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7 EXPOSURE TO ENVIRONMENTAL TOBACCO Smoke Involuntary exposure to environmental tobacco smoke (ETS), or passive smoking, has been extensively investigated with re- spect to its potential health effects, particularly on respiratory health. There is a significant body of research on its potential ef- fects regarding the incidence, prevalence, and exacerbation of es- tablished asthma. While attention has focused upon possible as- sociations with childhood asthma, associations with asthma in adults also have been investigated. The following analysis relies heavily on several very detailed and comprehensive reviews, in- cluding those of the U.S. Environmental Protection Agency (EPA) (U.S. EPA, 1992), the California EPA s Office of Environmental Health Assessment (California EPA, 1997), the World Health Or- ganization (WHO) International Consultation on Environmental Tobacco Smoke (ETS) and Child Health (WHO, 1999), the report of the United Kingdom s Scientific Committee on Tobacco and Health (SCOTH, 1998), and the series of ten meta-analyses (to date) of the health effects of ETS by Cook, Strachan, and col- leagues (Anderson and Cook, 1997; Cook et al., 1998; Cook and Strachan, 1997, 1998, 1999; Strachan and Cook, 1997, 1998a-1998c). 263
264 CLEARING THE AIR DEFINITION OF ENVIRONMENTAL TOBACCO SMOKE (ETS} Environmental tobacco smoke has been defined (Daisey et al., 1994) as: . . . the smoke to which non-smokers are exposed when they are in an indoor environment with smokers. It is composed largely of sidestream tobacco smoke (SS), the smoke emitted by the smolder- ing end of a cigarette between puffs, with minor contributions from exhaled mainstream smoke (the smoke which is directly inhaled by the smoker) and any smoke that escapes from the burning part of the tobacco during puff-drawing by the smoker. ETS differs from SS in that it is highly diluted and dispersed within a room and it undergoes aging. Tobacco smoke contains many chemical products with known or suspected adverse health effects. These products include eye and respiratory irritants, systemic toxicants, mutagens and car- cinogens, and reproductive toxicants (California EPA, 1997~. ETS consists of solid particulates, and semivolatile and volatile organic compounds (VOCs). The solid particulates have a mean diameter of 0.32,um (National Research Council, 1986~. "The aging process includes volatilization of nicotine, which is present in the particu- late phase in mainstream smoke but is almost exclusively a com- ponent of the vapor phase of ETS" (U.S. EPA, 1992~. The mean and standard deviation of the total emission factor for PM 2 5, de- termined for six commercial cigarettes and Kentucky reference cigarette 1R4F, is 8,100 + 2,000 ,ug per cigarette. Bacterial endot- oxin (lipopolysaccharide), previously associated with environ- mental lung diseases, has been reported to be a respirable con- stituent of both mainstream and sidestream smoke (Hasday et al., 1999~. Significant amounts of nearly 30 volatile organic compounds have been measured, including acetaldehyde, formaldehyde, nicotine, 3-viny~pyridine, toluene, pyridine, benzene, pyrrole, xy- lene, 2-butanone (methyl ethyl ketone iMEK]), phenol, and oth- ers. Many of the more volatile VOCs (such as aldehydes) remain in the air for prolonged periods of time following the smoking of a cigarette (at least four hours) and do not appear to undergo significant chemical reactions within this period. Some of the less volatile compounds and particulates appear to decrease over time
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 265 due to deposition as well as ventilation effects. With the excep- tion of nicotine, the emission factors for VOCs are significantly greater in ETS than in SS (U.S. EPA, 1992~. Additional information on the physical and chemical proper- ties of ETS and the biological activities can be found in the U.S. and California EPA reports (California EPA, 1997; U.S. EPA, 1992~. FACTORS CONTROLLING EXPOSURE TO ETS Variations in Concentration of ETS in Indoor Environments Exposure Assessment Nicotine and particulate matter (PM), in addition to carbon monoxide, have been the constituents most extensively measured as a means of assessing ETS concentrations in indoor air. Nicotine is considered an adequate tracer for PM under certain conditions, and, possibly, for VOCs ranging from slightly to very volatile compounds (Dailey, 1999~. Among the documented conditions influencing the concentration of nicotine are emission rates, ven- tilation, and (for VOCs/SVOCs) resorption and Resorption from surfaces (Dailey, 1999~. The EPA (1992) and Guerin et al. (1992) summarized more than 25 studies of nicotine concentration in more than 100 different indoor environments and found that the average concentrations of nicotine ranged from 0.3 to 30,ug/m3, a hundredfold difference. In residences with one or more smokers, the typical range was from 2 to 10 ,ug/m3, typically being higher in winter than in summer. Bars and smoking sections of commer- cial airplanes recorded the highest levels up to 50-75 ,ug/m3, although nonsmoking regulations and ordinances have signifi- cantly altered this. In general, the concentrations of nicotine have been found to increase with the number of smokers and number of cigarettes consumed in a given indoor environment (U.S. EPA, 1992~. One study involving personal monitor measurement of approximately 100 individuals in 16 metropolitan areas in the United States reported mean 24-hour time weighted average nico- tine concentrations of 3.28 ,ug/m3 for those exposed to ETS both
266 CLEARING THE AIR at work and away from work; 1.41,ug/m3 for those exposed away from work only; 0.69 ,ug/m3 for those exposed at work only; and 0.05 ,ug/m3 for those exposed at neither location Jenkins et al., 1996; Jenkins and Counts, 1999~. Particulate concentrations, un- like nicotine, are not specific to ETS as a source. However, al- though not unique to the combustion of tobacco, the quantity of respirable particulates produced by cigarette smoking, is large- significantly greater than the amounts produced by other com- mon combustion sources within the home, such as wood-burning fireplaces, gas stoves, and kerosene space heaters (California EPA, 1997~. Respirable suspended particles in homes with at least one smoker average about 20-100 ,ug/m3 higher than the levels in similar nonsmoking homes. The highest concentrations have been reported in restaurants and bars a maximum of 1,379,ug/m3 and a range of average concentrations of 35-986 ,ug/m3 (U.S. EPA, 1992~. Ott et al. (1996) documented a 77°/O decrease in the average concentration of respirable suspended particles in a northern California tavern after a prohibition against smoking was insti- tuted. In addition to the influence of the number of smokers and the amount smoked on the concentration of ETS in a given indoor environment, concentration is affected by the ventilation rate. Long-term exposure to ETS has been of most concern from the standpoint of effects on lung development and cancers. How- ever, ETS concentration varies over an extreme spatial and tem- poral range in indoor and outdoor environments, making it in- feasible to comprehensively assess the ETS exposure history of an individual over their lifetime by direct exposure assessment or air sampling in all of the relevant environments. Critical aspects of this history can, however, be determined and more compre- hensive and accurate assessment is often feasible for infants and very young children. Because of the difficulties involved, epide- miologists have tended to use questionnaires and interviews to determine individual history with regard to ETS exposure, classi- fying people into categorical groups to provide a semiquantitative measure of exposure. Direct measurement of exposure at or near the breathing zone is often done via personal monitors and can provide an assessment of integrated exposure, but this is feasible for monitoring only over a relatively limited period of time.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE Biomarkers of Exposure 267 The most direct assessment of exposure involves the measure- ment of ETS constituents or their breakdown products in body fluids. To date, the most reliable of these biomarkers is cotinine, a metabolite of nicotine (Benowitz, 1999~. Cotinine has an average half-life of approximately 16-19 hours (Benowitz and Jacob, 1994; larvis et al., 1988), making it highly useful for the assessment of integrated ETS exposure over the two to three days prior to the measurement. In infants and children, the half-life is appreciably longer, from approximately 40 hours in children more than 18 months old to approximately 65 hours in neonates (U.S. EPA, 1992~. Because urinary cotinine excretion varies markedly among individuals as a result of renal function, urinary flow rate, and urinary pH (Benowitz et al., 1983), results often are expressed as nanograms of cotinine per milligram of creatinine, rather than simply in nanograms per milliliter of fluid. However, the produc- tion of creatinine is a function of muscle mass; hence excretion varies with age, sex, and other individual factors. In particular, the low level of creatinine produced in children means that the cotinine-to-creatinine ratios in children may fall into the range reported for active smokers (Watts et al., 1990~. The levels of exposure of nonsmokers to ETS are sufficient that nicotine and cotinine are detectable in their urine, blood, and saliva (Benowitz, 1996~. Values are typically in the range of 0.5 to 10-15 ng/mL in the saliva and plasma, respectively, of nonsmok- ers, with urinary concentrations approximately three times higher as much as 50 ng/mL or more (Guerin et al., 1992; U.S. EPA, 1992~. A cutoff of 90 ng/mL has been used to distinguish active smokers from exposed and unexposed nonsmokers (Cummings et al., 1990), and studies consistently have been able to distinguish active smokers from exposed and unexposed non- smokers Jarvis et al., 1987~. It has been more difficult to distin- guish exposed from non-exposed non-smokers for a variety of reasons related to the validity of self-reported smoking status and ETS exposure, variability in nicotine metabolism, variability in sampling procedures, and the limits of sensitivity of the assay methods used (Idle, 1990~. Increasing levels of cotinine have been generally found to be associated with increasing levels of self
