The Role of Airborne PAHs and DEP in the Pathogenesis of Childhood Asthma

This proposal is submitted in response to the RFA-ES-06-001 DISCOVER initiative. The fetus and young child have physiologic, developmental, metabolic, and behavioral patterns that make them uniquely vulnerable to hazards in their environments. Ambient air pollution has been implicated as a major risk factor for asthma and asthma exacerbation, however epidemiological studies have been hampered by uncertainties in exposures and the nature of airway responses. The Columbia Center for Children's Environmental Health (CCCEH) Disease Investigation through Specialized Clinically-Oriented Ventures in Environmental Research (DISCOVER) seeks to understand when and how airborne polycyclic aromatic hydrocarbons (PAHs) and diesel exhaust particles (DEP) increase the risk for childhood asthma and airway inflammation, develop new biomarkers to identify children at risk and improve clinical treatment, evaluate the success of a public policy intervention, and implement physician education initiatives as a mode of intervention. This proposal includes four closely linked projects and Administrative and Data Management and Biostatistics Cores each ensuring the seamless coordination of the multiple research activities involved in this proposal. The cores play vital roles in the quality of research information and statistical analyses and the administrative/financial oversight and translational components of the four main DISCOVER research project initiatives. The four project aims are: 1) Take advantage of repeat PAH measurements pre- and post-natally to distinguish between the biological effects of prenatal PAH exposure versus postnatal exposure during early childhood and pre-adolescence;2) To advance the understanding of the influence of diesel exhaust exposures, which include PAHs, in acute asthma exacerbations by linking innovative exposure and outcome measures;3) To determine whether epigenetic changes related to PAH exposure are involved in the pathogenesis of childhood asthma;4) To ascertain if traffic related PAHs affect B2AR function in airway smooth muscle cells in vitro, alter B2AR function following in utero and early life exposures, affect B2AR expression and function in airway epithelial cells in vitro. The research is translational to asthma prevention, clinical treatment, physician education, and policy.