3c 1 Sum 1, I1 1 I III1 1 I 10 20 30 40 5c 60 FIGURE 3.-Pattern of inhalation of cigarette smoke mixed with air, in two smokers SOURCE Modified from Tobm et al c 1982b! al. 1980a), 450 to 485 ml (Guillerm and Radziszewski 1978), 389 to 1,136 ml (Adams et al. 1983), 750 to 2,000 ml (Rawbone et al. 1978), and 170 to 1,970 ml (Tobin et al. 1982b). A major factor in the discrepancies between these studies is probably the inaccuracies inherent in some of the methods employed in the measurements, as discussed by Tobin and Sackner (1982). When inhalation volumes are standardized for body size by relating them to vital capacity, marked interindividual variation is still observed (Figure 3), with inhalation- al volumes ranging from 9 to 47 percent of the vital capacity and a group mean value of 20 percent (Tobin et al. 1982b). Smokers show considerable variation in inhaled volumes while smoking a single cigarette. The volume of inhalation bears no relationship to cigarette consumption in terms of pack-years (Tobin et al. 1982b). Similarly, duration of inhalation shows considerable variation between sub- jects, with mean individual values ranging from 1.7 to 7.3 seconds (Adams et al. 1983; Tobin et al. 1982b). Repeat measurements at intervals of up to 10 months apart indicate that individual subjects tend to maintain a fairly constant inhalation volume, duration of inhalation, and associated breathhold time (Tobin et al. 1982b; Adams et al. 1983). The pattern of cigarette smoking shows a wide degree of intersub- ject variability, including differences in the number of puffs, puff volume, holding pause in the mouth, exhalation of smoke from the mouth before inhalation, partitioning of airflow between the nose and mouth, and volume and duration of inhalation. Given this degree of variation, it is not surprising that smokers might show wide differences in their individual susceptibilities to lung injury. In a study relating inhalation volume-standardized for vital capaci- ty-to the time-volume and flow-volume components of a forced vital capacity maneuver, no significant correlation was observed (Tobin et al. 1982b). Although this lack of a relationship might be interpreted as indicating that the pattern of smoking is unimportant in the development of lung disease, it may also reflect the fact that pulmonary function was normal or near normal in the majority of subjects and that the study was of a cross-sectional design. Use of Additives in Low Tar and Nicotine Cigarettes The nominal tar and nicotine yield of cigarettes has continually decreased since the time of the initial reports linking smoking with lung cancer (USDHHS 1981). In 1954, the average tar yield per cigarette was 38 mg, and in 1980 it was less than 14 mg. Initially, tar reduction was achieved by decreasing the cigarette tobacco content or removing tar by smoke filtration, both of which probably resulted in a lower smoke exposure. Since 1971, the reduction in tar yield has exceeded the relative reduction in the weight of tobacco per cigarette; this difference has increased since 1975 (USDHHS 1981). Manufacturing technology has progressed beyond simple reduction in tobacco content: the yield and composition of smoke can be modified by genetic modification of the tobacco leaf (Tso 1972a), changes in its cultivation and processing (Tso 1972133, changes in the porosity of cigarette paper, and alterations in filter design (Kozlow- ski et al. 1980b). When initially introduced, lower yield cigarettes lacked palatabili- ty and acceptability. Advertisements for the current low tar and nicotine cigarettes emphasize their flavor, presumably achieved by the use of additives in the processing of the tobacco. Additives employed may include artificial tobacco substitutes (Freedman and Fletcher 1976), flavor extracts of tobacco and other