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SEMINARS IN RESPIRATORY MEDICINE-vOLUME 11, NUMBER 1, JANUARI' 1990 Health Effects of Involuntary Smoking: Impact on Tobacco Use,. Smoking Cessation, and Public Policies Vijay K. Mahajan, M.D.,* and Gary L. Huber, M.D.t In 1964, the subject of involuntary tobacco smoke inhalation was not addressed in the first re- port by the Surgeon General on the health conse- quences of tobacco smoking.' In the reports that were to follow, the first discussion of involuntary smoking did not appear until the fifth report, re- leased in 1971.2 Some 15 years later, substantial literature had been published on this subject and the 1986 report by the Surgeon General focused almost exclusively on this subject.' The Surgeon General's silver anniversary edition, released in 1989, incorporated additional discussions on this topic, including a review of national, state, and lo- cal legislative policies.'t Probably no aspect of to- bacco use has generated more controversy or had a greater impact on smoking practices by Americans; in addition, probably no other aspect of the to- bacco and health issue has had more shoddy re- search and less reproducible results published. The purpose of this contribution is to review some of the more important data that are available; more than a thousand reports on this subject now appear in the literature and a comprehensive or complete review of all publications is beyond the intent and scope of this endeavor. We have tried to review in some detail the most frequently cited publications, including a summary of relevant supporting stud- ies and specific criticisms. Unfortunately, the most frequently cited publications are not always the sci- entifically best investigations. It also is within the intent of this contribution, at least in some degree, to assess the impact of public policies pertaining to involuntary smoking on tobacco consumption in the United States, as well as on the development of successful smoking cessation strategies. The potentially harmful effects of tobacco smoke on the nonsmoker have become an ever pro- gressively more important topic of debate. Until 1979, no more than about 300 articles had ap- peared in the literature on the health effects of tobacco smoke on the nonsmoker. At that time, in the United States, an estimated 54 million men and women smoked 615 billion cigarettes. A much larger number of nonsmokers most likely were ex- posed passively to the smoke resulting from this active and extensive cigarette consumption. Today, there are an estimated 50 million Americans still smoking only a somewhat slightly lesser number of cigarettes. Considering the very large number of persons still exposed to environmental tobacco smoke, detection of even a small percentage of nonsmokers experiencing the harmful effects of tobacco smoke from others would have important public health consequences. Because of the public health concerns for this matter, a fervent contro- versy has developed both in the scientific and in the lay press. The issue also has gained a tremen- dous momentum with the general public, because differing claims are made by those who smoke and by those who do not want to be exposed incolun- tarily to the smoke of others. It is common to see now on an almost daily basis well-publicized reports, as well as well- publicized distortions, in the national news media, including newspapers, magazines, and television, dealing with passive smoking. A number of these reports quote on a regular basis highly placed pub- lic health officials who have major influence on the national policies related to tobacco smoking. How- ever, unlike the direct health effects of tobacco smoking on the voluntary consumer, only sparse, and not nearly as solid, scientific data are available on the health effects of passive smoke inhalation. Far too frequently, reports receiving widespread *Medinl College of Ohio and St. Vincent's Hospital. 7'otedo. Ohio tUniversity of Texas Heahh Center. Tyler. Texas Reprint requests: Dr. Mahajan. St. Vincent's Hospital, 2213 Cherry Street, Tokdo. OH 4b60a-Y691 Copyright O 1990 by Thieme Medical Publishers. Inc.. 38 1 Park Avenue South. New York, NY 10016. AN rights reserved. 87

SEMINARS IN RFSI'IRA'1'()R1' MF.I11(:INF.-VC)t,UMf. 11. NUMttF.R I. fANUAR)' 199n dissemination have not undergone careful scien- tific scrutiny. Indeed, there is no other sphere of tobacco and health research where more citations that have not passed peer review and have not been scientifically reproduced are commonly accepted _ as unquestioned fact. A significant ntimber of those studies that pertain to the health effects of smoking in the nonsmoker that now do exist are poorly de- signed, structurally unsound, uncontrolled, and have major statistical problems. However, despite this, there are available a number of reasonable studies that address the effects of passive smoking in children, as well as in adults. Some of these will be reviewed in detail in this article. The major ctifliculty in stuelying the cflicts of tobacco smoke on the nonsmoker is that non- smokers are exposed to a qualitatively different smoke; more importantly, it is very difficult to quantitate smoke exposure in nonsmokers, com- pared to the active smoker. In this article sonie of the more important of the available information on the health consequences of tobacco smoke in the nonsmoker will be reviewed in an effort to gain a better understanding of this rather important and continually growing controversy. Because of the extraordinary volume of literature that now exists on the topic of environmental tobacco smoke, our review cannot be complete. Nevertheless, the number of citations included is extensive, hope- fully providing some degree of balance and a re- source for further reading on the singular aspect of tobacco and health that has emerged with un- paralleled importance. TERMINOLOGY Inhalation of tobacco smoke by the non- smoker has been described with different terms. Most frequently, these include: passive smoking, involuntary smoking, inhalation