268 CLEARING THE AIR reported ETS exposure (NRC, 1986; U.S. DHHS, 1986; U.S. EPA, 1992~. As would be expected from the results of measurement of ambient concentrations of nicotine, the maximum reported expo- sure levels have occurred in bars and restaurants and on commer- cial airline flights approximately 30 ng/mg creatinine (Mattson et al., 1989~. One study in which adults in an enclosed area were exposed to sidestream smoke from four cigarettes being smoked simultaneously and injected into the room continuously by ma- chine, with ventilation conditions equivalent to those in the aver- age office environment, found the air concentration of nicotine rapidly reached a stable level of 280,ug/m3. Average nicotine con- centration in saliva reached a maximum of 880 ng/mL after 60 minutes of exposure, and cotinine concentrations reached 3.4 ng/ mL in serum and 55 ng/mg creatinine in urine, a little more than six hours after exposure. A number of studies have compared biomarkers in active smokers with those in exposed and nonexposed nonsmokers. larvis and Russell (1984), for example, found mean urinary cotinine levels in these three groups of 1,390.0,7.7, and 1.6 ma/ mL, respectively (p < .001 between exposed and nonexposed non- smokers). Cotinine concentrations of self-reported smokers and nonsmokers have generally been found to overlap. In infants and children exposed to ETS, levels of cotinine have been found to be significantly higher in exposed than in nonexposed children. Direct exposure assessment has detected cotinine in the urine on the first day of life in neonates of both active smokers and ETS-exposed nonsmokers with significantly higher levels in the latter than in neonates of unexposed non- smokers Jordanov, 1990~. Henderson et al. (1989) found that air nicotine concentration in the home was significantly associated with the average log urinary cotinine level (r = 0.68, p = .006~. Greenberg et al. (1989) found a median concentration of 121 ng cotinine/mg creatinine (range 6-2,273 ng cotinine/mg creatinine) in children with any detectable cotinine. Chilmonczyk et al. (1990) found median levels of urinary cotinine of 1.6 mg/mL in non- smoking households, 8.9 mg/mL where someone other than the mother smoked, 28 mg/mL where only the mother smoked, and 43 mg/mL where both the mother and someone else smoked.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE Exposure Prevalence 269 In reviewing studies of ETS exposure prevalence, the Califor- nia EPA (1997) concluded, "Taken as a whole, the various studies [at least 10 separate investigations including large representative sample surveys] . . . indicate that within California and the United States, exposure to ETS was widespread during the time period of the studies (1979 through 1992~. Analysis of ETS exposure within California indicated that the workplace, home, and other indoor locations contributed significantly to the exposure of adults. For children, the home was the most important single lo- cation contributing to ETS exposure. In all studies using both self- reporting and a biological marker (cotinine level) as measures of exposure, prevalence was higher when determined using the bio- logical marker." It further cited indirect evidence that "the preva- lence of ETS exposure in the rest of the U.S. population is higher than that in California." It is particularly noteworthy that despite aggressive antismok- ing education and regulation, and documented reductions in smoking rates (to 16.7% of the adult population in 1995 [CDHS, 1995~), in 1992 an estimated 9.4% of California women pregnant within the previous five years had smoked throughout pregnancy, and an estimated 19.6% of those 17 years of age may be exposed to ETS in their homes (Pierce et al., 1994~. By inference from stud- ies of adult smoking, it also would appear that the rates may be appreciably higher in specific subpopulations. Influence of Activity Patterns on Exposure The activity patterns of both children and adults have been studied in relation to exposure to ETS. For all ages, the home is the location in which the average person spends the most time 921 minutes per day for adults and 1,078 minutes per day for children in California. Time within the home is spent primarily in the bedroom an average of 524 minutes per day for adults and 674 minutes per day for children (Wiley et al., 1991~. The next greatest amounts of time are spent by children in school or child care (an average of 109 minutes for all children and 330 minutes for those attending school), in other people's homes (80 minutes
270 CLEARING THE AIR average and 251 minutes for those doing this), and in-transit (69 minutes overall and 83 minutes for those traveling). Overall, chil- dren spend an average of 1,230 min. (20.5 hours) each day in- doors, 141 minutes outdoors, and 69 minutes in enclosed transit. Infants and other children ages 2 and under spend the most time indoors (an average of 21.6 hours), but somewhat less in enclosed transit (48 minutes). For adults, the times are 1,253 minutes in- doors, 73 minutes outdoors, and 111 minutes in enclosed trans- portation, with time in the workplace replacing time spent in school or child care by children. For children, the home is clearly the most likely source of ex- posure to ETS and the place that the child is most likely to sleep. While smoking is not permitted in schools or day care facilities and is prohibited in some states in licensed child care in private homes when children are present, the fact that many children are in nonlicensed child care arrangements or in states or communi- ties where smoking prohibitions are not well enforced means that significant regular exposure may occur in home settings. Expo- sure during travel in the private automobile is another potential source of exposure. For adults, research in California (Lum, 1994a, 1994b) has shown that exposure in the workplace is the most prevalent loca- tion for exposure of nonsmokers to ETS, with the home as the second most prevalent location. To the extent that workplaces adopt antismoking regulations, this exposure source may dimin- ish in importance. The private automobile represents another po- tentially significant location for adult exposure. It is possible for both adults and children to be exposed to ETS the majority of the time they are indoors, both during the day and at night. For the average preschool child, this could be virtu- ally all of the time, for the school-aged child as many as 15.5 hours a day, and for adults anywhere from 12 hours (for those working in a nonsmoking environment) to 24 hours for those working as well as living in environments in which smoking is permitted. The only reliable exception would be time spent in school, public buildings, or public transit where smoking is prohibited. There is no reason to believe that the activity patterns of persons with asthma differ significantly from those of nonasthmatics, except for the possibility of their having lower activity levels that could
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 271 result in more time spent indoors and hence greater exposure to any ETS present in indoor environments. Further, there are ques- tions as to whether the sensitization of children to allergens (e.g., dust mites, cockroaches) in the home environment may be in- creased by the presence of ETS, as well as whether increased time spent in the indoor environment, if this occurs, results in greater exposure to ETS as well as to indoor allergens. One study of children between the ages of 2 and 12 in Scot- land, having at least one parent who smoked, found that salivary cotinine levels were nondetectable in only four children, all of whom had only a father who smoked (Irvine et al., 1997~. In the remaining 493 children, the levels ranged from 0.5 ng/mL (barely detectable) to 21.2 ng/mL, with a mean of 4.35 ng/mL. The au- thors cite two studies in which levels of 14.3 ng/mL or higher have been taken as indicative of active smoking by a child. How- ever, 13 of the 18 children who scored between 14.3 and 21.2 ng/ mL were younger than 6 years of age and are presumed not to be active smokers. This study found that the age of the child, cotinine level and self-reported amount smoked in the home by the index parent, self-reported frequency of smoking in the same room as the child, whether the index parent's partner smoked, whether the child had contact with other smokers, the number of persons per room in the home, and whether the home had a yard or gar- den were all significantly and independently related to the child's cotinine level. EVIDENCE OF A RELATIONSHIP BETWEEN ETS AND ASTHMA Action of ETS on the Lungs Tobacco smoke, whether mainstream, sidestream, or ETS, is a lung irritant. From a pathophysiologic point of view, active smok- ing is associated with significant structural changes in both the airways and the pulmonary parenchyma (U.S. DHHS, 1984), in- cluding hypertrophy and hyperplasia of the upper airway mu- cous glands, leading to an increase in mucous production with associated increased prevalence of cough and phlegm. Chronic inflammation of the smaller airways also occurs, leading to bron