plants, exogenous enzymes, powdered cocoa (Gori 19771, and other synthetic flavoring substances. Perhaps more additives are being used in the new lower tar and nicotine cigarettes than in the older brands, and new agents may also be in use. Some of the substances, such as powdered cocoa, have been shown to further increase the carcinogenicity of tar (Gori 19771, and others may result in increased or new and different health risks. The pyrolytic products of these additive agents may produce novel toxic constituents. A characterization of the chemical composition and adverse biologic potential of these additives is urgently required, but is currently impossible because cigarette companies are not required to reveal what additives they employ in the manufacture of tobacco (USDHHS 1981). No government agency is empowered with supervisory authority in the manufacture of tobacco products. With this lack of basic information and the usually prolonged latent period before manifestation of the adverse effects of smoking, it is likely that a long time period will elapse before we know the hazards of the new cigarettes in current use. Research Recommendations 1. Longitudinal epidemiologic studies are needed to determine the risk for pulmonary symptoms and dysfunction in smokers of cigarettes with the low tar and nicotine yields found in currently popular brands. 2. Further research is needed to determine the relative potency of high and low tar and nicotine cigarettes in inducing elastase release and producing functional inhibition of al-antitrypsin activity. 3. Development of an animal model of cigarette-smoke-induced emphysema would be advantageous in determining the relative risk of lung injury of cigarettes of different composition. 4. More information is required on the smoking behavior of smokers who have voluntarily switched from high to low tar and nicotine cigarettes. 5. The role of cigarette tar, as opposed to nicotine content, in determining smoking behavior needs to be defined. 6. Standard research cigarettes of varying tar and nicotine contents that are palatable and acceptable to smokers need to be developed. 7. The role of variation in smoking behavior in determining susceptibility to lung injury needs to be defined. Studies are required to determine the effect of smoking patterns on the distribution and penetration of the smoke aerosol into the lung. 8. More information is needed on the composition and adverse biologic effects of flavor additives in cigarettes and their pyrolytic products. Summary and Conclusions 1. The recommendation for those who cannot quit to switch to smoking cigarette brands with low tar and nicotine yields, as determined by a smoking-machine, is based on the assumption that this switch will result in a reduction in the exposure of the 353 lung to these toxic substances. The design of the cigarette has markedly changed in recent years, and this may have resulted in machine-measured tar and nicotine yields that do not reflect the real dose to the smoker. 2. Smoking-machines that take into account compensatory changes in smoking behavior are needed. The assays could provide both an average and a range of tar and nicotine yields produced by different individual patterns of smoking. 3. Although a reduction in cigarette tar content appears to reduce the risk of cough and mucus hypersecretion, the risk of shortness of breath and airflow obstruction may not be reduced. Evidence is unavailable on the relative risks of developing COLD consequent to smoking cigarettes with the very low tar and nicotine yields of current and recently marketed brands. 4. Smokers who switch from higher to lower yield cigarettes show compensatory changes in smoking behavior: the number of puffs per cigarette is variably increased and puff volume is almost universally increased, although the number of ciga- rettes smoked per day and inhalation volume are generally unchanged. Full compensation of dose for cigarettes with lower yields is generally not achieved. 