of environment tobacco smoke, and secondhand smoking. In this review, these terms will be used interchangeably, for they all mean essentially the same thing. "Pas- sive smoking" is defined as the inhalation from the environment by the nonsmoker of tobacco com- bustion products that are generated by active smokers. The terms "sidestream smoke" and "environ- mental smoke" are frequently encountered in the literature that pertains to passive smoking; these two terms do not mean the same thing. "Side- stream smoke" is the smoke that originates from the burning end of a cigarette. The smoldering temperature of this burning cone is about 500 to 600°C between puffs, and approximately 860 to 88 900°C during puffing. About 50% of the burned cigarette is released as sidestream smoke. A very small amount of sidestream smoke_ is inhaled by the smoker. For the most part, nonsmokers do not inhale sidestream smoke released directly from the burning cigarette before it is extensively di- luted. Most of the sidestreani smoke is diluted imrne- diately into the surrounding air. "Environmental tobacco smoke" is the term used for this highly- diluted sidestream smoke; a certain additional component of exhaled smoke not retained by the smoker during inhalation is added to the environ- mental tobacco smoke. It is the highly diluted environmental tobacco smoke that nonsmokers in- halc. CHEMISTRY OF ENVIRONMENTAL TOBACCO SMOKE The chemical and physical properties of to- bacco smoke have been discussed in some detail elsewhere." A more detailed assessment of side- stream smoke and of environmental tobacco smoke will be presented herein. In addressing this subject, however, far fewer publications are avail- able for our consideration. Of those that are available, including those that discuss the chemis- try and potential toxicity of sidestream and of environmental tobacco smoke, many are contro- versial; these are reviewed in greater detail else- where.2-17 - Several studies have reported on assessments of undiluted sidestream smoke from tobacco cigarettes. Table I summarizes some of the poten- tially toxic and potentially tumorigenic compo- nents of undiluted sidestream smoke.7 Table 2 summarizes similar constituents of environmental tobacco sntoke.7 'i'he results presented in these tables have not as yet been reproduced. Specific measurements of actual environmental tobacco smoke are much more difficult to obtain in that environmental tobacco smoke is significantly fur- ther diluted by a factor of approximately 100- to 1000-fold. Tobacco smoke in the environment is contrib- uted by only two sources: exhaled mainstream smoke and sidestream smoke. The environmental component of exhaled mainstream smoke that is inhaled by others is that smoke that has been puffed by the smoker through the tobacco prod- uct (most commonly a cigarette), inhaled and cir- culated within the respiratory tract, and then exhaled by the smoker into the_ environment. During its passage within the respiratory tract, sig- nificant amounts of gas and particulate phase con- stituents are knt from the inhaled mainstream

HEALTH EFFECTS OF INVOLUNTARY SMOKIN(:-MAIIAIAN, FIUneR Table 1. Polentlal Toxic and Tumortpenlc Agents In Undiluted Cigarette Sidestream Smoke• Compound Type of To:/ckyt S/destresm Smoke (per Cfparette) Sldestream to Malnstra.m Ratio Yaporphase Carbon monoxide T 26.8061 µq 2.5-14.9 Carbpnyl sulfide - T 2-3 µg 0.03-0.13 Berrzene - C 400-400 µg d-10 Formaldehyde - C 1500 µq 50 g.yw"rdvv SC 300-450 µq 24-34 Hydyogen cyanide T 14-110 µq 0.06-0.4 Hydrazine C 90 t.9 3 Niftw oxides - T S00-2000 µq 3.7-12.8 N-N C 200-1040 ng 20-130 N-NitrosopyrroRdine C 30-390 ng 6-120 'artkrdate phase Tar C 14-30 mg 1.1-15.7 f8op(ine T 2.1-46 mg 1.3-21 Pow ~ TP 70-250 pg 1.3-3.0 Ciftchol - CpC 58-290 µ9 0.67-12.6 oToluidine C 3 µg 16.7 2.Nayhtylamhro - C 70 ng 39 I-MtNropjplynyl C 140 ng 31 Beru(a)anthracene C 40-200 ng 2-4 8ento(e)tmene C 40-70 ng 2.5-20 ptinloline - C 15-20 µg 8-11 N'-Nitr<>:onomiooline C 0.15-17 µq 0.5-5.0 4-(rtASthyktitr()aamino)-(3-pyridyt)-1=butanone C 0.2-1.4 yg 1.0-22 N-N4itrosodiethanolarnirw C 43 ng 1.2 Cadmium - C 0.72 µg 7.2 Nickel C 0.2-2.5 µq 13-30 Prllonium-210 C 0.5-1.6 pCi 1.06-3.7 • Adapted from Hofffman and Hecht' as cited in the Surgemn (9eneral's report in IQ84.' 1 C: carcinogenic; GoC. cocarcinogenic; SC. suspected carcinogen; T: toxic; Tf : tumor promoter. Table 2. Potenttat Toxic and Tumorigenic Agents from Tobacco Smoking In lndoor Envlronments• Pollutant Location Coneentrattorurn' Nitrit oxide Workrooms 50-440 vg Restaurants 17-270 pg Bars 80-520 ug Cafeterias 2.5-48 µq Nitrogen dioxide Workrooms 68-410 µ9 Restaurants - 40-190 µq Bars 2-116 µq Cafeterias 67-200 µg Hydrogen cyarlide t.iving rooms 8-122 µg 8enzene Public plarxs 20-317 rµg Fonnaldehyde LNbtp rpoms 23-50 µg Acrolein Public places 30-120 µq Acetone PubGc places 360-5800 pg Phenols (volatik) Cotlee houses 7.4-11.5 ng N-NitroloEinrelhytamine Reslaurants. public places 0-240 np N-NiMosodialhylKrtyne Restaurants, public places 0-200 np f~i0otlns P(blic places 1-6 µq Rataxants 3-10 t,q Workrooms 1-13.0 pg 6ento(a)pyrene Restaurants. public places 3.3-23.4 ng • Adapted from Ho6man and Hecht,' as cited in the SurReon Generat's repon.' smoke to the lungs of the smoker. It has been cal- culated, for instance, that as much as approxi- mately 70 to 90% of actively inhaled smoke is retained by some smokers, with others retaining as little as 10% of the smoke.ts The amount of smoke retained by the smoker depends on the depth of inhalation of the puff and several other factors.19 The sidestream smoke is introduced di- rectly into the environment by the burning cone of the tobacco product. This is generally of an al- kaline pH, as opposed to the slight acidity of most mainstream smoke, and as such is much more ir- ritating to the nonsmtrker. From one cigarette, as an example, this sidestream smoke contributes ap- proximately two thirds of the total aerosol partic- ulate matter that is delivered to the environment,s the remainder coming from exhaled mainstream smoke.

