Tobacco Documents Online

A-6 should better assess past and current exposure to tobacco smoke in the home and elsewhere." RESPIRATORY DISEASES AND CONDITIONS -- CHILDREN [551 "The Attack of Asthma," E. Friebele, Environ- mental Health Perspectives 104: 22-25, 1996 "The number of people with asthma increased by 42% in the last decade, according to a recent report by the Centers for Disease Control. Not only is asthma becoming more prevalent, but it is also more severe. According to the National Heart, Lung, and Blood Institute, the number of people who die of asthma jumped 58% between 1979 and 1992. Emergency room visits and hospital admissions for asthma are increasing. Children, ethnic minorities, and the urban poor are at the greatest risk. Researchers suspect that a variety of factors such as air contaminants and height- ened exposure to aeroallergens in airtight homes trigger bouts of asthma or cause chronic airway inflammation that may lead to permanent lung dysfunction." "What could be making a respiratory disease, trig- gered by an allergic response and aggravated by a multitude of factors, more common, more acute, and potentially more fatal?" "The rising number of asthmatics might be attributed to increased awareness among physicians, said Gale Weinman of the National Heart, Lung, and Blood Institute (NHLBI). 'Physicians may now be recogniz- ing ailments previously diagnosed as a cold or bronchitis as the long-term, chronic illness of asthma. However, increased diagnosis of asthma cannot [totally] explain the rise in its prevalence,' she said." "For the 70-75% of asthmatics who have allergic asthma, their respiratory systems have developed a very specific response to a specific allergens [sic]. Nonallergic asthmatics, on the other hand, may wheeze after exercising or taking aspirin, and show little sensitivity to allergens. Asthma and allergies appear to be inher- ited separately, but they are mysteriously associated." "The increase in asthma is not unique to the United States.... In Great Britain, deaths and hospital ETS/IAQ REPORT, ISSUE 123 admissions due to asthma doubled between 1979 and 1985. In Finland, the proportion of military recruits with asthma increased 20-fold between 1961 and 1989." "Asthma is the number one cause of absenteeism for schoolchildren and a common reason for adult absen- teeism from work." "Though death from asthma is relatively rare, it is becoming more frequent. Asthma mortality in the United_States declined by nearly 8% per year during the 1970s, but by 1977, the trend reversed, and the number of deaths due to asthma began to climb steadily, increasing about 6% per year." "Most asthma deaths occur in urban areas." "Although some evidence suggests that asthma's death tcll could be leveling off, the rising rate of hospital admissions and emergency room and doctor's office visits for asthma suggests that the disease is becoming » more severe. "Blacks, Hispanics, and people living in urban environ- ments seem to be at the greatest risk for asthma." "These findings raise important questions about why the economically disadvantaged are at greatest risk of dving from asthma. 'Poverty is assol-;-red with all sorts of diseases,' said Gergen [Peter] [of the National :nstitute of Allergy and Infectious Diseases]. `Pour people in the United States die more than the rich of all causes, and the gap is widening. General health is poorer, as well as access to medical care. Exposure, environmental quality of life, stress, and social factors all play a role,' said Gergen." "Spurred by the alarming statistics, researchers are focusing on direct exposures to allergens indoors where people are spending more of their time. Allergen levels are thought to be higher in less well-ventilated homes, where moisture accumulates, allowing mildew and molds to grow." "'We're also concerned about second-hand tobacco smoke,' said Alfred ATunzer, pulmonary specialist at Washington Adventist Hospital and former president of the ALA. 'There is increasing evidence that child- hood exposure to environmental smoke can be a predisposing factor to developing asthma."' -"Infants of women who smoke have higher levels of the antibody immunoglobin E (IgE) in umbilical cord SHB 93140331

MAY 10, 1996 blood compared to infants of nonsmokers, indicating an immune reaction. Whether children born to smoking mothers develop asthma pre- or postnatally is an unanswered question." "Increasing asthma incidence cannot totally be explained by smoking in the United States, however. Between 1965 and 1990, cigarette smoking in the United States declined by 40%. Though the greatest number of smokers are 25-44 years of age, poorly educated, and live below the poverty level, according to statistics from the CDC's Office on Smoking and Health, the proportion of smokers in this group is also following a downward trend." "Other studies are exploring the influence of a child's surroundings during the vulnerable first weeks and months of life. It is precisely during this period, scientists believe, that the environment of a child with a genetic disposition can tip the scales toward develop- ing a full-fledged allergy." "`The consensus seems to be that the environment is playing a tremendous role in the increasing prevalence of asthma,' said Munzer. In addition to the provoca- tion of asthma by allergens, he says, `air pollution is a big factor."' "The nation's air has improved dramatically in the past 25 years. Emissions of soot and smog-forming volatile organic compounds have decreased