Windows of Susceptibility to PAH/DEP Exposure and Asthma

本提案是根据RFA-ES-06-001 DISCOVER倡议提交的。胎儿和幼仔 儿童具有生理、发育、代谢和行为模式，使他们独特 易受环境中的危害。环境空气污染是一个主要的危险因素 对于哮喘和哮喘加重，然而流行病学研究受到以下因素的阻碍： 暴露的不确定性和气道反应的性质。 哥伦比亚儿童环境卫生中心（CCCEH）疾病调查， 环境研究专业临床导向风险投资（DISCOVER）旨在了解 空气中的多环芳烃（PAHs）和柴油机尾气颗粒物（DEP） 增加儿童哮喘和气道炎症的风险，开发新的生物标志物来识别儿童 风险和改善临床治疗，评估公共政策干预的成功，并实施 医生教育举措作为一种干预模式。 该提案包括四个密切相关的项目，以及一个行政和数据管理项目， 每个生物统计学核心都确保了参与此研究的多个研究活动的无缝协调。 提议核心对研究信息和统计分析的质量以及 DISCOVER四个主要研究项目的行政/财务监督和翻译部分1 举措该项目的四个目标是：1）利用产前和产后的重复PAH测量 区分产前PAH暴露与产后暴露的生物学效应， 2）提高对柴油机尾气影响的认识 通过将创新暴露与结果联系起来， 3）确定与PAH暴露相关的表观遗传变化是否参与了 研究交通相关多环芳烃对儿童哮喘发病机制的影响; 4）交通相关多环芳烃对儿童哮喘气道[32] AR功能的影响 体外平滑肌细胞，改变|子宫内和生命早期暴露后的32AR功能影响P2 AR 在体外气道上皮细胞中的表达和功能。这项研究可以转化为哮喘预防， 临床治疗、医师教育和政策。

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 both an Administartive and Data Management and Biostatistics Core each ensuring the seamless coordintion of the multiple research acivities 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 components1 of the fourmain 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 [32AR function in airway smooth muscle cells in vitro, alter |32ARfunction following in utero and early life exposures, affect P2AR expression and function in airway epithelial cells in vitro. The research is translational to asthma prevention, clinical treatment, physician education, and policy.