SFMINARS IN RFSPIRA"I()R1' MF.IIIt:INF-Vt)I.UMf. 11. NUMRFR I, fAA'UARI' 1990 CHEMISTRY OF ENVIRONMENTAL TOBACCO SMOKE The mainstream, sidestream, and environmen- tal tobacco smoke all differ significantly in their na- ture, their quantity, and their potential toxicity. It is extremely difficult to assess these differences, in part because the concentration of environmental to- bacco smoke, once diluted, is extremely small. Be- cause the absolute amounts of smoke per volume of environmental air are so small, quantification of smoke constituents, as well as assessments of their biologic effects, are extremely difficult. Much of the reported data that are widely quoted were derived from laboratory experiments that generated "side- stream smoke" from a mechanical smoking machine and experimental chambers; data on siclestream smoke generated by real smokers under usual life conditions are extremely sparse. Many of the extrapolations concerning the po- tential health effects of environmental tohacco smoke have been derived frrrnt reporrtcd ratios rrf constituents in sidestream sntoke to the same con- stituent in mainstream smoke. For example, such a ratio of carbon monoxide in sidestream smoke was 20 times that of the carbon monoxide in mainstream smoke. These experimentally derived ratios are af- fected by the experimental burning rates, the hu- midity or moisture content of the tobacco, the porosity of the cigarette pal>er, and several other factors. The significance of sidestream to main- stream ratios for smoke constituents must be inter- preted with great reservation, for they seldom reflect the true ratio of the smoke constituent in the much diluted environmental tobacco smoke that is available for passive inhalation. In other words, the nonsmoker does not passively inhale smoke constit- uents in the concentrations reported for sidestream smoke, expressed either as a ratio or in absolute amounts, because these constituents are diluted an additional 100- to 1000-fold prior to their passive inhalation, and are altered in other ways. The amount of tobacco smoke released from a cigarette during puffing and smoldering depends on several factors. One of the most important in- dicators for the release of sidestreatn stnokc into the environment is the static burning rate of the cigarette between puffs, which generally ranges from 5 to 7 mm of tobacco column in a cigarette per minute. Between 55 and 70% of the tobacco in a cigarette is burned between puffs, and this thus serves as the main source of sidestream smoke and ashes.3 The second most important factor producing differences in the chemistry of the mainstream and sidestream smoke is the temperature of combus- tion of tobacco during puffing and smoldering. 90 During puffing, temperature in the burning cone reaches generally about 800 to 900°C and at some spots on the periphery of cigarette perhaps as high as 1050°C. Over a distance of 3 cm away from the burning center of the tobacco column, three major reaction zones can be defined. These include the high temperature zone (900 to 600°C), the oxygen- depleted pyrolysis or distillation zone (600 to 100°C), and the low temperature zone (less than 100°C). The high temperature zone is free of ox- ygen and contains up to 8 vol% of hydrogen and 15 vol% of carbon monoxide. Within these three zones, the actual mainstream smoke is produced by hydrogenation, pyrolysis, oxidation, carboxylation, dehydratiom, chemical condensation, distillation. and stthlintatirrn. '!'he exit temperature of the mainstream smoke at the cigarette buu ranges from 25 to 50°G or even higher, depending on the butt length. The sidestream smoke is generated primarily during smoldering of the cigarette. At a distance of a few centimeters from the burning cone, the sidestream smoke reaches the ambient temperature.' Another variahle that contribtues to difler- ences in the chemistry of the mainstream and side- stream smoke is the inhalation profile of the smoker. Based on the depth of inhalation, dura- tion of the puff, and breath holding during smok- ing. different types of inhalation profiles have been defined."' Uepcncling on the inhalaticrn profile of the puffs, different amounts of gas phase and par- ticulate phase constituents will be- absorbed by the- respiratory tract from the mainstream smoke; for sidestream smoke, of course, no such changes take place. Other factors responsible for the differences in the sidestream and mainstream smoke include length and circumference of the cigarette, filter material, tobacco type and blend, tobacco cut, and packing density. The filters affect the character of the mainstream smoke as a function of the fiber material, draw resistance, construction, and the de- gree of dilution by perforation. These factors have essentially no significant effect on the chemical and physical properties of the sidestream smoke, ex- cept as burning rate is altered. Since the chemical and physical propetties difler, and since the dilu- tion factor of environmental tobacco smoke is-so profound, it is not practical to extrapolate any known effects of mainstream smoke inhalation on the potential biological responses of nonsmokers who are exposed only to tobacco smoke. QUANTIFICATION OF PASSIVE SMOKE EXPOSURE Quantification of passive smoke exposure and dosimetry have been one of the most difficult con-

