To investigate the effects of environmental factors (including diet) on respiratory health in adults, and their interactions with genetic factors, we have established several high-quality population resources. ? ? The first population is a cohort of 63,000 older adults of Chinese ethnicity in Singapore. The cohort was established with NCI extramural funding to examine the relationship between diet and cancer. We have expanded the study to include the assessment of asthma and chronic bronchitis and expanded questions on environmental exposures. The Singapore Chinese cohort is of particular interest because of the prospective collection of risk factor data. Another major strength of the study is the high quality dietary assessment, which was developed specifically for, and validated in, this population. The Singapore cohort also follows dietary patterns quite distinct from the Western populations included in existing adult respiratory studies. Other strengths of the study are the large proportion of nonsmokers and the availability of genetic samples. We have previously published findings from this cohort on environmental tobacco smoke, dietary patterns, dietary fiber and occupational exposures in this cohort. Notably, our was the first study to report on examine dietary patterns in relation to nonmalignant respiratory disease and others have subsequently replicated our findings. We have also found that dietary fiber is protective for incident asthma and are writing up this publication. A second wave of active follow-up is currently ongoing. When this is completed, we will be able to examine genetic by environment interactions to follow-up these questionnaire based findings. ? ? We are also collaborating with another extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We added the assessment of exposure to traffic to this dataset and have examined this surrogate of traffic related air pollution in relation to respiratory and cardiovascular endpoints. We have found that higher exposure to traffic was related to lower pulmonary function (Kan et al, 2007 - reported in previous annual report) and myocardial infarction (Kan et al, EHP, in press). We will be examining the association with deep venous thrombosis when case validation is complete. ? ? In the ARIC study, we have also followed up our findings some Singapore regarding the protective effect of fiber. In the ARIC cohort, we found that higher fiber intake was associated with better lung function and a lower prevalence of chronic obstructive pulmonary disease (Kan et al. 2008). This association, as well as the association in the Singapore study, were independent of a wide range of confounders as well as intakes of antioxidants. This finding is especially important because there are many reports of protective effects of antioxidant vitamins but none have considered or adjusted for fiber. We also found that fiber was protective against retinal microvascular abnormalities, an intermediate endpoint for cardiovascular disease (Kan et al. AJCN 2007). ? ? Having found both traffic exposure and fiber intake to be associated with pulmonary function, we wish to identify gene by environment interactions that could underlie these findings. To do this, we will work with the whole genome association data generated by ARIC. Genotyping for one million single nucleotride polymorphisms (Affymetrix platform) has recently been completed. We are involved in the writing group that will examine genetic main effects on pulmonary function. We have also received approval for manuscript proposals looking at whole genome by environment interaction with each of the two exposures diet and traffic. We anticipate receiving the data in FY2009 and will benefit from the analysis expertise that we are gaining with our whole genome association study of asthma in children. ? ? Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We were therefore interested in improving our phenotype data to understand these observations better. To this end, I have designed a new data collection, with Dr. Hoppin, to obtain objective measures of asthma phenotypes (including spirometry before and after bronchodilator, exhaled nitric oxide, and atopic status by specific IgE) on likely cases of asthma in cohort and a sample of the cohort for a comparison group. We will also obtain DNA and store other biologic samples on this nested case-cohort study. Subject enrollment is expected to begin in early 2009. Because of the major scope of this project, it now has a separate annual report where it is described in greater detail - ES102385-01. ? ? The third population is the NIEHS Sister Study. This NIEHS cohort will have 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is still being enrolled. ? ? In collaboration with investigators at the EPA-UNC Human Exposure Facility, I have established a study to follow-up on recent experimental work showing that obese mice have greater respiratory response to ozone than lean mice. This work also follows up our recent finding that subjects with higher BMI have greater drop in pulmonary function (FEV1) in response to acute ozone exposure(Bennett et al., Inhalation Toxicology, 2007). We have established an experimental study where we expose centrally obese and lean women to ozone and measure spirometry, air resistance, airway hyperresonsiveness and inflammatory responses to the exposure. Enrollment is approximately 30% complete for this study.
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