the fol- lowing claims. The relevant studies are sum, marized in Appendix Table 1: a) increased frequency of respiratory infec- tions, particularly in the lower respiratory tract, is claimed'n in infants; b) this effect is suggested to be age-related, being most marked in the first year of life ; c) i increased wheeze is reported in several sur- veys, separately or included amongst "res- piratory symptoms", d)i reduced lung function, detected via spiro- metry is reported in older children; e) exacerbation of asthma is claimed via hastening allergy development or, effects related, to bronchial reactivity; 1) the claimed! effects in some studies appear related more strongly to maternal than, to paternal smoking, especially when infants are involved. EXPOSURE OF CHILDREN TO ENVIRONMENTAL TOBACCO SMOKE: TOXICOLOGICAL EVALUATION While the effects, of environmental tobacco smoke (ETS) exposure remain largely specula- tive, a detailed literature exist upon the acute and chronic effects of active tobacco smoking on control systems which maintain home- ostasis. In relation to the respiratory system~ ETS has been showm to infltrence a variety of factors which contribute to the maintenance of health. These are discussed below in the con- text of the two major sets of symptoms claimed to be associated with~ ETS exposure im child- hood:. Infection Apart from~ immutable genetic factors asso- ciated' with host infectivity, and frequency of contact with sources of infection, susceptibility to respiratory infection is determined by a col- lection of factors which display varying degrees of sensitivity to tobacco smoke exposure (see 1, 2 for comprehensive reviews). The major factors in this category, summarized in Table 1, are as follows: a) Intrinsic exclusion mechanisms: Ciliostasis fol- lowing brief exposure to tobacco smoke has
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110 for many years provided a sensitive index of acute in vitro toxicity, and defective esliary clearance in the upper respiratory tract has been proposed as as contributing factor in a number of diseases related to smoking: In the lower respiratory tract a similar func- tiom is fulfilled by the alteolar macrophages: The resident population in chronic smokers is recognized to be expanded in number and metabolic activity, and to exhibit a variety of malfunctions in in vit+o and in vitrn test systems. More recently, the physical intcgrity of the nspiratory mucosa itself has been sug- gested to break down in response to the irritant effects of smoke (3) whi& may assist both in the penetration of invading microorganisms and (as discussed further below) allergenic material. Damage to the mucosa here has been suggested to result either from the direct irritant effect of smoke on the membrane, or from ~ the toxic products of killed alveolar macrophages ('3).. This latter cell i population has been shown experimentally to adapt to survival in the toxic environment of the lung chronically exposed to smoke (4) via a process of bio- chemical activation (5). However, alveolar macrophages from hings whichi have not previously encountered tobacco smoke exposure are highly susceptible to thiss agent, and a sizeable proportion of the cells are killed upon their first exposure (4). b) Immunolagical mechanisms: The first line of humoral immune defence against respira- tory infection, is provided! byncrrtory IgA in the upper airways -reliable data are not available upon sufficiently large samples of smokers for firm conclusions to be drawn regarding the susceptibility of local IgA re- sponses to smoke exposure. However, animal studies do indicate that, local anti- body responses within the lung are particu- larly sensitive to smoke in exposed animals TABLE 1. Factora determining sxrceptibility to rarpirator tract infectroa: rrkvant reported efficts of tobacco smoke. Factor Contact frequency Physical exclusion mechanisms (i) Mucociliary clearance (ii) Alveolar macrophages (iii) Mucosal barrier Antibody (i) Secretory IgA (ii) Others Cell Mediated Immunity Effect of Tobacco Smoking Increased respiratory infection rates amongst smoking parents Tobacco smoke induces ciliostasis in vitro; Highly toxic on first contact; with chronic exposure, population adapts via biochemical activatiom and cell death, not seen; Increased permeability of respiratory mucosa to tracer molecules Insufficient data; Decreased IgM/IgG responses in man ; biphasic sys- temic changes in exposed animals but marked suppres- sion of local lung responses Biphasic changes in systemic T-cell function in both man and exposed animals; T-cells from lungs of young smokers depressed In Gob Mu su S) a di in. pr eo m: rel lut yo U m: Bmncb A nuu report invoh
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)een shown vivali in the chronically cess of bio- er, alveolar h have not cco smoke 31e to this : of the cells sure (4). irst line of nst respira- rrtory IgA in ata are not - samples of o be drawn xal IgA re- However, : local anti- are particu- sed animals a tmmke. ngst smoking -tic exposure, tion and cell ::osa to tracer biphasic sys- rked suppres- -tion in both ;ngs of yotutg Epitheiiai damage_ o ~ Z afnage to o , nw. IJ// 1 Enzyme raleas. Infection Mucus Airway narrowing (6). Systemic antibody responses appear depressed both in man (1, 2) and in a chron- ically exposed animals, whereas acute expo- sure appears stimulatory (1, 6): Systemic cellmediated immunity (CMI) exhibits a biphasic pattern of change in animals during chronic smoke exposure, being initially stimulated and subsequently de- pressed as exposure continues (1, 7), and comparable findings have been reported for man (8, 9). It has also recently been reported that T-lymphocytes isolated from~ lung lavage fluids from asymptomatic young smokers exhibit depressed in vitro CMI responses relative to those of age- matched non-smoking controls (10). Bronchial symptomt A number of the surveys listed in Table 1 report symptoms in smokers' children~ which involve narrowing of the small airways. These bacco smoke T Immunosuppression ~ Aaarp.n p.naauon . Inoreasad penetratCon 'i of bthen irritanta (e.p... partituiuet) ~ Frgxre 1. Potential mechanisms for ETS-mediated changes in lung func- tion. may be an indirect result of the excessive mucus production which may potentially be trigged by the irritant effect of ETS inhalation on bronchial tissue. The scheme proposed in Figure 1 presents a hypothetical framework for discussion of the interacting processes which may be operative in these circumstances. Firstly, respiratory infectionsperse may con- tribute to many of these symptoms, either as a direct result of excessive mucus production, or indirectly via a series of effects which stem from damage to the integrity of the respiratory epithelium. It has been observed that vagal sensory nerve endings lie beneath the tight junctions of the airway epithelium, and it has been proposed that damage to the junctions by a variety of agents "sensitizes" these receptors; and results in exaggerated reflex responses, i.e. bronchial hyperreactivity (reviewed in 11). Such agents include rhinovirus, influenza (12,. 13) and a variety of other infections (14), and also a range of chemical!irritants, such as ozone k I I
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112 (15; 16); SOz (17, 18) NO2 (19) and CO at levels approaching those encountered during smoking , (20). Epithelial damage of this nature may also cause airway hyperreactivity by increasing airway permeability, thereby allowing higher concentrations of inhaled irritant material (e.g. particulates) to reach "target" cells such as sen- sory nerves (1Q). Penetration of allergenic material may also increase in these circum- stances. It is noteworthy in this regard that increased penetration of molecules such as horseradish peroxidase into the intercellular gaps of the respiratory epithelium has been observed in animals exposed to cigarette smoke (21, 22, 23), and a range of other irri- tants including histamine and methacholine (24), ozone (25) and NO2 (26), the latter agent also promoting uptake via pinocytotic ves- icular transport in the secretory cells of thee airways. Experimentally induced chronic pul- monary inflammat2on in the rabbit is also asso- ciated with increased permeability to aerosol- ized protein (27). The recent development of a non-invasive procedure for assessing the permeability of the pulmonary epithelium has permitted prelimi- nary studies on cigarette smoke effects of this nature in human smokers. Employing an aerosol of 99M Tc-diethylenetriamine penta- acetate (particle size one micron) to measure the rate of passage of inhaled! tracer into the blood, epithelial permeability has been~shown to be significantly increased amongst symp- tomless cigarette smokers (28),,and to return to normal limits after cessation of the habit (3). The authors also reported a correlation between half-time lung clearance and carboxy- haemoglobin concentration (3) which suggests a role for CO in this process.. A further issue which must be considere&in this context is the potential effect of increased permeability of the respiratory epithelium to allergens. It is conceivable that such circum- stances may promote allergic sensitization via the stimulation of allergen-specific IgE syn- thesis; the latter would become fixed to locali mucosal mast cells, and serve as a trigger for allergic responses to subsequent allergen pen- etration. Recent' studies have shown that the passive deposition of allergen on the intact respiratory epithelium protects against allergic sensitization via stimulation of specific sup- pressor T-lymphocytes (29, 30) whereas acute co-exposure to allergen and inflammatory agent(s) which affect mucosal permeability, such as ozone (31, 32) or NOz (31i, 33) or acid fumes (34) instead promotes IgE antibody production. The possibility that tobacco smoke may be capable of similar effects has not been tested'directly: However„adult smokers exhibit higher overallQevels of serum IgE than do non- smokers (35), and a recent study suggests that the age-related increase of serum IgE levels in high-risk groups of children (viz. both parents atopics) is accelerated by the presence of adult smokers in the household (36). Respiratory infection, must also be con- sidered in relation to this process, from two viewpoints. Firstly, epitheliali damage as a result of infection may promote IgE responses directly via accelerating penetration of allergens. Secondly, it is recognized that immune responses of the IgE class are tightly controlled by a subset of labile T-cells. Inter- ference in overall T'cell function by the impo- sition of any form of exogenous immunosup- pression may temporarily free IgE-B-cells from regulation and thus promote IgE production and subsequent allergic sensitization (reviewed in 37). Viral infections have been observed to depress T-lymphocyte function for several weeks (38). The association of virus infections in children with the appearance of immuno- logical evidence of allergic sensitization repor both , The whicl tobac huma catior possit tion f ETS4 The c attain are ca above publi: house respo, the ac dose obtair equipp child' lkrgel expos lived loads TABL 1. 2. 3. 4: 5. 6. 7: 8. 9. 10.
