Air Pollution, Inflammation and New Onset Asthma

空气污染、炎症和新发哮喘

• 批准号: 7254062
• 负责人: FRANK D. GILLILAND
• 金额: $ 69.35万
• 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/7254062
• 关键词: Acids; Address; Adult; Air Pollutants; Air Pollution; Allergens; Antioxidants; Aromatic Polycyclic Hydrocarbons; Asthma; Biological Process; Birth; California; Candidate Disease Gene; Chemicals; Child; Childhood Asthma; Chronic; Clinical; Cohort Studies; Collection; Communities; Community Services; Count; Data; Development; Diagnosis; Environmental Health; Epidemiologic Studies; Etiology; European; Exhalation; Exposure to; GSTM1 gene; GSTP1 gene; Gases; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Immune; Impairment; Incidence; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Intervention Studies; Link; Measurement; Measures; Mediating; Metabolism; Molecular Biology; NAD(P)H dehydrogenase (quinone) 1, human; NOS1 gene; NOS1 protein, human; NOS2A gene; NOS3 gene; NQO1 gene; Nitric Oxide; Nitrogen; Numbers; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; Particulate; Pattern; Personal Satisfaction; Phase; Play; Population; Predisposition; Prevalence; Prevention; Process; Prospective Studies; Public Health; Quinones; Research; Research Personnel; Resources; Respiratory System; Risk; Role; Sampling; School-Age Population; Stress; Structure; Techniques; Testing; Time; Transition Elements; Uncertainty; Variant; Wheezing; airway inflammation; atopy; base; benzoquinone; cohort; design; experience; glutathione S-transferase M1; glutathione S-transferase pi; human NOS2A protein; human NOS3 protein; improved; innovation; particle; pollutant; programs; prospective; research study; response; tool; trafficking; vapor

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）：环境空气污染被公认为哮喘急性发作的原因，但其在新发哮喘病因学中的作用尚不清楚。从流行病学研究中发现了环境空气污染物致病作用的证据;然而，哮喘患病率增加与某些污染物水平下降同时发生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学中的关键过程，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。在本申请中，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;颗粒物（PM10和PM2.5及其化学成分、颗粒物计数、NOx（NO和NO2）、酸蒸气;以及新鲜尾气排放）。在拟议的研究计划中评估的主要假设是：1）环境空气污染暴露的儿童有慢性气道炎症，如升高的eNO所示。2)对来自环境空气污染的气道炎症和氧化/亚硝化应激的易感性因NOS 1、NOS 2而异。NOS3。GSTM 1。GSTP 1。NQO 1和HO-1单倍型和功能变异，和3）慢性气道炎症的儿童，如升高的eNO所示，新发哮喘的风险增加。为了检验这些假设，拟议的研究建立在哮喘发病风险（AIR）研究的人口资源，一个正在进行的前瞻性队列研究的新发哮喘的决定因素在6000名儿童在13个南加州社区，和一个广泛的计划，在这些社区的环境空气污染暴露特征。在本申请中，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。一些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，以及来自南加州粒子中心和Supersite的专业知识。拟议研究计划的结果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。