5. Nicotine has long been regarded as the primary reinforcer of cigarette smoking, but tar content may also be important in determining smoking behavior. 6. Depth and duration of inhalation are among the most impor- tant factors in determining the relative concentration of smoke constituents that reach the lung. 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Journal of the American Medical Association 213(13): 2221-2228, September 28,197O. 360 CHAPTER 7. PASSIVE SMOKING 361 480-244 0 - 85 - 13 CONTENTS Introduction Differences in Composition of Sidestream Smoke and Mainstream Smoke Measurement of Exposure Acute Physiologic Response of the Airway to Smoke in the Environment Symptomatic Responses to Chronic Passive Cigarette Smoke Exposure in Healthy Subjects Respiratory Infections in Children of Smoking Parents Pulmonary Function in Children of Smoking Parents Pulmonary Function in Adults Exposed to Involuntary Cigarette Smoke The Effect of Passive Smoke Exposure on People With Allergies, Asthma, and COLD Summary and Conclusions References 363 Introduction This chapter explores recent data that relate involuntary cigarette smoke exposure to the occurrence of physiologic changes, symptoms, and diseases in nonsmoking adults and children. Health effects related to fetal exposure in utero, a subject that has been extensively studied, are not discussed, although instances where such exposure may relate to potential development are pointed out. The interested reader is referred to several excellent recent reviews for a more complete treatment of this issue KJSDHEW 1979; USDHHS 1980; Abel 1980; Weinberger and Weiss 1981). Differences in Composition of Sidestream Smoke and Mainstream Smoke Involuntary (passive) smoking is defined as the exposure of nonsmokers to tobacco combustion products from the smoking of others. Analysis of the health effects of passive smoking requires not only some knowledge of the constituents of tobacco smoke, but also some quantitation of tobacco smoke exposure. Tobacco smoke in the environment is derived from two sources: mainstream smoke and sidestream smoke. Mainstream smoke emerges into the environment after having first been drawn through the cigarette, which filters some of the active constituents. The smoke is then filtered by the smoker's own lungs, and exhaled. Sidestream smoke arises from the burning end of the cigarette and enters directly into the environ- ment. Differences in the temperature of combustion, the degree of filtration, and the amount of tobacco consumed all lead to marked differences in the concentration of the constituents of mainstream smoke and sidestream smoke (USDHEW 1979; Sterling et al. 1982; Brunneman et al. 1978; National Academy of Sciences 1981; Rylander et al. 1984). Many potentially toxic gas phase constituents are present in higher concentration in sidestream smoke than in mainstream smoke (Brunneman et al. 1978) (Table 11, and nearly 85 percent of the smoke in a room results from sidestream smoke. Smaller amounts of smoke are contributed to the environment from the nonburning end of the cigarette by diffusion through the paper wrapping and by the smoke exhaled by the smoker. Therefore, both active and passive smokers may be similarly exposed to sidestream smoke. Mainstream smoke is inhaled directly into the lungs and is diluted only by the volume of air breathed in by the smoker when he or she inhales. Sidestream smoke is generally diluted in a considera- bly larger volume of air. Thus, passive smokers are subjected to a quantitatively smaller and qualitatively different smoke exposure than active smokers. The quantification