signifi- cantly in the United States since 1970 despite crowded highways where more vehicles are driven twice as many miles. Release of sulfur oxide has decreased by 30% since 1970. Between 1988 and 1993, overall industrial emissions of toxic compounds decreased by 39%." "The distribution of asthma in other countries also fails to implicate pollution as an aggravating factor. Some of the highest asthma mortality rates occur in Australia and New Zealand, which have excellent air quality. Asthma is more prevalent in rural areas of the Scottish highlands, which have some of the lowest ozone concentrations in the world, than in more urban and polluted parts of the United Kingdom, according to a recent report." "In spite of overall improvements in air quality, many Americans are not breathing risk-free air, according to EPA Administrator Carol Browner. Almost 100 million people live in areas where the air does not meet A-7 national air quality standards. Eighty percent of Hispanics and 65% of blacks live in 'nonattainment areas' for air standards." "The question remains whether small particles in the atmosphere provoke asthma episodes." "While many factors that provoke asthma, such as air pollution and cigarette smoking are decreasing, the disease is becoming more prevalent. Its increasing severity is concentrated in urban pockets where children live under poor conditions, are frequently exposed to allergens and air pollution episodes, and have sporadic medical care. Research suggests that education, controlling exposure to antigens in the indoor environment, and improving urban air quality could improve the quality of life for these children." [56] "Fungus Spores, Air Pollutants, and Other Determinants of Peak Expiratory Flow Rate in Children," L.M. Neas, D.W. Dockery, H. Burge, P. Koutrakis, and F.E. Speizer, American Journal of Epidemiology 143: 797-807, 1996 "The present investigation has replicated the previous Uniontown summer study [of haze episodes and daily variations in symptoms and peak expiratory flow rates] in a cohort of children in State College, Pennsylvania, and has included daily measurements of specific pollen and fungus spore concentrations." "Airborne spore concentrations of Cladosporium, Epicoccum, and Coprinus were associated with deficits in the mean deviation of morning PEFR for the entire cohort." _ "Precipitation afE°cted both the mean deviation in PEFR and the concentrations of airborne contaminants." "In this study, a 12-hour daytime time-weighted exposure to an additional 125-nmol/m3 particle-strong acidity was associated with a mean 1.2-liters/minute decrease in evening PEFR.... Cough episodes were associated with 12-hour daytime exposures to particle-strong acidity and total sulfate particles." "The principal determinants of the day-to-day variation in PEFR among children include time of observation, growth, temperature, precipitation, air pollutants, and airborne aeroallergens. The effects of time of observation, growth, and temperature are very consistent across two studies, with similar measure- SHB

A-8 ments for comparable children's cohorts. In this study, airborne spore concentrations of Cladosporium, Epicoccum, and Coprinus were associated with deficits in the mean deviation of morning PEFR for the entire cohort; and five children showed significant child-specific declines in morning PEFR v.th increased Ganoderma spore concentrations. The effect of particle-strong acidity on the mean deviation in evening PEFR was somewhat less in this study. These data are not incompatible with the previous finding of an association of PEFR with aerosol acidity among the Uniontown children. These results are also compatible with a respirable particle hypothesis. Daytime expo- sures to ozone and particulate air pollutants were associated with the increased incidence of summertime cough and cold symptoms that evening or on the subsequent morning. Precipitation days and fungal spore concentrations did not confound the association of PEFR with the levels of particulate air pollutants. Fungus spore concentrations affected the mean devia- tion in morning PEFR, and air contaminants affected the mean deviation in evening PEFR. We conclude that summer episodes of excessive aerosol acidity and particulate pollution are acutely associated with declines in peak expiratory flow rates and increased incidence of cough and cold episodes in children. Similar, if not stronger, effects were associated with variation in fungus spore counts, which suggests that additional exploration of the influence of aerobiologic contaminants in conjunction with summertime haze episodes is warranted." [57] "The Impact of Lung Development on Respiratory Disease Later in Life," L.I. Landau, Monaldi Archives of Chest Diseases 3: 167-169, 1995 "The airways are fully mature in their structure and branching pattern at birth, and no major changes occur after birth. However, considerable alveolar develop- ment occurs in early postnatal life and probably continues through to adult life, although the peak development is completed within the first 3-4 yrs. After 8 yrs of age, there is most probably a greater increase in size than in number of alveoli. The growth of blood vessels supplying the conducting airways parallels the development of the airways." "The effect of various insults on lung growth and function will depend on the timing of that insult. It is ETS/IAQ REPORT, ISSUE 123 becoming increasingly clear that insults from concep- tion until early school years may have