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113 ;, epithelium to it~ such circum ensitization via ecific IgE syn- .e fixed to local as a trigger for it allergen pen- shown that the : on the intact against allergic )f specific sup- whereas whereas acute inflammatory I permeability, (31, 33) or acid IgE antibody tobacco smoke ts has not been ;mokers exhibit ;E than do non- iy suggests that rn IgE levels in z. both parents -esence of ad'ult reported by Frick (39) 1 may reflect either or both of these processes: EXTRAPOLATION OF FINDINGS TO CHILDREN EXPOSED TO ETS The foregoing discussion draws upon data which, for the most part, pertain to high-dose tobacco smoke exposure in smoking adult humans and experimental animals. The impli- cations of the published findings in relation to possible effects on children require considera- tion from two viewpoints: ETS dose letklr encountered in the bome The question of whether ETS components attain levels in the home environment which are capable of affecting the processes detailed above, cannot yet be answered directly. Few published studies are available which contain household measurements, and published dose- response experiments referred to above in the adult literature mainly pertain to high dose exposures. However, preliminary data obtained employing personal air sampling equipment have suggested~ that an individual child's total respirable particulate load is largely determined by the indoor environment, exposures being higher amongst children who lived with~ smokers, where daily particulate loads oftem exceeded the primary air quality standard (40). Direct information on gas phase components such as carboxyliemoglobin levels in children exposed to ETS is not available; however, the data from adults (e.g. see 41) suggests that moderate CO exposure is likely in the home environment of smoking families. also be con- cess, from two damage as a : IgE responses enetration of cognized that lass are tightly T-cellk. Inter- 'n by the impo- is immunosup- ;E-B-cells from gE production tion {reviewe& zn observed to n for several irus infections e of immuno- sensitization Relative sensitivity of ad ults versur c6ildren A number of points summarized' in Table 2 must be considered when assessing potential effects of ETS in children relative to their par- ents. Firstly, T-lymphocyte an& macrophagee function are not fully developed at birth, and the factor(s) which determine their rate of maturation in early life have not been def ned. In the context of allergic sensitization, the early postnatal period is considered! by many workers to be criticali in relation to the subse- quent expression of genetic potential for al- lergic disease, and both immature T-cell func- tion and defective mucosal exclusion mechan- isms have been implicatedi Consequently, exogenous factors which may contribute further to immune depressiom (Table 1) or increased~mucosal permeability (Fig. 1) may be disproportionately injurious at this stage of life. Secondly, a variety of factors may heighten the child's susceptibility(relative to the adult's) to small airway obstruction. These (reviewed TABLE 2. Intnnsic dicrlopmental fpctors mhich' may influence the tobacco smoke serrsitrvity of the napiratory tract of children, n4rtlve to that of adulti. 1. T-celll function immature at birth 2.. Macrophage function immature at birth, 3: Relatively small airway diameter in, children 4. Relatively high density of submucosal glands 5. Relatively large size of glands in relation to bronchial wall 6. Red'uced elastic properties of the lung 7: Greater air flow relative to lung,size 8. Greater permeability of respiratory epithelium (?) 9. Less reserve lung surface area for added metabolism 1O1 Less vibrissac in ~ vestibule of the nose
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114 in 42) include increased susceptibility to infec- tion as a result of comparatively immature immune defence mechanisms, the relatively smallldiameter of the airways, the high density of submucosal glands and their comparatively large size in relation to the bronchial wall, and perhaps reduced elastic properties. Thirdly, it has been suggested that changes in pulmonary function in children are espe- cially sensitive to particulate pollution (43), which may be related to the relatively poor development of vibrissae on the epithelium lining the vestibule of the nose in childiren (42), the principal function of which is to filter out inhaled particles. It must also be remembered that such basic functions as temperature and humidity adjust- ment of inspired air are under more stress in the child than~ the adults the conditioning mechanism of the infant's upper airway being called upon to handle a greater volume of air in proportion to lung size than that of the adult (42): In this context4 increased airflow may also infer increased contact with air contaminants relative to an adult in the same room. One further inference may be drawn in rela- tion to function which stems from the dimen- sional relationship of the lung at different ages (44). It has been observed that the numbers of alveoli and airways increase about 10-fold from infancy to adulthood, whereas lung sur- face area increases approximately 20-fold, in line with increases in body weight. Superfi- cially, this would appear to be a reasonable relationship, as area for gas exchange should theoretically bear some relationship to the mass of metabolizing cells. However, the meta- bolic rate of the infant is up to double that of adults when expressed on a per body weight basis. Therefore, the infant would appear to have less reserve lung surface area for added metabolism than the adult (44). Consequently, agents such as CO may exert deleterious effects at levels considerably below those toxic for adults, particularly under conditions of stress. Finally, the question of respiratory mucosal permeability in~ adults and children warrants consideration, as this appears at the focal point of the proposed~ effects of ETS (F'ig: 1). Tracer molecules such as horseradish peroxidase are capable of broaching epithelial!barriers in the fetal lung, as shown in studies of fluid resorp- tion in newborn animals (44). However, stu- dies on age-related changes in permeability during, childhood are not available, but may now be feasible as appropriate technology becomes available (3, 28). CONCLUSIONS' AND RECOMMENDATIONS The proposed effects of ETS exposure on~ the children of smokers, notably increased prevalence of respiratory infections and bronchial symptoms, are supported by a variety of epidemiological data and'thus warrant more comprehensive investigation. In examining the theoretical basis for these claims,, an integrated' pathway comprising a variety of interrelated immunological and inflammatory processes which are known to be sensitive to tobacco smoke exposure in~ adults and which collectively result in increasediper- meability of the respiratory membrane, is pro- posed as a possible mechanism for the indilc- tion of respiratory symptoms in the child exposed to ETS. It should be stressed that this scheme (Fig. 1) is presented as a tool rather than a series of conclusions, and is intended to assist in focussing,research upon specific con- trol mechanisms with a view to obtaining more precise information on this question than is available in the current literature. In examining the relevance of the individual components of this pathway, it will be neces- sary to collect new data at three levels. Firstly, the existing experimental literature pertains
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115 e toxic for di'tions of ,ry mucosal n warrants focal point 1). Tracer oxidase are riers in the uid resorp- wever, stu- ermeabiiity e, but may technology ATIONS ;ure on the increased •tions and by a variety rrrant more is for these mprising a 3gical and nown to be x in adults reased per- ane, is pro- the induc- the child ed that this tool rather ntended'to ecific con- ining more on than is individual 1 be neces- els. Firstly, -e pertains exclusively to adult animals; given the poten- tial age-dependent variation im tobacco smoke sensitivity (Table 2), much of this work should be repeated employing younger animals. Secondly, both the experimental and human literature on mechanism(s) of tobacco smoke mediated effects is restricted to relatively high dose studies, which may not encompass the range relevant to the child exposed to ETS. Thirdly, there are no reported studies on actual absorption of ETS by childten. Such studies should be performed as soon as possible to provide some form of baseline for future work. The recent development of non-invasive mon- itoring methods employing saliva and urine samples (45) ~ have supplied convenient tools for this task. REFERENCES 1. Holt P. G, Keast D. Environmentally induced changes in immunological function: Acute and chronic effects of inhalation of tobacco smoke and other athmospheric contaminations in man and experimentali animals. Bact Rev 1977: 41:205-216. 2. U. S: Public Health Service. Smoking and Health : A Report to the Surveyor General of the Public Health Service. DHEW Publication No. (PHS) 1979: 79-50066. 3. Minty B. D, Jordan C, Jones Jl G. Rapid im- provement in abnormal pulmonary epithelial' permeability after stopping cigarettes. Br Med J 1981: 282:1183-1186. 4. Holt P. G, Keast D. Cigarette smoke inhalation: effects on cells of the immune series in the murine lung. Life Sci 1973: 12:377-383. 5, Holt P. G,,Keast D. Acute effects of cigarette smoke on murine macrophages. Archs envir Hlth 1973: 26:300-304. 6. Thomas W. R, Holt P. G, Keast D. The devel- opment of alterations in the primary immune response of mice by exposure to fresh cigarette smoke. Int Arehs Allergy appl Immun 1974: 46:481-586. 7: Thomas W. R, Holt P. G, Keast D. Cellular immunity in mice chronically exposed to fresh cigarette smoke. Archs envir Hlth 1973: 27:372-375, 8. Silvermore N: A, Potvil C, Alexander J. C, Chre- tien P. B. In vrtm lymphocyte reactivity and T- cell levels in chronic cigarette smokers. Clin exp Immunol 1975 c 22:285-292. 9. Vos-Brat L. C, Runke P. H. Immunoglobuline concentraties, PHA reacties van lymfocytenlm tfftm e eukele antistof titers van gezonde rokers. Jaarb Kanker Kanker Neder 1969: 19:49-53. 10: Daniele R. P, Dauber J. H, Althose M. D, Rowlands D. T. Gorenbcrg D. J. Lymphocyte studies in asymptomatic cigarette smokers. A comparison between lung and peripheral blood. Am Rev resp Dis 1977: 116:997-1008: 11. Bouchey H. A, Holtzman M. J, Sheller J. R, Nadel Jl A Bronchial hyperreactivity: Am Rev resp Dis 1980: 1211:389-413. 12. Little J. W, Hall W. Jl Douglas R. G, Mudholkar G. S, Speers D. M, Patel K Acute hyperreacti- vity and' peripheral airway dysfunction in Influenza A infection. Am Rev resp Dis 1978:, 148:295-306. 13: Minor T. E, Drok E: C, Baker J. W, Qulette J. J, CohenM„Reed C. E. Rhinovirus and Influenza Type A infections as precipitants of asthma. Am Rev resp Dis 1976: 113:149' 153:. 14. Empey D. W, Lartinen C. A. Jacobs L, Gold W. M, Nodel J. A, Mechanisms of bronchial hyper- reactivity in ~normal subjects after upper respira- tory tract infection, Amer Rev resp Dis 1976: 113c131-361. 15: Golden Jl A, Nadel J. A, Boushey J. A. Bronchial hyperirritability, in healthy subjects after expo- sure to ozone. Am Rev resp Dis 1978 : 118:287- 294. 16. Lee L-Y, Blbecker E. R, Nodel J. A. Effect of ozone on bronchomotor response to inhaled his- tamine aerosol in dogs. J appll Physiol 1977: 43:626-631. 17. Islam M. S, Vastag E, Ulmer W. T. Effect of various stimulants onibronchial reactivity. Bull Physiopath respir (Nancy) 1972: 8:509-517. 18. Islam M. S, Vastag E; Ulmer W. T, Sulphur dioxide induced' bronchial hyperreactivity against methacholine. Int Arch Arbeitsmed' 1972: 29 t221-223: 19. Orehele J. Massari J. P, Gayrard P„Grimaud C, Charpin, J. Effect of short-term, low level nitrogen dioxide exposure on bronchial sensitivity of asthmatic patients. J clin Invest 1976c 57:301-307.
