Tobacco Documents Online

ENVIRONMENTAL TOBACCO SMOKE - Measuring, Exposures and Assessing Health Effects Committee on Passive Smoking Board on Environmental Studies and Tbxicology National Research Council 1. Ca vJ-•u'" sc.. 1- NATIONAL ACADEMY PRESS Washington, D. C. 1986

National Academy Press • 2101 Constitution Avenue, NW • VVashington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Boar&of the National Research Council; whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The National Research Council was established by the National Academy of Sciences in 1916 to associate the broad community of science and'technol: ogy with the Academy's purposes of'furthering knowledge and of advising the federallgovernment. The Council operates in accordance with general policies determined by the Academy under the authority of its congressional charter of 1863,,which establishes the Academy as a private, nonprofit, self-governing membership corporation. The Council has become the principali operating agency of both the National Academy of Sciences and the National Academy of Engineering in the conduct of their aervices to the government, the public, and the scientific and engineering communities. It is administered jointly by both Academies and the Institute of Medicine. The National Academy of Engineering and the Institute of Medicine were established in 1964 and 1970, respectively, under the charter of the National Academy of Sciences. This study was prepared' under EPA Contract #68-02-4073 and De- partment of Health and Human Services, Public Health Services Grant #ASU000001-06-S1. The content of this publication does not necessarily reflect the views or policies of the U.S. Environmental Protection Agency or the Department of Health and Human Services, and an of$cial' endorsement should not be inferred. INTERNATIONAL STANDARD BOOK NUMBER 0-309-03730-1 LIBRARY OF CONGRESS CATALOG CARD NUMBER 86-28622 Copyright Qc 1986 by the National Academy of Sciences No part of this book may be reproduce& by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use„without written permission from the publisher, except for the purposes of official use by the United States Government. Printed in the United States of America E P

14 Cardiovascular System f f The effects of active smoking on exercise tolerance, blbod pressure, and the risk of developing cardiovascular disease have been reviewed el§ehwere (U.S. Public Health Service, 1983)I. This chapter discusses studies of ETS exposure to nonsmokers and subsequent possible cardiovascular effects. The constituents that are thought to have the greatest effect on the cardiovascular system are carbon monoxide (CO), and nicotine. The possibility exists that the mechanisms, as well as the magnitude of the effects, for acute and' chronic cardiovascular effects may be different for exposure to whole smoke and to ETS. ACUTE CARDIOVASCULAR EFFECTS OF ENVIRONMENTAL TOBACCO SMOKE EXPOSURE Administration of nicotine at level similar to those induced by active cigarette smoking is shortly followed by increases in heart rate and' blood pressure (U.S. Public Health Service, 1983). Platelet aggregation has been shown to be increased in in vitro studies. CO rapidly combines with hemoglobin in the blood to form carboxyhemoglobin (COHb), thereby leading to some degree of tissue hypoxia. CO combines with muscle myoglobin, which is followed by some muscle hypoxia. The level of exposure of the nonsmoker to these cigarette smoke constituents, however, is less than~ that' of the active smoker,, and the effects are expected to be less. Table 14-1 reviews some of the increases in COHb levels as seen in both experimental and observational studies. The levels of 257

258 i t TAsLr 14-1 Carbon~ Monoxide and Carboxyhemogfobin Levels in Nonsmoking Individuals Ezperimental Studies IControlled Chambersf. No: of No, of' Carboxyhemoglobin CO! Study Cigarettes/h/10 mj Subjects ppm" Controll Change ( Anderson and' Dalhamm. 3;1 - 4.5 0.3 0 ~ 1973 i Dahms et al-. 1981 - 10: 15-20, 0.6 +0.4 Harke, 1970 3:9 7 30 0.9 + 1.2 Huch et a1.. 1980 2:3 12 - 11.3 +0.5 Hugod'tt'al., 1978 2.5 1,0, 20 0.7 +0.9 Pimm et al., 1978' 2.4: 10 24: 0.5 +0.3 1 2.4: 10 241 0.7 +0.2 ~ Polak, 1977 6,7 15 23' 2.0 +0.3 Russell et al.. 1973 15:1 12 38 1.6 + 1.0 I Seppanen and Uitsitalo; 3.8 28 16 1.6 + 0.4 HI 1977 Srch.1967 50 - 90 2 +3 P Observational Studies Nonexposed: Exposed' Study Subjects/Exposure No. of Subjects Carboxy- hemogfobin; % CO Ex- pired, ppm Q Folian et a1.. 1982' Flight attendants/8 h 6 1.0:0.7 el Jarvis et al:, 1983 Normal/public house 7 4.7:1016 for 2 h V1 Lightfoot, 1972 Normal submarine -:1.0 Wald et al.,,1981 Participants in health 6.6411 screening program Jarviset al., 1984 Normal/self report 10 0.9:0!8' 5.7:5.5 Seppanen and Restaurant for 5 h Uusitalo, 1977 (CO:2.S-15 ppm) 47 2.1:2.1 ea Office for 8 h 15 2,3:2.3' 2 (CO:2.5 ppm)! 9i1 'Carbon monoxide (CO)'measured'as a proxy to indicate the concentration of ETS in the chamber. COHb commonly observed in active smokers are higher, ranging between 4 to 6 percent, rarely greater than 12 percent (Schievel- bein and Richter, 1984). Because exposure of the nonsmoker is qualitatively different than exposure to smokers, a simple scaling down of effects observed in active smokers does not appear to be fully appropriate. Therefore, the effects of exposure to nicotine, 41 g e w p P~ erl

