Low levels of antibodies for the oral bacterium Tannerella forsythia predict cardiovascular disease mortality in men with myocardial infarction: A prospective cohort study.

Antibody levels to periodontal pathogens in prediction of cardiovascular disease (CVD) mortality were explored using data from a health survey in Oslo in 2000 (Oslo II-study) with 12 1/2 years follow-up. IgG antibodies to four common periodontal pathogens; Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all termed collectively the "red complex", and Aggregatibacter actinomycetemcomitans(AA) were analysed. The study sample consisted of 1172 men drawn from a cohort of 6,530 men who participated in the Oslo II-study, where they provided information on medical and dental history. Of the study sample, 548 men had reported prior myocardial infarction (MI) at baseline whereas the remaining 624 men were randomly drawn from the ostensibly healthy participants for comparative analyses. Dental anamnestic information included tooth extractions and oral infections. An inverse relation was found for trend by the quartile risk level of TF predicting CVD mortality, p-value for trend = 0.017. Comparison of the first to fourth quartile of TF antibodies resulted in hazard ratio (HR) = 1.82, 95% confidence interval 1.12-2.94, p = 0.015, adjusted for age, education, diabetes, daily smoking, and systolic blood pressure. Specificity comparing decile 1 to deciles 2-10 of TF predicting mortality was 92.3%. We found an increased HR by low levels of antibodies to the bacterium T. forsythia predicting CVD mortality in a 12 ½ years follow-up in persons who had experienced an MI but not among non-MI men. This novel finding constitutes a plausible causal link between oral infections and CVD mortality.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Prenatal and postnatal parental smoking and acute otitis media in early childhood.

AIM: To explore the associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure. METHODS: Subjects were 32 077 children born between 2000 and 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media. RESULTS: Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0 to 6 months was 4.7% in unexposed children and 6.0% in children exposed both prenatally and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0-6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06-1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared with non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both prenatally and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01-1.52. CONCLUSION: Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood.

Folic acid supplements in pregnancy and early childhood respiratory health.

BACKGROUND: Folate supplementation is recommended for pregnant women to reduce the risk of congenital malformations. Maternal intake of folate supplements during pregnancy might also influence childhood immune phenotypes via epigenetic mechanisms. OBJECTIVE: To investigate the relationship between folate supplements in pregnancy and risk of lower respiratory tract infections and wheeze in children up to 18 months of age. METHODS: In the Norwegian Mother and Child Cohort Study, questionnaire data collected at several time points during pregnancy and after birth on 32,077 children born between 2000 and 2005 were used to assess the effects of folate supplements during pregnancy on respiratory outcomes up to 18 months of age, while accounting for other supplements in pregnancy and supplementation in infancy. RESULTS: Folate supplements in the first trimester were associated with increased risk of wheeze and respiratory tract infections up to 18 months of age. Adjusting for exposure later in pregnancy and in infancy, the relative risk for wheeze for children exposed to folic acid supplements in the first trimester was 1.06 (95% CI 1.03 to 1.10), the relative risk for lower respiratory tract infections was 1.09 (95% CI 1.02 to 1.15) and the relative risk for hospitalisations for lower respiratory tract infections was 1.24 (95% CI 1.09 to 1.41). CONCLUSIONS: Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. The results suggest that methyl donors in the maternal diet during pregnancy may influence respiratory health in children consistent with epigenetic mechanisms.

Residential outdoor air pollution and allergen sensitization in schoolchildren in Oslo, Norway.

BACKGROUND: Epidemiological studies that have investigated the association between air pollution and atopy have found inconsistent results. Furthermore, often exposure to outdoor air pollution has had limited quality, and more individual exposure is needed. OBJECTIVE: To investigate the relations between early and lifetime exposure to residential outdoor air pollution and allergen sensitization in 9-10-year-old children in Oslo, Norway. METHODS: Sensitization to common allergens was measured by skin prick tests (SPTs), which were performed in 2244 children who had lived in Oslo since birth. Several definitions of positive SPT were used. Information on potential confounding variables was collected by a parental questionnaire. Exposure to outdoor air pollution was assessed by the EPISODE dispersion model, which calculates hourly concentrations of nitrogen dioxide (NO2), particulate matter (PM) with aerodynamic diameter <10 microm (PM10) and <2.5 microm (PM2.5), respectively. RESULTS: We found no associations between long-term air pollution exposure and sensitization to any allergen, any indoor or any pollen allergen. However, lifetime air pollution exposure was associated with sensitization to the house dust mite Dermatophagoides farinae. One interquartile increase of lifetime exposure to NO2, PM10 and PM2.5 was associated with 1.88 (adjusted odds ratio) (1.02, 3.47) [95% confidence interval (CI)], 1.61 (0.96, 2.72) and 1.46 (0.96, 2.22), respectively, for D. farinae. Lifetime exposure was also associated with sensitization to cat in a subpopulation. Both associations diminished after adjusting for a contextual socio-economic factor. CONCLUSION: Long-term exposure to traffic-related pollutants was generally not associated with allergen sensitization in 9-10-year-old Oslo children. However, lifetime exposure was associated with sensitization to D. farinae, and with sensitization to cat in a subpopulation, which may be explained by socio-economic confounding or multiple comparisons. The air pollution levels in Oslo may be too low to reveal associations with sensitization.