272 CLEARING THE AIR chial obstruction. In addition, airway narrowing may occur con- sequent to destruction of the alveolar walls, decreased Jung elas- ticity, and development of centrilobular emphysema (U.S. EPA, 1992~. Smoking also may increase mucosal permeability to aller- gens, increasing total and specific immunogiobulin E (IgE) levels (Zetterstrom et al., 1981) and blood eosinophi] counts (Halonen et al., 1982~. The adverse health effects and pathophysiologic changes as- sociated with active smoking have been observed at low-dose ex- posures, suggesting that ETS might have similar adverse effects, a suspicion that was heightened by the fact that ETS contains some volatile substances in greater quantities than are found in mainstream smoke (U.S. EPA, 1992~. In addition, since large pro- portions of the population are involuntarily exposed to ETS, in- cluding more susceptible infants and children, the index of suspi- cion for adverse effects of ETS is high. Exposures early in life, when the lung is undergoing significant growth and remodeling, could plausibly alter Jung development and increase the risk of various respiratory illnesses, including asthma. It is also plausible that, in addition to the marked susceptibility of young lungs, there is variable individual susceptibility in other respects, including genetic predisposition, lung injury such as bronchopulmonary dysplasia consequent to premature birth, and greater contact with a primary caregiver who smokes. Maternal Active Smoking During Pregnancy Exposure of the fetus to the products of maternal tobacco smoking is a form of "environmental" exposure to tobacco smoke, although not in the same proportions as in airborne ETS and not to all constituents of ETS (notably, not the particulates). It is plau- sible that virtually all products of active maternal smoking that enter the bloodstream of the mother, including products arising from mainstream and sidestream smoke, cross into the fetus through the placenta with a diffusion gradient. This has been con- firmed in the case of carbon monoxide (Longo, 1970) and cotinine. A biomarker for nicotine exposure, cotinine has been detected in the amniotic fluid of ETS-exposed women and the urine of their neonates in significantly higher concentrations than in
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE . . 273 nonexposed nonsmoking women Jordanov, 1990~. Transplacen- tal passage of the bloodborne products of passive maternal ETS exposure also would be expected, although at lower levels and with a different chemical com Position than if the mother were an active smoker. Active maternal smoking has been associated with reduced size of the placental arteries (Asmussen, 1979), a reduction in av- erage birthweight of 75~00 am. (Abell et al., 1991; Asmussen, 1979; Lodrup Carisen et al., 1997; Miiner et al., 1999; Sherwood et al., 1999; Wang et al., 1997), and altered lung function measured shortly after birth (Lodrup Carisen et al., 1997~. Small but statisti- cally significant deficits in forced expiratory volume in one sec- ond (FEVER and other spirometric indices (forced vital capacity [FVC], mid expiratory flow iMEF], and end expiratory flow [EEF]) have been fairly consistently demonstrated in school-aged chil- dren (data reviewed in Cook and Strachan, 1999) and as early as three days after birth (Lodrup Carisen et al., 1997), thereby strongly implicating maternal smoking during pregnancy as the cause of these deficits. However, in Turkey, where there is heavy smoking by men and virtually none by women, exposure of chil- dren also has been associated with significant deficits in lung function (e.g., Bek et al., 1999~. Experimental studies in animals have demonstrated that ETS exposure of pregnant rats is associ- ated with reduced Jung volume, number of saccules and septal crests, and elastin fibers in fetal lungs (Collins et al., 1985~. More recently, Sekhon et al. (1999) reported that nicotine alone, when administered to pregnant rhesus monkeys, altered the expression of nicotine receptors in the developing fetal lung, leading to lung hyperplasia with structural alterations and reduced complexity of the gas-exchange surface. ETS and Children's Respiratory Health Recent reviews of an extensive body of cross-sectional, case- control, and longitudinal epidemiologic research on the effects of parental smoking on children's respiratory health have come to very similar, although not identical, conclusions. These reviews include both systematic, quantitative meta-analyses (Cook and Strachan, 1999) and narrative reviews (California EPA, 1997; U.S.
274 CLEARING THE AIR EPA, 1992; SCOTH, 1998; WHO, 1999). In updating their earlier quantitative meta-analysis to include additional studies con- ducted between April 1997 and June 1998, Cook and Strachan (1999) summarize their earlier general conclusions (Cook and Strachan, 1997, 1998; Cook et al., 1998; Strachan and Cook, 1997, 1998a-1998c) as follows: Overall, there is a very consistent picture with odds ratios for respi- ratory illnesses and symptoms and middle ear disease of between 1.2 and 1.6 for either parent smoking, the odds usually being higher in pre-school than school-aged children and higher for maternal smoking than for paternal smoking. Virtually all of the evidence with regard to the effects of chronic ETS exposure in children comes from epidemiologic re- search, with very limited investigation of acute exposures. True experimental investigations of controlled acute exposure in cham- bers has been limited to adults. Chronic ETS Exposure and Asthma Incidence, Prevalence, and Severity in Infants and Children With respect specifically to the prevalence of asthma and res- piratory symptoms in school-aged children, both the previously analyzed and the newer studies reviewed by Cook and Strachan (1999) supported the conclusion that parental smoking is associ- ated with "increased prevalence of asthma and respiratory symp- toms in school children" and that "among children with estab- lished asthma, parental smoking was associated with more severe disease." Indicators of disease severity for which such an associa- tion has been documented include emergency room visits, life- threatening attacks, and symptoms. As indicated in Table 7-1, among children ages 5-16, pooled odds ratios (ORB) for asthma prevalence in studies reported through April 1997 were 1.21 (95% confidence interval [CI] 1.10- 1.34, 21 studies) for either parent smoking from cross-sectional studies and 1.37 (1.15-1.64, 14 studies) from case-control studies, 1.36 (1.20-1.55, 11 studies) for maternal smoking only, 1.07 (0.92- 1.24, 9 studies) for paternal smoking only, and 1.50 (1.29-1.73, 8 studies) for both parents smoking. Maternal smoking was associ
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 275 ated with an OR of 1.31 (1.22-1.41, 4 studies) for asthma incidence under age 6 and with an OR of 1.13 (1.04-22, 4 studies) over age 6. In younger children (0-2 years of age), the odds ratio for wheezing illness was 1.55 (95°/O CI 1.16-2.08, 5 studies) for either parent smoking and 2.08 (1.59-2.71, 7 studies) for mother smok- ing. These data suggest that parental smoking is more influential as a cause of "wheezy bronchitis" in infants and toddlers than of later-onset asthma. There is, at present, some inconsistency with regard to the interpretation of studies that have attempted to separate the in- fluence of maternal smoking during pregnancy from postnatal maternal smoking. Separation of the effects is difficult since those who smoke during pregnancy are very likely to continue to do so after the birth of the child, although some smokers may quit dur- ing the first trimester and abstain for the remainder of the preg- nancy, often resuming thereafter. One U.S. study of 705 Chicago fifth graders (Hu et al., 1997) found that maternal smoking dur- ing pregnancy was more strongly related to doctor-diagnosed asthma than was current maternal smoking. Similarly, a Scandi- navian study of nearly 16,000 children 6-12 years of age (Forsberg et al., 1997) found that asthma attacks, dry cough, and asthma treatment in the preceding year were inversely associated with current smoking in the home but positively associated with smok- ing in the first two years of life. The inverse relationship with current smoking suggests that parents (at least in Scandinavia) may modify their smoking behavior as a result of the child's asthma. Several observations may be relevant in understanding the lower odds ratios for asthma prevalence and incidence in school- aged children than for wheeze in younger children, especially where the data come from cross-sectional studies and relate to current smoking in the home. ETS exposure of older children may be lessened by virtue of the greater amounts of time spent outside the home and may not reflect their smoke exposure at a younger age. Cotinine, a marker for smoke exposure, has been shown to be lower in school-aged than in younger children, among chil- dren with comparable levels of smoking in the home (Irvine et al., 1997~. As already noted, maternal antenatal smoking has been asso
276 CLEARING THE AIR TABLE 7-1 Summary of Effects of Parental Smoking on the Respiratory Health of Chilclren Outcome Either Parent OR (95% Cl) Mother Or Lower respiratory illnesses (LRI) at age 0-2 All studies 1.57 (1.42-1.74)  1.72 (1.5~ Community studies of wheeze 1.55 (1.16-2.08)  2.08 (1.5C Community studies of LRI, 1.54 (1.31-1.80)  1.57 (1.33 bronchitis and/or pneumonia Hospital admission for LRI, 1.71 (1.21-2.40)  1.53 (1.2 bronchitis, bronchiolitis, or pneumonia Prevalence rates at age 5-16 Wheeze 1.24 (1.17-1.31)  1.28 (1.1C Cough 1.40~1.27-1.53)  1.40 (1.2C Phlegm 1.35 (1.13-1.62)  Breathlessness 1.31 (1.08-1.59)  Asthma (cross-sectional studies) 1.21 (1 .1 0-1 .34) [21 ] 1.36 (1 .2C Asthmatcase-controlstudies) 1.37~1.15-1.64~  1.293~11 Bronchial reactivity Skin prick positivity 0.87b (0.6 Incidence of asthma Underage6 113c(1C Over age 6 Middle-ear disease Acute otitis media Range 1.0-1.6  Recu rrent otitis media 1.48 (1 .08-2.04)  Middle-ear effusion 1.38 c (1.23-1.55)  Referral for glue ear 1.21 c (0.95-1.53)  Sudden infant deaths 2.13 (1 .8E NOTE: Numbers in square brackets are numbers of studies on which pooled odds ratios (OR) are based. aRelates largely, but not entirely to maternal smoking. bResults relate to maternal smoking during pregnancy or exposure to ETS in infancy. Data for ETS exposure during later childhood are too heterogeneous for meta-analysis. Ceased on fixed-effects estimate.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE Tory 277 % Cl) Mother Only OR (95% Cl) Father Only OR (95% Cl) Both parents OR (95% Cl) 1.72 (1.55-1.91)  2.08 (1.59-2.71)  1.57 (1.33-1.86)  1.53 (1.25-1.86)  .28 (1.19-1.38)  .40 (1.20-1.64)  1.36 (1.20-1.55) [11 ] 1.29 a(1.10-1.50)  0.87b (0.64-1.24)  1 1.31 c (1.22-1.41 )  .1 3 c (1 .04-1 .22)  2.13 (1.86-2.43)  1.29 (1.1 6 - 1.44)  1.32 (0.87 - 2.00) [6} 1.14 (1.06-1.23)  1.21 (1.09-1.34)  1.07 (0.92-1.24)  1.47 (1.14-1.90)  1.67 (1.48-1.89)  1.46 (1.04-2.05)  1.50 (1.29-1.73)  dEstimates and confidence limits differ due to exclusion of the study by Bulterys et al. (1993) (see Erratum at the end of Cook and Strachan, 1999~. SOURCE: Cook and Strachan, 1999; based on studies published through April 1997. Reprinted with permission of BMJ Publishing Group.