of the exposure of a passive smoker to these sidestream smoke constituents is often difficult. Factors such as the type and number of cigarettes burned, the size of the room, the ventilation rate, and the smoke residence time are all important variables in determining levels of exposure. Thus, no single variable accurately characterizes exposure to smoke constitu- ents. Repace and Lowrey (1980, 1982, 1983) have shown that, to a reasonable approximation, exposure to the particulate phase is predicted by the ratio of the smoker density to the effective ventilation rate of the area in which the smokers are located. Measurement of Exposure Levels of indoor byproducts of tobacco smoke, with measurements made under realistic exposure conditions, are presented in Table 2. Among the constituents that have been measured, nitrogen oxide, carbon monoxide, nicotine and respirable particulates, nitrosamines, and aldehydes have been shown to be significantly elevated indoors as a result of cigarette smoking. Nitrogen oxide is rapidly oxidized to nitrogen dioxide (NOZ) in air, and reaches equilibrium with outdoor levels of NOa, provided there are suitable air exchange rates and no other indoor sources, such as a gas stove. The particulate concentra- tion indoors clearly increases with increasing numbers of smokers, although the background level is determined by the outdoor level. The conclusions from the few studies that actually measure ventila- tion rates during exposure suggest that under "normal" air circula- tion conditions, carbon monoxide (CO) levels will be relatively low, but still may exceed the ambient air quality standard of 9 ppm (NIOSH 1971). However, even modest reductions in ventilation rates can lead to CO accumulation. A variety of measures have been utilized to quantify the nonsmok- er's exposure to tobacco smoke. No single measure has been uniformly accepted as characterizing the level of smoke. Nicotine is the most tobacco-specific of these measures, but it is relatively complicated and expensive to measure and settles out of the air with the particulate phase, making it a poor measure of gas phase constituents. In addition, nicotine may rapidly deposit on surfaces and subsequently evaporate into the environment (Rylander et al. 1984), making it a poor measure of acute smoke exposure levels. Measurements of total particulate matter are a broader measure of smoke exposure, particularly if the measurements are limited to particles in the respirable range and to environments without other major sources of respirable particles. The smoke particles also settle out of the air and therefore may not reflect the levels of gas phase constituents, and a wide variety of other dusts may contribute particulates to the air, particularly in the occupational setting. A number of authors have measured levels of CO. This measurement is relatively simple and a measure of absorption (carboxyhemoglobin) 366 TABLE l.-Ratio of selected constituents in sidestream smoke (SS) to mainstream smoke (MS) a.9 phase aJn#tituenta MS s/MS ratio Particulate phase constituents MS ss/Ms ratio Carbon dioxide Carbon monoxide Methane Acetylene Ammonia Hydmgen cyanide Methylfuran Acetnnitrile Pyridine Dimethylnitwamine 8.1 TM 2.5 Water 3.1 Toluene 0.8 Phenol 73.0 Methylnaphthalene 0.25 Pyrene 3.4 Benuo(a$wne 3.9 Aniline 10.0 Nicotine 52.0 SNaphthylamine 1.3 2.4 5.6 2.6 28 3.6 3.4 30 2.7 39 Adapted from U.S. Department of Health. Education. sod Welfare (1979). TABLE 2a.