Outdoor air pollution and bone mineral density in elderly men - the Oslo Health Study.

UNLABELLED: The association between bone mineral density (BMD) and outdoor air pollution has not previously been explored. In this study including 590 elderly men, total body BMD was inversely associated with indicators of air pollution. Further studies to address any relation between air pollution and BMD and bone fracture are warranted. INTRODUCTION: The relation between air pollution and bone mineral density (BMD) is unknown. Based on higher fracture rates and more osteoporosis in urban compared to rural populations, this exploratory study aimed at investigating the association between indicators of air pollution and BMD. METHODS: In an osteoporosis sub-study of the population-based Oslo Health Study (2000-2001) BMD of total body and total hip (mg/cm(2)) was measured by DXA in 590 men 75-76 years old. Exposure to air pollution (particulate matter (PM(10) and PM(2.5)) and nitrogen dioxide (NO(2))) at each participant's home address was estimated from 1992 to 2001. RESULTS: Air pollution was inversely associated with total body BMD, whereas no significant association was found for total hip BMD. The adjusted odds ratio (OR) [95% confidence interval] for low total body BMD (Z-score

Particulate matter properties and health effects: consistency of epidemiological and toxicological studies.

Identifying the ambient particulate matter (PM) fractions or constituents, critically involved in eliciting adverse health effects, is crucial to the implementation of more cost-efficient abatement strategies to improve air quality. This review focuses on the importance of different particle properties for PM-induced effects, and whether there is consistency in the results from epidemiological and experimental studies. An evident problem for such comparisons is that epidemiological and experimental data on the effects of specific components of ambient PM are limited. Despite this, some conclusions can be drawn. With respect to the importance of the PM size-fractions, experimental and epidemiological studies are somewhat conflicting, but there seems to be a certain consistency in that the coarse fraction (PM10-2.5) has an effect that should not be neglected. Better exposure characterization may improve the consistency between the results from experimental and epidemiological studies, in particular for ultrafine particles. Experimental data indicate that surface area is an important metric, but composition may play an even greater role in eliciting effects. The consistency between epidemiological and experimental findings for specific PM-components appears most convincing for metals, which seem to be important for the development of both pulmonary and cardiovascular disease. Metals may also be involved in PM-induced allergic sensitization, but the epidemiological evidence for this is scarce. Soluble organic compounds appear to be implicated in PM-induced allergy and cancer, but the data from epidemiological studies are insufficient for any conclusions. The present review suggests that there may be a need for improvements in research designs. In particular, there is a need for better exposure assessments in epidemiological investigations, whereas experimental data would benefit from an improved comparability of studies. Combined experimental and epidemiological investigations may also help answer some of the unresolved issues.

Association between level of physical activity and lung function among Norwegian men and women: the HUNT study.

OBJECTIVE: To estimate the association between level of physical activity in 1984-1986 and 1995-1997 and lung function in 1995-1997 among Norwegian men and women aged 28-80 years. DESIGN: In 1984-1986 and 1995-1997, all residents of Nord-Trøndelag County, Norway, aged > or =20 years were invited to participate in the Nord-Trøndelag Health Studies. These analyses included a sample that took part in both studies and underwent spirometry (n = 8047). We used linear regression models adjusting for potential confounders stratified by sex and age groups (28-49 years, 50-69 years and > or =70 years) to estimate the association between forced expiratory volume in 1 second (FEV1) and physical activity. RESULTS: Men and women who were physically active in 1985 and 1995 had the highest lung function in both sexes and in all age groups. The reduction in FEV1 ranged from 20 ml to 170 ml, similar to 1-7% of predicted values dependent on physical activity level. Lung function was also associated with body mass index (BMI), height, smoking and subjective health. CONCLUSIONS: The findings show that a high level of physical activity corresponds to about 3-5 years of normal decline in FEV1 (30 ml/year), and may therefore overcome the disadvantages of a decline in FEV1 from increasing age.

Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years.

The aim of the study was to establish whether metabolic syndrome predicts the incidence of prostate cancer. The hypothesis was tested using the 27-year follow-up of the prospective cohort of 16,209 men aged 40-49 years who participated in the Oslo Study in 1972-1973. Men with established diabetes and men with cancer diagnosed before screening were excluded, leaving 15,933 for analyses. Metabolic syndrome is here composed of body mass index, nonfasting glucose, triglycerides, and blood pressure or drug-treated hypertension. Two analytical approaches were compared, namely, predefined (adjusted from National Cholesterol Education Program) and quartile values of risk factors. Age, body mass index, and sedentary versus intermediate physical activity at work were significant predictors in univariate proportional hazards regression analyses. Combinations of any two (relative risk = 1.23; p = 0.04) or any three (relative risk = 1.56; p = 0.00) factors of the metabolic syndrome using quartile values of risk factors were predictive of prostate cancer. The number of cases for four factors was too small for analyses. Predefined values of the risk factors were not found to be predictive. In conclusion, metabolic syndrome was found to predict prostate cancer during 27 years of follow-up, indicating an association between insulin resistance and the incidence of prostate cancer.

Childhood asthma under the north face of Mount Everest.

We assessed prevalences of symptoms of asthma, allergic rhinitis, and atopic eczema and their associations with environmental exposures among school children living in high altitude and rural Tibet. After watching an asthma symptom video, 2.8% of the children reported ever wheezing at rest and 1.4% ever severe wheezing. Residential dampness problems were the only environmental exposure that was clearly associated with children's symptoms (odds ratios 1.3 to 2.5), even if several other exposures were common. The low symptom prevalences are in accordance with the hypothesis that the western lifestyle in some way increases the risk of asthma.

Respiratory infections in schoolchildren: co-morbidity and risk factors.

AIMS: To assess co-morbidity and risk factors for otitis media, tonsillopharyngitis, and lower respiratory infections in school children. METHODS: Logistic regression analysis of co-morbidity and risk factors for airway infections in a population based sample of 10 year old children living in Oslo, Norway. MAIN OUTCOME MEASURES: otitis media, tonsillopharyngitis, and lower respiratory infections in past 12 months. RESULTS: Airway infections in 10 year old children were common, and significant co-morbidity was found between the various airway infections. Home dampness was a risk factor for all infections, adjusted odds ratios ranging from 1.2 (95% CI 1.0 to 1.5) to 1.4 (95% CI 1.1 to 1.6) for otitis media and tonsillopharyngitis respectively. Atopic disease was a constitutional risk factor, particularly strong for lower airway infections (adjusted odds ratio 2.4, 95% CI 1.8 to 3.1). African or Asian ethnicities were associated with the airway infections, adjusted odds ratios ranging from 1.2 (95% CI 0.9 to 1.7) to 1.7 (95% CI 1.2 to 2.3). CONCLUSIONS: Respiratory tract infections were common in 10 year old children. There was substantial co-morbidity between upper and lower airway infections. Environmental and constitutional factors were identified and positively associated with the infections. Results support the hypothesis of 1957 that the whole respiratory tract is one unit.

Allergens and endotoxin in settled dust from day-care centers and schools in Oslo, Norway.

UNLABELLED: Allergy to indoor allergens can cause frequent and severe health problems in children. Because little is known about the content of allergens in the indoor environments in Norway, we wanted to assess the levels of cat, dog and mite allergens in schools and day-care centers in Oslo. Allergen levels in dust samples from 155 classrooms and 81 day-care units were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Additionally, we measured the levels of endotoxin in 31 day-care units, using the limulus amebocyte lysate test. Most of the dust samples contained detectable amounts of cat and dog allergens. In mattress and floor dust (day-care centers), and curtain and floor dust (schools) the median Fel d 1 levels were 0.17, 0.002, 0.02 and 0.079 microg/m2, while the median Can f 1 levels were 1.7, 0.03, 0.1 and 0.69 microg/m2, respectively. Levels of cat and dog allergens in school floor dust were associated with the number of pupils with animals at home. In contrast, <1% of the samples had measurable levels of the mite allergen Der p 1. Moreover, the levels of endotoxin tended to be higher in dust from floors (1.4 ng/m2) compared with that from mattresses (0.9 ng/m2). PRACTICAL IMPLICATIONS: To reduce allergen exposure, allergic individuals should be placed in the classes/rooms with the fewest pet owners. Moreover, mattresses in day-care centers are major reservoirs of cat and dog allergens and should be cleaned frequently.