278 CLEARING THE AIR ciated with reduced size of the placental vessels and decreased blood flow to, if not oxygenation of, the fetus, a reduction in birthweight of infants carried to term, and decreased airflow. In addition, the risks of prematurity, neonatal respiratory distress syndrome, and bronchopulmonary dysplasia (BPD) are greater in children of mothers who smoke during pregnancy. Antenatal smoke exposure is associated with decreased airflow, which is considered likely to be related to airway size (Hanrahan and Halonen, 1998), and it has been suggested that postnatal expo- sure may induce or augment airway inflammation, both of which could contribute to the observed greater likelihood of develop- ment of wheezing and respiratory infections in young children (Cook and Strachan, 1999; U.S. EPA, 1992~. Arguably, this may also increase the likelihood of both respiratory infections and sen- sitization to aeroallergens. All of these factors may, especially in an infant genetically predisposed to allergen sensitization and asthma, increase the likelihood that a persistent inflammatory condition will be established in the airways, thus promoting the development of asthma and perhaps hastening its manifestation. However, since asthma clearly occurs in children from nonsmok- ing homes with little or no ETS exposure, the gradual addition of such children to the pool of "cases" might tend to weaken the observed association between asthma and ETS exposure among older children, whether they are considered cross-sectionally or as a birth cohort followed longitudinally. A possibly more delayed development of asthma in some non-ETS-exposed children would not dilute the observed relationship between ETS exposure and early wheezing. Dose-Response Relationship Between ETS Exposure and Asthma As summarized in Table 7-1 and noted above, the OR for asthma prevalence when both parents smoke tends to be higher than when only the mother smokes, which in turn is higher than when only the father smokes. The presumed explanation is that, in general, fathers have less intense contact with the child (and/ or that a nonsmoking mother may exert some influence in pro- tecting the child against ETS exposure due to the father's smok
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 279 in"). The relative risks associated with these four situations with respect to tobacco smoke in the home (i.e., both parents smoke, only the mother smokes, only the father smokes, neither parent smokes) suggests a dose-response relationship to asthma preva- lence as well as to wheeze, cough, phlegm, and breathlessness. This further suggests that a reduction in exposure, short of total avoidance, confers some benefit. However, the OR for either par- ent smoking and for paternal smoking is still greater than 1, indi- cating that this level of exposure is not without risk. Moreover, once asthma is established, the evidence supports the conclusion that ETS exposure is associated with more frequent asthma exac- erbations. Although a threshold may exist, there is no evidence as to what, if any, level of ETS exposure of a child, especially a child with asthma, could be said to be "risk free." ETS Exposure and Asthma Incidence in Adults There do not appear to be any studies linking chronic adult ETS exposure to adult onset asthma or any findings of an in- creased prevalence of asthma in adults exposed to ETS compared to those not exposed. In fact, if adults with asthma purposely avoided such exposure, a negative association might be observed. However, one study has shown an increased likelihood of new onset of wheezing in young adults, as well as children, attribut- able to maternal smoking during pregnancy, even after control- ling for exposure in the home and other risk factors (Strachan et al., 1996~. Acute ETS Exposure and Asthma Exacerbations Assessing the contribution of acute ETS exposure to asthma exacerbations is difficult since, for a significant proportion of ex- posed individuals, exposure is likely to be chronic (although vari- able). The evidence from studies comparing reported recent ETS exposure and cotinine levels in children seen for acute asthma versus similar children seen for well-child visits is somewhat equivocal (Ehrlich et al., 1992; Ogborn et al., 1994~. These studies suffer from small sample sizes and low power. One large study of adults correlated asthma symptoms with reported daily ETS ex
280 CLEARING THE AIR posure and reported an OR of 1.61 (95°/O CI 1.06-2.46) for restricted activity days in relation to ETS exposure level, with a somewhat higher ratio (2.05; 95°/O CI = 1.78-2.40) for the level of asthma symptoms associated with having a smoker in the home, suggest- ing an effect of chronic as well as acute ETS exposure (Ostro et al., 1994~. ETS exposure in a chamber under controlled conditions has been investigated predominantly in adults with asthma, rather than in children. These studies, which were reviewed in detail by the California EPA (1997), have shown slight to moderate tran- sient effects on lung function in at least a portion of participants but have not demonstrated a consistent effect. The studies had significant design limitations, including exclusion of participants who had recently been ill or had brittle asthma and, in many cases, the use of exposures of an hour or less in duration. A1- though participants in some of these studies may have been vul- nerable to the effects of psychological suggestion because re- searchers did not disguise the concentration of ETS delivered, others with effective "blinding" of participants had observed ef- fects. CONCLUSIONS REGARDING THE HEALTH IMPACTS OF ETS WITH RESPECT TO ASTHMA The evidence cited above permits the following conclusions with regard to the relationships between ETS exposure and asthma: · There is sufficient evidence to conclude that there is a causal relationship between ETS exposure and exacerbations of asthma in preschool-aged children. · There is sufficient evidence to conclude that there is an as- sociation between ETS exposure and the development of asthma in younger children. In the limited number of studies that have been able to separate the effects of maternal active smoking dur- ing pregnancy from the effects of ETS exposure after birth, evi- dence suggests that while both exposures are detrimental ma- ternal smoking during pregnancy has the stronger adverse effect. · There is limited or suggestive evidence of a relationship
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 281 between chronic ETS exposure and exacerbations of asthma in older children and adults. Limited or suggestive evidence of an association between acute ETS exposure and exacerbation also exists for asthmatics sensitive to this exposure. · There is inadequate or insufficient evidence to determine whether or not an association exists between ETS exposure and the development of asthma in school-age children. EVIDENCE REGARDING MEANS OF SOURCE MITIGATION OR PREVENTION Ventilation and Air Cleaning At present, source control appears to be the only reliably ef- fective means of preventing ETS exposure. As discussed in Chap- ter 10, ventilation and air cleaning measures are available that have the technical capability of reducing the particulate compo- nents of ETS in indoor environments. However, these measures would be unlikely to appreciably reduce exposure of the fetus of a pregnant woman who smokes. Further, there is currently no direct evidence as to how much a reduction in the concentration of ETS particulates in a home, if achieved, would reduce the dem- onstrated adverse effects of ETS exposure on asthma. Also, there is no evidence regarding the degree of reduction in ETS particu- late concentration that actually would be achieved through venti- lation and air cleaning in the homes of smokers who continue to smoke indoors, even if these were introduced by an aggressive educational intervention. Any changes in ventilation that smok- ers did implement might also vary in effectiveness as a function of season and weather conditions. Nor is it known how such mea- sures would affect the actual exposure of the residents, particu- larly children, and how this might vary as a function of who smokes and how many smokers are in the home. A more thor- ough discussion of ventilation and air-cleaning technologies is contained in Chapter 10. Gas-phase air cleaning systems are available and potentially effective for some gas-phase constituents of ETS; however, no proven, reliable, and cost-effective means of air cleaning currently exists of removing the broad range of gaseous components of ETS
282 CLEARING THE AIR from the indoor air. Until the components of ETS that affect asthma are better characterized, including the role, if any, of spe- cific VOCs, the importance of developing a means for the removal of ETS-related VOCs as a means of addressing the asthma prob- lem will remain unclear. Source Control If all ETS exposure were eliminated for fetuses, infants, and children, and for persons of any age who have already developed asthma, it is reasonable to assume that the population risk of de- veloping wheezing with respiratory infections and the risk of asthma exacerbations would decrease to the levels currently ob- served among similar persons who are not exposed. This conclu- sion, however, is inferred primarily from the epidemiologic data comparing persons from homes with smokers to those living in homes with no smoker. No demonstration has been reported showing that exposure can be totally eliminated by an educational intervention, much less that doing so achieves beneficial asthma outcomes. However, Eisner et al. (1998) have reported an associa- tion of asthma severity, health status, and health care initiation with ETS exposure in 451 nonsmoking adults. They also reported that cessation of ETS exposure at follow-up was associated with an improvement in the severity of asthma scores and reduced health care utilization. Even in accepting the likelihood that a benefit would result from truly effective elimination of exposure, questions remain about the extent to which this can be achieved in practice. Suc- cessful elimination of exposure is dependent on the extent to which the initiation of smoking can be prevented, especially in young women of childbearing age; that women who do smoke can be induced to cease smoking during and following preg- nancy; that all persons, particularly parents but also other caregivers and frequent visitors, can be induced not to smoke at all or not in the environment of a child with asthma; and that adults with asthma will actually eliminate their exposure to ETS. The evidence that these changes can be induced by regulatory or educational means is reviewed below.