HEALTH EFFECTS OF INVOLUNTARY SMOKINtr-MAHAJAN, HVRfR siderations in the study of smoke inhalation by the nonsmoker. In an active smoker, it is relatively easy to obtain at least some measure of smoke inhala- tion by keeping an account of cigarettes smoked each day, by using certain biologic markers,s or by other means. However, even in an active smoker the actual smoke exposure will be affected by the type of cigarettes consumed, presence or absence of filter, draw resistance, depth of inhalation, and the ultimate butt length. In the nonsmoker the problem of quantification of smoke inhaled from the environment_is further complicated by the in- herent differences in the nature of sidestream and mainstream smoke, the dilution factor as side- stream smoke becomes environmental tobacco smoke, the size of the room, related ventilation, number of cigarettes smoked, number of people in the room, and ambient humidity. In the active smoker, the smoke is diluted by the volume of the inhaled puff (in a range of 5:1 dilution or so), whereas for the passive smoker the environmental smoke has been diluted (in a range of 100:1 to 1000:1 dilution) by the almost infinitely larger vol- ume of the enclosed space where the smoking is_ being done. Therefore the nonsmoker is not only exposed to a qualitatively different smoke than the active smoker, but there are, in addition, pro- foundly significant quantitative differences in ex- posure between active and passive smoking.3 A number of markers of passive smoke inha- lation have been identified. These include mea- surement of carbon monoxide, total particulate matter, nicotine in blood or in the atmosphere, plasma cotinine levels, plasma thiocyanate levels, and polonium-210. There are many problems that arise, however, in any attempt to quantify the amount of environmental tobacco smoke present by any of these markers. Of the proposed markers, only nicotine or its breakdown product, cotinine, is unique to tobacco smoke. All other markers of en- vironmental tobacco smoke may originate from a variety of nontobacco sources in the environment. There also is great concern about the validity of sampling and analytic methodologies. There is not a concurrence in the selection of their use, nor in the standardization of their measurements.16•17 Most of the development and testing of these analytic procedures occurs in laboratories with pre- cisely controlled conditions; validation in the set- ting of more realistic conditions of a variety of nor- mally encountered ambient conditions has been less than a hallmark of their application. Sterling and coauthon,l0 in a recent review related to the methodologies of measuring the various markers, have emphasized the lack of reliable information that is available. Furthermore, it also has been em- phasized that ntost of the studies have been per- formed in various controlled circumstances and not under realistic exposure conditions.s" Measurement of carbon monoxide and car- boxyhemoglobin levels has been the most com- monly used parameter for biologic monitoring of passive smoke exposure. Carbon monoxide is rel- atively easy to measure, but unfortuna(el) lacks specificity. Carbon monoxide is present ubiqui- tously in the environment, especially in urban areas; the primary source is automobile exhaust. Endogenous production of carbon monoxide fur- ther decreases the reliability of this measurement as an index of passive smoke exposure in humans. It has been estimated that as much as 0.4 to 0.6% of the measured circulating carboxyhemoglobin is dcrivcd front endnRenoin prixluction of' carlxin monoxide. likxxd carboxyhemoglobin levels in smokers, however, are usually almost double those of nonsmokers. Stewart and associates?1 using blood donors, found the median blood carboxyhe- moglobin for smokers and nonsmokers to be 5 and 1.29fr., respectively, which would correspond to a steady-state ambient carbon monoxide concentra- tions of about ?45 ppm and 7 ppm, respectively.22 Russell and coworkers2' similarly measured carbon monoxide in a highly artificial smoke-filled room and carboxyhemoglobin levels in volunteers who were nonsmokers or who were smokers prior to their exposure to passive smoke inhalation un- der these conditions.'ts In this study the average ambient carbon monoxide concentration was 38 ppm. The mean carboxyhemoglobin concentration of the 12 nonsmokers increased from 1.6 to 2.6% during this passive inhalation exposure, whereas the six cigarette smokers, who were all inhalers, increased their carboxyhemoglobin levels from a resting value 5.9 to 9.6% after passive exposure. It is difficult to apply the results of this study to con- ditions normally encountered in everyday life-80 cigarettes and two cigars were pyrolyzed in a small, unventilated room over a period of slightly longer than just 1 hour. In another study incorporating fairly unreal- istic conditions nine cigarettes were smoked rontrn- twucfj within an unventilated and tightly sealed automobile =' Under these kinds of experimental conditions, the increase of carbon monoxide in the blood of nonsmokers is high, as would be antici- pated. Unfortunately, similar environmental con- ditions are rarely encountered in real-life situa- tions. Application of such studies should not be extrapolated to environmental tobacco smoke in ordinary room air. A number of studies and theoretical assess- ments of environmental tobacco smoke have been conducted in more realistic settings.ls'SO The changes reported in the circulating carbon monox- 91

SEMINARS IN RFSPIRATt)RY MF.f)ICINF.-VCII.UMF. 11. NUMftF.R I, fANUARI' 1990 92 ide levels in passive smokers under these more re- alistic conditions have been minimal. An extensive, recent evaluation of more than 3000 sites in the United Kingdom revealed that ambient carbon monoxide levels did not differ significantly in non- smoking and smoking environments.s' These re- ports would suggest that, except in highly artificial circumstances, tobacco smoking probably has little effect on the carbon monoxide of ambient room air.s1 - Carboxyhemogiobin has a half life of approx- imately 4 hours and, if preexposure levels and ambient concentrations are precisely known, it ap- pears to have some limited usefulness as an index of acute smoke exposure; however, it is not a reli- able index exclusively of chronic smoke exposure. There are many sources of carbon monoxide in the environment of nonsmokers other than envi- ronmental tobacco smoke.s3's7 The primary sources are industrial effluent gases and atttomo- bile exhaust fumes. Indoor sources are primarily from heating systems and from cooking. Exclusive of indoor sources,-indoor carbon monoxide levels follow external concentrations and fluctuations. Total particulate matter measurement in the environment has been used as an index of tobacco smoke exposure, but any ambient measurement of particulates is complicated by the presence of ad- ditional matter in the environment that originates from sources other than tobacco smoke. Probably the most widely referenced citation on measure- ments of particulate matter from environmental tobacco smoke is that by Repace and Lowrey.38 The levels of particulate