Day care center characteristics and children's respiratory health.

UNLABELLED: Day care centers provide an important exposure arena with potential harmful health effects for children. This study has linked health effect data from a survey among 942 3-5-year-old Oslo children with information on day care center characteristics collected during inspection of the 175 day care centers these children attended. The aim of the study was to estimate associations between dampness problems and other building characteristics and several respiratory health outcomes. Dampness problems (sign of molds, water leakage, damage to floor/wall) were observed in 51% of the day care centers. In multiple logistic regression analyses none of the studied symptoms and diseases (nightly cough, blocked or runny nose without common cold, wheeze, heavy breathing or chest tightness, the common cold, tonsillitis/pharyngitis, otitis media, bronchitis, pneumonia, asthma, and allergic rhinitis) were systematically associated with dampness problems or type of ventilation in day care centers. None of the studied indicators of day care center exposures were found to have a clear effect on day care children's respiratory health. Even so this study does not rule out negative health effects of day care center exposures. The study demonstrates that population-based studies of these relations are demanding with regard to assessment of exposure and health outcomes. PRACTICAL IMPLICATIONS: Simple and easy-to-register indicators of exposures like dampness problems and type of ventilation assessed in 175 day care centers were not related to respiratory health among 3-5-year-old Norwegian children attending the day care centers. The study does not rule out negative health effects of day care center exposures, but demonstrates methodological challenges needed to be addressed in studies of health effects of the day care environment.

Lung cancer and air pollution: a 27 year follow up of 16 209 Norwegian men.

BACKGROUND: The well documented urban/rural difference in lung cancer incidence and the detection of known carcinogens in the atmosphere have produced the hypothesis that long term air pollution may have an effect on lung cancer. The association between incidence of lung cancer and long term air pollution exposure was investigated in a cohort of Oslo men followed from 1972/73 to 1998. METHODS: Data from a follow up study on cardiovascular risk factors among 16 209 40 to 49 year old Oslo men in 1972/73 were linked to data from the Norwegian cancer register, the Norwegian death register, and estimates of average yearly air pollution levels at the participants' home address in 1974 to 1998. Survival analyses, including Cox proportional hazards regression, were used to estimate associations between exposure and the incidence of lung cancer. RESULTS: During the follow up period, 418 men developed lung cancer. Controlling for age, smoking habits, and length of education, the adjusted risk ratio for developing lung cancer was 1.08 (95% confidence interval, 1.02 to 1.15) for a 10 micro g/m(3) increase in average home address nitrogen oxide (NO(x)) exposure between 1974 and 1978. Corresponding figures for a 10 micro g/m(3) increase in sulphur dioxide (SO(2)) were 1.01 (0.94 to 1.08). CONCLUSIONS: Urban air pollution may increase the risk of developing lung cancer.

Baby swimming increases the risk of recurrent respiratory tract infections and otitis media.

AIM: To estimate the association between baby swimming and recurrent respiratory tract infections and otitis media in the first year of life in children of parents without and with atopy. METHODS: Norwegian schoolchildren (n = 2862) was enrolled in a cross-sectional study of asthma and allergy using the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC). The outcomes were parental retrospective report of recurrent respiratory tract infections and otitis media diagnosed by a physician in the first year of life. The exposure was baby swimming during the same period. Parental atopy reflects a history of maternal or paternal asthma, hayfever or eczema. RESULTS: The prevalence of recurrent respiratory tract infections was higher (12.3%) among children who took part in baby swimming than among those who did not (7.5%). The prevalence of recurrent respiratory tract infections during the first year of life was 5.6% and 10.5%, respectively, in children of parents without and with atopy, whereas the prevalence of baby swimming was 5.6% and 5.1%, respectively, in the two groups. Stratified analysis using parental atopy as strata showed that the increased risk of recurrent respiratory tract infections was only present among children of parents with atopy [adjusted odds ratio (aOR) 2.08, 95% confidence interval (95% CI) 1.08-4.031. A similar trend was present for otitis media (aOR 1.77, 95% CI 0.96-3.25). CONCLUSION: The results of this study suggest that baby swimming and infant respiratory health may be linked. The findings need to be examined in a longitudinal study.

Feasibility of measuring lung function in preschool children.