259 TABLE 14-Z Resting,Acute Cardiovascular Effects in Nondiseased Humans of Exposure to Environmental Tobacco Smoke Results Authors Studc Population Conditions Measured Variable Before AHer Luguerte ef aI.,J970 40!children Room: 9 ml Heart rate 89 97 No: cig.: ti Blbodipressure 116,6' 120'72 Harke and Bleichert, 101 T'imer15 min Room: n.g; Heart rate 72 = 8 74I= 12 1972 1vo: cig.: 150 Blood pressure 123'8a 121/8a Time: 20 min Skin temperature ('-`C/min) 0 0.0273 Rummellet al:. 1975 96 Room: 30 m-1 Heart rate 72 = 10 71 ± I 1 No,,cig,: 6-8 Blood pressure 1i171 117/71 Hurshman et al., 1978 8 T'ime:,20 min Roomc n.g. Hean rate 73 79 No: cig.: 2-b Blood pressure 107/6'' 114/b8 Time: 10 min Pimm et al.. 1978' 101males Room: 14.b ml Hean rate 8a(F) 80(iF) 10 females No. cig:,: 7 77(M V 70tW Age = 22.3 Time: 2 h CO, or ETS need to be separately studied. In addition, consid- eration needs to be given to persons of different sensit'ivity' or vulnerability. Healthy Subjects Table 14-2 lists studies that report on the consequences of exposure of nondiseased individuals to ETS for periods up to 2 hours under experimental~ resting conditions: There were no significant changes noted in heart rate or blood pressure inl school- age& children or in adult men and women. Two studies evaluated the physiologic responses to exercise with and without exposure to ETS. In the first, Pimm et al. (197$) (see also Table 1'4-2) had subjects perform a 7-minute pro- gressive exercise test! on an electronic bicycle ergometer. During exercise, the women had higher heart rates after exposure to ETS when compared with control conditions (differences ofl 6.3 beats per minute at 2 minutes and 4.5 beats per minute at 7 minutes, p< 0.01). The recovery heart rates were not significantly differ- ent. The men, however, showed little difference between test and

260 control conditions (differences of -0.1 beats per minute at'~ 2 min- utes and 1.5 beats per minute at 7 minutes). In the second study, Sheppard and colleagues (1979b) tested 11 males and 12 females at two different levels of ETS (i.e., 7 cigarettes over 2 hours, CO = 20 ppm, or 9 cigarettes over 2 hours, CO = 31 ppm). Under both exposure conditions, contrary to expectations, both the increment in heart rate and average heart rate were less:with ETS exposure. In summary, for normaL young adult males and females, no significant acute effects of ETS exposure on heart rate or bloo& pressure have been reported, either under resting or aerobic con- ditions. There have been several studies of exposure of normal sub- jects under resting and'aerobic conditions to low levels of CO but higher than those found with ETS exposure (reviewed in Envi, ronmental Protection Agency, 1984). No significant effects were found in healthy, exercising subjects during short-te= exposure (e.g., Drinkwater et al., 1974; Raven et al., 1974a,b; DeLucia et al., 1983). Angina Patients Angina pectoris is a symptom complex involving feelings of pressure and pain in the chest; which is produced by mild exercise or excitement, presumably because of insufficient oxygen supply to the heart muscle. Under conditions of ETS exposure, the CO Ievels are increased, thus possibly placing individuals with angina at an: increased risk of recurrent episodes. Anderson et al. (1973) and Aronow and his colleagues, in a series of experiments (1973,,1974, 1978, 1981) (Table 14-3), stud- ied angina patients under aerobic conditions with~ exposures to lbw levels of CO and to ETS. Ten~ patients with diagnosed angina pec- toris, of whom two were smokers and eight exsmokers,,were tested (Aronow et al., 1978). Significant increases in systolic blood pres- sure and heart rate, and decreases in time to onset of angina, were noted when the subjects were exposed to smoke in either venti- lated or unventilated rooms (the actual levels of CO under these conditions were not noted). There were some subjective elements in the evaluation of these patient's, and the physician conducting, these tests was aware of the test condi'tions,, i.e., smoking or not and ventilated or not. Consequently„the findings of this study, in N A