matter reported by these in- vestigators were very high and, for the most part, appear to be inconsistent with others."''"" Sev- eral studies measuring particulates in home resi- dencies, working sites, office buildings, restaurants, and other places report particulate levels only about one-fifth to at most one-half that recorded by Repace and L.owry.s'-"-4' The probably enor- mously high levels of particulate reported by Repace and Lowry did not adequately control for other environmental particulate matter, half or more of which originates from nontobacco sources.'s''9 Other criticisms of this study include lack of control for humidity, inadequate calibra- tions, and use of obsolete and perhaps inaccurate equipment.'s•t7•.g Nicotine is specific for tobacco smoke. There are a very few other sources of nicotine, including certain agricultural sprays, but these are unlikely to be a contaminant of most indoor environments. Nicotine therefore is a potential ideal marker that is unique to tobacco smoke exposure. With the ex- ception of water, nicotine is the largest single com- ponent of the particulate phase of tobacco smoke and its concentration within the total particulate matter is unaffected by the moisture content of the smoke. Hinds and Firstso measured the nicotine levels in various indoor public places, such as com- muter trains, waiting areas, cocktail lounges. In their study, the average nicotine concentration in the environment varied from about I to 400 µg/ ms. Based on these results, Hinds and First calcu- - lated the number of filter cigarettes smoked per hour that would be equivalent to direct passive smoke inhalation; their calculated inhalation val- ues for passive smoke inhalation varied from 0.001- to 0.009 cigarettes per hour in a bus waiting room to a smoke-filled cocktail lounge, respectively.50 Hinds and First concluded that although tobacco smoke concentrations under these measured con- ditions often exceed the annual average air quality standards for clean air, these levels should not be expected to produce a strong public concern for passive tobacco smoke inhalation that has devel- oped in the past few years. One criticism of this study is that the nicotine samples obtained in these public places did not include appropriate calibra- tions obtained under the same circumstances, sug- gesting that the reported values later analyzed in the laboratory were artifactually low. However, two other studies indicated that in crowded private rooms concentrations of tobacco smoke often exceeded 200 µg/ms.s1•s2 Hoeggs' es- timated that in residences, meeting rooms, or pri- vate automobiles, the nonsmoker passively inhaled in I hour the equivalent to smoking about 0.01 to 0.20 of a cigarette. The differences in these re- ported studies are significant and have been attrib- uted to various factors, which include evaporative and diffusing losses of nicotine, the number of peo- ple smoking-in the room, and the room sizes.SO Nicotine is very difficult to quantify precisely in the environment, however, and it is apparent that even measurements of nicotine do not necessarily pro- vide reproducible assessments of passive smoke in- halation. Badre and coworkersss reported higher levels of passive tobacco smoke exposure based on envi- ronmental nicotine levels measured by a different methodology than Hinds and First S0 but they con- cluded that smoking does not present a health risk to nonsmoken.ss In two other studies, the f apa- nese reported that environmental tobacco smoke exposure in public places, such as offices, restau- rants, public transportation terminals, lobbies, re- ~ sulted in the passiveinhalation, at most, of 1/10t10 ~ to 4/100 of one cigarette equivalent per hour, s'•ss (n a nne comparable to that reported by Hinds and ~ First. In general, the majority of reports indicate ,r,' that overall tobacco smoke contributes very little to 6A indoor environmental pollution=e.st.4s.44.ss-57 and N

HEALTH EFFE(,'TS OF INVOLUNTARY SMOKINt-MAHAJAN, HveFa imply that the amount so added would have little or no detectable physiologic efl-ects.s't-st Russel and Feyerabend measured plasma and urine concentrations of nicotine in nonsmoking adults and found significant increases after exper- imental passive smoke exposure in smoke-filled rooms 6R Increased levels of nicotine in both the urine and the saliva of nonsmoking adults who were exposed passively-to tobacco smoke during a working day have been noted. Greenberg and coauthorss'; measured nicotine and cotinine levels in urine and saliva of 32 infants with household exposure to tobacco smoke. In both the urine and saliva the cotinine levels were significantly higher in infants exposed to tobacco smoke. A significant dose-response relationship was also found between the cotinine excretions and smoke exposure. These investigators believed that the presence of demon- strable cotinine can act as an indicator of chronic exposure to tobacco smoke, whereas the presence of nicotine provides information about recent exposure.6' - - Significant concern has been reported for the potential effects of nitrosamines as carcinogens in tobacco smoke, with the implication that the levels of nitrosamines in sidestream smoke exceed those in mainstream smoke!'66 The amount of detect- able nitrosamines in ene•ironmental tobacco smoke, however, is extremely low." Nitrosamines are found in nontobacco sources, including environ- mental air free of tobacco smoke, many foods. and often in water supplies, usually above concen- trations encountered in tohacco smoke.c'"-r" Nitro- samines, in the concentrations found in main- stream and sidestream smoke, have not been demonstrated to be carcinogens in humans; their concentrations in environmental tobacco smoke, at hundred- to thousand-folds less, can hardly repre- sent a carcinogenic factor in the health of passive smokers. - Several other constituents of environmental tobacco smoke have received attention. Blood thio- cyanate kvels and polonium-210 are additional alternatives that have not gained popularity as re- liable indices of passive smoke exposure. Nitrogen dioxide, formaldehyde, and volatile organic vapors are present in very small concentntions in envi- ronmental tobacco smoke, but in ksser amounts than are