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE Regulatory Strategies 283 Where they exist and are enforced, regulatory strategies pro- hibiting smoking in public buildings, schools and child care fa- cilities, on public transit, and in the workplace (e.g., offices, plants, commercial airplanes, restaurants, bars) have clearly been associ- ated with decreased population exposure to ETS (California EPA, 1997~. Within private homes, however, regulatory strategies have been deemed unacceptable, except where licensed child care is being provided. This leaves source control in the major environ- ment where ETS exposure occurs the home to be addressed by indirect regulatory forces (e.g., increased cigarette taxes, con- trols on cigarette advertising, etc.) and by educational or behav- ioral change methods. The overall prevalence of cigarette smoking in the United States declined substantially from 40°/0 in 1965 to 29% in 1987, but the decline has leveled off and has not reached the public health goal of 15% set for the year 2000 (U.S. DHHS, 1991~. In 1995, the overall prevalence of cigarette smoking was 25% (CDC, 1997~. The decline has been marginal among those with low education aspi- rations. Of every five persons who use tobacco, four begin before age 18 (CDC, 1989~. After several years of substantial decline among adolescents in four ethnic minority groups, smoking prevalence increased during the l990s among African-American and Hispanic youth (CDC, 1998~. These trends and the success of efforts at smoking prevention and cessation among young women in particular are especially relevant to the issue of avoiding ante- natal and postnatal exposure of children to maternal smoking. Adolescent Smoking Prevention and Cessation School-based programs to prevent the initiation of smoking can be successful if they include social reinforcement and other strategies demonstrated to promote behavioral change (Bruvold, 1993~. Moreover, properly designed school smoking policies (i.e., multiple components including a greater emphasis on prevention and less emphasis on cessation) are associated with lower amounts of smoking in adolescents (Pentz et al., 1989~. It also has been shown that certain strategies directed at adolescents can
284 CLEARING THE AIR have an effect opposite from that intended (McKenna and Will- iams, 1993~. Success of Smoking Cessation Efforts Directed at Adults Public health strategies to prevent initiation of smoking and encourage cessation have clearly been associated with a decline in smoking prevalence. However, smoking is an addictive behav- ior with many personal and social factors that support its con- tinuation. Many unsuccessful strategies to get smokers to quit have been attempted, notably those based on simply providing information and/or those directed at the general population of smokers who have not evidenced an interest in quitting (e.g., Gritz et al., 1992~. Programs directed at smokers who are highly addicted or who initiated smoking earlier in their lives have been less successful than those directed at shorter-term, less addicted smokers (Chen and Millar, 1998; Killen et al., 1988; Senore et al., 1998; Smith et al., 1999~. As overall smoking cessation rates in the United States have decreased, those who continue to smoke tend to be heavier smokers (COMMIT, 1995~. However, the compari- son of less and more successful programs has enabled a distilla- tion of the components of the more successful approaches. It has been clearly demonstrated that well-designed smoking cessation programs, delivered by trained counselors, can be effective in achieving smoking cessation in adult men and women, including ethnic and minority groups (AHCPR, 1996~. Such programs are associated with greater and more sustained short- and longer- term quit rates than the rates among persons who quit on their own, without the benefit of such assistance. Cessation programs are more successful to the extent that they are more intensive, take account of the varying motivations and level of addiction of participants, and are attuned to the individual's readiness to con- sider and initiate cessation attempts. With regard to smoking cessation attempts in the clinical set- ting, strong cessation messages from clinicians, structured in rela- tion to the readiness and personal needs of the patients and utiliz- ing nicotine replacement therapy and supplementary educational and behavioral interventions, have been associated with an in- crease in both initial and sustained quit rates in controlled trials
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 285 (Law and Tang, 1995; Ockene and Zapka, 1997). The Agency for Health Care Policy and Research (AHCPR) recently reviewed more than 3,000 scientific articles that addressed the assessment and treatment of tobacco dependence, nicotine addiction, and clinical practice in order to develop guidelines for smoking cessa- tion for primary care and specialist physicians (AHCPR, 1996; Fiore et al., 1997~. These guidelines emphasize the importance of several components: nicotine replacement therapy (NRT), social support from the clinician, and skills training or problem solving based on practical advice and techniques to help individuals adapt to life as a nonsmoker. The inclusion of NRT is associated with pooled ORs of smoking cessation at six months, compared with a placebo, of from ~1.6 to ~3.0, depending on the method of delivery. Odds ratios are lowest for gum, rising to ~2.0 for the transdermal patch, and 2.92 and 3.05 for nasal spray and inhaled nicotine (Cepeda-Benito, 1993; Fiore et al., 1994; Law and Tang, 1995; Li Wan Po, 1993; Silagy et al., 1994; Tang et al., 1994; Viswesvaran and Schmidt, 1992~. Smoking Cessation Interventions in Pregnant Women As discussed above, maternal smoking, in particular, has been associated with adverse respiratory and asthma outcomes. In the United States in 1994,23.1% of all women and 14.6% of pregnant women smoked (Kendrick and Merritt, 1996~. Special efforts to obtain cessation in women, particularly pregnant women and mothers, appear to be warranted. A meta-analysis of randomized trials of prenatal smoking cessation interventions that measured effects between the sixth and ninth months of pregnancy con- cluded that "prenatal smoking cessation interventions increase rates of smoking cessation during pregnancy" (Dolan-Mullen et al., 1994~. Haddow et al. (1991), not included in the review, re- ported only modest success in getting pregnant women to cease smoking during pregnancy using a cotinine-assisted intervention. The relative success of such interventions with women of various ages, ethnicities, and education has not been analyzed, although most of the reported studies took place with patients seen in pub- lic clinic settings, suggesting that the results are not limited to middle- or upper-income and education groups. There is evidence
286 CLEARING THE AIR that many women who quit smoking during pregnancy resume soon after delivery (McBride and Pirie, 1990; Mullen et al., 1997~. Three studies were reviewed that included low birthweight and other pregnancy outcome measures in addition to smoking cessation risk ratios. Reduced risk of low birthweight was found in studies that achieved higher rates of smoking cessation. Al- though these studies are suggestive of a potential beneficial effect on respiratory outcomes, no studies to date appear to have inves- tigated these outcomes directly. Long-term follow-up is also needed to determine the effectiveness in sustaining cessation af- ter delivery. Reduction of ETS Exposure in Children with Asthma by Source Control Methods Other Than Smoking Cessation Efforts to reduce the exposure of children, with or without asthma, by getting family members who smoke and others to limit their smoking to outside the home or even to certain well-venti- lated areas within the home appear to face significant challenges due to the inherent inconvenience to the smoker and the limita- tions posed by inclement weather and building characteristics. Nevertheless, it is useful to consider what is known about the effectiveness of educational programs in achieving the goal of protecting children from exposure. Intervention attempts to reduce passive smoking of infants and children, with or without asthma, have had mixed success. Greenberg et al. (1994) reported on an intervention designed to assist families in reducing infants' ETS exposure. The interven- tion was based on social learning theory and was delivered dur- ing four nurse home visits within the first 6 months of life. There was a tendency for nonparticipants to include higher proportions of mothers who smoked, as well as black, younger, and less edu- cated mothers. Intervention effects were considered separately for families where the mother smoked and families where the mother did not smoke. Among those randomized, when the mother smoked the intervention was associated with significantly lower self-reported exposure of the infant to tobacco smoke from the mother and from nonmaternal household members. Infants whose mother did not smoke had low reported exposure from