profound effects on lung development, which persist into later life." -"Genetic disorders are present from conception but their effect on the lungs will depend on the disease process that results from the genetic abnormality." "Those at risk of subsequent atopy and asthma may have abnormalities detected at birth, such as increased airway responsiveness, and raised cord blood immuno- globulin E (IgE) levels. Although these may evolve in relation to in utero exposure to allergens or mediators from the mother, the genetic predisposition is a vital component of this response." "Gender is a very important factor influencing lung development and the increased predisposition of boys for lower respiiatory tract symptoms and asthma during early childhood. Boys have lower flow rates for lung size than girls from birth until puberty." "There is increasing evidence that in utero events have an effect on lung development manifest at birth, which may predispose to respiratory symptoms in infancy, asthma during early childhood and young adult life, and chronic lung disease in later adult life. Those with the familial predisposition demonstrate a maternal pattern of inheritance to atopy and asthma. This may be genetic with paternal imprinting, so that the gene acquired from the father is not expressed. It could equally be related to allergen exposure transplacentally or to the movement of m..eiiators from the mother to the foetus. The presence of abnormalities at birth does suggest that aims at prevention of asthma will need to take into account events during pregnancy." "Maternal smoking has now been well documented as an important cause of lower respiratory tract symptoms during the first 2 yrs of life. Babies of mothers who _ smoke have reduced flow rates and increased airway responsiveness present soon after birth and before symptoms have developed. The timing of the effect of smoking on the foetus has not yet been definitely identified, and it may be gender specific. However, in line with other effects of tobacco smoke, the major influence probably occurs after the first 3 months of gestation. The effect appears more marked in girls and may, in fact, represent a masculinization of the female during intra-uterine lung development." SHB g3140333

MAY 10, 1996 "Young, et al. reported a cohort in whom up to 10% of apparently normal infants were found to have considerably reduced flow rates soon after birth. These infants had a very high rate of subsequent lower respiratory tract symptoms and asthma. Although many can be shown to have had a high risk oi'ast .:na on the basis of family history and exposure to environ- mental tobacco smoke, there are almost certainly many more risk factors and insults predisposing to abnormal airway development during foetal life that have not yet been identified." "Bacterial infections in early life cause considerable lung damage but, in the developed world, are rarely associated with long-term functional disability." "The effect of viral infections during the first year of life on subsequent lung development and function is particularly interesting. Although uncommon, some can certainly cause significant, permanent damage." "On the other hand, there is some evidence that a reduction of viral infections during early life may be associated with sensitization to common allergens rather than tolerance." "Bronchial responsiveness appears to decrease with age. However, tests of airway responsiveness in differ- ent sized children are difficult to interpret, as one can never been sure whether the challenge dose is equiva- lent. Whether airway responsiveness does decrease with age or not, it appears likely that those with increased airway responsiveness will maintain this status, with allergen exposure through early life leading to subse- quent atopy and asthma." "Chronic obstructive airways disease in adults has frequently been shown to be associated with childho-id respiratory trouble. It is becoming increasingly clear that these childhood respiratory symptoms are not the cause of subsequent lung disease but a reflection of abnormalities of luing development through intra-uterine life and early postnatal life. Prospective longitudinal studies are giving us important insights into these events, and should lead to interventions which will prevent respiratory illness both in childhood and later adult life." A-9 [58] "Breastfeeding as Prophylaxis Against Atopic Disease: Prospective Follow-Up Study Until 17 Years Old," U.M. Saarinen and M. Kajosaari, Lancet 346: 1065-1069, 1995 "Environmental exposure during early infancy may be particularly important for sensitization and later devel- opment of atopy, probably because of the physiological immaturity of the immune system. The possibility of a primary defect in intestinal absorption of macromol- ecules in atopic individuals has also been suggested." "The role of breastfeeding and/or avoidance of cows' milk-based formulas in early infancy has been the focus of much controversy.... The purpose of the present study was to evaluate the very-long-term effects of breastfeeding by assessing the occurrence of atopic manifestations in the same prospective series through- out childhood and adolescence in a follow-up study until the age of 17 years." "The results of this prospective, very-long-term follow-up study from infancy until early adulthood indicate that breastfeeding can protect against develop- ment of atopic disease. In the group with short or no breastfeeding there was a consistently higher prevalence