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116 20. Niden A. H. The effecn of low levels of carbon monoxide on the fine structure of the therminal airways. Am Rev resp Dis 19711: 103:898. 21. O'Connell E. J, Logan G. B. Parental smoking in childhood asthma. Ann Allergy 1974: 32:142-145. 22. Boucher R. C, Johnson J. Inoue S, Hulbert W, Hogg J: C. The effect of cigarette smoke on the permeability of guinea pig airways. Lab Invest 1980 : 43:94-100. 23. Hulbert W: C, Walker D. C, Jackson A, Hogg J. , C. Airway permeability to horseradish peroxi- dase in guinea pigs: the repair phase after injury by cigarette smoke. Am Rev resp Dis 1981: 123:320-326. 24. Simani A. S, Inoue S, Hogg J. C. Penetration of the respiratory epithelium of guinea pigs follow- ing exposure to cigarette smoke. Lab Invest 1974: 31:75-81. 25. Matsumura Y. The effect of ozone, NOZ and SOZ,on the induced allergic respiratory disorder in guinea pigs. II. Effects of ozone on the absorptionand retention of antigen in the lung. Am ~ Rev resp Dis 1970: 102:438. 26. Bouchen R. C,, Ranga V, Pare P. D. Inoue S, Moroz L. A, Hogg J. C. Effect of histamine and methacholine on guinea pig tracheal permeabil- ity to HRP. J appl Physiol 1978: 45:939-948. 27. Ranza V, Kleinerman J. Ip M. P. C, Collins A. M. The effect of NO~ on tracheal uptake and transport of horseradish peroxidase in the guinea pig. Am Rev resp Dis 1980: 122:483. 28. ThralliR. S, Peterson L. B, Broley J. F, Linehan J. H, Dawson C. A, Moore V. C. Chronic pul- monary inflammation modulates the fate of pro- teins administered by the respiratory tract. J, Lab clin Med 1980: 95:343-350. 29. Jones J. G, Lawler P„Crawley J. C. W, Minty B. D, Husland G„Neall N. Increased alveolar epi: theliali permeability in cigarette smokers. The Lancet 1980: 1:66-68. 30. Holt P. G, Batty J. E, Turner K. J. Inhibitionof specific IgE responses by pre-exposure to inhaled antigen, Immunology 1981: 42:409: 4i17. 31. Matsumura Y. The effects of ozone, NO2 and! SO2 on the experimentally induced allergic sen- sitization with albumin, through the airways. Am Rev resp Dis 1970: 102:430-441L 32. Holt P. G, Leivers S. Tolerance induction via antigen inhalation: isotype specificity, stability and involvment of suppressor T-cells. Int Arch Allergy APpI Immunol 1982: 67:155-172. 33. Holt P. G, Rylander R. BergstrSm~ R. Manu- script in preparation. 1983. 34. Osebold J, W, Gerswin L. J, Zee Y. C. Studies on the enhancement of allergic lung senitizationby inhalation of azide and sulfuric acid aerosol. J Environ Pathol Toxicol 1980 : 3:221-234. 35. Burrows,B. Halonen M. Barbee R. A, Lebowitz, M. The relationship of serum IgE to cigarette smoking. Am Rev resp Dis 19811: 124:523- 525. 36. Kjellman N-L M. Effect of parental smoking on IgE levels in childten. The Lancet. 1981: 1 r993- 994. 37. Katz D. A. Control of IgE antibody production by suppressor substances. J Allergy clin Immunol 1978 : 62 :44.55. 38: Wybran J; Fudenberg H. H. Thymus-derived rosette-forming cells in various human disease states;, cancer, lymphoma„ bacterial and viral infections and'other diseases. J clin Invest 1973: 52:1026-1034., 39. Frick D. L, German D. F, Mills J, Development of allergy in children. II Association with~virus infections. J Allergy clin Immunol 1979: 63:228-241. 40. Binder R. E, Mitchell C. A„Hosein H. R„Bou- huy,s A. Importance of the indoor environment in air pollution exposure. Archs envir Hlth 1976 c 311:277 279. 4E Schmeltz I, Hoffman D, Wynder E: L. The influence of tobacco smoke on indoor atmos- phere. I. An overview:: Preventive Medicine 1975: 4a66-81 42. Scarpelli E. M. Pulmonary physiology of the fetus, newborn and child. Lea & Febiger, Phi- ladelphia. 1975. 43. Ferris B. G. Effects of air pollution on school absences and differences in lung function in first and second graders in Berlin. New Hampshire. Am Rev resp Dis 1970: 19:653. 44. Avery Mi E, Fletcher B. D, Williams R, G„The lung and its disorders in the newborn infant. W. B. Saunders Co Philadelphia. 1981. 45. Jarvis M. J, Russell M. A. H. Measurements and estimation of smoke dosage to non-smokers from environmental'tobacco smoke. Eur J Resp. Dis 1984~: Suppl 133: 68-75. 46. Cameron P. Kostin J. S, Zaks J. M, Wolfe Jl H, Tighe G, Oselett B, Stocker R, Winton J. The he Al 47. Ca to Ps 48.Cc In ph ch 49: H: hc 19 50.Le to: Cr 51.Le W or: dc lc: 52: Sa sn le 53. B: E re V 54. R ki i tc 6' 55. a Ic al 56. T EE m V' 57. H h- T 1: 58. L P
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1117 Int Arch -172. R. Manu- itudies on -ization by aerosol. J -234. Lebowitz ~ cigarette 124:523- noking on 3f:1:993- >roduction ergy clln ls-derived an disease and viral vest 1973: elopment t with virus iol 1979:, {. R, Bou- ri'ronment nvir Hith E. L The )or atmos- Medicine ,3gy of the biger, Phi- on school tion in first lampshire. R. G, The infant. W. health of smokers and non smokers children. J, Allergy 1969: 43:336-341. 47. Cameron P, Robertson D. Effect of home envi- ronment tobacco smoke on family health. J applI PsychioU1973: 57:142-147: 48. Colley J. R. T, Holland W: W, Corkhill R. T. Influence of passive-smoking and parental phlegm on pneumonia and bronchitis in early childhood. The Lancet 1974: 2:1031i-37: 49. Harlap S;, Davies A. M. Ihfant admissions to hospital and maternal smoking. The Lancet 1974. 1:529-532. 50. Lebowitz M. D, Burrows B. Respiratory symp- toms related to smoking habits of family adults. Chest 1976: 69:48-50:. 51. Leeder S., R. Corkhill R, Irwig C. M, Holland W. W; Colley J. R. T. Influence of family factors on the incidence of lower respiratory illness during the first year of life. Br J prev soc Medl 1976: 30:203-212. 52. Said G, Zalokar J. Lellouch J, Patois E. Parental smoking related to adenoidectomy and tonsil- lectomy in children. J'Epidem Community Hlth 1978: 32:97-101. 53. Bland M, Bewley B: R, Pollard V,,Banks M.,H. Effect of'~ children's and parents' smoking on respiratory symptoms. Archs Dis Childhood 1978 : 53 :100 -105. 54': Rantakallio P. Relationship of maternal smo- king to morbidity and mortality of the child up to the age of five. Acta paediat Scand 1978: 67:621-631. 55: Wittig H. J, McL'oughlin E: T, Leifer K L, Bel- loit J. D. Risk factors for the development of allergic disease: Analysis of 2190, patient records. Ann Allergy 1978: 41:84-8& 56. Tager I. B, Weiss S. T, Rosner B, Speizer F. E. Effect of parental cigarette smoking on the pul- monary function of children, Am J Epidem 1979: 110;:15-26. 57: Holma B, Kjaer G, Stockholm J: Air pollution, hygiene and health of Danish schoolchildren. The Science of the Total' Environment 1979: 12:251-286. 58: Datau G, Corberand J. Enjaume C, Rochicciolil P. Passive inhalation of tobacco smoke in pre- school age children.. Clinical an& biological study. Bordeaux Med 1979: 12:933-936. 59. Yarnell J. W. J~ St. Leger A. S. Respiratory ill- ness, maternal smoking habit and lung function in childreni Br J Dis Chest 1979: 73:230-236.. 60. Kasuga H, Hasebe A, Osaka F, Matsuki H. Res- piratory symptoms in school childi-en and the role of passive smoking. Tokai J Exp Clin Med 1979: 4:101-104. 61. Weiss S. T, Tager I. B, Speizer F. E, Rosner B. Persistent wheeze. Its relation to respiratory i111 ness, cigarette smoking, and level of pulmonary function in a population sample of children. Am Rev resp Dis 1980: 122:697-707. 62: Fergusson D. M, Horwood! L. J, Shannon F. T. Parental smoking and respiratory illness in, infancy. Archs Dis Childh 1980: 55:358-361. 63. Bonham G. S, Wilson R. W. Children's health in families with cigarette smokers. Am J publ Hlth 1981: 71:290-293. 64. Fergusson D. M, Horwood L. J, Shannon F. T, Taylor B. Parental smoking and'.lower respira- tory illness in the first three years of life. J Epidem Community Hlth 1981: 35:180-184. 65. Hasselblad V, Humble C. G, Graham M. G. Indoor environmental determinants of lung function in children. Am Rev resp Dis 1981: ~' 123:479-485. 66: Datau G, Enjaume C, Petrus M. Epidemiolbgy of passive smoking of children from 0 to 6 years. Arch fr Pediat 1981: 38:721i-725. 67. Gortmarker S. L, Walker D, Jacobs F. H, Ruch- Ross H. Parental smoking and the risk of child- hood asthma. Am J public Hlth 1982: 72:574- 578. 68. Liard R, Perdizet S, Reinert P. Wheezing bron- chitis in infants and parents' smoking habits. The Lancet 1982: 1:324-335. Patrick G. Holt Clinical Immunology Research Unit Princess Margaret Hospital for Children Subiaco 6008, Western Australia. ments and n-smokers EurJ Resp Y/olfe J. H, ton J. The
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APPENDIX TABLE 1. Rerpiratory rymptwnt in ebildrtm ar a, jfrrnction of panrnta! rnrokrng babitr. ear ample ocation Disease/symptom Method of associated with data parental smoking collection Respondent/ subjects Dose relation- ship claimed Exogenous factors controlled for 1969 1217 Detroit Respiratory ill- Interview Parent Yes 1973 children 2626 USA USA ness Acute respira- Interview Adults No Environmental households tory illnes factors 1974 628 Midwest Asthma Interview Child + Yes children USA Parent 1974 2598 Aylesbury Cough Question- Parents Yes Socioeconomic children UK naire factors 1974_ 2205 Harrow Bronchitis and Interview + Parents Yes Socioeconomic infants UK pneumonia medical factors, family size 1974 10 672 Jerusalem Bronchitis and records Interview + Mothers Yes Birthweight, social infants Israel pneumonia records class, birth order 1976 1655 Tucson Cough, phlegm, Question- Parent + No Socioeconomic households USA wheeze naire child status, family size 1976 2044 Harrow Bronchitis and Interview + Mothers No Family size, infants UK pneumonia in records disease amongst children under siblings, 1 year socioeconomic 1978 3920 Paris Frequency of Question- Children Yes factors Age, sex, day children France adenoid- & naire nursery attendance, tonsillectomy family size, appendicectomy history EzszzsCa 1978 6000 Devonshire Cough Question- Children No i iK naire Re- fer- Comments ence 46 47 21 Direct effect of smoke 13 secondary to cross infec- tion from parent Effects most marked in 48 ' children under 1 year Effects most marked in 49 infants of 6-9 months Smoking relationship 50 disregarded when adults symptoms controlled Sibling disease rates are 51 1 a contributing factor: upper respiratory dis- ease unaffected Frequency of appendi- 52 cectomy not affected 53
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1978 1978 1978 1979 1979 1979 1979 1979 79 1980 l,rcqucncy ot l2uesuon- l.htldren Yes adenoid- & naire tonsillectomy 6000 Devonshire nshire Cough Question-_ Children No UK naire 12 068 Finland Hospitalization Interview + Mother Yes mothers for respiratory records disease 2190 Florida Reduced age of Patient Patients_ No allergy USA onset allergy records . patients 444 Boston Decreased vital Interview + Children + Yes children USA capacity spirometry parents 3840 Denmark Bronchial symp- Interview + Children + No children toms spirornetry parent sore throat 56 Toulouse Recurring res- Interview, Children Yes children France piratory examination disorders 214 Cardiff Reduced lung u_ ng Interview + Child + children Wales function spirometry mother 1937 Tokyo Respiratory Interview Children Yes children Japan symptoms 650 Boston Persistent Interview + Children + No children USA wheeze spirometry parents decreased vital capacity Age, sex, day nursery attendance, family size, appendicectomy history Socioeconomic factors Race, maternal age, family structure, life style, feeding his- tory, environmental factors Socioeconomic status; household environment Socioeconomic status, housing ambient air, pollu- tion education Social class housing conditions ndi- Residential condi- tions tions Frequency of appendi- 52 cectomy not affected 53 Effect most marked in 54 children under 1 year 55 56 Bronchial symptoms 57 7 associated only with maternal smoking 58 Effects claimed asso- 59 ciated with maternal smoking during preg- nancy Smoking effects most 60 evident in children living adjacent to major highway Paternal smoking king irrele- 61 vant
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N 0 Dose Re- Disease/symptom Method of relation- associated with data Respondent/ ship Exogenous factors fer- Comments ence Year Sample Location parental smoking collection subjects claimed controlled for 1980 1180 Christchurch Bronchitis, Interview Mother No Perinatal history infants NZ bronchiolitis or socioeconomic pneumonia factor, postnatal diet 1981 37 000 USA Respiratory Interview , Adults Yes Age of child, households disease number of adults per house, socio- economic factors 1981 1265 Christchurch Bronchitis, Interview + Mother Yes Maternal age, edu- children NZ bronchiolitis or records cation, family size pneumonia 1981 16 689 USA Decreased vital Interview + Parent(s) + Yes Socioeconomic children capacity spirometry child status, presence of gas stoves in home, ambient air pollu- tion 1981 892 Toulouse Respiratory Interview Children Yes Day nursery children France symptoms attendance, heating 1982 3966 USA Asthma preva- Interview Mothers No Family size, race, children lence socioeconomic fac- tors, tors, education 1982 424 Val de Marne "Wheezy" bron- Interview Mothers Yes infants France chitis Upper respiratory dis- 62 ease not affected; paternal smoking habits irrelevant "Restricted activity" 63 taken as criterion of dis- ease Paternal smoking irrele- 64 vant; effects most marked in infants under 1 year Paternal smoking 65 irrelevant 66 Paternal smoking irrele- 67 vant smoking habits irrelevant Cough, upper respira- 68 tory disease and simple bronchitis unaffected sz9zzsEQ
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3.6. The effect of environmental tobacco smoke in two urban communities in the west of Scotland l CHARLES R. GILLIS, DAVID J. HOLE, VICTOR M. HAWTHORNE AND PETER BOYLE INTRODUCTION The question of whether environmental tobacco smoke (ETS) can damage health has not yet been clearly answered. It is known that a lighted cigarette emits more sidestream smoke than mainstream and that the smoke available for involuntary inhalation contains substantial amounts of carbon monoxide, tar, nicotine, benzo(a)pyrene and other carci- nogens, and oxides of nitrogen (1). Stiudies from Japan (2) and Greece (3) have suggested that non-smoking wives of heavy smokers have a two-fold increased'irisk of lung cancer when compared with~ non,smoking wives of non-smokers. In contrast, anaNysis of data from the prospective study of the Ame- rican Cancer Society volunteers (4) has sug- gested1 thar~ very little, if any, increased'risk of lung cancer exi'sts when non-smoking women marrie& to smoking husbandfi and non- smokers married to non-smoking husbands are compared. The present study has been carried out in a define& population group in an area of high incidence (5) of lung cancer with a precisely defined population base. It reports lung cancer data on both males and females. MATERIALS' AND METHODS The study comprises 16,171 apparently healthy individuals aged between 45 and 64, resident in Renfrew and Paisley, two urban areas in the West of Scotland. They took part in a multi- phasic screening survey for cardiorespiratory disease between 1972 and 1976. This repre- sented a response rate of 80 46 of those ran- domly sampled from the resident populatiom Details of this survey have been described by VMH (6). Information on each respondent's smoking habits and their experience of symp- toms of respiratory and cardiovascular disease were collected using a self-completed ques- tionnaire, carefully checked at the time of attendance at the screening unit~ The diagnosis of cancer in each individilali has been checked! in the West of Seotland' Cancer Registry and follow up for mortality carried out by'record linkage (7) with data from the Registrar General for Scotland. Follow up is complete until 31 December 1982. As members of the same household'attended the screening,unit, it was possible to identify smoking and non-smoking partners of smokers and non-smokers. These were allocated to categories defined so as to represent an increasing measure of tobacco exposure.