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 287 the outset of the study, and no intervention effect was observed. This differential self-reported exposure of infants of maternal smokers was not, however, accompanied by a significant differ- ential in the cotinine-to-creatinine ratios of the intervention and control children. In fact, the proportion with detectable urine cotinine levels tended to increase over the year of follow-up in both groups. The incidence of all acute lower respiratory illnesses (ALRIs) and of severe acute respiratory illnesses did not decrease in the intervention group, and in fact, there was a small but statis- tically significant difference in all ALRIs favoring the control group. There was a significant difference in the frequency of per- sistent lower-respiratory symptoms in the maternal smoking subsample, but only where the head of household had a high school education or less. The authors interpret the results as indi- cating that mothers took steps to protect the infant from exposure by removing them from the vicinity of the smoker and that the infants were nevertheless subsequently exposed to residual nico- tine but not to other ETS products, "which may be more likely than nicotine to have acute and chronic toxicity for passive smok- ers." The authors did not discuss whether parental report could have been biased in the direction of reduced reporting of expo- sure, and the unplanned subgroup analysis means that the posi- tive results with regard to persistent lower-respiratory symptoms are merely suggestive. Chilmonczyk et al. (1992) reported an unsuccessful phy- sician's office-based intervention strategy that used feedback from the physician to the parent on infant urine cotinine measurements in an attempt to reduce the infant's exposure to ETS. The 6% re- duction of urine cotinine levels for the intervention group at fol- low-up two months later was not statistically significant. This lack of success was in contrast to the investigator's previous success in getting women to stop smoking during pregnancy based on feedback on their own urine cotinine levels (Haddow et al., 1991), suggesting there may be greater motivation and ability of women to cease smoking and eliminate exposure of their fetus than to prevent exposure of infants and older children. An earlier unsuc- cessfu] attempt to reduce passive smoking in infancy was re- ported by Woodward et al. (1987~. Hovell et al. (1994) and Wahigren et al. (1997) have reported
288 CLEARING THE AIR that among children with asthma, a preventive medicine counsel- ing intervention was associated with a greater reduction in self- reported and air monitor-verified ETS exposure than a monitored or usual care control condition. McIntosh et al. (1994) did not re- port a significant benefit of a cotinine-assisted, minimal-contact intervention. Where positive results and promising interventions have been reported, there is a need for replication and, if possible, extension to other populations. Extensions of interventions should be made to populations including those who tend to be more resistant to cessation efforts and may be more typical of those whose children are being exposed to significant levels of ETS and are at risk for poor asthma outcomes for a variety of reasons. Wilson et al. (1996) i] have found that both adults with asthma who smoke and smok- ing parents of children with asthma are less likely than nonsmok- ers to attend an asthma education program, making it less likely that they will modify the child's exposure or experience the other benefits of such asthma education programs. None of the studies to date that have investigated educational nterventions to reduce ETS exposure have extended this to in- clude asthma outcomes either doctor-diagnosed asthma or wheezing illness incidence, or the prevalence or exacerbations of established asthma. Until this is done, it leaves unanswered the question of whether any ETS exposure reduction that may be achieved is sufficient to alter these disease outcomes, as well as whether there is any safe ETS exposure level. This is particularly important when the intervention aims to reduce infant exposure by means other than cessation of smoking by all caregivers and others in the child's environment. For this reason it also is impos- sible to directly answer questions regarding the cost-effectiveness of mitigation and prevention strategies. CONCLUSIONS REGARDING ETS SOURCE CONTROL OR MITIGATION: FEASIBILITYAND BENEFITS Conclusions Regarding the Effects of Complete Avoidance of ETS Exposure Based on reasoning from the epidemiologic evidence pre
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 289 sensed above, the following conclusions can be reached regard- ing the potential benefits of essentially complete avoidance of ETS exposure, if this could be achieved: · There is sufficient evidence to conclude that complete avoidance of ETS exposure would be associated with a lower like- lihood of exacerbations of asthma in preschool children with es- tablished asthma. · There is limited evidence suggesting that complete avoid- ance of ETS exposure would be associated with a lower likeli- hood of exacerbations of asthma in older children and adults. · There is sufficient evidence to conclude that complete avoidance of ETS exposure, if this could be achieved, would re- duce the probability of the development of wheezing with respi- ratory illness in younger children. · There is limited or suggestive evidence that complete avoidance of ETS exposure, if this could be achieved, would re- duce the likelihood of the persistence of asthma or of new-onset asthma in children and adults. Conclusions Regarding Mitigation Through Source Control · There is sufficient evidence to conclude that increased ven- tilation and air-cleaning methods are technologically capable of reducing the concentration of ETS particulates in indoor air. · There is no evidence as to how readily the necessary venti- lation and air-cleaning methods or technologies would be adopted and how effectively they actually would be used to re- duce ETS concentration. · There is no evidence of whether interventions designed to encourage the use of the requisite ventilation and air-cleaning methods would be associated with a reduction in ETS concentra- tion, in the exposure of persons with asthma to ETS, or in asthma prevalence or exacerbations. · There is inadequate evidence to conclude that interven- tions intended to establish smoke-free homes where a family member has asthma and to require smokers to smoke only out- doors are associated with a reduction in ETS exposure or asthma exacerbations.
290 CLEARING THE AIR RES"RCH NEEDS A better understanding is needed of the mechanisms by which ETS and its individual constituents may · impair the normal development of the airways in the fetus, · promote allergic sensitization, · promote respiratory infections, · promote early wheezing illness, and · (possibly) induce pathophysiologic changes that may pro- mote the establishment of asthma. Research is also needed to understand the nature of the inter- actions, both at the population or epidemiologic level and at the molecular and cellular levels, between the genetic predispositions to allergic sensitization and bronchial hyperresponsiveness and ETS exposure as they relate to the development of asthma. The respective roles of antenatal and postnatal exposure to ETS in the pathophysiologic changes associated with asthma and other res- piratory illnesses are in need of further investigation. Behavioral research also is needed to better understand the factors that lead to the initiation of smoking in adolescents, espe- cially young women, and to the maintenance of smoking in preg- nant women and mothers. Additionally, there is a need to develop more effective interventions to achieve sustained pre- and post- natal smoking cessation in pregnant women and mothers, espe- cially those whose children are at higher risk of developing asthma due to their family history, socioeconomic status, and place of residence. Since ETS exposure of children at greatest risk for adverse asthma outcomes (especially low-income and minor- ity children of African-American ancestry) may come from other caregivers as well as the mother or parents (i.e., other family mem- bers with whom the mother and child live and from day care pro- viders), interventions must be developed that will be effective in reducing the child's exposure from all sources. The effectiveness of ETS exposure reduction interventions in actually improving asthma outcomes should be evaluated as well.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE REFERENCES 291 Abell TD, Baker LC, Ramsey CN Jr. 1991. The effects of maternal smoking on infant birth weight. Family Medicine 23~2~:103-107. AHCPR (Agency for Health Care Policy and Research). 1996. Smoking Cessation: Clinical Practice Guideline (No. 18~. DHHS Publication No. (AHCPR) 96-0892. U.S. Department of Health and Human Services, Public Health Service. Washington, DC. Anderson HR, Cook DG. 1997. Health effects of passive smoke. 2. Passive smoking and sudden infant death syndrome. Review of the epidemiological evidence. Thorax 52~11~:1003-1009. [Published erratum appears in Thorax 1999. 54(4):365-366.] Asmussen I. 1979. Fetal cardiovascular system as influenced by maternal smoking. Clinical Cardiology 2~4~:246-256. Bek K, Tomac N. Delibas A, Tuna F. Tezic HT, Sungur M. 1999. Department of Pediatric Allergy, Dr Sami Ulus Children's Hospital, Ankara, Turkey. Postgraduate Medicine Journal 75~884~:339-341. Benowitz NL, Jacob P III. 1994. Metabolism of nicotine to Cotinine studied by a dual stable isotope method. Clinical Pharmacology Therapeutics 56~5~:483- 493. Benowitz JL, Kuyt F. Jacob P III, Jones RT, Osman AL. 1983. Cotinine disposition and effects. Clinical Pharmacology Therapeutics 34~5~:604-611. Benowitz NL. 1996. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiologic Reviews 18~2~:188-204. Benowitz NL. 1999. Biomarkers of environmental tobacco smoke exposure. Environmental Health Perspectives 107(Suppl 2~:349-355. Bruvold WH. 1993. A meta-analysis of adolescent smoking prevention programs. American Journal of Public Health 83~6~:872-880. Bulterys M. 1993. Passive tobacco exposure and sudden infant death syndrome. Pediatrics 92~3~:505-506. California EPA (California Environmental Protection Agency). 1997. Health Effects of Exposure to Environmental Tobacco Smoke. Office of Environmental Health Hazard Assessment. Sacramento, CA. CDC (Centers for Disease Control and Prevention). 1989. Reducing the Health Consequences of Smoking: 25 Years of Progress A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, CDC, DHHS publication no. (CDC) 89-8411. Washington, DC. CDC. 1997. Cigarette smoking among adults United States, 1995. Morbidity and Mortality Weekly Report 46~51~:1217-1220. CDC. 1998. Tobacco Use Among U.S. Racial/Ethnic Minority Groups African Americans, American Indians and Alaska Natives, Asian American and Pacific Islanders, and Hispanics: A Report of the Surgeon General. U.S. Department of Health and Human Services, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Atlanta, GA.
