Smoking is clearly the major cause of chronic obstructive pulmonary disease in adults but other environmental factors including ambient air pollution, environmental tobacco smoke, occupational exposures, and diet play a role. High quality data on these exposures in relation to the development of airway obstruction in adults is limited, especially prospective data. These same environmental factors also are important in the etiology of asthma in adults. Genetic factors likely play a role in modulating the effects of diet, smoking, occupational exposures, and ambient pollution on the risk of cardiac and respiratory outcomes in adults. Genetic factors may influence the metabolism of nutrients in food that are responsible for health effects. Both diet and genetics may combine to influence susceptibility to adverse effects of air pollution. Effects of air pollution are likely to be weak when averaged over whole populations and identification of susceptibility factors will help to clarify health consequences of air pollution. To investigate the effects of environmental factors we are establishing several high-quality population resources to prospectively investigate effects of air pollution, diet, genetics and their interactions in relation to asthma and COPD in adults. 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. I have expanded the study to include the assessment of asthma and chronic bronchitis and expanded the assessment of 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. We are currently working on analyses of incident asthma and are following the cohort for the development of additional incident respiratory endpoints. The second study is a collaboration with another extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study. We are examining traffic-related air pollution in relation to a range of respiratory and cardiovascular endpoints. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiac and respiratory phenotypes including pulmonary function and retinal examination data. We have observed associations between a valid surrogate of traffic related air pollution and both pulmonary function (Kan et al., Thorax 2007 epub) and incident myocardial infarction (soon to be submitted). We have also found that fiber is protective against impairment of pulmonary function and chronic bronchitis and that this protection is independent of intake of antioxidant vitamins (submitted, in revision). These data confirm our finding from the previous year in the Singapore cohort and are important because virtually no one else has examine the role of fiber in these conditions whereas there are many reports of protective effects of antioxidant vitamins. In the past year, we have also discovered that fiber is protective against retinal microvascular abnormalities, an intermediate endpoint for cardiovascular disease (in press). I continue to collaborate with Jane Hoppin and others at NIEHS and NCI on examination of agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study, a large cohort of farmers and their spouses in Iowa and North Carolina. To date, Dr. Hoppin has 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 been closely involved in two efforts. The first is improved questionnaire assessment of respiratory outcomes on the current wave of cohort follow (Phase III). The second approach is to design a study where we would 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 would also obtain DNA on this nested case-cohort study. The goal of this study is to examine in greater detail that we have previously been able to with questionnaire data several hypothesis. The first is related to the hygiene hypothesis of asthma suggesting that early exposures to pathogen associated molecular patterns (such as endotoxin, beta-glucans and peptidoglycans) whereas later exposures may be deleterious. The second hypothesis is that exposure to pesticides is related to development of asthma. Central to both hypotheses is the examination of interaction with genes likely to be involved in pathways of response to these two classes of agents.
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