of atopy, which increased to a demonstrable difference at 17 years of age. When the• gr.,,.p with short or no breastfeeding was compared with the prolonged breastfeeding group, atopy was observed in 65% and 42% of subjects, respectively, and substantial atopy in 54% and 8%. The difference in substantial atopy was significant irrespective of positive or negative atopic heredity. Unexpectedly, the differences between the infant feeding groups were pronounced at the age of 17 years." "According to our follow-up data, breastfeeding for 6 months or longer is required for prophylaxis of atopic eczema for the first 3 years of life. On the other hand, exclusive breastfeeding for longer than 1 month already seems beneficial in preventing food allergy with its prevalence peak at 3 years, and respiratory allergy with the prevalence peak at 17 years. With regard to sub- stantial atopy at the age of 17 years, greatest benefit was achieved by prolonged breastfeeding." "Heredity has hitherto been considered to be the strongest predictive risk factor for atopic disease. In our series, the differences in atopy among children grouped according to early milk feeding were of the same order SHB

A-10 of magnitude as were the differences caused by positive or negative atopic heredity; at the age of 17 years, the differences due to infant feeding were even more pronounced, suggesting an influence of early milk feeding that may exceed the heredity burden." OTHER CANCER [59] "Relation of Breast Cancer with Passive and Active Exposure to Tobacco Smoke," A. Morabia, M. Bernstein, S. Heritier, and N. Khatchatrian, American journal ofEpidemiology 143: 918-928, 1996 "It is ... paradoxic that the work on passive smoking has consistently shown a tendency toward an increased risk of breast cancer while studies on active smoking have failed to demonstrate an association. This appar- ent contradiction may stem from not separating passive smokers from the unexposed when assessing the effect of active smoking.... If passive smokers are at greater risk of breast cancer than are the unexposed, grouping passive smokers with the unexposed in the referent category may reduce thc excess risk for active smokers to nonsignificant levels. This was the a priori hypoth- esis that motivated the design of the present study." "There were 126 cases (52 percent) and 620 controls (60 percent) who were never active smokers. Among them, 28 cases (22 percent) and 241 controls (39 percent) were neither active nor passive smokers and were used as the referent 'unexposed' group." "[T]he adjusted odds ratios of breast cancer for ever active smokers, compared with women unexposed to either passive or active smoke, were 2.2 (95 percent CI 1.0-4.4) for an average lifetime consumption of 1-9 cigarettes per day, 2.7 (95 percent CI 1.4-54) for 10-19 cigarettes per day, and 4.6 (95 percent CI 2.2-9.7) for 20 or more cigarettes per day." "To examine the effect of cleaning up the referent category from the passive smokers, we computed the odds ratios using never active smokers as the referent category, that is, pooling passive smokers with the unexposed. Among ever active smokers, the two-step odds ratios were 1.2 (95 percent CI 0.8-2.0) for 1-9 ETS/IAQ REPORT, ISSUE 123 cigarettes per day, 1.7 (95 percent CI 1.1-2.5) for 10-19 cigarettes per day, and 1.9 (95 percent CI 1.2-2.9) for [greater than or equal to] 20 cigarettes per day (not shown in a table)." "[A] mong nonactive smokers, the multivariate odds ratio for ever being exposed to passive smoking at home, at work, or during leisure time for at least 1 hour per day for at least 12 consecutive months of smoking was 2.3 (95 percent CI 1.5-3.7). The odds ratio became 3.2 (95 percent CI 1.7-5.9) after addi- tional adjustment for saturated fat and alcohol intakes. There was no statistically significant trend according to the number of hours per day-years; the two-step odds ratios were 3.1 (95 percent CI 1.5-6.2) for 1-50 hours per day-years and 3.2 (95 percent CI 1.6-6.3) for more than 50 hours per day-years." "The present results suggest that both passive and active smoking increase breast cancer risk. They seem biologically plausible, since it is reasonable to postulate that constituents of tobacco smoke have a direct and/or an indirect influence on the carcinogenic process leading to breast cancer." "[T] he observed associations for active smoking are surprisingly strong in contrast to those of most previ- ous studies." "[A] detailed assessment of lifetime exposure may be necessary to show the relation of active smoking with breast cancer." "The present results are not directly comparable with previous literature reports on active smoking and breast cancer since, to our knowledge, none of them separated passive smokers from subjects unexposed to active and passive smoke. Removing passive smokers from the referent category increased the odds ratio by a factor of 1.5-2.5 according to the active smoking category. It is therefore possible that the strength of the breast cancer-smoking association has been underestimated in the available body of literature." "Lifetime exposure to passive smoking is clearly difficult to assess. In the present study, to be classified as a passive smoker, a woman had to have been exposed at least 1 hour per day for 1 consecutive year or more. This definition was relatively strict in order to identify women with at least one period of substantial exposure in their lifetime. It was more difficult to assess accu- SHB 93140335