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122 TABLE 1. Number and pemntage of individxals by cattgory. 1. Nxmder of individxalr attending seraning = 16,17?, Nxmber aitbin partnen6i~r sarened = 8,128 (ex-smokers exclirded). 2. Male Category N 96 N Female 96 3: Controls 517 12.7 523 12.9 ETS exposure 310 7.6 1394 34.3 Smoking - 1395 343 310 7.6 Smoking + ETS exposure 1845 45.4 1834 45.2 Total 4067 100 4061 100 4. TABLE 2: Age standardised p-lence of telf-nported nspiratory ytxptonrs by category: Per cent of all mrthix eac6 groxp. Maks 45 wf Smoking Respiratory ETS + ETS symptom Controls exposure Smoking exposure me Infected spit 3.3 4.2 11.1 12.5 Persistent spit 10.1 14.5 * 33.9 35.6 Dyspnoea 7.4 11.9 * 14.0 15.4 Th the 1. Hypersecretion 7.2 11.9 * 20.6 21.6 Number of individuals 517 310 1395 1845 par *P value < 0.05 for comparison of control and ETS exposure group syn eac TABLE 3. Age standardisud prevaknce of self-rtported napiratory symptoms by category. Per cent of all n+it.bin eacb gmxp. Female.t Respiratory symptom Controls ETS exposure Smoking Smoking + ETS exposure Infected spit 2.1 2.8 10.0 9:1 Persistenrspit 6.3 7.2 23.9 23;1 Dyspnoea 9.7 14.7** 16.2' 18~3 Hyperseeretion 3.9 4:8 17.6 17:1 Number of individuals 523 13941 310 1834 _ ** P value < 0.0 1 for comparison of control and ETS' exposure group TAI Mak Ang MajQ Fem~ Ang:
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123 1. Control-an individual who does not smoke and who lives at the same address as another individual who does not smoke. 2. ETS exposed -an individual who does not smoke but who lives at the same address as another individual who does smoke. 3. Smoker- an~ individual ~ who is a smoker or who has given up smoking up to five years agp but who lives at the same address as an individual who does not smoke. 4. Smoker and ETS exposed-an individual who is or who has been a smoker up to five years ago and who lives at the same address as an individual who also smokes. All individuals in these categories were aged 45-64 at the time of the survey. Ex-smokers who had given~ up smoking for five years or more have been excluded from this analysis. RESULTS The number of males an& females in each of the categories defined! above is shown in Table 1. 97.6% of the pairings were male/female partnerships. The prevalence of self-reported respiratory symptoms (6) found at the survey is shown for each category for males in Table 2'and for females in Table 3. For each measure, infected spit, persistent spit, dyspnoea and hypersecre- tion an increasing dose response relationship was evident in males. The prevalence of these four symptoms was slightly higher in the exposed to ETS than in the controls. This observation was consistent in both males and females: The prevalence of cardiovascular symptoms found at the time of the survey is shown in Table 4. In~females angina and ECG abnorma- lities (6) were slightly, more common in the group exposed to ETS than in the controls, although the magnitude of the differences was small. The reverse trend was shown for males. Male mortality for the different categories is shown in Table 5. A dose-response relation« ship was found for lung cancer rising from a rate of 4 per 10,000 for the control group to 13 per L0;000 for the group exposed to ETS to 22 per 10,000 ~ for the smoking group and 24 per 10;000 for the smoking group also exposed to ETS. The rates for other smoking related cancers and!for smoking related diseases (8) did not show a difference between the control and groups exposed to ETS except for the rate for myocardial infarction (ICD4,10) ~ which was TABLE 4. Age .rtandardired prenalence of cardrovascutar rymptomi by evtegory: Per cent of all within eacb8mxp Cardiovasculgr . symptom Controls ETS exposure Smoking Smoking + ETS exposure Mate.r: Angina: 6.6 6.4 9.6 12.3 Major ECG abnormality 1.4 1.3 2.0 2.2 Females: Angina 4.2 5.3 5.4 6.1 Major ECG abnormality 0.4 0.6 0.6 0.5
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TABLE 5. Axnual age standardised mortaliy ratei per 10,000 by smoking category Males Cause of death Controls ETS exposure Smoking All causes 91 901 156 Lung ca 4(2) 13(4) 22(30) Other Ca 12(6) 6(2) 24(34) MI (410) 31(16) 45(14) 60(84) IHD (411-4) 4(2) 0(0) 11(15) CVD 10(5) 3(1) 12(17) Others 31(16) 23(7) 27(38) Smoking related 75(39) 77(24) 140(195): Non-smoking related 16(8) 13(4) 17(23) Totalinumber of deaths 47 28 218 Smoking + EfiS exposure 156 25(44) 22(41) 46(84) 14(25) 16(29) 35(64) 134(247), 22(40) 287 Figures in parenthesis are the numbers of deaths TABLE 6. Annual age standardised mortallty rates per 10, 000 by smoking category Femalts Cause of ETS Smoking + ETS deaths Controls exposure Smoking exposure All causes 40 58 87 77 Lung Ca 4(2), 4(6)! 7(2) 6(11) Other Ca 19(10) 24(33) 26(8)' 22(40) MI (410) 4(2), 12(:17) 19(6) 21(39) IHD (411-4), 0(0)' 1(2) 3(l) 2(4) CVD 2(1) 4(5) 7(2) 9(16) Others 12(6) 13(18) 26(8) 17(31) Smoking related 15(8) 30(42) 55(17) 52(96) Non-smoking related Total number of deaths 23(12) 21 27(37) 81 36(11) 27 24(44) 141 Figures in parenthesis are the numbers of deaths TABLE 7. Perrentage smoking 15 or mon cigarettes per day Males Females slight than Fei cause. to E'I case f myoc expos trols. Di• smok' ducec ETS . On tionsl consu amou categ, grouF 53.4 4 rettes tnaleE grour Insuff tion c (1976 dent allbw result annua total r of dea sure € Th, indivi screer can: those range not :
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oking ETS )osure i(44) 1(4t) )(84) :(25) 1(29) ;(64) 1(247) '_(40) oking ETS 'osure 7 G(11) 2(40) 1(39) 2(4) 9(16) 7(31) 2(96). 4(44) 1 oking ETS 1osure ;7:3 ~3:4 slightly higher in the group expose& to ETS than in the controls. Female mortality is shown in Table 6: All causes mortality is higher in the group exposed to ETS than in the controls. This was not the case for lung cancer although mortality from myocardial infarction was higher in the group exposed to ETS when compared with the con- trols. Divi'sion of all diseases into those considered smoking and non-smoking related' (8) pro- duced a higher rate in the group exposed to ETS when compared with controls. On, account of the apparently unusual rela- tionship between lung cancer risk and tobacco consumption in the West of Scotland (9) the amount smoked by individ'uals in the define& categories is shown in Table 7. In the smoking group also exposed to ETS 57.3 % of males and 53.4 % of females smoked more than 15 ciga~ rettes per day. This compares with 4ll8 % of males and 46.5 % ' of females in the smoking, group. DISCUSSION Insufficient time has elapsed since the comple- tion of the recruitment phase of this study (1976) for sufficient numbers, either of inci- dent cases of cancer or of other diseases, to allbw firm conclusions to be based on the results. The results have been expressed ass annual age standardised rates per 10,000, as the total'number of incident cases and the number of deaths is small in the control and ETS expo- sure groups (Tables 5, 6). The results relate to only 8i 128 of the 16,171 individuals who attended the multi-phasic screening unit (50 %). Some of this discrepancy can be accounted' for by those living, alone,, those living with a partner outwith the age range, and those living with~a partner who has not attended. Those who have been ex- 1i25 smokers for five years or more were also excluded from the analysis. As there is stilll doubt whether these groups account, for the total discrepancy, given an initial response rate of 80 %, the authors require to continue their investigation of this apparent dlscrepancy: This study has unique features which allow even preliminary results to be of interest. These are: 1. The study has been carried' out ini an area with the highest national incidence rate of lung cancer recorded (5). 2. It is a prospective cohort study carried out in a geographically defined' population whose members are homogeneous by social dass and ethnic group. 3. Other reports (2, 3, 4) concentrate on, females. This study includes both sexes. 4. No questions concerning exposure to ETS were asked, thus avoiding the bias inherent in self-reported assessments of partnership dosage. Given the strengthi of the epidemiological association between cigarette smoking and lung cancer, it is this disease rather than ischaemic heart disease that would be first to appear in excess in the cohort if a dose response relationship existed, especially as the respon- dents were all apparently healthy at the time of screening. Inmales, the cases of liing,cancer occurring, in non-smokers were found more frequently in those exposed to ETS (4/310) than in the con- trols (2/517),(Table 5). No dose-response rela- tionship was apparent in females for lung cancer deaths though an effect was present when all smoking related (8) deaths including deaths from myocardial infarction were taken into account (Table 6)i These findings may be supported to an extent by the dose-response relationship that exists for self-reported respiratory symptoms
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126 (Tables 2, 3), all of which are more frequently reported in the group exposed to ETS than in the controls and four of which achieve statis- tical tical significance. The number of deaths in the control and ETS exposure groups is very small and may explain the lack of an apparent dose-response in females. However, as the relative risk for lung cancer for active smokers is much higher in males than females it may be too early to expect many females in the ETS exposure group to be affected. This would also apply to male as well as female deaths from myocardial infarction. Occupation has not been taken into account in this analysis, as its effect on lung cancer risk in non-smokers is thought to be marginali (4, 10). The West of Scotland is a valuable area to continue examination of the effect of ETS on account of the relatively high rate of lung cancer in non-smokers and the flattening of the dose-response relationship above an average consumption of 20 cigarettes per day (9). In conclusion; the clear dose-response rela- tionship with lung cancer observe& in males exposed to ETS supports observations from previous studies. Although the number of deaths on which the current analysis is based is small. The nature of the findings makes conti- nuation of this study important. REFERENCES 1. US Department of Health; Education and Wel~ fare. Smoking and Health: A report of the Sur- geon General, Washington, DC: US Public Health Service 1979. 2. Hirayama T. Non-smoking wives of heavy smokers have a higher risk of lung cancer: aa study from Japan. Br Med J 1981: 282:183- 185. 3. Trichopoulos D, Kalandidi A, Sparros L, McMahon B. Lung Cancer and' Passive Smoking. Int J Cancer 1981: 27:14. 4. Garfinkel L. Time trends in~ lung,cancer mor- tality among non-smokers and a note on passive smoking. J natn Cancer Inst 1981: 66:1061- 1066. 5: Gillis C. R, Boyle P, Holh D. J, Graham A. Cancer incidence in UK, Scotland West 1975- 1977. In Waterhouse J, Muir C, Shanmuga- ratnam K, Powell J(Eds), Cancer incidence in five continents„Volume IV, Lyon„IARC Scien- tific Publications No 42, 1982. 6. Hawthorne V. M, Greaves D: A, Beevers D. G. Blood pressure in a Scottish town. Br Med J 1974: 2696600-603: 7. Hole D. J„Clarke J. A, Hawthorne V. My Mur- doch R. M. Cohort follow-up using computer linkage with routinely collected data. J chron Dis 1981: 34:291-297: 8. Doll R, Peto R. Mortality in relation to smoking: 20 years observations in male British doctors: Br Med J 1976: 273:1525•1536. 9. Gillis C. R, Hole D. J, Hawthorne V. M, Boyle P. Male lung cancer and cigarette smoking in the West of Scotland (submitted). 10. Friedman G. D, Petitti D. B, Bawol R. D. Pre- valence and correlates of passive smoking. Am J, publ:Hlth 1983': 73:401-405. 11. Office of Census and Surveys. Occupational mortality: The Registrar General's decennial supplement for England and! Wales. 1970-72. London: HMSD 1978, . Charles R. Gillis Greater Glasgow Health Board West of Scotland Cancer Surveillance Unit Ruchilli Hospital Glasgow, G20 9NB; SCOTLAND. 3.7. Enviro- INTROD Environmental tobacc prises the portion of t exhaled by the smoke smoke from, the burnin The smoker as well exposed to ETS, alth smoke constitutes the h lung burden in the smi the information availal ETS exposure will be e: reference to the chemic smoke and to dose esti Exro Tobacco smoke aerosol process involving comb lation and other chemi( sidestream smoke com Wenusch (1) demonss smoke was more alka smoke. Since then sevei ical composition of f stream smoke have bet was recently presented The sidestream smokc larger proportion of tl present in cigarette str