contributed by cooking units, heatin~sys- tems, and other common nontobacco rources. °'7s Because of the failure of other constituents to serve as reliable markers of passive exposure to environmental tobacco-smoke, and because of its stability as a breakdown product unique to tobacco, efforts have been made to use cotinine as a biologic marker.76'"t Several reports indicate that the amount of cotinine detectable in biologic fluids is a reliable indicator of environmental tobacco smoke exposure;76-As others are not in concurrence.ss-*a Nicotine metabolic rates vary widely among indi- viduals and are altered by many factors, thus re- ducinR, in turn, the validity of cotinine as a biologic marker. In addition, cotinine excretion rates also vary among individuals, further reducing its valid- ity and reliability as a marker. Rarely, nicotine or cotinine may be ingested by nonsmokers, but this would not represent a very common compounding consideration. Furthermore, analytic methods are not consistent from laboratory to laboratory, add- ing additional confusion to the issue. In summary, then, quantitative passive smoke exposure has been very difficult to evaluate and no single tracer has provided a reliable and reproduc- ible measurement of passive tobacco smoke expo- sure. A better biologic marker of chronic smoke exposure in nonsmokers is clearly needed to obtain reproducible and comparable data before any de- finitive conclusions about the harmful effects of passive smoking can be drawn. ACUTE EFFECTS OF PASSIVE SMOKING The acute exposure to the smoke of others clearly can produce both subjective symptoms and objective physiologic changes. These effects have been studied in normal subjects and in patients with cardiopulmonary illnesses. The studies usu- ally have used either questionnaires or experimen- tal exposure chamlxrs to evaltiate the acute effects of passive smoking. In that a psychologic c<tmpu- nent to these reactions is common, substantial cau- tion must be used in the interpretation of those studies that employ in their experimental design the confinement of the subjects studied within ar- tificial environments, such as closed chambers and rooms. GENERAL EFFECTS Eye irritation seems to be the most common symptom reported by nonsmokers exposed pas- sively to environmental tobacco smoke. Speer and Mission" noted this symptom in 69 percent of their subjects. Other manifestations reported are nasal symptoms, such as dryness, running nose, itching, and sneezing, as well as headache, cough, wheezing, sore throat, nausea, hoarseness and dizziness.22•9s-9' These symptoms all are more com- mon in nonsmokers with history of various aller- gies. Such subjective symptoms appear, however, most likely to be related to irritation of the mucous membranes of the eye and nose rather than to a g true allergy to tobacco smoke." Acrolein and 93

SEMINARS IN Rt:51'IRA'fURY MEI)It:INE-VOt.UMF. 11. NUMRf.It I. JANUARY 1990 certain aldehydes may be important as irritants producing these subjective symptoms in concentra- tions as low as I part per billion or per trillion in environmental tobacco smoke. The intensity of the subjective symptoms is affected markedly by the extent of ventilation, number of smokers present, the extent of smoking. the size of the smoking area, the humidity, the temperature of the ambient air, and other factors. All of these factors are very dif- ficult to control and each independently can affect the response of an experimental subject to passive exposure to environmental tobacco smoke under the artificial conditions of experimental exposure systems. Psychologic reactions, particularly in per- sons with reactive airways disease, are almost im- possible to assess independently in many of the reported studies, but clearly appear to be impor- tant and unquantified compounding variables. S.%. ALLERGY I-t is extremely common, especially for pulnio- nologists and allergists, to hear complaints by patients that they are "allergic to_tobacco smoke." Actually, allergic reactions to tobacco smoke are extremel~ rare; in fact, they probably do not exist °7-t Various proteins in the tobacco leaf can be allergenic, especially to those who are frequently and recurrently_ exposed to them, such as field workers on tobacco farms, employees of tobacco warehouses, and-workers elsewhere in the tobacco product manufacturing industries.to3-tos Such re- active persons usually also respond to other treated agricultural products or contaminants, such as weeds, agricultural chemicals, and other sub- stances. These allergic reactions to unpyrolyzed to- bacco products usually are manifested as skin reactions and only rarely are systemic. Once pyro- lyzed, however, the leafs proteinaceous compo- nents, including those that are potentially allergenic, are converted to tobacco smoke chemi- cal species that have no known or proved aller- genic capacity.10°-Tobacco leaf antigenic sensitivity has not established pulmonary reactivity, or known cross-reactivity with tobacco smoke components.10S As an irritant, passive inhalation of environ- mental tobacco smoke may provoke reactions in alkric persons, especially -those with asthma.t 107 This potentially may be due to the direct irritating effect of the smoke components on the airways directly or due to a triggering effect as a reflexive reaction to the irritation of sensitive membranes around the eyes and within the nose and upper airways exposed even to extremely low dosages of environmental tobacco smoke compo- nents. Even the sight of tobacco use may provoke 94 reactions, by as yet not well-established mecha- nisms. There is no clear evidence, however, that true allergic reactions occur to the passive inhala- tion of environmental tobacco smoke.10S-111 SICK eUf1.DING SYNDROME Evidence is apparently ever emerging for a "sick building syndrome," wherein habitants so ex- posed experience recurrent symptoms of head- ache, conjunctivitis, nausea, cough, dyspnea, and other complaints.11z•t1s This syndrome profile could potentially occur with any building structure, including the home, but _ it has been most com- monly associated with modern office buildings. Generally, these symptom complexes are attrib- uted to indoor air pollution of one kind or another. Environmental