-Acrolein measured under realistic conditions Study Type of premisea Ventilation Monitoring conditions MMtl Badre et al. (1978) cafea Room Hospital lobby 2 train compartmenta cm Fischer et al. (1978) and Weber et al. (1979) Rentaurant Restaurant Bar cafeteria Varied Not given 18 smokera Not given 12 to 30 smokenr Not given 2 to 3 smokers Not given 3 emokem Natural, open 2 smokers Natural, closed 50-M/470 m' 60-lCW440 m' 3&40/50 m' &I-150/574 m' Mechanical Natural Natural. open 11 ehanges/hr loo mL sample.8 loo mL Bamples 100 mL samples loo mL .samples 100 mL Eamplea loo mL samples 27 x 30 min samples 29 x xl mill samples 28 X 30 min samples 24 x 30 mill samplea 0.03-0.10 mg/m' 0.185 mg/m' 0.02 mglm O.Ou).lZ mg/m* 0.03 mg/m' 0.30 mg/ms 7 wb 8 wb 10 Ppb 6 wb (5 ppb nonsmoking section) TABLE 2b.-Aromatic hydrocarbons measured under realistic conditions Study Ventilation Monitoring conditions Levels Nommokmg controls Mean Range Mean Range Badre et al. (1978) cafes Room Train compartmenta car cafea Varied Not given 100 mL samples 004-1.04 Room 18 smokers Not gwen 100 mL samples 0 215 Train compartmenta 2 to 3 smokers Not given 100 mL samples 1.87 car 2 smokers Natural, clceed 100 mL samples 0.50 Elliott and Rowe (1975-l ArHla Galuskinova (1964-l Restaurant Varied Not given 100 mL samples 005-0.15 18 smokenr Not given 100 mL samples 0109 2 to 3 smokers Not given 100 mL eamplea 0.024 10 3 smokers Natural, open 100 mL samples 0.04 2 smokers Natural, closed 100 mL samples 0 15 8,647-10,786 people Mechanical 12,000-12.8-44 people Mechanical 13,W14J77 people Mechanical Not given Not given Not given Not given Not given Separate non- activity days 20 days m .3ummel 18 days in the fall Benzene (n&m') Toulene (mglm') Etenxjajpyrene (,ng/m') 71 99 21.7 0 69 6.2 282-144 Y TABLE 2b.-Continued a Level0 Nonsmoking controls lLpe of Monitoring Study premises ~UpancY Ventilation conditiona MSII Ranse Mean bnge Just et al. (1972) Coffee houses Not given Not given 6 hr continuous 0.25-10.1 4.M.3 (outdcom) Berw$ehymne (nglm') 3.3-23.4 3.0-5.1 (outdoord Benz&&erylene (w/m') 5.9-10.5 6.9-13.8 (outdoors) Perylene (rig/m') 0.7-1.3 0.1-1.7 (OUtd~Ia) Perry (1973 14 public placee Not given Not given 4.1-9.4 2.C7.0 (outdoors) Anthanthmne (ng/m") O.Sl.9 0.61.8 (outdoors) Coronene (ng/m') OS-l.2 1.0-2.8 Phenols C&m') samples, 5 outdoor locations 7.4-11.5 Benzo(aipyrene (r&m') < 20-760 <2O-QJ TABLE 2c.-Carbon monoxide measured under realistic conditions Study Type of pmllliSW Ventilation MOd.OliDg conditions Levels @pm) Nonsmoking controls @pm) MWll Ranse Mean Badre et al. (1978) Gcafea Room Hospital lobby 2 train compartments car Can0 et al. Submarines (19703 66 m' ChappeU and Parker (1977) 10 OfflQs 15 rwtaurant.9 14 night&be and taverna Tavern Varied 18 smokers 12 to 30 smokers 2 to 3 smokers 3 smokers 2 smokers 157 cigfuettes per &Y 94-103 cigarettes per bY Not given Not given Not given Not given Not given Not given Not given Not given Natural, open Natural, cloeed Yea Yea values not given valuee not given valuw not given Artificial offia? 1440 ft' Natural, open 20 min samples 20 min @amplea 20 min samples 20 min Bamplea 20 min enmplee 20 min aamplee 17 x 2-3 min WIllpleS 17 x 2-3 min samples 19xMmin WlUPlW 16 x W min BampleS 2x2-3min SampIeS 2-3 mill eamples 3ominafter smoking 50 5 1.4 20 (40 PPm (40 wm 2.5 + 1.0 4.0 k 2.5 13.0 Ik 7.0 8.5 1.5-4.5 l.cL9.5 3.0X9.0 2.5 + 1.0 1.5-45 (outdoom) 2.5 f 1.5 1.a5.0 (outdoom) 3.0 + 2.0 1.0-5.0 35 @?ak) 10.0 (peak) 1.0 : TABLE 2c.-Continued Levels @pm) Nonsmoking controls (ppm) lLpe of Monitoring Study premieee ~F-7 Ventilation conditions Mean Ranse MWIl Range C&urn et al. (19653 Cuddeback et al. (1976-I U.S. Dept. of Transportation U971P Elliott and Rowe (1975F Fisher et al. (1978) and Weber et al. (2979) Codin et al. Ferryboat Not given Not given 11 grab eamplee 18.4 + 8.7 3.0 f 2.4 (nonsmoking room) (197.8 Theater foyer Not given Not given Glnh samplea 3.4 + 0.8 1.4 _t 0.8 (auditorium) Rooms Not given Not given Tavern 1 10-294 people 6 changeslhr Tavern 2 Not given l-2 che.ngea/hr I8 military Plan= 8 domestic ph.W 165-219 people 27-113 people Mechanical Arena 1 11.806 people Mechanical Arena2 2,ooO