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3.7. Environmental tobacco smoke and lung cancer R.AGNAR RYLANDER INTRODUCTION Environmental tobacco smoke (ETS) com- prises the portion of the mainstream smoke exhaled' by the smoker and' the sidestream smoke from the burning point of the tobacco. The smoker as well as the non-smoker is exposed' to ETS, although the mainstream smoke constitutes the largest proportion of the lung burden in the smoker, In the following, the information available on lung cancer and ETS exposure will be examined with particular reference to the chemical characteristics of the smoke and to dose estimates. EXPOSURE Tobacco smoke aerosol is created, in a complex process involving combustion; pyrolysis, distil- lation and other chernicalireactions. Main and sid'estream smoke compositions are different. Wenusch (1) demonstrated that sidestream smoke was more alkaline than mainstream smoke. Since then several studies on the chem- ical composition of freshly generated, side stream smoke have been performed;, a review was recently presented by Klus and Kuhn (2). The sidestream smoke generally contains a larger proportion of the various compounds present in cigarette smoke on a per cigarette basis. Examples include ammonia, nitrosam- ines, and' other components which appear in the volatile phase of the smoke. Due to the rapid dilution of sidestream smoke this differ- ence between main and sidestream is less important in view of other factors determining the final concentration of ETS, such as venti- lation and room size. Smoke aging, particularly oxidation, dilu- tion and changes in particle size, influence the chemical and physicali characteristics of ETS. For those reasons, theoretical~ models for expo- sure to ETS are not reliable estimates of the biological exposure. For example, Hugod et al (3) showed that exposure models which are based' on calculations of cigarette equivalents for either whole tobacco smoke or its gas phase are inaccurate because of the different dissipa- tion rates for each tobacco smoke component. The individual rates are affected by such factors as ventilation~ and the presence of people and their activity. Another g;oup of researchers found that when cigarette smoke was generated and sampled from~ a 10 m3 chamber, the collected amount of nitrosamines was about 25 % lower than the theoretical value (2). Regarding the lung burden of smokers, about 95 percent of the total particulate matter
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128 and volatile compounds in cigarette smoke are retained in the respiratory tree (4): It is con- ceivable that differences in~inhalation patterns exist between smokers and non-smokers. After taking a puff from the cigarette, the smoker keeps the smoke in his mouth for a few seconds and then inhales moderately to deeply. The active smokers'' degree of inhalation is prob- ably greater than that observed during normal breathing. Among non-smokers exposed' to high con- centrations of ETS the reaction can be sus- pected to be the reverse-a more shallow breathing when an irritating substance enters the airways. The extent to which these possible differences indnhalation patterns result in dif= ferences in the retention of the inhaled dose of ETS and mainstream smoke, and hence the total body burden, has not been determined.. Relatively little information is published on the toxic properties of sidestrearn smoke. The higher amounts of gases, such as acrolein and ammonia, are presumably responsible for thee irritating property of the sidestream smoke. The biological significance of the larger amounts of nitrosamines is unclear. Although these compounds are carcinogenic in some animal experiments, their biological signifi- cance for the development of human~cancers is not known. For smokers, the definition of the smoking habits of an individual makes it possible to group individuals into populations with varying exposure categories (1-5, 6-10, 11-1i5 cigarettes/day, etc). The data on the health status of each individilal will then be incorpo- rated into such exposure categories and the frequency of disease in the population can be related to the dose in the population (dose- response). Previous studies on the relation between the number of cigarettes smoked and 'an~ increased lung cancer incidence report that the ratios as compare& to non-smokers : are about 20 for those smoking 20 cigarettes or more/day, 5-12 for those smoking 10 cigarettes/day and about 5 for those smoking 5 cigarettes/day (5): Previous estimations of maximum dose levels of ETS for non-smoking persons have suggested a dose equivalent up to 0.3 cigarettes per day for heavily exposed individuals (6). Such informationds not, however, appropriatee to describe the exposure situation for groups of non~smokers in the general population. No estimates have been presented on the exposure level for a population of non-smokers. One wayto define the ETS exposure for such groups would be to measure the exposure using an indicator, such as cotinine in urine or saliva. The estimate for a highly exposed individual also represents the minimum amount of ETS' to which the smoker is exposed. The exposure to ETS among non-smokers thus cannot exceed the leveliof this exposure to the smoker. The total amount of smoke to which persons smoking a low number of cigarettes are exposed is thus considerably higher than the amount of ETS exposure for the non- smoker. EPIDEMIOLOGICAL EXPERIENCE The epidemiological studies concerning the relation of ETS to lung cancer are summarized in~table 1. Hirayama (7) reported data from a cohort investigation~ among non-smoking femaiess married to smokers. The data were obtained from 29 health~ centers in Japan in which females aged! 40 years or more were inter- viewed in~ 1965. A total material of 91,540, females was defined as non-smokers. Smoking habits of females and males were assessed'at the beginning of the study with questionnaires containing a series of question on health related' matters.
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about 20 for ore/day, 5-12 iay and about /day (5). ximum dose persons have 0.3 cigarettes dividuals (6). r, appropriate for groups of pulation. No the exposure mokers. One )r such groups ;ure using an inc or saliva. ,ed individual iount of ETS The exposure thus cannot o the smoker. !hich persons igarettes are ;her than the )r the non- rom a cohort cing females ~ere obtained' an in which were inter- ial of 91,5401 :ers. Smoking Lssessedv thee uestionnaites n on ~ health A total of 346 lung cancer deaths was rec- orded im the female population up to 1979. Apart from squamous carcinomas,, generally related to an~exogenous exposure, the material also contained adenocarcinomas which have generally not been related to environmental exposure (17 out of 23 cases in one sample, according to Lee (8). Of the total number of cases,,174 were non- smokers. These cases were classified according to the husband's smoking habits (datafrom the 1965 questionnaire). The age-occupation stan- dardized risk ratio for womeri married to ex- smokers or men smoking 1-19 cigarettes days was 1.61 (86 cases versus 32) and for those married to men smoking 20 or more cigarettes day 2.08 (56 cases versus 32). The data were also divided according to agricultural work and'1 other occupations of the husband. The standardized' lung cancer mor- tality rate for wives of husbands engaged in agricultural work was higher thani for other occupations-14.03 and 15.92/100,000 in the two smoking,categories as compared to 8.09' and 11.05/100,000 for wives of non-agricul- tural male workers in the same two smoking, categories. The risk ratio among wives of agri- cultural workers aged 40-59 years who smoked more than 20 cigarettes per day was 4.6, although the number of cases in this group was smalli The incidence of other major cancers among females, such~ as stomach and cervix cancer, was not related to the husbands' smoking habits. This study has been criticised in detail by other researchers from the point of view of questionnaire reliability, absence of hi'stolog- ical diagnosis, statistical treatments grouping of smoking habits among husbands and con- founding factors, suchi as air pollution from heating and/or cooking (see general refer- ences). In the absence of data on, these para- TABLE 1l Review of imnstigationr on ETS exposure and lung cancer. ETS exposure defrned'as spouse being ligbt'or fitavyy smoker F = Female, M = Male Author Hirayama;, 1981i • Triehopoulos et al., 1981 Triahopoulos et al., 1983' (extension of 1981 study). Garfinkel, 1981 Correa et al., 1983 Chan and Fung, 1982 Gilli's et'al,, 1983 129 Cases of lung cancer Risk ratio Basis of data collection non-smokers low ETS high ETS health centre register F 174: 1.6 2.1 hospital cases/referents F 40~ 2.4 3.4 hospital cases/referents F: 77 2.0 * 2.5 *' cancer register F 153 1.3 1.1 hospital F 22 cases/referents M 8 1L5 3.1 hospital F 84 0.75 cases/referents M 2 rate/10,000: health~ F 8' non-exposed 4', ETS 4 survey M 6 non-exposed 4, ETS 13 *Calculation using,crude ratios in authors' table
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t 130 meters it is difficult to evaluate the importance of the criticism, but they should not be dis- counted. A major point to be considered in the study relates to the dose response. Lung cancer rates among non-smoking women exposed to ETSS were 1.78 in the whole group married to smoking husbands as compared to 3.77 among smoking women. In some subgroups among agricultural workers, the risk ratio among non- smoking women was even higher than among smokers, although the number of cases was very small. In view of the dose-response rela- tionships among smokers, the difference between these figures is unexpectedly small. The reason for this discrepancy with regard to dose i's not clear. One possibility could be the admixture of smoking females among the group reporting themselves in 1965 to be non, smokers. The presence of non-smokers in the group of smokers or persons who had stopped smoking since the interview in 1965, is another possibillty: Other reasons could be the influence of different histopathological diag- noses, particularly adenocarcinomas. The latter is a likely explanation for the high risk ratios obtained for the wives of the younger age group married to agricultural workers. Trichopoulos et al. (9) reported a case- referent study in which~ 51 females with lung cancer and 163 patients : at the department of orthopaedic disorders at another hospital were interviewed regarding their smoking habits and the smoking habits of their husbands. Cases of adenocarcinomas or alveolar carci'~ nomas were not included among the 51 sub- jects. Of the 51 cases,,11 were smokers; of the 163 referents,, 14 were smokers (relative risk 2.9). When the non-smoking females were classified according to the husbands smoking, habits,, a statistically significant association was found between the husbands' amount of smoking and the number of lung cancer cases in the group of non.smoking females. The rela- tive risk for females married to men smoking more than 20 cigarettes was 3:4. Essentially the same results were reported in an extension of this study (77 cases)~ published during, the editing of this article, although the risk ratios were slightly lower (10): From a dose-response point of view;, the risk _ difference between non-smokers exposed to ETS and! smokers was again rather small (2.4- 3.4 versus 2.9): Using mortality rates from the American Cancer Society's (ACS) prospective study (11); lung cancer mortality rates for non-smokers married to smokers were calculated. The mate- rial was collected from October 1959'to March 1960 and comprised 375,000 female non- smokers. Mortality data were obtained from~ July 1960 to June 1972 and the follow-up rate was 92.8%. Among the 375,000 female non,smokers originally selected, smoking habits of the hus- bands were identified for 176,739 (47 %). The material comprised 153 cases of lung cancer among non-smoking females. Of these, 88'' were married to smokers. A small but statisti- cally non-significant increased risk for lung cancer was found for those married to men smoking less than 20 cigarettes per day (1,27). The relative risk for those marrie& to men smoking 20 or more cigarettes per day was 1i10. A matched group analysis was made in order to control for age, race, educational status, resi- dence and husbands' exposure to air pollutants. The ri'sk ratios of lung cancer deaths in women were 1.37 and 1.04 for the two exposure cate- gories. Although this study is based upon a large number of persons in the original cohort,, smoking habits couldbe identified for only less than half of the original cohort. As smoking habits are tied to social characteristics, this drop-c study. Chai survey Amonn and arr Amon(45 46)) were Regarc (40.5 4, as com orthop: Thei and cc (never cook a gested nomas, female. dietary Duri where were ar and co habits:. smoker smoker withou The i smoker The lur age star was 4 i. ETS, I smoker: differer For fen ETS ex the oth the stuc clusion, studied.