292 CLEARING THE AIR CDHS (California Department of Health Services). 1995. Are Californians protected from environmental tobacco smoke? A summary of the findings on work site and household policies. California adult tobacco study. CDHS Tobacco Control Section, Sacramento, CA. Cepeda-Benito A. 1993. Meta-analytical review of the efficacy of nicotine chewing gum in smoking treatment programs. Journal of Consulting Clinical Psychology 61~5~:822-830. Chen J. Millar WJ. 1998. Age of smoking initiation: implications for quitting. Health Reports 9~4~:39-46. Chilmonczyk BA, Knight GJ, Palomaki GE, Pulkkinen AJ, Williams J. Haddow JE. 1990. Environmental tobacco smoke exposure during infancy. American Journal of Public Health 80~10~:1205-1208. Chilmonczyk BA, Palomaki GE, Knight GJ, Williams J. Haddow JE. 1992. An unsuccessful cotinine-assisted intervention strategy to reduce environmental tobacco smoke exposure during infancy. American Journal of Diseases of Children 146~3~:357-360. Collins MH, Moessinger AC, Kleinerman J. Bassi J. Rosso P. Collins AM, James LS, Blanc WA. 1985. Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis. Pediatric Research 19~4~:408-412. COMMIT. 1995. Community Intervention Trial for Smoking Cessation (COMMIT): I. Cohort results from a four-year community intervention. American Journal of Public Health 85~2~:183-192. Cook DG, Strachan DP. 1997. Health effects of passive smoking. 3. Parental smoking and prevalence of respiratory symptoms and asthma in school age children. Thorax 52~12~:1081-1094. Cook DG, Strachan DP. 1998. Health effects of passive smoking. 7. Parental smoking, bronchial reactivity and peak flow variability in children. Thorax 53~4~:295-301. Cook DG, Strachan DP, Carey IM. 1998. Health effects of passive smoking. 9. Parental smoking and spirometric indices in children. Thorax 53~10~:884-893. Cook DG, Strachan DP. 1999. Health effects of passive smoke. 10. Summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax 54~4~:357-366. Cummings KM, Markello SJ, Mahoney M, Bhargava AK, McElroy PD, Marshall JR. 1990. Measurement of current exposure to environmental tobacco smoke. Archives of Environmental Health 45~2~:74-79. Daisey JM, Mahanama KRR, Hodgson AT. 1994. Toxic volatile organic compounds in environmental tobacco smoke: Emission factors for modeling exposures of California populations. A133-186; California Air Resources Board, Sacramento, CA. Daisey JM. 1999. Tracers for assessing exposure to environmental tobacco smoke: what are they tracing? Environmental Health Perspectives 107(Suppl 2~: 319-327. Dolan-Mullen P. Ramirez G. Groff JY. 1994. A meta-analysis of randomized trials of prenatal smoking cessation interventions. American Journal of Obstetrics and Gynecology 171~5~:1328-1334.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 293 Ehrlich R. Kattan M, Godbold J. Saltzberg DS, Grimm KT, Landrigan PI, Lilienfeld DE. 1992. Childhood asthma and passive smoking. Urinary cotinine as a biomarker of exposure. American Review of Respiratory Disease 145(3):594-599. Eisner MD, Yelin EH, Henke J. Shiboski SC, Blanc PD. 1998. Environmental tobacco smoke and adult asthma. The impact of changing exposure status on health outcomes. American Journal of Respiratory and Critical Care Medicine 158(1):170-175. Fiore MC, Smith SS, Jorenby DE, Baker TB. 1994. The effectiveness of the nicotine patch for smoking cessation. Journal of the American Medical Association 271(24):1940-1947. Fiore MC, Jorenby DE, Baker TB. 1997. Smoking cessation: principles and practice based upon the AHCPR Guideline, 1996. Agency for Health Care Policy and Research. Annals of Behavioral Medicine 19(3):213-219. Forsberg B. Pekkanen J. Clench-Aas J. Martensson MB, St~ernberg N. Bartonova A, Timonen KL, Skerfving S. 1997. Childhood asthma in four regions in Scandinavia: risk factors and avoidance effects. International Journal of Epidemiology 26(3):610-619. Greenberg RA, Bauman KE, Glover LH, Strecher VJ, Kleinbaum DG, Haley NJ, Stedman HC, Fowler MG, Loda FA. 1989. Ecology of passive smoking by young infants. Journal of Pediatrics 114(5):774-780. Greenberg RA, Strecher VJ, Bauman KE, Boat BW, Fowler MG, Keyes LL, Denny FW, Chapman RS, Stedman HC, LaVange LM, et al. 1994. Evaluation of a home based intervention program to reduce infant passive smoking and lower respiratory illness. Journal of Behavioral Medicine 17(3):273-290. Gritz ER, Berman BA, Bastani R. Wu M. 1992. A randomized trial of a self-help smoking cessation intervention in a nonvolunteer female population: testing the limits of the public health model. Health Psychology 11(5):280-289. Guerin MR, Jenkins RA, Tomkins BA. 1992. The Chemistry of Environmental Tobacco Smoke: Composition and Measurement. Boca Raton, FL: Lewis Publishers. Haddow JE, Knight GJ, Palomaki GE, Wald NJ. 1991. Cotinine-assisted intervention in pregnancy to reduce smoking and low birthweight delivery. British Journal of Obstetrics and Gynaecology 98(9):859-865. Halonen M, Barbee RA, Lebowitz MD, Burrows B. 1982. An epidemiologic study of interrelationships of total serum immunoglobulin E, allergy skin-test reactivity, and eosinophilia. Journal of Allergy and Clinical Immunology 69(2):221-228. Hanrahan JP, Halonen M. 1998. Antenatal interventions in childhood asthma. European Respiratory Journal 12(Suppl 27):46s-51s. Hasday JD, Bascom R. Costa JJ, Fitzgerald T. Dubin W. 1999. Bacterial endotoxin is an active component of cigarette smoke. Chest 115(3):829-835. Henderson FW, Reid HF, Morris R. Wang OL, Hu PC, Helms RW, Forehand L, Mumford J. Lewtas J. Haley NJ, et al. 1989. Home air nicotine levels and urinary cotinine excretion in preschool children. American Review of Respiratory Disease 140(1):197-201.
294 CLEARING THE AIR Hovell ME, Meltzer SB, Zakarian JM, Zakarian JM, Wahlgren DR, Emerson JA, Hofstetter CR, Leaderer BP, Meltzer EO, Zeiger RS, O'Connor RD, et al. 1994. Reduction of environmental tobacco smoke exposure among asthmatic children: a controlled trial. Chest 106~2~:440-446. [Published erratum appears in Chest 1995. 107~5~:1480.] Hu FB, Persky V, Flay BR, Zelli A, Cooksey J. Richardson J. 1997. Prevalence of asthma and wheezing in public schoolchildren: association with maternal smoking during pregnancy. Annals of Allergy, Asthma, and Immunology 79~1~:80-84. Idle JR. 1990. Titrating exposure to tobacco smoke using cotinine a minefield of misunderstandings. Journal of Clinical Epidemiology 43~4~:313-317. Irvine L, Crombie IK, Clark RA, Slane PW, Goodman KE, Feyerabend C, Cater JI. 1997. What determines levels of passive smoking in children with asthma? Thorax 52~9~:766-769. [Comment in Thorax 1998. 53~3~:233-234.] Jarvis MJ, Russell MAH. 1984. Measurement and estimation of smoke dosage to non-smokers from environmental tobacco smoke. European Journal of Respiratory Disease Supplement 133:68-75. Jarvis MJ, Tunstall-Pedoe H. Feyerabend C, Vesey C, Saloojee Y.1987. Comparison of tests used to distinguish smokers from nonsmokers. American Journal of Public Health 77:1435-1438. Jarvis MJ, Russell MA, Benowitz NL, Feyerabend C.1988. Elimination of cotinine from body fluids: implications for noninvasive measurement of tobacco smoke exposure. American Journal of Public Health 78~6~:696-698. Jenkins RA, Palausky A, Counts RW, Bayne CK, Dindal AB, Guerin MR. 1996. Exposure to environmental tobacco smoke in sixteen cities in the United States as determined by personal breathing zone air sampling. Journal of Exposure Analysis and Environmental Epidemiology 6~4~:473-502. Jenkins RA, Counts RW. 1999. Personal exposure to environmental tobacco smoke: salivary cotinine, airborne nicotine, and nonsmoker misclassification. Journal of Exposure Analysis and Environmental Epidemiology 9~4~:352-363. Jordanov JS. 1990. Cotinine concentrations in amniotic fluid and urine of smoking, passive smoking and non-smoking pregnant women at term and in the urine of their neonates on 1st day of life. European Journal of Pediatrics 149~10~:734-737. Kendrick JS, Merritt RK. 1996. Women and smoking: an update for the 1990s. American Journal of Obstetrics and Gynecology 175~3 Pt 1~:528-535. Killen JD, Fortmann SP, Telch MJ, Newman B. 1988. Are heavy smokers different from light smokers? A comparison after 48 hours without cigarettes. Journal of the American Medical Association 260~11~:1581-1585. Law M, Tang JL. 1995. An analysis of the effectiveness of interventions intended to help people stop smoking. Archives of Internal Medicine 155~18~:1933-1941. Li Wan Po A. 1993. Transdermal nicotine in smoking cessation. A meta-analysis. European Journal of Clinical Pharmacology 45~6~:519-528. Lodrup Carlsen KC, Jaakkola JJ, Nafstad P. Carlsen KH. 1997. In utero exposure to cigarette smoking influences lung function at birth. European Respiratory Journal 10~8~:1774-1779.
