Air Pollution, Inflammation and New Onset Asthma

描述（由申请人提供）：环境空气污染已被广泛接受为哮喘加重的原因，但其在新发哮喘病因学中的作用尚不清楚。流行病学研究中出现了环境空气污染物的病因学作用的证据；然而，哮喘患病率上升与某些污染物水平下降的生态模式对这些关联的有效性提出了质疑。更好地了解调节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的关键过程，这些相互关联的过程可能介导空气污染引起的哮喘风险增加。在本应用中，我们建议使用呼出NO （eNO）来研究炎症和氧化/亚硝化应激在新发哮喘病理生物学中的作用，重点关注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（O3）、颗粒物（PM10和PM2.5及其化学成分）、颗粒物计数、氮氧化物（NO和NO2）、酸性蒸气；以及新的尾气排放)。在拟议的研究计划中要评估的主要假设是：1)高环境空气污染暴露的儿童有慢性气道炎症，这表明eNO升高。2)不同NOS1、NOS2对气道炎症和氧化/亚硝化应激的易感性不同。NOS3。GSTM1基因。问题。NQO1、HO-1单倍型和功能变异体，以及3)eNO升高提示的慢性气道炎症患儿新发哮喘的风险增加。为了验证这些假设，提出的研究建立在哮喘发病率风险（AIR）研究的人口资源基础上，这是一项正在进行的前瞻性队列研究，研究了13个南加州社区6000名儿童新发哮喘的决定因素，以及这些社区环境空气污染暴露特征的广泛计划。在这项应用中，我们建议使用离线技术测量eNO，并对来自AIR队列的3000名儿童进行基因分型。许多资源将加强拟议的研究，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Supersite的专业知识。拟议研究项目的发现可能有助于解决空气污染对哮喘风险影响的不确定性，为识别哮喘风险最高的儿童提供新的工具，并有助于哮喘预防工作。

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.