MAY 10, 1996 rarely the number of hours per day of passive smoking, especially during leisure time. Misclassification orthe_ intensity of exposure may therefore have diluted a__ possible dose-related effect." - "For comparison purposes with the_litera_ture, we computed the odds ratio of passive smoking among women ever married to an active smoker compared with women never married to an active smoker. The t<vo-step odds ratio was 2.0 (95 percent CI 1.1-3.7) (not shown in a table). The lower bound of the confidence interval was consistent with the odds ratio of 1.4 computed by Wells. However, this proxy measure for passive smoking probably underestimates the association, since women married to nonactive smokers may have been exposed at home by someone other than their spouse. They also may have been exposed somewhere other than at home." "Being exposed to passive smoking 2 hours per day for 25 years was equivalent to having actively smoked an average of 20 cigarettes per day for 20 years. This was disturbing, since the effect of passive smoking was not a priori expected to be as strong as that of active smoking. A similar problem is encountered when studying cardiovascular diseases.... A better under- standing of the biologic effect of tobacco smoke on the mammary gland is needed to decide whether this phenomenon reflects a different etiologic mechankm from that for lung cancer. Direct exposure to tar deposition should not be an issue for breast cancer or atherosclerosis." "The risk factors of breast cancer were incorporated as potential confounders in logistic regression models. Alcohol and saturated fat intakes were not strong confounders." "The present study had limited statistical power to perform subgroup analyses.... None of them indi- cated that the effects of passive and active smoking could be limited to a subgroup of women." "A strength of the present study design was to incorporate variables allowing us to quantify potential selection, detection, and recall biases." "[S]eparating passive smokers from unexposed women resulted in a group of 28 cases in the referent category. The odds of being unexposed drive the findings related to passive smoking. We were not able to identify a methodological flaw that could have A-ri generated the relatively small proportion of cases unexposed to active and passive smoke. The most serious consequence of an_ unsuspected bias for the present results would have been that some truly unexposed women had been classified as passive smokers." "The present study findings do not allow us to conclude that there is a causal association between smoking and breast cancer. There is no dose-response relation between the intensity of passive smoking and the odds ratio of breast cancer. The strengths of the associations for passive and active smoking are of similar magnitude, while one would expect the risk of one's own smoke to be much larger." "However, recent reports offer evidence that can reconcile these apparent incongruities with a plausible biologic mechanism. ...`3Ue can speculate that women who develop breast cancer as a consequence of passive smoking are likely to be slow acetylators, rapid acetylators being able to metabolize low doses of the toxin." "The absence of a dose-response relation for passive smoking, if true, may be due to a low threshold of exposure among slow acetylators. Above that threshold, the risk associated with passive smoking would increase rapidly and then plateau. The latter hypothesis would also explain the relatively small magnitude of difference between the odds ratios for passive and active smoking." "In conclusion, the present findings may be surpris- ing, but they suggest uiat it is important to consider the effect of passive smoking when examining the association between active smoking and breast cancer. Previous studies may have failed to find an effect of active smoking, because they did not exclude passive smokers from the unexposed category. The association is not entirely explainable by analogy with the biologic mechanisms involved in established tobacco-related diseases. Additional studies of comparable design are needed to decide whether these intriguing findings are causal or not." [60] "Molecular Epidemiology: Insights into Cancer Susceptibility, Risk Assessment, and Preven- tion," F.P. Perera, Journal of the National Cancer Institute 88: 4_9 _6-509, 1996 "For more than a decade, there has been wide agree- ment that most cancer results from man-made and SHB

A-12 natural environmental exposures (such as tobacco smoke; chemical pollutants in air, water, food, drugs; radiation; dietary constituents; radon; and infectious agents) acting in concert with both genetic and ac- quired characteristics. It has been estimated that without these environmental factors, cancer incidence would be dramatically reduced, by as much as 80%-90%. Cancer risk from these environmental carcinogens is strongly influenced by many factors, including genetics, age, ethnicity, sex, immune function, pre-existing disease, and level of nutrition. Genetic predisposition acting in isolation probably explains no more than 5% of all cancers in the United States." "The counterpoint between the environment and host susceptibility has been elaborated in recent years through molecular epidemiologic studies of biologic markers present in human cells, tissues, and body fluids. Examples of 'biomarkers' are chemical-specific genetic damage in the form of carcinogen-DNA adducts or changes in key oncogenes or tumor suppres- sor genes that either trigger or block cancer development. Others document genetic and acquired susceptibility traits affecting processes such as carcino- gen metabolism, DNA damage, and repair. Analysis of biomarkers is ir...