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 295 Longo LD. 1970. Carbon monoxide in the pregnant mother and fetus and its exchange across the placenta. Annals of the New York Academy of Sciences 174(1):312-341. Lum S. 1994a. Duration and location of ETS exposure for the California population. Memorandum from S. Lum, Indoor Exposure Assessment Section, Research Division, California Air Resources Board, to L. Haroun, Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health Hazard Assessment, February 3. Lum S. 1994b. Corrections to the table of duration and location of ETS exposure for kids 6-11 years old transmitted February 3,1994. Memorandum from S. Lum, Indoor Exposure Assessment Section, Research Division, California Air Resources Board, to L. Haroun, Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health Hazard Assessment, July 19. Mattson ME, Boyd G. Byar D, Brown C, Callahan IF, Corle D, Cullen JW, Greenblatt J. Haley N. Hammond K, Lewtas J. Reeves W. 1989. Passive smoking on commercial airline flights. Journal of the American Medical Association 261~6~:867-872. McBride CM, Pirie PL. 1990. Postpartum smoking relapse. Addictive Behaviors; 15(2):165-168. McIntosh NA, Clark NM, Howatt WF. 1994. Reducing tobacco smoke in the environment of the child with asthma: a cotinine-assisted, minimal-contact intervention. Journal of Asthma 31~6~:453-462. McKenna JW, Williams KN. 1993. Crafting effective tobacco counter- advertisements: lessons from a failed campaign directed at teenagers. Public Health Report 108 (Suppl 1~:85-89. Milner AD, Marsh MJ, Ingram DM, Fox GF, Susiva C. 1999. Effects of smoking in pregnancy on neonatal lung function. Archives of Disease in Childhood. Fetal and Neonatal Edition 80~1~:F8-F14. Mullen PD, Richardson MA, Quinn VP, Ershoff DH. 1997. Postpartum return to smoking: who is at risk and when. American Journal of Health Promotion 11~5~:323-330. National Research Council. 1986. Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects. Washington, DC: National Academy Press. Ockene JK, Zapka JG. 1997. Physician-based smoking intervention: a rededication to a five-step strategy to smoking research. Addictive Behaviors 22~6~: 835-848. Ogborn CJ, Duggan AK, DeAngelis C. 1994. Urinary cotinine as a measure of passive smoke exposure in asthmatic children. Clinical Pediatrics 33~4~: 220-226. Ostro BD, Lipsett MJ, Mann JM, Weiner M, Selner JS. 1994. Indoor air pollution and asthma: results from a panel study. American Journal of Respiratory and Critical Care Medicine 149~6~:1400-1406. Ott WR, Switzer P. Robinson J. 1996. Particle concentration inside a tavern before and after prohibition of smoking: evaluating the performance of an indoor air quality model. Journal of the Air and Waste Management Association 46:1120-1134.
296 CLEARING THE AIR Pentz MA, Brannon BR, Charlin VL, Barrett EJ, MacKinnon DP, Flay BR. 1989. The power of policy: the relationship of smoking policy to adolescent smoking. American Journal of Public Health 79~7~:857-862. Pierce JP, Evans N. Farkas SJ, Cavin SW, Berry C, Kramer M, Kealey S. Rosbrook B. Choi W. Kaplan RM. 1994. Tobacco use in California: an evaluation of the tobacco control program, 1989-1993. La Jolla, CA. Cancer Prevention and Control, University of California, San Diego. Scientific Committee on Tobacco and Health (SCOTH). 1998. Report of the Scientific Committee on Tobacco and Health. Her Majesty's Stationery Office (United Kingdom). URL: http://www.official-documents.co.uk/document/ doh/tobacco/contents.htm. Accessed December 10,1999. Sekhon HS, Jia Y. Rab R. Kuryatov A, Pankow IF, Whitsett JA, Lindstrom J. Spindel ER. 1999. Prenatal nicotine increases pulmonary 7 nicotinic receptor expression and alters fetal lung development in monkeys. Journal of Clinical Investigation 103~5~:637-647. Senore C, Battista RN, Shapiro SH, Segnan N. Ponti A, Rosso S. Aimer D. 1998. Predictors of smoking cessation following physicians' counseling. Preventive Medicine 27~3~:412-421. Sherwood RA, Keating J. Kavvadia V, Greenough A, Peters TJ. 1999. Substance misuse in early pregnancy and relationship to fetal outcome. European Journal of Pediatrics 158~6~:488-492. Silagy C, Mant D, Fowler G. Lodge M. 1994. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 343~8890~:139-142. Smith PM, Kraemer HC, Miller NH, DeBusk RF, Taylor CB. 1999. In-hospital smoking cessation programs: who responds, who doesn't? Journal of Consulting and Clinical Psychology 67~1~:19-27. Strachan DP, Cook DG. 1997. Health effects of passive smoking. 1. Parental smoking and lower respiratory illness in infancy and early childhood. Thorax 52~10~:905-914. Strachan DP, Cook DG. 1998a. Health effects of passive smoking. 4. Parental smoking, middle ear disease and adenotonsillectomy in children. Thorax 53~1~:50-56. Strachan DP, Cook DG. 1998b. Health effects of passive smoking. 5. Parental smoking and allergic sensitisation in children. Thorax 53~2~:117-123. [Published erratum appears in Thorax 1999. 54~4~:366.] Strachan DP, Cook DG. 1998c. Health effects of passive smoking. 6. Parental smoking and childhood asthma: longitudinal and case-control studies. Thorax 53~3~:204-212. Strachan DP, Butland BK, Anderson HR. 1996. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. British Medical Journal 312~7040~:1195-1199. Tang JL, Law M, Wald N. 1994. How effective is nicotine replacement therapy in helping people to stop smoking? British Medical Journal 308~6920~:21-26. U.S. DHHS (U.S. Department of Health and Human Services). 1984. The Health Consequences of Smoking: Chronic Obstructive Lung Disease. A Report of the Surgeon General. U.S. DHHS, Public Health Service, Office of the Assistant
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE 297 Secretary for Health, Office of Smoking and Health, Washington, DC. DHHS Pub. No. (PHS) 84-50205. U.S. DHHS. 1986. The Health Consequences of Involuntary Smoking. A Report of the Surgeon General. DHHS (CDC) Pub. No. 87-8398. Washington, DC: U.S. Government Printing Office. U.S. DHHS. 1991. Healthy People 2000: National Health Promotion and Disease Prevention Objectives. DHHS Pub. No. (PHS) 91-50212. Washington, DC: Office of the Assistant Secretary for Health. U.S. EPA (U.S. Environmental Protection Agency). 1992. Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. EPA/600/6- 90/006F. Washington, DC. Viswesvaran C, Schmidt FL. 1992. A meta-analytic comparison of the effectiveness of smoking cessation methods. Journal of Applied Psychology 77~4~:554-561. Wahlgren DR, Hovell ME, Meltzer SB, Hofstetter CR, Zakarian JM. 1997. Reduction of environmental tobacco smoke exposure in asthmatic children. A 2-year follow-up. Chest 111~1~:81-88. Wang X, Tager IB, Van Vunakis H. Speizer FE, Hanrahan JP. 1997. Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study. International Journal of Epidemiology 26~5~:978- 988. Watts RR, Langone JJ, Knoght GJ, Lewtas J. 1990. Cotinine analytical workshop report: consideration of analytical methods for determining cotinine in human body fluids as a measure of passive exposure to tobacco smoke. Environmental Health Perspectives 84:173-182. WHO (World Health Organization). 1999. Tobacco Free Initiative Consultation Report. WHO/NCD/TFI/99.10. International Consultation on Environmental Tobacco Smoke (ETS) and Child Health proceedings, January 11-14, Geneva, Switzerland. Wiley JA, Robinson JP, Cheng YT, Piazza T. Stork L, Pladsen K. 1991. Study of children's activity patterns. ARB/9-93/489; California Air Resources Board, Sacramento, CA. Wilson SR, Latini DM, Starr-Schneidkraut N. Fish L, Loes L, Page A, Kubic P. 1996. Education of parents of infants and very young children with asthma: a developmental evaluation of the Wee Wheezers program. Journal of Asthma 33~4~:239-254. [Published erratum appears in J Asthma 1997. 34~3~:261.] Woodward A, Owen N. Grgurinovich N. Griffith F. Linke H. 1987. Trial of an intervention to reduce passive smoking in infancy. Pediatric Pulmonology 3~3~:173-178. Zetterstrom O. Osterman K, Machado L, Johansson SG. 1981. Another smoking hazard: raised serum IgE concentration and increased risk of occupational allergy. British Medical Journal (Clinical Research Edition) 283~6301~:1215- 1217.