The proposed study will determine whether early childhood exposures to phthalates are associated with the development of current asthma and proallergic immunoglobulin (Ig) E production at ages five to seven and whether current exposures to phthalates are associated with augmented airway inflammation and diminished lung function at ages five to seven. The research will confirm or refute recent epidemiologic findings of associations between phthalate exposures and childhood asthma, atopy and reduced lung function. This prior research is limited by incomplete exposure and outcome measures. However, results from a pilot undertaken for the proposed study also support the hypothesis that phthalate exposures are risk factors in the development of asthma. The proposed study will be conducted among a cohort of 400 children who reside in minority communities in New York City. These communities experience some of the highest childhood asthma rates in the world. Phthalate exposures are also widespread. The research will be performed within the ongoing longitudinal birth cohort study being conducted by the Columbia Center for Children's Environmental Health (CCCEH). The CCCEH is evaluating the contribution of prenatal and postnatal exposures in the development of asthma and other health outcomes. Children are followed from pregnancy through age seven years. The proposed research is cost effective in that many of the required exposure and outcome measurements are already being gathered within the CCCEH cohort. These include detailed history of respiratory and allergic symptoms, asthma treatment and emergency room visits; lung function testing at age six; allergen levels in house dust samples collected from pregnancy through age five; and measurement of allergic sensitization (total and specific IgE measured at ages two, three, and five years). The phthalates will be measured in stored urine samples collected from the mother during pregnancy and from children at ages three and five years and in newly collected indoor air and urine samples at ages five to seven. Also at age five to seven years, exhaled nitric oxide will be measured as an indicator of airway inflammation and total and allergen-specific IgE levels will be determined. The case ascertainment of current asthma at ages five to seven will be made by a designated board- certified pediatric pulmonologist at the Morgan Stanley Children's Hospital of New York Presbyterian Hospital. Hypotheses to be tested are: (1) that early childhood exposures to the phthalates, as measured by metabolite levels in urine samples collected during pregnancy and at ages three and five years, predict current asthma at ages five to seven and production of IgE antibodies at age seven; and (2) after correcting for early phthalate exposure, current exposure as measured by levels of the parent compounds in indoor air samples and metabolites in urine samples collected at ages five to seven years, will be associated inversely with lung function and positively with airway inflammation at ages five to seven years. ? ? ? ?
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