TABLE 14-3 Acute Cardiovascular Effects of Exposure to CO or Environmental Tobacco Smoke by Nonsmoking Angina Patients f 1 Study Design No. Conditions Results Anderson eual., Double-blind. 10" CO:50 ppm Mean duration before onset 1973 Cross-over or 100 ppm oflpain shortened'd50 ppm Time: 4 h and~ 100ppm):, duration for 5 days oflpain longer (100 ppm only) Aronow and Isbell, Double blind. 10" CO: 50 ppm Times until onset decreased; 1973 Cross-over Time:,2 h dettease in BP and heart rate at angina Aronow, 1978 Not blinded 10' No. cig:: 15 Earlier onset of angina: in- Time: 2 h ereased s•stolic BP and Room: 30.28 m3 heart rate at angina Aronow et al., 1979 Double-blind, 20 COHb: 4% Impairment in visualization Cross-over test Aronow, 1981 Double-blind. 1,5 CO: 50 ppm Time until onset decreased; Cross-over Time: I It decreased systolic BP and COHb: 2% heart rate at angina "Includes five smokers and'five nonsmokers. hNot current smokers. `lneludes eight exsmokers andtwo eurrenrsmokers. the absence of a true double-blind approach, require verification by other research workers. The effects of rapid angina onset would be expected to be due to increased: COHb levels. And'erson~ et al. (1973)' and Aronow et al. (1973y 1981), exposed angina patients to low levels of CO. In these studies, angina pain appeared'when COHb levels of patients were measured' at 2 and 4%. These studies have been reviewed ex- tensiveNy as part of the Environmental Protection Agency's (1984) activity in establishing air quality criteria for carbon monoxide. The review group found that the results were suggestive for ef- fects at COHb levels above 3%, based on animal and theoretical models. There is concern t'hat elevated levels of CO exposure may affect the electrical stability of the heart in previously compro- mised heart muscle, thus possibly leading to sudden death, The levels reviewed in~ Table 14-1 are close to the 3% levell This sug- gests that there is reason to be concerned with possible effects of exposure. However, a firm quantitative estimate of the risk to nonsmoking persons, under conditions of ETS exposure, cannot be made from the literature at this time.

262' CARDIOVASCULAR DISEASE MORBIDITY AND MORTALITY Possible pathophysiologic mechanisms for the atherogenic in- fluence of cigarette smoking were reviewed' in the 1983 Report of the Surgeon General. Experimental studies of subcutaneous or intravenous administration of nicotine in rabbits (Schievelbein~ et al., 1970; Schievelbein and Richter, 1984) and monkeys (Liu et al., 1979) have demonstrated that long-term exposure leads to ar- teriosclerotic lesions. Exposure to carbon monoxide also leads to atherosclerosis in rabbits, pigeons,,and other animals (Astrup and Kjeldsen, 1979). Studies of whole tobacco smoke indicate that to- tal serum cholesterol concentrations are increased and the ratios of the various lipoprotein fractions are changed (McGill, 1979). The contribution of whole tobacco smoke to modifying the lipoprotein fractions is not conclusive. However, there have not been experi- mental studies of the effects of ETS exposure or administration of ETS extracts. Smoking and Cardiovascular Disease The effects of active smoking on human health are summa- rized in the Surgeon General's report The Health Consequences of Smoking: Cardiovascular Disease (',U.S. Public Health Service, 1983). The principal conclusions are that cigarette smokers ex- perience a 70% greater coronary heart disease (CHD)~ death rate than do nonsmokers and that smokers of more than two packs per day have 2 to 3 times greater CHD death rates than nonsmokers. The incidence of CHD in smokers is twice that of nonsmokers. Heavy smokers (more than~ two packs per day) have an almost fourfold increase. The relative risk in smokers for sudden death~ is greater than that for all deaths from CHD. The relative risk in~ young smokers is greater than that in older smokers. The rela- tive risk for young women smokers, especially those who use oral contraceptives, is greater than 5. The excess relative risk associated with smoking declines rapidly upon cessation of smoking, in some studies as much as 50% in 1 year. For exsmokers who previously smoked more than one pack per day, the residual excess risk also declines, but never completely disappears. The decline in risk on cessation of smoking cannot be explained by differences in known cardiac risk factors sto of l wei