__asingly being incorporated into cross-sectional, retrospective, prospective, or nested case-control studies to gain improved resolution of the risk factors and mechanisms responsible for cancer." "Molecular epidemiology has the advantage of being directly relevant to human risk, unlike animal or other experimental models that require extrapolation to humans. In contrast to traditional epidemiology that relies on cancer incidence or mortality as the end point, molecular epidemiology has the potential to give early warning by flagging the preclinical effects of exposure and increased susceptibility, thus signaling opportuni- ties to avert cancer through timely intervention. Moreover, biomarker data on the distribution of procarcinogenic changes and susceptibility factors in the population can improve estimation of cancer risk from a given exposure." "However, molecular epidemiology is also subject to many of the limitations of epidemiology, such as the vulnerability to confounding factors that can give misleading results.... At the present time, many biomarkers can be useful in assessing exposure, dose, ETS/IAQ REPORT, ISSUE 123 and potential risk for a group or population; most are not, however, sufficiently characterized in terms of their ability to predict disease for use in screening, diagnosis, or quantitative estimation of individual risk. ... Although routine screening for cancer susceptibility is not justified, the substantial body of molecular epidemiologic and other data on susceptibility now in existence can be helpful in shaping cancer risk assess- ment, public health, and environmental policy." "Unfortunately, prevention is not well served by current methods to assess environmental risks. Al- though sometimes characterized as overly conservative, risk assessment methods currently used by government agencies, such as the Environmental Protection Agency, may underestimate the risk of certain environ- mental carcinogens because of the inherent assumption tiiat all individuals in a population have the same biologic response to a specified dose of a cancer-causing agent. The result can be regulatory and health policies aimed at protecting the 'average American,' ignoring the sizable, more vulnerable, fraction of the popula- tion. While the assumption of population homogeneity has long been in question, considerable quantitative information on the range of susceptibility within populations now shows that it is invalid." "This review discusses representative examples of molecular epidemiologic research during the last 10 years into the nature of susceptibility to common environmental carcinogens. These are viewed within the context of related experimental and epidemiologic data on carcinogenesis. A brief summary of recent evidence on molecular mechanisms in carcinogenesis provides a framework for an in-depth discussion of molecular and epidemiologic evidence of the role of the environment in cancer. The sources of variation in individual susceptibility to environmental carcino- gens are then described in detail, with illustrative examples from the recent literature. The final section discusses some of the implications of individual variability for current policies concerning risk assess- ment and cancer prevention." SHB

MAY 10, 1996 REPRODUCTIVE AND DEVELOPMENTAL_ISSUES [61] "Neuroendocrine Cell Expression in Fetal Lungs After Maternal Exposure to Aged and Diluted Sidestream Cigarette Smoke (ADSS)," K.P. Allamneni, C.G. Plopper, and K.E. Pinkerton, The Toxicologist 30(1, Part 2): 235, 1996 "Pulmonary neuroendocrine cells (PNEC) are specialized airway epithelial cells that may be involved in chemoreception and cellular differentiation. These cells are most abundant during the fetal and neonatal stages of development. The purpose of this study was to examine the effects of maternal exposure to ADSS on the expression of PNEC. Timed-pregnant Sprague-Dawley rats were exposed to ADSS for 6 hours/day, 7 days/week, from gestational day (DGA) 5 to the day prior to sacrifice, while control mothers were exposed to filtered air only....(CGRP), a neuroendo- crine marker was used to visualize PNEC immunohistochemically in lung tissues at 14, 18 and 21 DGA. The frequency of positive cells in the airways was measured per mm of basal lamina. At 14 DGA, CGRP positive cells were not detected in the airway epithelium of either group. At 18 DGA, CGRP positive cells were found to be in greater abundance in central airways compared with peripheral airways. Maternal exposure to ADSS resulted in a significant increase in CGRP positive cells at 18 DGA within central and peripheral airways. These differences were also found at 21 DGA in central and peripheral airways. We conclude that PNEC differentiation in the fetal lung is site-specific and that maternal exposure to ADSS at environmentally relevant concentrations significantly increases the number of neuroendocrine cells within airways during cellular differentiation of the fetal lung." OTHER HEALTH ISSUES A- 13 [621 "Risk Factors for Chronic Otitis Media With Effusion in Infancy: Each Acute Otitis Media Episode Induces a High but Transient Risk," O.P. Alho, H. Oja, M. Koivu, and M. Sorri, Archives of Otolaryngology and Head-Neck Surgery 121: 839-843, 1995 "Our current research was conducted to measure the biologic