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131 Che rela- smoking tially the :nsion of ring the .sk ratios -, the risk posed to aa11(2.4- lmerican udy (11), -smokers 'he mate- to March .tle non- ied from v-up rate -smokers the hus- , 46). The g cancer hese, 88'. .t statisti- for lung I to men iy (1,27). to men~ day was - in order itus, resi- Alutants.. n women ure cate- I upon a il cohort, only less smoking tics, this drop-out could have introduced a bias in the study. Chan and Fung (12) usedla material from a survey of bronchial cancer in Hong Kong. Among 208 male cases, 2 were non-smokers and among 189'females, 841were non-smokers. Among the non-smoking female cases, 38' (45 °7a) were adenocarcinomas and 15 (18 %)' were squamous or epidermoid! cancers. Regarding the smoking habits of husbands, 34 (40.5 %) of the cases were married to smokers as compared to 66 (47.5 %) of controls from an orthopaedic ward (odds ratio 0.75). There were no differences between cases and controls with regard! to cooking habits (never cook, never cook with kerosene, neverr cook with~ kerosene or gas): The authors sug- gested that the high proportion of adenocarci- nomas, which was particularly apparent among females of Cantonese origin, could be due to dietary factors. During the Workshop, a study was presented where 16,171 individuals from a health surveyy were analysed (13). 8,128 of these were couples and could be paired according to smoking habits. The materials was divided into non- smokers not exposed to ETS (controls), non- smokers exposed to ETS and smokers with and without external' ETS exposure. The number of lung cancer cases among non- smokers was very, low (6 males and 8 females). The lung cancer mortality expressed as annual age standardized rate per 10,000 among males was 4 ini controls, 13 among those exposed to ETS„ 22 among smokers and 24 among smokers also exposed to external ETS: The differences were not' statistically significant. For females, no difference was found due to ETS exposure contrary to what was found in the other studies. The low number of cases in the study, makes it difficult to draw any con- clusions regarding the exposure parameters studied. During the editing of the present article another study on lung cancer and smoking habits of spouses was published. Correa et al.(14).studied 1,338 lung cancer patients and 1,393 referent cases in Louisiana, which has an unusually highi incidence of lung cancer as compare&to other areas in the U.S. Broncho- alveolar carcinomas were not includedl in the material, which contained' 8 male and 22 female non-smokers for whom information on spouses' smoking habits was available. The exposure to ETS was calculate& as total lifetime pack/years, smoked by the spouses at~ the time of the interview. Among females, the odds ratio for lung cancer was about 2 among persons married to smokers, with a tendency to a dose-response relationship. In the non- smoking women, 54 % of the cases were ade- nocarcinomas but the trends with regard to. ETS exposure remained if these cases were excluded: COMMENTS All of the studies discussed have methodolog- ical limitations. In none of the studies were any measurements made of the degree of exposure to ETS. The information that one is marrie&to ' a smoker is not a precise description of the degree of exposure to ETS. The number of hours spent together may vary considerably, as may smoking habits over the day for the hus- bands. The time spent at home or in other locations where smokers may be present intro- duces an important variation in the exposure characterization. Friedman etal. (1i5) found in a questionnaire study that, 47 % of women mar- ried to smokers reported zero hours of expo- sure to ETS at home. On, the other hand, an imprecise dose description would tend to mask differences if such were present. In case-referent studies it cannot be excluded! that persons with lung cancer seek to
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132 interpret their disease as related to ETS expo- sure (recall bias). Two studies have reported an unexpectedly small difference in lung cancer risks between non-smokers exposed to ETS and regular smokers. Whem making this comparison it must be realized that the risk figures have been obtained'using different reference populations: In the first case, the reference group is non- smokers not exposed to ETS; in the other case,, the reference group is non-smokers, some of whom are also exposed to ETS. If the ETSS exposure as such had an effect, a lower ratioo would be obtained for smokers versus non- smokers in general than ~ if the reference group had consisted of non-smokers not exposed' to ETS. It cannot, however, be exchided'that the small difference between ETS-exposed and smokers is caused by some other bias in the material. The number of cases in the different studies is small and„ even if statistically significant' increases are found in certain ~ subgroups, con- fidence limits are large. Diamond and For- rester (15), pointed out that both the results from Hirayama's (7) positive study and Gar, finkel's (11) negative study have confidence intervals for the relative risks which largely overlap. In order to attain a reasonable statis- tical accuracy in a register study,, one would need more than a million females or a follow- up study comprising 300,000 females over a 40 year period: Case-referent studies thus repre- sent a more powerful tool for evaluating the association between ETS exposure and lung cancer. The results from such studies are contradic- tory. In two studies (9, 14), a higher proportion of the lung cancer cases who were not smokers were married to spouses who smoked, com- pared to the non-smoking referents. A dose- response for lung cancer risk and ETS exposure '(husband's degree of smoking) was present in one of the studies (9)j In a third case-referent study (11), the lung cancer risk for those exposed to ETS was lower than in the refer- ents. In conclusion~ the relation between ETS exposure and 1ung,cancer has been studied in few studies, each one based on a small number of cases. Although some studies present data suggestive of a relationship, an overalli eval- uation of the available material leads to the conclusion that an increased' risk for non- smokers from ETS exposure has not been established. Conceptually, it does not seem unreasonable that, under conditions with high exposure to ETS, an increased risk for lung cancer could be present. The risk for an individual in the gen~ eral population of non-smokers : would, how- ever, be very small, a conclusion which agrees with previous estimates (17). In view of the smalll number of cases involved, future studies should preferably use the case-referent technique. Difficulties in defining the actual exposure to ETS as well as the influence of different histological diagnosis are potential shortcomings in such studies which will influence the possibilities for drawing conclusions concerning,a causal rela- tionship: In future studies, particular emphasis should be placed on the ETS dose description, preferably by measurements in well defined' groups in the population or by extensive ques- tionnaires evaluating all possible sources of ETS exposure. Acknowledgement The assistance by Gosta Axelsson, Ph.D., in the preparation of this article is gratefully acknowledged. 1. W Ge 2: 2. K] tot an( Ta 3. Ht Pu Int 29. 4. Da tior lur 5. U. We Sur Put 6. Ryl tob sup 7. Hit kcr: fror con list) 8. Lee 20:- 9. Tric Mc. Int this 10. Tric can< Gre 678.
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133 :en ETS udied im number ent data all eval- .s to the or non. ot been isonable osure to could be the gen- d, how- h agrees )f cases .ibly use lties in : well as iagnosis studies ies for ial rela- nphasis ription, defined 'e ques- rces of .D., in tefully REFERENCES. 1. Wenusch A. The reactions in tobacco smoke (in German). Fachl Mitt 1'Ssterr Tabakregie 1930: 2:13-15. 2. Klus H, Kuhn H. Distribution~ of various tobaccclsmoke components among mainstream and sidestream smoke (in German), Beitr Tabaksforsch 1982: 11: 229=265. , 3: Hugod C, Hawkins L. H, Astrup P. Exposure of passive smokers to tobacco smoke constituents. Int Arcli occup Environ Hlth 1978:. 42:21- 29. 4. Dalhamn T, Edfors M-L, Rylander R Reten- tion of cigarette smoke components in human lungs. Archs envir Hlth 1968: 17:746-748: 5. U. S. Department of Health, Education and Welfare. Smoking and Health : A Report of the Surgeon General: Washington D. C.: U. S. Public Health Service 1979: 6. Rylander R. Perspectives on environmental tobacco smoke effects. Scand J resp Dis 1974: suppl 91 p. 79-87. 7: Hirayama T. Non smoking wives of heavy smo- kers have a higher risk of lung cancer: a study from Japan. Br Med J 1981: 282:183-185. (For comments to this article see general reference list). 8. Lee P. N. Passive smoking. Fd Chem Tox 1982: 20:223-229. 9. Trichopoulos D, Kalandidi A, Sparros L, McMahon B. Lung cancer and passive smoking. Int J Cancer 1981: 27:1 4. (For comments to this article, see generali reference list). 10. Trichopoulos D;,KalandidiA, Sparros L. Lung cancer and passive smoking: conclusion of the Greek study. The Lancet, Sept 1i7 1983: 677- 678: 11. Garfinkel L. Time trends in lung cancer morta- lity among non-smokers and a note on passive smoking. J natn Cancer Inst 1981: 66:1061- 1066. 12. Chan W: C, Fung S. C. Lung cancer in non- smokers in Hong Kong. Cancer Campaign: Geographical Pathology in Cancer Epidemio• logy. E: Grundtnann (Ed). Gustav Fischer Verlag, Stuttgart 1982: 6:199-202. 13. Gillis C. R, Hole D. J, Hawthorne V. M, Boyle. P. The effect of environmental tobacco smoke in tavo urban communities im the West of Scotland„In Rylander R, Peterson Y and Snella M-C (Eds) ETS-Environmental Tobacco Smoke. Eur J Resp Dis 1983: suppl' 133; 119- 124. 14., Correa P, Pickle L. W, Fonthain E, Lin Y,. Haenzsel W, Passive smoking and lung cancer. The Lancet II 1983 : 595-597~ 15, Diamond G. A, ForresterJ. S. Clinical trials and statistical verdicts: probable grounds for appeal. Ann ~ inter Med 1983 : 98 :385-394. 16. Friedman G. D, Petitti ID. B, Bawol R. D: Pre- valence and'correlates of passive smoking. Am J publ Hlrh 1983: 73:401-405. 17. Peto R, Statement at the V World Conference ow Smoking and' Health, Winnipeg, Canada, July, 1983. Ragnar Rylander, M. D Department of Environmental Hygiene University of Gothenburg Box 33031, S-400 33 GOTHENBURG, SWEDEN
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3.8. Discussion RAPPORTEURS GORAN PERSHAGENI AND ANTHONY COSENTINO Following the paper by Gillts;, Pershagen and' Lynch, inquired about the selection of con- trols. Hospital based controls were used and only those subjects without obvious smoking related diseases were included. It was pointed out by Lynch that according to his experience, hospital and neighbourhood controls did' not differ in characteristics for the kindi of studies discussed here. Russell pointed out that the levelling off in the dose response curve for cigarette consumptiori~and lung cancer at high doses was consistent with concentrations of biochemical markers of tobacco smoke expo- sure which also flatten out at high levels of cigarette consumption (1, 2, 3). There were no data in the case-referent part of the study to make it possible to analyse effects of environ- mental tobacco smoke. Information~ on occu- pation was included in the questionnaire but no detailed! analysis of this data had yet been performed. It was mentionedlthat some of the cases of bladder cancer could be related to occupationaU exposure. Following the presentation by Weber, the discussion was startedlon the maximum partic- ulate concentrations in the expired air of a smoker. Lebowitz confirmed the data by Weber, that a concentrationlof 100 mg/m3 was not unrealistic. Rylander suggested that the poor association between levels of odorous compounds and annoyance, which has been seen in several earlier studies, may explain the low correlation between the measures of tobacco smoke concentrations and annoyance in Weber's studies. It was also pointed out that the particulate concentrations indoor may be influenced' by several factors other than tobacco smoke. At the end! of the presentation by Holt,, a question~was put to Lebowitz on the peculiar- ities of the respiratory system in children. Lebowitz mentioned that the airways in boyss tend to have smaller diameters than in girls and that childten are more susceptible to respira- tory infections that adults. The respiratory infections cause a more pronounced bronchial hyperreacti'vity in children an&their mediator response is different from t'hose in adults. Following the presentation by Rylander on environmental tobacco smoke and lung cancer, it was pointed' out by Sterling that the usac of kerosene stoves by the women may be a confounding factor in the studies from Japan and Greece. He also stressed that occupational factors were not sufficiently controlled in any of the studies. Following Bake's presentation, Lebowitz confirmed'that Bake's concerns on the study by
