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

描述（由申请人提供） 本提案是根据RFA-ES-06-001 DISCOVER倡议提交的。胎儿和幼儿具有生理、发育、代谢和行为模式，使他们特别容易受到环境中危害的影响。环境空气污染已被认为是哮喘和哮喘恶化的主要危险因素，然而，流行病学研究受到暴露和气道反应性质的不确定性的阻碍。哥伦比亚儿童环境健康中心（CCCEH）通过环境研究中的专门临床导向风险投资进行疾病调查（DISCOVER）旨在了解空气中的多环芳烃（PAH）和柴油机尾气颗粒物（DEP）何时以及如何增加儿童哮喘和气道炎症的风险，开发新的生物标志物以识别风险儿童并改善临床治疗，评估公共政策干预的成功，并将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行政和数据管理和生物统计核心，每个核心都确保该提案所涉及的多项研究活动的无缝协调。这些核心在研究信息和统计分析的质量以及DISCOVER四个主要研究项目倡议的行政/财务监督和翻译组成部分方面发挥着至关重要的作用。该项目的四个目标是：1）利用出生前和出生后的重复PAH测量，以区分出生前PAH暴露与出生后儿童早期和青春期前暴露的生物学效应; 2）通过将创新的暴露与结果措施联系起来，促进对柴油机废气暴露（包括PAH）在急性哮喘加重中的影响的理解; 3）确定与多环芳烃暴露相关的表观遗传学改变是否参与儿童哮喘的发病机制; 4）确定交通相关的多环芳烃是否影响？2体外培养的气道平滑肌细胞AR功能，改变（？）2AR功能在子宫内和生命早期暴露后，影响（？2体外培养气道上皮细胞AR的表达及功能。这项研究是转化为哮喘预防，临床治疗，医生教育和政策。 综合性（临床和基础）和跨学科性质 产品描述：由哥伦比亚大学佩雷拉博士提交的DISCOVER中心的目标是扩大现有的哥伦比亚儿童环境健康中心（CCCEH）的工作，以了解空气中的多环芳烃（PAH）和柴油机尾气颗粒（DEP）如何以及何时增加儿童炎症和哮喘的风险。该中心还将开发新的生物标志物，以识别风险儿童并改善临床治疗，评估公共政策干预的成功，并实施医生教育倡议作为干预模式。

DESCRIPTION (provided by applicant) 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 ?2AR function in airway smooth muscle cells in vitro, alter (?2AR function following in utero and early life exposures, affect (?2AR expression and function in airway epithelial cells in vitro. The research is translational to asthma prevention, clinical treatment, physician education, and policy. INTEGRATED (clinical and basic) and INTERDISCIPLINARY NATURE OF PROGRAM Description: The goal of the DISCOVER Center submitted by Dr. Perera, Columbia University, is to expand the work of the existing Columbia Center for Children's Environmental Health (CCCEH) to understand how and when airborne polycyclic aromatic hydrocarbons (PAHs) and diesel exhaust particles (DEP) increase the risk for childhood inflammation and asthma. The Center will also develop new biomarkers to identify children at risk and improve clinical treatment, evaluate the success of a public policy intervention and implement physician education initiative as a mode of intervention.