effects of different risk factors on chronic otitis media with effusion." "Our results indicate that previous acute otitis media episodes pose the greatest risk for chronic otitis media with effusion. Each episode induces an increased risk, which is highest immediately after the episode (> 10-fold) and gradually vanishes after 3 months. The number of earlier episodes or an early first episode do not affect the risk directly, ie, the risk associated with acute otitis media episodes is not cumulative, as earlier reports have indicated. It is true retrospectively that the risk for chronic otitis media with effusion is higher if a child has had numerous acute episodes, because tran- sient risk is involved in each of them, but at any fixed point of time, if the child has avoided chronic otitis media with effusion so far, only information about the _ current month and the past 3 months is relevant." "Accumulations of acute episodes proved to be especially risky. This high risk attached to successive episodes decreased rapidly. More aggressive treatment of acute episodes, such as performing a tympanocentesis and prescribing a beta-lactam antibi- otic, did not affect the risk." "The risk introduced by extrinsic factors is markedly lower than that in previous acute episodes. On the other hand, more powerful extrinsic risk variables exist for chronic otitis media than were found for acute otitis media earlier in this series." _ "Attendance at a group day nursery posed a twofold risk, confirming earlier results. Previous screenings have shown a clear seasonal variation in the occurrence of abnormal rympanograms; the risk is markedly higher during spring, autumn, and winter. Children typically have acute otitis media episodes and attend day care outside the home during these months, which affects the figures. The dynamic model showed that the risk estimates for autumn were especially high, but SHB

A-14 those for the spring and winter were similar to the summer figures. The maximum occurrence of chronic otitis media with effusion was at the beginning of the second year, even after adjustment for the other time-dependent risk factors. Male sex also increased the_ risk twofold. Atopy, bottle-feeding, number of siblings, and parental smoking [OR = 1.44, 95% CI 0.86 - 2.41] had an effect only through acute otitis media episodes, and their effect was more modest than reported earlier, probably because of better stand.rdiza- tion of the effect of previous episodes." "The risk of chronic otitis media with ::cfusion is highest for a boy who has just had his first birthday, is attending a day nursery outside the home during the autumn, and has just experienced successive episodes of acute otitis media. Previous acute otitis media episodes were the greatest risk factor, and this investigation adds to our earlier understanding of how this risk is medi- ated; each acute episode induces an increased risk for chronic otitis media with effusion that is highest immediately after the episode and gradually vanishes after 3 months. Successive acute episodes are especially risky, but this high risk similarly decreases rapidly. The number of previous acute episodes or an early first episode do not affect the risk directly, ie, the risk associated with acute otitis media episodes is not cumulative as reported earlier." [63] "Epidemiology in the Assessment of Small Risks," D. Coggon, Transactions of the Institu- tion of Chemical Engineers 73 (Part B, Suppl.): S36-S38, 1995 "Bias occurs when deficiencies in the design or execution of studies cause risks to be systematically underestimated or overestimated.... Some bias is unavoidable, even in the best designed epiderniological studies, and the effects cannot be quantified precisely." "Statistical uncertainty arises because we are limited in the numbers of people we can study ... Uncertainty of this sort can be quantified rather better than that resulting from bias, for example, by calculation of confidence intervals around risk estimates, but again it cannot be eliminated." "Confounding occurs when the people under investi- gation differ not only in their exposure to the hazard_of interest but also in other ways which independently ETS/IAQ REPORT, ISSUE 123 influence their risk of disease....[R]eliable adjustment for confounders depends on the accuracy of their measurement. Furthermore, one can never exclude the possibility of unrecognised confounders." "The uncertainties in the interpretation of epidemio- logical data are most troublesome when relative risks (le the ratios of risk in people with and without exposure to hazards) are small -- less than a 20% elevation say. At this level, it becomes very difficult to distinguish the effects of a hazard from those of bias, chance and confounding." "While the ability of epidemiology to detect effects depends on the relative increase in disease incidence associated with an exposure, risk management is based on the absolute increase in risk and the number of people affected. Uncertain risk estimates may be tolerable when the disease caused is rare and few people are exposed to the hazard." "Difficulties arise when the diseases affected are more common. For example, a 20% excess of lung cancer represents an absolute increase of approximately one case per 100 people over a lifetime. This would be important if it applied to large numbers of people. Some regulatory authorities seek to prevent lifetime risks as low as one per million from environmental carcinogens. Such small increases in the occurrence of common diseases cannot be measured directly." "An alternative, therefore, is to extrapolate from the risks associated with higher exposures. This requires first that exposure-response relationships can be assessed reliably....