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135 odorous ias been ,lain the :ures of noyance out that may be ~r than Nalt, a 'ecullar- hildren. in boys ,>irls and respira- piratory •onchial iediator ults. inder on i lung 7hat the lay be a n Japan 3ational !1 in any -bowit¢ tudy by White and Froeb (4) were jpstified. He further reported that 3,000 subjects originally included were omitted from the first report when the data failed to show a significant difference. Lebowitz noted that some of the results would not be significant if corrections were made for the number of comparisons. Lebowitz had also reviewed the data im the Kauffmann study (5) and wondered if the measurements of MEF 25/75 were made from full vital capacity man- ceuvres. Regarding, the Hasselblad study (6), Lebo- witz felt' that socio-economic factors and pos- sible effects of gas stoves had not been suffi- ciently controlled for. Some effects disap- peared when other investigators controlled'& these factors (7, 8). He mentioned two other studies, those of Cameron (9) and Tager et al.(10): The latter group showed a slightly less rapid increase in function when exposed! to environmentall tobacco smoke. Lynch inquired as to the clinical significance of the minor changes possiblypresent and3ake answered that he did not know: After Coaentrno'rpaper,,the variability in spi- rometric measurements was discussed. Partic- ular mention was mad'e of the difficulties in measuring flow rates at low lung volumes and further, the wide range of normaL' The value of a good questionnaire and tests to detect asthmatics was emphazised. It was felt that in view of the report of Dahms er al. (11) 1 that this subset should be identified In those with, symptoms and/or abnormal spirometry measurements of diffusion capacity and exer- cise testing was recommended; Closing volume was not felt to be a useful measure- ment. Bake felt that the single breath nitrogen test had meritand~ that "sophisticated testing" was justified in research into this area. Cosentino felt that verysensitive tests which might be abnormal in individuals who were asymptomatic and, who otherwise had' normal i test results should be followed by exercise testing. He felt that what one perceives as a malady must be judged on the basis: of symp- toms, functional impairment or demonstrable anatomic abnormalities and that what one does with an isolated abnormal lung test in the absence of the above is a sociali decision. Cosentino stated that the FEVI, correlated very well'with disability and that researchlinto the physiologic significance of the closing volume must, be concluded before it can, be used, as an epidemiological tool. Likewise, minimal abnormalities in the terminal portion of the flow-volume curve with a normal FEVI without symptoms are of uncertain patholog- ical significance. Cosentino felt that the study of White and, Froeb (4), if anything, could be interpreted too indicate that exposure to ETS over 20 yearss does not lead to biologically significant changes. Le6ouwit:z' paper led to questions on what the flow rates were when exposed to high 03 con- centrations. He stated that it was 14 %. First asked, as to why the NOz and CO showed dif- ferent degrees of penetration into the homes. Lebowit¢ offered no explanation for this. REFERENCEs 1. Feyerabend C, Higenbottam T, Russell M. A. H. Nicotine concentrations in urine and saliva of smokers and, non-smokers. Br Med J 1982: 284:1002-1004. 2. Russell M. A. H, Jarvis M, Iyer R, Feyerabend C. Relation of nitotine yield of cigarettes to blood nicotine concentrations in smokers. Bt Med J 1980: 280: 972-975. 3. VeseyC. J, Salbojee Y, Cole P. V, Russell M. A. H. Blood carboxy haemoglobin, plasma thiocya- nate, and cigarette consumption: implications
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136 for epidemiologicallstudies in smokers. Br Med J 1982: 284 :1516-1518. 4. White J, Froeb H. Small-airways•dysfunction in nonsmokers chronically exposed to tobacco smoke. New Engl J Med 1980: 302:720-723. 5. Kauffmann F, Tessier J. F, Oriol P. Adult pas- sive smoking in home environment: A risk factor for chronic airflow limitation, Am J Epi- dem 1983: 117:269-280. 6. Hasselblad V, Humble C. G, Graham M. G, Andersson H. S. Indoor environmentali deter- minants of lung function in children. Am Rev resp Dis 1981i:,132:479-485. 7. Chapman R. S, Hasselblad V, Hayes C. G„Wil- liams Jl V. R, Hammer D. I. Air pollution1 andl childhood' ventilary function. 1. Exposure to particulate matter in two southeastern cities, 1971-1972. In Clinical Implications of Air Pol- lution Research A. J. Finkel, W. C. Duel (Eds) Acton, Mass: Publ Sci Group 1976: pp 285- 303: & Hammer D. I, Miller F. J, Stead A. G, Hayes C. G. Air pollution and! childhood' ventilatory function. I. Exposure to particulate matter in two southeastern cities, 1971-1972. In Clinical Implications of Air Pollution Research A. J. Finkel, W. C. Duel (Eds). Actont Mass: Publ Sci Group. 1976 c pp 321-337. 9. Cameron P. Second-hand tobacco smoke: children's reactions. J School Htlh. 1972t 42:2801284. 10. Tager I. B, Weiss S. T, Rosner B, Speizer F. E. Effect of parental cigarette smoking on the pui- monary functiom of children. Am J Epidem 1979: 110:15-26. 11. Dahms T. E;, Bolin J. F, Slavin R. G. Passive smoking, effects on bronchial asthma. Chest. 1981: 80:530-534. 1: Expaw Informat: is basic f environm human he their me cotininc ', unique do be related Only met: with hum: a meanin dose and with other notably o, demonstra between e: understanc and his en• An addii between c human effe costly, anc donors to ; than to ex, However, i cerning me tionships b been satisf:
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:ad A. G, Hayes C. ihood ventilatory. .ticulate matter in (-1972. In Clinical >n Research A. J. on, Mass: Publ Sci tobacco smoke: ool Htlh. 1972: :r B, Spcizer F. E. ioking on the puli i. Am J Epidtm .,in R. G. Passive il asthma. Chest. 4. Work group results 4.1. Exposure CHAIRMAN AND RAPPORTEUR: MELVIN W. FIRST 1. Farposu>x kucLr and Dose Rate Information concerning the total retained dose is basic for an understanding,of the effects of environmental tobacco smoke (ETS) on human health. Certain smoke components an& their rnetabolites, notably, nicotine and cotinine in blood, urine, and saliva, provide unique dose and dose rate information that can be related to effects in a quantitative manner. Only metabolite studies made in conjunction with human response evaluations camprovide a meaningful relationship between retained dose and effects. Nevertheless, experience with~ other environmental health study areas, notably occupatiom and air pollution, has demonstrated a need to establish a firm linkage between exposure and retained dose for a full understanding of the interaction between man and his environment. An additionalireason for pursuing linkages between environmental concentrations and human effects is that it is usually simpler, less costly, and less objectionable to potential donors to measure their environment rather than to extract biologicali fluids from them. However, it is not necessary to be rigid con- cerning, methodology because once the rela- tionships between exposure and dose have been satisfactorily established, investigations of the epidemiology of environmental tobacco smoke can be undertaken by either measure- ment method and it will be possible to inter- pret the results in either context; an outcome worthy of achievement. Finally, environmental measurements should be focused' on the most sensitive indi- viduals or on those exposed to the highest levels of environmental smoke as a first priority because useful information on effects is likelyto be obtained most rapidlyfromrhese populations. 2. Exposure l.ewl.r Carbon monoxide has been the most fre- quently used' indicator of ETS; but because there are numerous other sources of carbon monoxide in the environment that exist in quantities of the same or higher magnitude, carbon monoxide alone is not a specific surro- gate for, or indicator of tobacco smoke in the environment. There are, however, other substances that can serve as an index to ETS exposure but their selection willidepend to a large extent upon the specific effects on human health that are under investigation.
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138 For investigating acute efficts of ETS, it is believed that nicotine is the only specific indicator of tobacco smoke. Although the exact relationship has not been well' defined, it is hypothesized that nicotine represents a reasonable estimate of tobacco smoke concentrations in the environment because nicotine in air comes principally from the sidestream smoke and the nico- tine content of sidestream smoke does not differ greatly from cigarette to cigarette. However, sufficient care must be taken in sampling for environmental nicotine levels to ensure complete collection and reten- tion of this semivolatile smoke com- ponent. For chronic lung function impairment studies, it is believed that the total particulate matter fraction derived from tobacco smoke repre- sents the most relevant indicator of total' ETS. Photofluorescence methods are recommended for measurements of the cigarette product concentrationi although it is recognized that there are other sources of products that may be very similar, and possibly identical, with the tar fraction from tobacco smoke. For evaluating long term chronic effects such as lung cancer, it is believed that the particulate matter of ETS is the best indicator of expo- sure. To make this indicator of long term ETS exposure most valuable, it is necessary to relate total particulate matter to such suspect cancer causing compounds as nitro- samines and polycyclic aromatic hydrocar- bons. The determination of the relationship between a simple measurement and an indicationof what the exposure might have been to other important constituents is an important linkage to alli environmental measurements. Questionnains are considered a practical starting point for long term studies, but the relationship between questionnaire data and exposure levels needs to be verified by aerometric meas- urements. The final step will be to define the retained dose on the basis of questionnaire information. Personal sampling is as important as area moni- toring for better characterization of exposures to ETS and should be encouraged in future studies. 3. Human Dose Measurements Measurements of biochemical' markers of inhaledltobacco smoke have the advantage that they may characterize the dose inhaled and absorbed by the individiiali Howevery rela- tively few studies have as yet been conducted of the dose received from ETS, and it may not be possible to extrapolate with ~ accuracy from the level of one marker to that of another or to the magnitude of the overall~ exposure. Of the available markers, COHb and thiocyanate lack sensitivity and specificity and are influenced by exposures other than tobacco smoke. Nicotine is specific to tobacco smoke but many lack sensitivity in~non-experimental con, ditions. Howevery this may present a greater problem when determinationa are made on samples of blood than is the case for saliva or urine. Cotinine concentrations in different body compartments are highly, correlated, so that non-invasive measures of saliva or urine levels can provide a good guide to blood levels. This marker also has the advantage of a rela- tiively long half life. Preliminary evidence indicates that cotinine varies as a function of the degree of environ- mental exposure, and priority should be given to its evaluation as a marker for use in epidemi, ological investigations. Measurements of indi- vidual levels are crucial and vital to studies of t C t 4 4 :
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I starting ~tionship Vxposure ric meas- -fine the ionnaire a moni- rposures 1 future kers of age that ed and r, rela- iducted iay not y from =r or to Of the te lack ced by .e but tl con- zeater ie on iva or =erent .d, so urine :vels: rela- nine ron- iven _mi- ndi- .sof the effects of ETS but they should' be related quantitatively to environmental exposures and take into account the breathing rate and amount of air breathed. 4. Important confmrnding factors in interpreting ETS measurements are the following; Occupational exposures unrelated to tobacco smoke. Outdoor air pollution exposures unrelated to tobacco smoke. Contamination of indoor air by activities and sources other than tobacco smoke. Inability to make continuous measure- ments of long term cumulative exposures for chronic studies. Difficulties of conducting trace analyses of complex constituents in the atmosphere. Errors in questionnaire responses, particu~ larly misclassification of personal ~ smoking practices. 5. Research needs - Determination of the composition of side- stream~ smoke from, current market ciga- rettes. Relationship of ETS composition and con- centration to analytical smoke measure- ments of the same components in the side- stream smoke. - The effect of aging on ETS composition and'concentration. - Important components that, should be measured in ETS that are not now fre- 139 quently or adequately measured, even in mainstream smoke, are nitrosamines, polycyclic hydrocarbons, acrolein and formaldehyde. Methods should be developed to determine what fraction of these constituents that are found in the air can be related specifically to cigarette smoke contributions. - The linkage between ambient levels and uptake, using both area-wide measure- ments and' personal sampling measure- ments. Practical method§ for measuring the expo- sure of children and infants. These should be developed as a high priority; because it is believed on the basis of prior reports that this segment of the population is especially sensitive. Development of chemical dosimeters and biochemical markers for easy and reliable measurements of long term, average expo- sures to ETS products. Development of standardized question- naires for precise estimation of current and historical ETS exposure. For example, a better descriptor is needed of family member exposure, based on responses to detailed questions of smoking habits of other family members over time. Question- naires should include exposures to other relevant substances. Standard' methods for sampling and ana- lyzing sidestream and ETS should be devel- oped as consensus standards within ASTM, ISO, or a similar standard-writing organi, zation.