people Natural Ewtaurant 50-W/470 m' Mechanical R&aurant 60-lW440 m' Natural Bar 3J-i0/50 m' Natural, open Cafeteria W-150/574 m' 11 changea/hr Not given Nonsmokers' rooma 8 hr continuous 2 hr after smoking 8 hr continuous 2 hr after smoking 6-7 hr continuous 1 `I,-2'1, hr continuoue Not given Not given Nonsmoking srens 27 x 30 min Lwnplee 2SX3OlUiIl SampIeS 28X3Oti SampIeS 24X3Oti Nonsmoking rwm 11.5 -1 17 -12 4.3-9.0 lo-12 -3-22 <2-5 9.0 25.0 5.1 2.1-9.9 2.6 1.43.4 4.8 2.4-9.6 1.2 0.7-1.7 2.2 + 0.98 0.445 2 (outdoorL3) Values not given Values not given 3.0 (nonactivity day) 3.0 (nonactivity day) 9.0 4.8 (outdcmrs) 1.5 (outdoolB8) 1.7 (outdwrs) 0.4 (outdoors) 0.5 0.3-0.8 TABLE Lc.-Continued Study m of premises Ventilation Monitoring conditions Levels @pm) Nonsmoking controls (ppm) MWUl Ranse MWll Range Harke (1974a) Harke and Peters (19747 Harnwen and Effenherger f lY57v Perry t IY 7s Portheine I I.V71lS Sebhen et al (IH771 officed oflie car -72 m' -78 ma 2 smokers (4 cigs) 236 m'/hr Natural Natural Mechanical 14 public Pla= Rams Not given Not given One grab sample <: 10 Not given Not given Not given 625 9 night&be Not given 14 restauranta 45 rwtaurante 33 stmw 3 hospital lobbies 1-18 smokers Natural Not given O-40 Not given Not given Not given Not given Not given Not given Not given Not given 30 min samples 30 min samples Samples 77 x 1 min BarnpIeS outdmrs Spot checks Spot checks Spot checks Spot checks < 2.5-4.6 < 2.sJ.o 42 (peak) (Nonsmoking rums) 13.5 @eak) 32 @eak) (Nonsmoking runs) 15.0 @?ak) 13.4 6541.9 9.2 3.0-35.0 9.9 + 5.5 Values not given 8.2 f 2.2 7.1 + 1.7 (outdoom) 10.0 + 4.2 11.5 f 6.9 (outdoora) 48 Values not given Y TABLE 2c.-Continued IP Levels @pm) Nonsmoking controls @pm) Type of Monitoring Study pmilliSW &UpaneY Ventilation condition8 MWll Raose Mean seiff (1973) Intercity bus Not given 15 changeE/hr, 23 cigarettes burning wntiuuolWly 3 cigarettea burning continuously 33 wm 18 wm Slavin and Hertz (1975) 2 conference moms Not given 8 changealhr Continuous. morning 6 changeelhr Continuous, morning 8 (pdd 10 @& l-2 kleparate nonsmoking day) l-2 heparate nonsmoking day) &dkOWSki et al. (1976) 25 officea Not given Not given continuous 2.78 + 1.42 2.59 f 2.23 bqarate nonsmoking offi9s) `Thrseciganttesandooecigarsmokedin20minutee. whe Drager tube used is accurate only within f 25 percent. = The M6A Monitaire Sampler ubed in acnuate only within f 7.5 percent dAbout 40 t&srettw/day were smoked. o Ahout 70 cigar&Am/day were smoked. `Four filter cigar&m were smoked. rNoerperimentaldeacriptiongiven. TABLE U-Nicotine measured under realistic conditions Study nw of premises Ventilation Monitoring conditions Nonsmoking Levels Q/m') wntmls Mt?.tUl Range Man Range Badre et al. u978l Gcafea Boom Haspitnl lobby 2 train compartmenta car Can0 et al. (2970) Harmsen and Effenberger (f96Tl HindaandFirst (197.P Submarines 66m' Train Train Not given BIU Not given Bus waiting room Not given Airline waiting room Not given Ftastaurant Not given Cocktail lounge Not given Student lounge Not given Weher and Fischer m8w 44 oftk!s Varied Varied 18 smokers 12 to 30 smoker9 2 to 3 smokera 3 smokers 167 cigarett4w per day 94-103 cigarettea Per day Not given Not given Not given Not given Not given Natural, open Natural, clawed YeS YeS Natural. cloeed Not given Not given Not given Not given Not given Not given Not given Varied 50 min BarnpIe 25-52 50 min sample 500 50 min aample 37 50 min sample 3640 50 min anmple 65 50 min sample 1010 32 palm' 1535 palm' 30-45min samplea 2'/, hr aamplen 4.9 2'1, hr aamplea 6.3 2'1, hr aample 1.0 2'1, hr samples 3.1 2'1, hr samples 5.2 2% hr samples 10.3 2'1, hr samples 2.6 07.9.1 Values not given Values not given Values not given Values not given Values not given Values not given Valuea not given 140 x 3 hr samples 0.9 + 1.9 13.8 &AK) Values not given