tobacco smoke may con- tribute to this pollution, but most studies to date indicate that tobacco smoke has no significant role at most such sites.114 -1t7 Most commonly, however, the complaints associated with the "sick building syndrome" are attributed to inadequate ventilation overall, irrespective of whether or not tobacco cig- arette smoking is present. Inadequate ventilation, either secondary to a poorly designed or a poorly maintained ventilation system, serves as a breeding ground and dissemination reservoir for fungi, bac- teria, and other putential allergens and irritants. In the presence of inadequate or malfunctioning ven- tilation systems, it is extremely difficult to assess accurately the potential contributing role of envi- ronmental tobacco smoke to the overall level of indoor air pollution. OBSTRUCTIVE AIRWAYS DISEASE The acute and the long-term physiologic and the pathogenic effects of environmental tobacco smoke on acute reactive airways disease and on chronic obstructive pulmonary diseases have been the focus of many studies. Experimental designs in these studies have attempted to evaluate the effects of environmental tobacco smoke on both healthy persons and on those with known asthma, reactive airways diseases, or varying degrees of the chronic obstructive lung diseases. ACUTE rULMONARY EFFECTS Pimm and colleagues,tts using an environ- ~ mental chamber, exposed nonsmoking adults M passively to environmental tobacco smoking. Lung ~ volumes, flow volume curves, and heart rate were ,p measured in all subjects at rest and following exer- 1A cise under controlled conditions, before, during. Ab and after passive smoke exposure. Carbon monox-

HEALTH EFFEt."1'S OF INVOLUNTARY SMUKINt;-MAIiAJAw. tiueert ide kvels in the chamber were kept relatively con- stant in these studies, at approximately 24 ppm. Under these controlled conditions, prior to expo- sure, the carboxyhemoglobin levels in the subjects were less than 1%. During smoke exposure, signif icant and comparable increases in the carboxyhe- moglobin levels in both the male and female subjects were noted. These investigators reported that, under these passive inhalation exposure con- ditions, flow at 25% of vital capacity decreased sig- nificantly with smoke exposure at rest in males and- with exercise in females. However, the magnitude of change was small:- a 7% decrease in males and 14% decrease in females. They did not find any other consistent changes in any other tests of lung function. The clinical significance of these rela- tively small changes in the "more sensitive" mea- surements of lung function can be questioned. Additional studies have attempted to evaluate the effect of passive inhalation of environmental to- bacco smoke on persons with asthma or known re- active airways disease. Dahms and associatestt" studied ten patients with well-established bronchial asthma passively exposed to sidestream and envi- ronmental tobacco smoke for 1 hour in an exper- imental chamber. Ten normal subjects, without known or established reactive airways disease, also were exposed to passive smoking under similar conditions. Blood carboxyhemoglobin levels were measured before and after the exposures. In nor- mal subjects the carboxyhemoglobin levels in- creased on the average from 0.62 to 1.06%, whereas in the asthmatic subjects the average in- crease was from 0.82 to 1.20% reflecting perhaps an increased level of ventilation. The change in carboxyhemoglobin levels in the two groups was not statistically significant and corresponded to ap- proximately 15 to 20 ppm of ambient carbon mon- oxide incremental increases in environmental concentration. Pulmonary function parameters were measured in both groups at intervals up to I hour after beginning of the passive exposure to environmental tobacco smoke. The asthmatic group demonstrated a significant decrease in forced vital capacity (FVC), forced expiratory vol- ume in I second (FEV I), and forced expiratory flow between 25 and 75% vital capacity (FEF 25- 75%) starting at 15 minutes after experimental ex- posure. The deterioration in these parameters was progressive with increased duration of passive smoke exposure. After 1 hour of exposure, the FFVt decreased by 21.496, the FEF 25-75% de- creased by 19.2%, and the FVC decreased by 20%. These changes were easily reversed with adminis- tration of a bronchodilating aerosol. The control, healthy subjects who did not have reactive airwaya disease did not reveal any significant changes in pulmonary function when exposed passively to tobacco smoke under identical conditions. The pri- mary criticisms of this study, which the investiga- tors themselves offer, is the- artificial nature of the exposure chamber and the lack of control of sev- eral variables, including the psychogenic effects of the experimental conditions. In a similar study, Shepard and asso- ciatest 19•t40 exposed- 14 asthmatic subjects in a closed room to 2 hours to passive tobacco smoke inhalation. A carbon monoxide concentration of 25 ppm above the ambient air and a suspended particulate concentration of 2 to 6 mg/m? was at- tained in the experimental exposure chamber. Car- boxyhemoglobin levels were not measured in this study. Subjects were randomized and blinded to sham exposure and to true smoke exposure, and then tested on two separate occasions. Lung vol- umes were measured and flow volume loops were obtained before and after passive exposure to to- bacco smoke. The results of this study did not show any significant changes in any of the forced expi- ratory volumes after exposure to tobacco smoke for 2 hours. In this study, subjective responses re- ported by the asthmatic subjects did not necessarily correlate with measurements of pulmonary func- tion. The researchers concluded that their data did not support the perception that asthmatic subjects have an unusual sensitivity to exposure levels of these lower concentrations, although certain sub- groups may, in fact, be extremely reactive. These studies make it rather difficult to draw any definitive conclusions regarding the acute ef- fect of passive smoking. even in patients with pre- existing reactive lung disease, such as bronchial asthma. Both studies were done under comparable experimental conditions and the