This Program Project proposal is submitted to request funding for 4 research Projects and 4 supporting Cores building on the Children?s Health Study, an ongoing cohort study of some 6,000 children from 12 communities in Southern California which has yielded a wealth of data on the chronic effects of air pollution, but the results leave open questions that need further attention. The 4 Projects address the question of whether the observed changes in pulmonary function persist to adulthood, involve studying asthma incidence with the goal of identifying environmental and host factors, examine the genetic variation in oxidative stress pathways that modulate response to air pollution, and develop new biostatistical methods. Core 1 provides field logistics and technical support for the data collection, Core 2 provides biostatistical and data management support, Core 3 obtains data needed for exposure assessment, and Core 4 provides the genotyping and sample storage capability. Combining the 4 Projects into one Program Project promotes the interdisciplinary activity required to tackle complex projects while creating efficiencies that take advantage of existing resources and cores. The major hypotheses are: (1) Oxidative stress is the main biological pathway by which air pollution leads to adverse respiratory effects. Specific pollutants that give rise to reactive oxygen species (ROS) will have the greatest effects and these effects will be modified by genes involved in xenobiotic metabolism, inflammatory oxidant production, antioxidant production, ROS metabolism, and detoxification of oxidation products. Dietary antioxidant intake and other lifestyle factors such as physical activity will also modify these effects. (2) Pollutants contributing to these long-term effects are combustion-related and the biggest contributor is derived from motor vehicle emissions, and that the contributions from diesel emissions and freshly emitted automobile emissions can be distinguished by measurements of relevant markers such as fine elemental carbon (EC) particles and carbon monoxide (CO) and by spatial modeling of traffic density. (3) The respiratory effects of air pollution are multifaceted and interrelated. Thus, air pollution has effects on pulmonary function, on chronic respiratory diseases such as asthma, and on the frequency of respiratory illnesses. (4) The effects of air pollution on lung function and respiratory disease are irreversible and lead to permanent deficits continuing into adulthood.
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