BACKGROUND: There have been difficulties in applying spirometric tests to children of preschool age. METHODS: The feasibility of measuring lung function was examined in 652 children aged 3-6 years using dynamic spirometry with an animation programme and the guidelines approved by the European Respiratory Society. RESULTS: Data from 603 (92%) children with at least two acceptable forced expiratory manoeuvres were analysed; 408 (68%) achieved at least three acceptable manoeuvres. Children with only two acceptable manoeuvres were younger, shorter, and weighed less (p<0.001). The lower levels of lung function in this group were partly explained by body size. 63% of those with three acceptable manoeuvres had a difference of

The use of a feather quilt, childhood asthma and allergic rhinitis: a prospective cohort study.

BACKGROUND: Feather bedding has long been considered as a potential source of allergen exposure and thus a potential risk factor for allergic diseases. However, recent cross-sectional studies have reported a higher risk of allergic diseases among users of synthetic bedding compared with feather-bedding users. OBJECTIVE: To explore associations between early life exposure to feather bedding and the risk of developing asthma allergic rhinitis in childhood. METHODS: We assessed the association between early life exposure to feather quilts and the risk of bronchial obstruction during the first 2 years of life and asthma and allergic rhinitis in a prospective 4-year cohort study of 2531 Norwegian children. RESULTS: At the age of 6 months, 24% of the children had a quilt with feathers, decreasing to 20% at the age of 2 years. The adjusted odds ratio for bronchial obstruction 0 to 2 years by exposure to a feather quilt at the age of 6 months was 0.59, 95% confidence interval 0.41 to 0.86, for asthma at the age of 4 years 0.38, 0.23 to 0.64 and for allergic rhinitis at the age of 4 years 0.73, 0.43 to 1.18. CONCLUSION: The use of a feather quilt in early life does not seem to increase the risk of asthma and allergic rhinitis later in childhood.

Physical activity affects the prevalence of reported wheeze.

The present study examines whether physical activity level (hours per week) among children with and without asthma are associated with the prevalence of reported wheezing and whistling in the chest in the last 12 months. The data are based on a survey of school children, aged 7-16 years (n = 2188), in Oslo in 1994 that employed the ISAAC questionnaire. In children reporting asthma, wheezing and whistling in the chest in the last 12 months was less prevalent among inactive children (66.7%) compared to those who exercised (89.4%) (p = 0.05). The prevalence of wheeze also differed among inactive (4.4%) and active (8.8%) children not reporting asthma (p = 0.02). Positive associations between physical activity and wheezing and whistling in the chest remained present using multiple logistic regression analysis adjusting for sex, age and atopy. Children who are engaged in sports or exercise seem to report asthma symptoms differently than inactive children. These findings raise the question whether level of physical activity could affect some of the variability in reported asthma symptoms when such morbidity is measured as 'wheeze in last 12 months'.

Relation between occurrence of type 1 diabetes and asthma.

A negative association has been observed between type 1 diabetes and atopic diseases in individuals, a finding that supports the Th1/Th2 paradigm. By using published data on disease occurrence in different countries, we show a strong positive association between the occurrence of type 1 diabetes and symptoms of asthma at the population level in Europe and elsewhere. Our finding suggests that there may be common factors influencing susceptibility to the two disorders at the country level. Our observation must be accommodated in explanations of the epidemiology of type 1 diabetes or atopic diseases.

Environmental tobacco smoke, parental atopy, and childhood asthma.

We hypothesized that the joint effect of genetic propensity to asthma and exposure to environmental tobacco smoke on the risk of childhood asthma is greater than expected on the basis of their independent effects. We performed a population-based 4-year cohort study of 2,531 children born in Oslo, Norway. We collected information on the child's health and environmental exposures at birth and when the child was 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma at the age of 4 years. Parental atopy was defined as a history of maternal or paternal asthma or hay fever. Exposure to environmental tobacco smoke was defined on the basis of questionnaire information on household smokers at birth. In logistic regression analysis adjusting for confounding, parental atopy alone increased the risk of bronchial obstruction [odds ratio 1.62; 95% confidence interval (CI) 1.10-2.40] and asthma (1.66; 95% CI, 1.08-2.54). In children without parental atopy, there was little effect of exposure to environmental tobacco smoke on bronchial obstruction (1.29; 95% CI, 0.88-1.89) and asthma (0.84; 95% CI, 0.53-1.34). The presence of parental atopy and exposure had a substantial effect both on bronchial obstruction (2.88; 95% CI, 1.91-4.32) and asthma (2.68; 95% CI, 1.70-4.22). The results are consistent with the hypothesized joint effect of parental atopy and exposure to environmental tobacco smoke. This phenomenon--denoted as effect modification of environmental exposure by genetic constitution, or gene by environment interaction--suggests that some genetic markers could indicate susceptibility to environmental factors.