baseline pulmo= nary function parameters of the two experimental groups were not significantly different. Because psychologic factors are known to produce bron- ehospasm in asthmatic patients, it is quite possible that the decrease in pulmonary function noted in the asthmatic study group could be related to the psychologic factors of the experimental partici- pants, perhaps reflexively triggered by minutely small concentrations of environmental smoke components affecting highly sensitive mucous membranes. The lack of objeaive changes in pul- monary function testing, however, does not neces- sarily mean that patients with preexisting lung disease are not affected by passive smoking. To- bacco smoke does indeed contain large numbers of chemicals that can be irritating to an already dam- aged respiratory system. Asthmatic patients cer- tainly can become symptomatic because of the increased responsiveness of their bronchial pas- sages, even from very small_amounts of an irritat- 95

SEMINARS IN RESPIRA'TORY MEDICINE-VOLUME 11, NUMBER I, fANUARI' 1990 ing substance. Murray and Morrison;t2' for exam- ple, demonstrated a fourfold increase in bronchial responsiveness to aerosolized histamine in asth- matic childreri whose mothers- smoked. These investigators also were able to demonstrate a sig- nificant correlation between airway responsiveness and the number of cigarettes the mother smoked while she was in the house. ts' Aronow et al "2 eval- uated the effect of breathing 100 ppm of carbon monoxide for 1 hour on exercise performance in ten patients with chronic obstructive pulmonary -disease.'22 In these studies there was a significant reduction in exercise performance after heavy ex- posure to carbon monoxide, but the investigators attributed this reduction to impaired-cardiovascu- lar function rather than to any effect of passive inhalation on the lungs directly. 122 CHRONIC PULMONARY EFFECTS IN ADULTS Several studies have been undertaken to eval- uate whether or not chronic exposure to environ- mental tobacco smoke has an adverse effect on airflow in nonsmokers so exposed. Most of these assessments have involved measurements of pul- monary function tests, and most have originated from the United States. Probably the most cited publication is the investigation by White and Froeb,123a study that was initially rejected for pub- lication following exclusion of approximately one third of the original data that resulted in its origi- nal rejection! White and Froeb'2'studied the effects of long- term passive smoking in a group of 2100 adults. Carbon monoxide levels in working environments were used as an index of apparent tobacco smoke exposure. The carbon monoxide levels varied be- tween 3.1 and 25.8 ppm during various times of the day. The highest levels were seen during the noon hours and the lowest levels were in the morn- ing and the evening hours when there were fewer smokers in the workplace. These investigators demonstrated a statistically significant reduction in FEVt and maximum midflow in nonsmokers ex- posed for many years to passive smoking compared to the nonsmoking subjects not exposed to passive smoking. They calculated that the decrease in pul- monary function in the nonsmokers was compara- bk to smokers inhaling one to ten cigarettes per day, a level much higher than has been projected by several other studies already reviewed. How- ever, the absolute magnitude of difference for FEV t and other sensitive tests of airflow in the smoke-exposed and nonexposed groups was rather small and of highly questionable significance. As pointed out by Weiss et al,'s' potential bias could 96 have affected the results of this study. The popu- lation was self-selected and the response was re- lated to current workplace exposure and did not take into account the job changes; exsmokers were excluded. There have been several other substan- tial criticisms of this publication.tY'-1t2 One major criticism is that the carbon monoxide levels mea- sured under these circumstances was not a valid reflection of environmental tobacco smoke expo- sure, and carbon monoxide could have come from other*sources.12" In addition, the values reported and the significance of the alterations in mid-flow values werc~uestioned,/2" t~ even by the authors themselves'' and others;"'-' s' other criticisms in- cluded concerns for selection of a biased study pop- ulation, poor experimental design, and incorrect statistical evaluations. t" In a study from France, it was reported that some nonsmoking wives, aged 40 years or oider, of smokers also had small reductions in some pulmo- nary function parameters, although the finding was not consistent across all segments of the pop- ulation studied.t" Eight other studies, however, some of which were quite large, have reported es- sentially no abnormalities in pulmonary functions in persons chronically exposed to the environmen- tal tobacco smoke of others."'-t'3 In summary, therefore, niost of the data available indicate that the eHects of environmental tobacco smoke on airflow function of passively exposed adult non- smokers varies, as was summarized by an NIH Workshop Conference, "from negligible to quite small.""' CHRONIC PULJNONARY EFFECTS IN CHILDREN The effects of passive smoking on pulmonary function has been studied more extensively in chil- dren than in adults; the published results unfortu- nately, are no easier to sort out. Burchfiel et al"s measured pulmonary function in 3482 nonsmok- ing males and females 0 to 19 years -of age and members of their households. Mean FEV t and FVC measurements for males, and some more sen- sitive measurements for airflow in females, were significantly lower if both parents were current smokers, as opposed to conditions in which the par- ents were not smokers. The results were identical for groups between ages of 10 to 16 and 15 to 19 years. The decrease in the ventilatory parameter for maks and females was inversely related to the number of parental smokers during a child's life- time among nonsmoking children 10 to 19 years of age. Abnormalities in lung function tests were also inversely related to duration and amount of paren- tal smoking among nonsmoking males 10 to 19 years of age but not among females. Tashkin and associates studied pulmonary