The aim of this project is to examine prospectively the role of diet, environmental, and genetic factors, along with their interactions, in determining the risk of developing asthma and chronic bronchitis in a cohort of over 63,000 older adults of Chinese ethnicity in Singapore. We have expanded the scope of a cohort study, established with NCI funding to examine the relation between diet and cancer, to include asthma and chronic bronchitis as outcomes. At baseline enrollment, the cohort completed a detailed interviewer administered dietary questionnaire developed specifically for, and validated in, this population. We have added questions to the follow-up questionnaire on asthma and chronic bronchitis. We are now examining associations between diet at baseline and the development of asthma and chronic bronchitis. Our primary hypotheses are that higher intake of fruits and anti-oxidant micronutrients reduce the risk of developing asthma and chronic bronchitis. There is suggestive evidence for a role of diet in the etiology of asthma and chronic bronchitis. However, there are few prospective data. Oxidative stress from production of free radicals in the lung appears to play a role in the pathogenesis of both asthma and COPD. Given the potential importance of oxidative stress in the pathogenesis of asthma and COPD, antioxidants may be useful for preventing illness and decreasing morbidity. There is evidence from primarily cross-sectional data that intakes of anti-oxidant micronutrients (vitamins C and E) are protective for asthma and chronic obstructive pulmonary disease in adults. In addition, there is evidence that fruit intake, may be important, independent of a contribution of vitamin C, suggesting that other nutrients in fruit may be important. There is strong evidence for a role of genetics in the etiology of asthma and increasing evidence for a role in chronic obstructive pulmonary disease, including chronic bronchitis. There are few data on interactions with smoking but some recent suggestive data. There are no data on potential interactions between genetic factors and diet in relation to these disorders. Genes involved in processes of inflammation and oxidative stress are candidates for interaction with dietary anti-oxidants. This population is of particular interest because the Chinese women in Singapore and elsewhere have been reported to have high rates of chronic bronchitis in the face of low levels of smoking. The reason for this pattern is unknown. This Chinese population differs dramatically in dietary intakes compared to Western populations that have been the focus of studies of diet and nonmaligant respiratory disease. Administration of the telephone follow-up questionnaire, which contains the asthma and chronic bronchitis questions, has been completed by than 30,000 subjects, about half of the cohort. Adminstration will be completed over the next two years. In addition, blood or buccal cells are being collected on the cohort. We have begun preliminary analyses of the relation between dietary intakes at baseline and the development of asthma and chronic bronchitis. Prelminary results for asthma, presented at the international conferences of the American Thoracic Society and International Society for Environmental Epidemiology show a protective effect of fruit intake. This association is seem for both citrus and noncitrus fruits suggesting that nutrients other than vitamin C contained in fruit may be important. We have found similar associations for chronic bronchitis. We completed a proposal to expand this collaboration with the Singapore Chinese Cohort to study diet, smoking, genetics and their interactions in relation to asthma and chronic bronchitis. The proposal includes outcome validation. This proposal was favorably reviewed by four outside experts and approved for funding.