Air Pollution, Inflammation and New Onset Asthma

空气污染、炎症和新发哮喘

• 批准号: 7112414
• 负责人: FRANK D. GILLILAND
• 金额: $ 72.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112414
• 关键词: air pollution; asthma; breath tests; clinical research; disease /disorder etiology; disease /disorder onset; disease /disorder proneness /risk; environmental exposure; genetic susceptibility; genotype; human genetic material tag; human subject; inflammation; middle childhood (6-11); nitric oxide; oxidative stress; pollution related respiratory disorder; respiratory disorder epidemiology

DESCRIPTION (provided by applicant): Ambient air pollution is well accepted as a cause of asthma exacerbations, but its role in the etiology of new onset asthma is less clear. Evidence for an etiologic role of ambient air pollutants is emerging from epidemiologic studies; however, the ecologic patterns of increasing asthma prevalence concurrent with decreasing levels of some pollutants have raised questions about the validity of these associations. A better understanding of the biological processes that mediate the effects of ambient air pollution on asthma occurrence is likely to contribute to answering these questions. Chronic oxidative/nitrosative stress and airway inflammation are probably critical processes in asthma etiology and these inter-related processes may mediate the increased asthma risk from air pollution. In this application, we propose to use exhaled NO (eNO), to study the role of inflammation and oxidative/nitrosative stress in the pathobiology of new onset asthma, with a focus on ambient air pollution and genetic susceptibility. We choose ambient pollutants based on potential contribution to oxidative/nitrosative stress (O3; particulates (PM10 and PM2.5 and their chemical constituents, particle counts, NOx (NO and NO2), acid vapors; and fresh tailpipe emissions). The primary hypotheses to be assessed in the proposed program of research are: 1) children with high ambient air pollution exposures have chronic airway inflammation as indicated by elevated eNO. 2) susceptibility to airway inflammation and oxidative/nitrosative stress from ambient air pollution varies by NOS1, NOS2. NOS3. GSTM1. GSTP1. NQO1, and HO-1 haplotypes and functional variants, and 3) children with chronic airway inflammation as indicated by elevated eNO are at increased risk for new onset asthma. To test these hypotheses, the proposed study builds on the population resource of the Asthma Incidence Risk (AIR) study, an ongoing prospective cohort study of the determinants of new onset asthma in 6000 children in 13 southern California communities, and an extensive program of ambient air pollution exposure characterization in these communities. In this application, we propose to measure eNO using off-line techniques and to genotype 3000 children from the AIR cohort. A number of resources will enhance the proposed study, including the Children's Environmental Health Center, the Molecular Biology Core of Southern California Environmental Health Sciences Center, and expertise from the Southern California Particle Center and Supersite. The findings from the proposed research program is likely to contribute to resolving uncertainties about the effects of air pollution on asthma risk, provide new tools for identifying children at highest risk for asthma and aid in asthma prevention efforts.

描述（由申请人提供）：环境空气污染被广泛接受是哮喘恶化的原因，但其在新发作哮喘的病因中的作用尚不清楚。环境空气污染物的病因作用的证据是流行病学研究的出现。然而，随着某些污染物水平降低，增加哮喘患病率的生态模式引发了有关这些关联有效性的问题。更好地了解介导环境空气污染对哮喘发生影响的生物学过程可能有助于回答这些问题。慢性氧化/亚硝化应激和气道炎症可能是哮喘病因中的关键过程，这些相关过程可能会介导空气污染中增加的哮喘风险。在此应用中，我们建议使用呼出的NO（ENO）研究炎症和氧化/亚硝化应激在新发作哮喘的病理生物学中的作用，重点是环境空气污染和遗传易感性。我们根据对氧化/亚硝化应激的潜在贡献选择环境污染物（O3；颗粒（PM10和PM2.5及其化学成分，颗粒计数，NOX（NO和NOX），酸蒸气），酸性蒸气；以及新鲜的尾管排放）。与拟议中的概述有关：1）的主要假设是：1）：1）概述的是：1）概述的儿童：1）概述的儿童是：1）空中的范围是：1）：1）空中概述的是：1）升高的Eno。 2）对环境空气污染的气道炎症和氧化/亚硝化应激的敏感性因NOS1，NOS2而异。 NOS3。 GSTM1。 GSTP1。 NQO1，HO-1单倍型和功能变体，以及3）慢性气道炎症儿童如升高的ENO所示，新发作哮喘的风险增加。为了检验这些假设，拟议的研究基于哮喘发病率风险（AIR）研究的人口资源，这是一项对13个南加州社区6000名儿童的新发作哮喘决定因素的前瞻性队列研究，以及这些社区环境空气污染暴露的广泛计划。在此应用程序中，我们建议使用离线技术和来自空气队列的3000名儿童进行测量ENO。许多资源将增强拟议的研究，包括儿童环境健康中心，南加州环境健康科学中心的分子生物学核心以及南加州粒子中心和超级站点的专业知识。拟议的研究计划的发现可能有助于解决有关空气污染对哮喘风险影响的不确定性，提供新的工具，以识别哮喘最高风险的儿童并帮助预防哮喘。