[E]rrors in the assessment of exposure can seriously distort exposure-response relationships." "A second requirement for the extrapolation of risks to low exposures is that the shape of the exposure-response curve can be predicted reliably outside the range of empirical assessment. Calculations often assume a linear relation between exposure and risk, but this may not always be justified." "Another consideration in the extrapolation of exposure-response relationships is the comparability of the populations from which data are derived and those _ to which the results are then applied. Often exposure-response is assessed in occupational popula- tions from which potentially vulnerable groups such as children and the elderly are excluded." SHB 9314,0339

MAY 10, 1996 "Can anything be done to counter these method- ological problems? One approach which could reduce the uncertainties in extrapc'.ation of exposure-response relations is to examine intermediate endpoints in epidemiological studies as well as looking at clinically manifest disease." - "While developments such as the measurement of DNA adducts may eventually lead to improved assessment of the risks posed by low exposures, many of the problems will persist for the foreseeable future. Thus decisions in risk management will continue to rely on data that are often incomplete and uncertain." [64] "The Epidemiology of Haemophilus influenzae Type b Disease in the Republic of Ireland," J. Fogarty, A.C. Moloney, and J.B. Newell, Epidemiology oflnfectioru 114: 451-463, 1995 "The importance of Haemophilus influenzae type b (Hib) as a cause of serious disease in infants and children is well recognized. Meningitis is the principal clinical disease but other conditions such as epiglottitis, pneumonia, cellulitis, bone and joint infections and septicaemia also occur. The major disease burden occurs in children under 5 years." "The purpc..,., of this study was to document baseline incidence data on Hib disease for the Republic of Ireland (ROI) against which Hib vaccine efficacy could be evaluated after its introduction. A case-control methodology was used to investigate the hypothesis that certain risk factors not previously investigated in the ROI or the United Kingdom (UK), were more common in children with Hib disease than in controls." "The annual incidence of Hib disease in Ireland was similar to that experienced in England and Wales, Scotland and France, lower than that in northern Europe, Australia and New Zealand and American populations of European origin, and substantially lower than rates experienced in native American, aboriginal and African children." "Two significant risk factors for primary Hib disease were identified: attendance at creche or day-care and the presence of chronic illness. A strong relationship between age and risk of Hib disease for creche or day-care attendance was observed with the highest risk experienced by children in the second year of life.... When stratified analysis was carried out for meningitis A-15 and non-meningitic disease, creche attendance emerged as a risk factor for non-meningitic Hib disease but not for meningitis alone." "The presence of chronic illness was another risk factor for Hib disease in Irish children." "No association with risk of Hib disease was observed with such family characteristics as household cigarette smoking, household crowding, presence of school-age siblings or breast-feeding, although many of these factors have been shown to be risk factors (or a protec- tive factor in the case of breast feeding) in other studies. The homogeneity of the Irish population may account for the similarity in distribution of many of these characteristics that have been shown to be risk factors elsewhere. Of the two risk factors identified, creche or day-care attendance may operate as an environmental factor by increasing the likelihood of children's exposure to Hib bacteria and chronic illness would appear to act as a host factor increasing the susceptibility to development of invasive Hib disease." "Until there is evidence that Hib immunization coverage rates reach 95% for eligible children in the ROI, it is essential that children with chronic illness and those who are creche or day-care attendees receive Hib conjugate vaccine as a priority." [65] "Inequality in Income and Mortality in the United States: Analysis of Mortality and Poten- tial Pathways," G.A. Kaplan, E.R. Pamuk, J.W. Lynch, R.D. Cohen, and J.L. Balfour, British Medical Journal312: 999-1003, 1996 "For the most part, socioeconomic level, whether it is measured by income, education, occupation, social class, or other measures, has been conceptualized as a property of the individual. This is not surprising as one's economic resources can determine, to a great extent, the availability and quality of food, housing, medical care, and other necessities. Recent findings, however, suggest that it may also be important to consider the overall distribution of wealth as a charac- teristic of a society or group." "We studied the relation between variations in income distribution between states of the United States and a variety of health outcomes, including variations in mortalities adjusted for age. In addition, we exam- ined some of the potential pathways, possibly reflecting SHB