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4.2. Effects on health CHAIRMAN: MICHAEL A. H. RUSSELL RAPPORTEUR: MICHAEL D. LEBOWITZ The workgroup considered effects on humans that have been studied, as well as potential' effects. Animal research results, as related to mechanisms, were discussed in, this context. An attempt was made to determine the cer- tainty of the knowledge and the extent of the problem in the community. The group exam- ined the effects of acute and chronic exposures separately. Within each type of effect, the group attempted to consider their relative importance. Acute effects The workgroup agreed' that annayance was the most common effect, for whichwe have more certain knowledge. The group referred to the specific annoyance or disturbance due to smoky atmospheres. There seems to be sub- stantial agreement that annoyance can take the form of negative attitudes: as well. Headaches may occur also but they have not been syste- matically studied. There is some quantified exposure-effect relation in the literature between environmental tobacco smoke (ETS) and specific annoyance. This may be repre- sented by a non-linear, threshold-type relationi In~ addition to annoyance, specific e''ects due to irritants also occur, especially eye and nose irritation. Quantitative exposure-effect rela- tions have been published; they appear to be linear with concentration and time. These effects were reported to be related primarily to particulate matter. Nitrogen dioxide, formal- dehyde and acrolein were not implicated, but other gas phase substance were not studied. Regarding acute lung fxnction changes, there was agreement that the published studies on adult asthmatics were contradictory andi inad- equate. Since asthma (bronchiohyperreac- tivity) is highly disabling, occurs in a mean, ingful fraction of the populationj and since the asthmatics react to irritants unfavourably, it was agreed that this area warranted more sub- stantial i research. The research should be sim- ilAr to that conducted for other irritants, such as SOZ and NOZ, even though the specific re- sponsible agents in tobacco smoke may be unknown. Future research should also include more specific exercise or other challenge (e. g. methacholine) protocols, and shouldinclude a spectrum of asthma-reversible and irrever- sible, atopic and~ non-atopic, as there is a: wide range of responses in asthmatics. There should be some further attempts to identify other "sensitive" or more responsive groups as well. It was decided that the limited published information on normal adults show cc re rCS n( th stt at ti: lei
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141, rela- to be I'hese -ily to rmal- 1„ but ied. :here :s on inad- reac- tean- e the ly, it sub- sim- such c re- y be lude e. g. de a ver, vide s to sive ited! low no objective changes due to exposure with and without exercise, and that this area needed fur- ther investigation too. Since there is very little published on acute changes in children and none on young asthmatics, it was agreed that this also would be an important area of future research as well. The acute effects of ETS on angina pectorir is another area requiring further research, because present information is inad- equate. Many studies have demonstrated a statusticall relationship between ETS exposure and lower rerpiratory disease in children -other studies have not shown such relationships. It was agreed that the evidence for an association was fairly strong, although factors other than ETS must also be considered. This problem may poten- tially affect many young children. Cbronic effectr Some studies have suggested a relationshipp between ETS'exposure and childhood chronic respiratory disease, though other studies have not. These diseases may have important chronic sequelae. Thus, it deserves further research. Present' studies might provide attri- butable risk estimates. Further consid'eration should be given also to possible stimulating effects on alletgrc sensitization, in view of pub- lished observations on increased serum IgE levels in smoking young people and adults. Ongoing and future studies could utilize new techniques to study the genetic, immunolo- gical and structure-function mechanisms and effects, and should be conducted long enough for examination of possible sequelae and their chronic implications. The specific agents are unknown and need'further work. There are no data on absorption in children either. The group agreed that non-invasive techniques,, such as urinary or salivary nicotine and cotinine, should be utilized to determine dose levels andl that contributions of maternal and paternal amount of smoking be examined as well. Although published data on ETS and lung cancer cannot be considered'. conclusive, the workgroup agreed that there was sufficient consistency of statistical association to support further work. It was agreed also that the attri- butable risk in exposed non-smoking wives in some studies was sufficient to indicate a poten- tially sizeable problem. Since new cohort stu- dies would be time-consuming and expensive, it might be possible to use present cohort stu- dies, by expansion or modifacation, A case- referent approach should be considered. The further research should measure actual expo- sure to ETS and should consider the contribu- tions of specific agents thought to produce cancer, such as nitrosamines and polycyclic hydrocarbons. The group agreed that the risks of chronic lung disease, i.e. chronic changes in~lung function or chronic respiratory symptoms, related to expo- sure to ETS should be considered in adults and children. It was agreed! that published studies, are contradictory in their estimation of these risks: There is no knowledge about direct effects-if any-on~ chronic air flow limita- tion. As chronic changes might affect many people, the group agreed that this area deserved further research. A potential risk of coronary artery di.tease and'of total mortali y associated with ETS exposure cannot be excludedi Nothing is presently pub- lished demonstrating such effects. However, the likely relative risk based on~ estimates of equivalent mainstream smoking, is so low that these effects-if present-would be dlfficultto detect. There are several other potential risks of ETS exposure which have been postulated, but for which there is no information regarding the effects or mechanisms. These include the potential risk to pregnancy and effect on ~
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142 migraines. These have not yet been suitably exposures of the non-smoking household studied. members, social status an&other risk variables: Further research on ETS should also include The group emphasized that future research on all other possible agents and confounding fac- ETS should attempt to evaluate the potential tors, such as occupational exposure, other effects of the specific components. The toba conc bust spac mos; mon aero Co dictc the volu actel It mate tion conc peric prox TI knov irrita sageE in th at w, persc tive r sitiwc also ,
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5. Workshop perspectives RAGNAR RYLANDER The previous workshop on environmental tobacco smoke (ETS) (1):found that data on the concentration ~and distribution of tobacco com- bustion products in different types of enclosed spaces were limited. These data pertained mostly to the average concentrations of carbon monoxide (CO), nicotine or tobacco smoke aerosoli particles. Average concentrations of CO were found to agree well with those pre- dicted from iequations which take into account the generation rate of tobacco smoke, room volume, ventilation rate and air cleaner char- acteristics. It was recommended that when dose esti- mates for ETS were established, a determina- tion should be made not only of the averagee concentration overr shorter and longer time periods but also of the concentration ini close proximity to the persons exposed. The workshop also concluded that the main known acute effect of exposure to ETS was irritation of the eyes andl the respiratory pas- sages. The extent of this non-specific reaction in the general population and the levels of ETS at which it occurred was not known. Atopic persons or persons who otherwise have a reac- tive respiratory tract would be particularly sen- sitive to ETS exposure although they would also react to other irritating agents in the envi- ronment, su& as dusts and vapours. It was recommended that the proportion of such reactive persons in the population be deter- mined as well as the levels of ETS'at which the reactions occurred. It was concluded that effects other than acute irritationj such as respiratory disease, could occur in certain population groups for example children. The data presented, though suggestive, were not considered conclusive. It was recommended that more sensitive indices of effects would be obtained' by using better descriptions of the ETS exposure and a control of other environmental factors which might contribute to the studied effect. It now remains to evaluate what has changed since the last workshop, which con- clusions need to be modified and what new conclusions can be drawn. New information on exposure has become available since 1974. Experimental data on~ nicotine metabolites in urine and saliva suggest that under extreme conditions the daily ETSS exposure could be xhe equivalent of up to a few cigarettes (2). A more realistic dose would
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1441 probably be about 0.1 cigarettes as evaluated by the previous workshop. No information is available on the average exposure level for the general population of non-smokers. In view of the uncertainty of the ETS expo- sure in the general population, calrulations can n©t be made regarding the presence of disease such as lung cancer in the non,smoking popu- lation due to exposure to ETS by, making,refer- ence to the data reported in epidemiological studies on the association between smoking, and lung cancer. In~ epidemiologicali studies on lung cancer among groups of persons, the ETS exposure has been characterized by the smoking habits of the spouses. Some studies have presented data that suggest a dose related, two fold risk increase in lung cancer among non•smokers subject to this ETS' exposure. Other studies have demonstrated a non-significant, not dose related tendency and one study demonstrated a lower risk. An overall evaluation~ based upon available scientific data leads to the conclusion that an increased risk for non-smokers from. ETS exposure has not been established. Fur- ther studies:should incorporate a more precise description of the ETS exposure in~ different groups of the general non-smoking popula- tion. Regarding possible effects on childien, more information is now available than was the case at the previous workshop. Data have been pre- sented both from animal experiments eval- uating models for the different reactions and' from ~ field studies. The results are still' contra- dictory: No adequate description of ETS dose levels in a population of children has been reported. New techniques for measurements of dose levels are now available as reported during the workshop and should be applied in future studies. These should preferably be pros- pective studies with well defined criteria for exposure and effect. The unimportance of carbon monoxide (CO) has been further confirmed. In this regard there was agreement with the finding from the previous workshop that CO from ETS is not important from a health point of view. Irritation and annoyance must still be con- sidered to be the most prevalent effects ascer- tained from exposure to ETS. Considerable knowledge has been gained regarding condi- tions during which eye irritation and general annoyance develop as well as on different com- pounds which may cause these effects. Information is still lacking as to the extent of this reaction in the community under everyday conditions. Most information on dose response relationships is derived from laboratory exper- iments and the application to normal condi- tions is as yet uncertain. It is thus premature to suggest maximal exposure levels for annoyance to be used in the workplace or the general environment. For future work, a major research priority is to determine exposure levels of ETS in dif- ferent segments of the non-smoking, popula- tion under normal everyday conditions, partic- ularly among children~ with smoking parents and non-smokers married to smokers. Not until such data are available can the possible effects related to ETS exposure be further eval- uated. Available evidence demonstrates that the possible health effects of ETS are not signifi- cant in comparison to the multitude of health problems facing society on a global scale. This does not exclude the possibility that ETS expo- sure may be important to certain individuals or parts of the population~ under special circum- stances. It is essential, however, that future activities regarding research and'exposure con- trol i be considered in comparison to what can be gained! from a public health point of view. Q
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145 REFERENCES' 1. Corn M. Kilburn K. H. and Rylknder R. Work- 2. Jarvis M. J, Russell M. A. H. and Feyerabend C. shop summary and recommcndations in Absorption of nicotine and carbon monoxide Rylander R. (ed). Environmental Tobacco from passive smoking under natural conditions of Smoke Effects on the Non-Smoker. Scand J Resp exposure. Thorax 1983: 38:829-833. Dis 1974. Suppl 91 k 88-90.
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w O r 64 03522651
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6. General references on studies of environmental tobacco smoke (ETS) These references contain data on original research on ETS. Review articles are not included Anderson G, Dalhamn T. Health risks due to passive smoking (in Swedish)j Lakartidningen 1973: 70:2833-2836. Andresen B. D, Kwokei KJ. Ng; Jay J. D, Bianchine J, R. Cotinine in amniotic fluids from~ passive smokers. The Lancet, April 3, 1982: Correrpondence: - The Lancet~ May 20, 1982. N. Smith and J. Austen. Antweiler H. The absorption and' action of carbon monoxid' during active and passive smoking (in German). Arbeitsmed Sozialmcd Praventivmed' 1975: 12:245-248. Aronow W. & Effect of passive smoking on angina pectoris. N Eng J Med11978: 299:21-24. Cotmporrdente: - N Eng J Med Oct 1978: 299:896-7. H: Wakeham. B. F. Robinson. C. I. Waite. A. Coodley. W. S: Aronow. Ayer H, E, Yeager W. D. Irritants in cigarette smoke plumes. Am J publlHlth 1982: 72:1283-1285. Badre R, Guillerm R, Abrani N, Bourdin M, Dumas C. Atmospheric pollution by smoking (in French). Annls pharm fr 1978 : 36 :443-452. Bergman, A. B, Wiesner L. A. Relation of passive cigarette-smoking to sudden infanti death syn- drome. Pediatrics 1976: 58:665-668. Binder R. E, Mitchell C.,A, Hosein H. R, Bouhuys A. Importance of the indoor environment in air pol- lution exposure. Archs envir Hlth 1976: 31:277- 279. Bland M, Bewley, B. R, Pollard V. Banks. M. H. Effect of children's and parents' smoking on res- piratory symptoms. Archs Dis Childh 1978: 53:100-105. Blue J. A. Cigarette Asthma and Tobacco Allergy. Ann Allergy, 1970: 28:110-115. Bonham G. S, Wil$on R. W. Children's health in families with cigarette smokers. AJPH 1981: 71:290-293. Bridge D. P, Corn M. Contribution to the assessment of exposure of non smokers to air pollution from cigarette and cigar smoke in occupied spaces. Environ~Res 1972: 5:192-209. Brunekreef B, Boleij Ji S. M. Long-term average suspended particulate concentrations in smokers' homes. Int Arch occup Environ Hlth 1982: 50 :299-302: Brunnemann K. D, Yu L,,Hoffmann D. Assessment of carcinogenic volatile N-nitrosamines in to- bacco and in mainstream and sidestieam smoke
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