263 between individuals who continue smoking and individuals who have quit. Smokers who have used only pipes or cigars did not appear to experience a substantially greater CHD risk than non- smokers. The rapid'. decline in risk associated with smoking cessation and the greater relative risk for sudden death suggest that active smoking can precipitate cardiac events in, individuals with preex- isting coronary artery disease. Autopsy evidence of increased arte- riosclerosis in smokers, coupled with the fact that'risk of exsmok- ers never returns to the levels found in nonsmokers, suggests that cigarette smoking is also implicated in the development of arte- riosclerotic cardiovascular disease (ASCVD). The mechanism by which cigarette smoke may lead to the development of chronic ASCVD, sudden death, or acute myocardial infarction is unknown. There appears, however, to be no threshold in the number of cigarettes smoked below which there is no increase in risk. Data on uptake of cotinine by nonsmokers exposed to ETS indicate that the exposure in~ nonsmokers chronically exposed to ETS is approximateUy 1% that of an active smoker (who smokes one pack per day) (see Chapters 8 and 12). If the excess relative risk for CHD mortality or morbidity is a linear, nonthreshold function of dose and!, further, if the excess risk of CHD in a one- pack-a-day smoker is twofold, then the relative risk from CHD in nonsmokers expose& to ETS (compared to true nonsmokers)i would be approximately 1.02. Such relative risks would be difficult to detect or estimate reliably in nonexperimental studies. Such~ smallincreases in relative risk are of the same order of magnitude as what might arise from expected residual confounding due to unmeasured covariates. Nonetheless, because of the large number of cardiovascular deaths each year, these possibilities deserve close attention and further study that could lead to firmer estimates of excess risk. Studies of Environmental Tobacco Smoke Exposure and Mortality from Cardiovascular Disease Garland et al. (1985) have reported that, in a prospective study of the effect of passive smoking, the age-adjusted rates of cardiac disease deaths in nonsmoking women whose husbands were former or current smokers were significantly elevated. It is c

264 Y not certain, however,,that the report is correct, because of a possi- ble miscalculation or misuse of the Mantel-Haenszel statistic and some other methodologic problems. Data for the wives of' former smokers were grouped with wives:of current smokers. If this group- ing were made after examining the d'ata„which indicated that the risk was greater among the women whose husbands were former smokers, then this combination would be suspect. The p values based on the Mantel-Haenszel test may be inappropriate in view of the small sample sizes. The authors employ the Cox Propor- tional Hazard analysis to control for other factors associated with cardiovascular risk, such as age, blood pressure, cholesterol, obe- sity, years of marriage,,etc. They report a relative risk for women married to current or former smokers compared withl women mar- ried to never-smokers of 2.7 (Garland, 1985, corrected from an earlier report)L The p value (< 0.10)' associated with this esti- mate is based on the asymptotic assumptions that are implicit in likelihood-based inference from~ the Cox model. These assump- tions may not hold for small sample sizes. In summary, because of the small sample sizes, the significance caltulat'ions ariaing from this study must be looked upon as approximations. Gillis et al. (1984) reported the results of a follow-up study of residents of two urban communities in Scot'land. Nonsmokers exposed to cigarette smoke in their homes had a slightly higher rate of myocardial infarction than those unexposed. The sample size was small, so that few of the results were statistically significant, and other risk factors for myocardial infarction were not controlled for. Hirayama (1984) reported the results of a 15-year prospective study of nonsmoking Japanese women classified at start of follow- up by the smoking status of their husbands. A relative risk from ischemic heart disease of 1.3 was found for nonsmoking women whose husbands smoked more than 19 cigarettes per day com- pared with nonsmoking women whose husbands did not smoke. A Mantel-Haenszel test for a linear trend was significant at the p < 0.01 level. It is unlikely that Hirayama's results can be explained by chance. The pot!ential biases inherent in this study (see Chapter 12) limit the weight that can be placed on these results. The observed relative risk of 1.3 is at the upper limit of the expec- tations derived' from extrapolations from active smokers, unless the uptake of the active component of cigarette smoke to which H