Asthma and respiratory infection pose major burdens to child health. Prenatal tobacco exposure is a key risk factor for wheeze in young children, but there is little data about the relationship of prenatal low level exposures to tobacco (e.g. passive exposure of nonsmoking pregnant women) with risk of childhood wheeze or respiratory infection. There is emerging, yet limited evidence for novel environmental risk factors for wheeze such as phthalates. Advances in biomarkers offer an ability to quantify indicators of internal dose directly, reduce exposure misclassification, and enhance our ability to link exposures with disease. The primary objective for this K23 proposal is to rigorously characterize the relationship of common environmental exposures with risk of wheeze and respiratory infection in early childhood using serial biomarkers of exposure. The specific aims are to: 1) Test which measure of prenatal tobacco smoke exposure (different biomarkers, parent-report) is most strongly associated with risk of wheeze, respiratory infection, and pulmonary inflammation (fraction of exhaled nitric oxide, FeNO) in the first three years of life; 2) Investigate the association of low levels of maternal passive tobacco smoke exposure during pregnancy with risk of wheeze, respiratory infection, and pulmonary inflammation (FeNO) in children of nonsmoking mothers in the first three years of life; and 3) Investigate the association of prenatal phthalate exposure with risk of wheeze, respiratory infection, and pulmonary inflammation in the first three years of life. This proposal is novel because it uses serial biomarkers to measure individual exposure burden and low levels of exposure objectively throughout pregnancy and early childhood. Additionally, we will be the first to explore the role of prenatal phthalate exposure with the risk of childhood wheeze, respiratory infection, and pulmonary inflammation using biomarkers. Through this K23, the applicant will develop expertise in pediatric environmental epidemiology to position him to help broaden the model of environmental toxicology and respiratory epidemiology in children. It will also provide the background and training needed to develop an independent research career in clinical pediatrics and enhance our understanding of how environmental risk factors affect the development and exacerbation of pediatric asthma and respiratory disease and integrate this knowledge into prevention and treatment efforts. ExpandCollapse Abstract