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

空气中的 PAH 和 DEP 在儿童哮喘发病机制中的作用

• 批准号: 7922993
• 负责人: FREDERICA P PERERA
• 金额: $ 21.22万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922993
• 关键词: Role; Airborne; PAHs; DEP; Pathogenesis

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.

描述(由申请人提供) 本提案是为了响应RFA-ES-06-001发现倡议而提交的。胎儿和幼儿具有生理、发育、代谢和行为模式，这使他们在环境中特别容易受到危险的影响。环境空气污染被认为是哮喘和哮喘加重的主要危险因素，然而，暴露和呼吸道反应性质的不确定性阻碍了流行病学研究。哥伦比亚儿童环境健康中心(CCCEH)通过专门的面向临床的环境研究风险投资(DISCOVE)进行疾病调查，旨在了解空气中的多环芳烃(PAHs)和柴油废气颗粒物(DEP)何时以及如何增加儿童哮喘和呼吸道炎症的风险，开发新的生物标记物来识别高危儿童和改善临床治疗，评估公共政策干预的成功，并将医生教育计划作为一种干预模式实施。该提案包括四个密切相关的项目以及行政和数据管理以及生物统计核心，每个核心都确保了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四个主要发现研究项目倡议的行政/财务监督和翻译部分中发挥着至关重要的作用。这四个项目的目标是：1)利用出生前和出生后重复测量多环芳烃的优势，区分出生前多环芳烃暴露和出生后儿童早期和青春期前多环芳烃暴露的生物效应；2)通过将创新的暴露和结果措施联系起来，促进对包括多环芳烃在内的柴油尾气暴露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变化是否参与儿童哮喘的发病机制；4)探讨交通相关多环芳烃是否影响体外培养的气道平滑肌细胞的β2AR功能，改变宫内和生命早期暴露后的气道上皮细胞的功能，影响体外培养的呼吸道上皮细胞的受体表达和功能。这项研究将转化为哮喘预防、临床治疗、医生教育和政策。 计划的综合性(临床和基础)和跨学科性质 描述：哥伦比亚大学佩雷拉博士提交的发现中心的目标是扩大现有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(PAHs)和柴油废气颗粒物(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记物，以识别高危儿童和改善临床治疗，评估公共政策干预的成功，并将医生教育倡议作为干预模式实施。