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Combustion Generated PM0.1 and Predisposition to Asthma

燃烧产生的 PM0.1 与哮喘易感性

基本信息

批准号：
7924645
负责人：
Stephania A Cormier
金额：
$ 33.16万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924645
关键词：
3-nitrotyrosine Accounting Address Adult Affect Age Air Allergic Antioxidants Apoptosis Apoptotic Asthma Biochemical Biological Biological Assay Biological Availability Blood Caliber Child Data Development Disease Drug Metabolic Detoxication Environment Environmental Policy Environmental Pollution Enzymes Epithelial Event Exposure to Free Radicals Functional disorder Gases Genetic Genetic Drift Hazardous Waste Health Hemeproteins Human Hygiene Immune System Diseases Immune response In Situ Nick-End Labeling Inflammatory Laboratories Lead Left Life Life Style Link Lipids Lung Lung diseases Measurement Mediator of activation protein Molecular Morbidity - disease rate Neonatal Outcome Outcome Study Oxidation-Reduction Oxidative Stress Oxygenases Particulate Matter Predisposition Prevalence Proteins Proteomics Public Health Rattus Reactive Nitrogen Species Reactive Oxygen Species Research Personnel Respiratory physiology Role Rural Staging Staining method Stains Stephania Superoxide Dismutase Surface T-Lymphocyte Therapeutic Intervention Time Urban Population Viral Respiratory Tract Infection Western Blotting allergic response dihydroethidium effective intervention expectation in vivo insight interdisciplinary approach mimetics mortality neonate nitration oxidation particle programs protective effect remediation response tempol ultrafine particle urban area wasting

项目摘要

DESCRIPTION (provided by applicant): The occurrence of inflammatory respiratory diseases, such as asthma, has increased dramatically in the past decade. This rate of increase is more than can be accounted for by genetic drift alone and suggests a role for the environment. Many hypotheses attempt to explain this phenomenon by citing better hygiene, environmental pollution, viral respiratory tract infections, and/or loss of some protective effect found in a rural lifestyle as culprits in disease initiation and exacerbation. This proposal seeks to determine if exposure during early neonatal life to ultrafine particles (PM0.1) typically produced from thermal remediation of hazardous wastes leads to predisposition, development of, or exacerbation of allergic respiratory disease in the adult. Our hypothesis is that PM0.1 generated from the combustion/thermal degradation of hazardous wastes contains persistent, surface-stabilized free radicals that in neonates interact with epithelial-mucosal surfaces and modulate the adaptive immune response leading to adult airways disease such as asthma. In the short term, this proposal will explore the validity of this hypothesis by accomplishing the following specific aims: 1) characterize the ability of PM0.1 to produce oxidative stress within the lung using biochemical and proteomic approaches; 2) define the impact of PM0.1 on pulmonary pathophysiology of neonatal rats; and 3) elucidate the cellular and molecular events by which PM0.1-induced increases in reactive oxygen species lead to pulmonary and/or immune dysfunction in adults. The long-term objective of our laboratory is to realize the initiators of the immunological and pathophysiological changes that occur during the early stages of pulmonary airways disease and ultimately to understand the fundamental causes of asthma so that more effective interventions and therapy may be developed. Completion of the proposed studies will provide insight into how combustion/thermal degradation of waste affects the development of inflammatory airways disease in children with the expectation of valid extrapolation to human inflammatory airways disease, such as asthma. The outcome of these studies will not only have important implications for public health but also for public environmental policy, since currently there are no air quality standards for PM0.1.

描述（由申请人提供）：在过去十年中，哮喘等炎性呼吸道疾病的发生率急剧增加。这种增长率不仅仅是遗传漂变所能解释的，而且表明了环境的作用。许多假说试图通过引用更好的卫生，环境污染，病毒性呼吸道感染和/或农村生活方式中发现的某些保护作用的丧失来解释这种现象，作为疾病发生和恶化的罪魁祸首。本提案旨在确定在新生儿早期暴露于通常由危险废物热处理产生的超细颗粒（PM0.1）是否会导致成人过敏性呼吸道疾病的易感性、发展或恶化。我们的假设是，PM0.1产生的燃烧/热降解的危险废物含有持久的，表面稳定的自由基，在新生儿与上皮粘膜表面相互作用，并调节适应性免疫反应，导致成人气道疾病，如哮喘。在短期内，本提案将通过实现以下具体目标来探索这一假说的有效性：1）使用生物化学和蛋白质组学方法表征PM0.1在肺内产生氧化应激的能力; 2）确定PM0.1对新生大鼠肺病理生理学的影响;和3）阐明PM0.1诱导的活性氧增加导致成人肺和/或免疫功能障碍的细胞和分子事件。我们实验室的长期目标是了解肺气道疾病早期发生的免疫和病理生理变化的始作俑者，并最终了解哮喘的根本原因，以便开发更有效的干预和治疗。完成拟议的研究将深入了解废物的燃烧/热降解如何影响儿童炎症性气道疾病的发展，并期望有效地外推到人类炎症性气道疾病，如哮喘。这些研究的结果不仅对公众健康有重要意义，而且对公共环境政策也有重要意义，因为目前还没有PM0.1的空气质量标准。