Acute Asthma Outcomes, Endotoxin and Oxidative Potential of Pollutant Particles

急性哮喘结果、内毒素和污染物颗粒的氧化电位

• 批准号: 8032030
• 负责人: RALPH J DELFINO
• 金额: $ 22.95万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8032030
• 关键词: Acute; Address; Aerosols; Affect; Age; Air; Air Pollutants; Air Pollution; Alveolar Macrophages; Archives; Asthma; Biological Assay; California; Carbon; Child; Cohort Studies; Data; Diagnosis; Dithiothreitol; Electrons; Endotoxins; Epidemiologic Methods; Exhalation; Exposure to; Forced expiratory volume function; Fossil Fuels; Future; Generations; Goals; Health; Inflammatory; Inflammatory Response; Joints; Knowledge; Measurement; Measures; Methods; Modification; Nitric Oxide; Outcome; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Particulate; Particulate Matter; Pathology; Production; Property; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; Quartz; Rattus; Reactive Oxygen Species; Research; Respiratory physiology; Sampling; Schools; Site; Source; Study Subject; Superoxides; Suspension substance; Suspensions; Teflon; Testing; Time; Toxicology; Tracer; United States Environmental Protection Agency; airway inflammation; ambient particle; aqueous; biological adaptation to stress; in vitro Assay; in vitro Bioassay; particle; pollutant; respiratory; trafficking

DESCRIPTION (provided by applicant): Experimental data suggest that endotoxin may interact with organic components of particulate matter (PM) air pollution to induce acute inflammatory response in the airways, but there are no repeated measures data to assess whether this occurs in children with asthma. We previously found associations between 10 repeated measures of daily personal air pollutant exposures and daily acute asthma outcomes in a panel cohort study of 58 school children with asthma ages 9-18 years who were followed in southern California. Using these existing data we will assess for the first time whether repeated personal exposure to endotoxin is an effect modifier of the relation between repeated exposure to air pollution and acute asthma outcomes in subjects with diagnosed asthma (Aim 1). Health outcomes will include airway inflammation (exhaled nitric oxide) and expiratory lung function. Air pollutants will include personal exposure to NO2 and to PM2.5 mass, elemental carbon, and organic carbon. Furthermore, experimental data also show that components of PM derived from the combustion of fossil fuels from traffic sources may have the potential to induce oxidative stress initiated by reactive oxygen species. However, the concentrations of these redox active components can be independent of total regulated PM mass (PM2.5). It is possible that associations previously observed between worsening asthma and PM2.5 were related to the ability of particle mixtures to induce oxidative stress and inflammatory responses, which are hallmarks of the underlying pathology of asthma. To address this issue, we will analyze the relation of asthma outcomes to the oxidant potential of ambient PM2.5 using in vitro bioassays of archived daily particle samples (Aim 2). We hypothesize that asthma outcomes will be related to the oxidant potential of the collected particle samples. We further hypothesize that the magnitude of associations of asthma outcomes with PM2.5 oxidant potential will be greater than that for PM2.5 mass. Finally, to tie the previous two aims together, we will evaluate effect modification of associations between asthma outcomes and the oxidant potential of ambient PM2.5 by exposure to endotoxin (Aim 3). The oxidant potential of ambient particle mixtures may interact more strongly with endotoxin than interactions of endotoxin with surrogate tracers of pro-oxidant organic particle components such as elemental carbon (Aim 1). In the proposed study, we will produce new findings from a panel cohort study to address gaps in knowledge and to demonstrate the potential usefulness of new methods of exposure assessment. This includes new data on the importance to asthma health from joint exposures to endotoxin and air pollution, and from exposure to PM that varies according to a key air pollutant property, its oxidant potential. Our long-term goal is to advance epidemiologic methods of researching air pollution and health by establishing greater coherence with experimental toxicology. PUBLIC HEALTH RELEVANCE: The knowledge that will emerge from the proposed study of these subjects will be of benefit to public health by identifying whether the joint exposure to endotoxin and air pollution affects respiratory health outcomes among children with asthma. We will address major gaps in scientific knowledge by advancing understanding on the components of particulate air pollution that are responsible for associations of acute changes in asthma outcomes with total mass concentrations of regulated fine particulate matter. Our proposed use of repeated measurements of personal exposure to particles with different oxidant potential may influence the way future studies of air pollution and asthma are conducted.

描述(申请人提供)：实验数据表明，内毒素可能会与颗粒物(PM)空气污染的有机成分相互作用，在呼吸道引发急性炎症反应，但没有重复测量的数据来评估这种情况是否发生在哮喘儿童身上。此前，我们在南加州对58名9-18岁患有哮喘的学龄儿童进行的小组队列研究中发现，每日个人空气污染物暴露的10次重复测量与每日急性哮喘结果之间存在关联。利用这些现有的数据，我们将首次评估反复暴露于内毒素是否是反复暴露于空气污染与确诊哮喘患者的急性哮喘结果之间关系的有效修饰物(目标1)。健康结果将包括呼吸道炎症(呼出的一氧化氮)和呼气肺功能。空气污染物将包括个人接触NO2和PM2.5质量、元素碳和有机碳。此外，实验数据还表明，来自交通来源的化石燃料燃烧产生的PM组分可能具有诱导由活性氧物种引发的氧化应激的潜力。然而，这些氧化还原活性成分的浓度可以独立于受监管的PM总质量(PM2.5)。以前观察到的哮喘恶化和PM2.5之间的关联可能与颗粒混合物诱导氧化应激和炎症反应的能力有关，而氧化应激和炎症反应是哮喘潜在病理的特征。为了解决这个问题，我们将使用存档的日常颗粒物样本的体外生物测定来分析哮喘结局与环境PM2.5氧化电位的关系(目标2)。我们假设哮喘的结果将与收集的颗粒样本的氧化电位有关。我们进一步假设，哮喘预后与PM2.5氧化潜势的关联程度将大于PM2.5质量。最后，为了将前两个目标联系在一起，我们将评估内毒素暴露对哮喘结局和环境PM2.5氧化潜力之间关系的影响修正(目标3)。周围颗粒混合物的氧化电位与内毒素的相互作用可能比内毒素与促氧化剂有机颗粒成分(如元素碳)的替代示踪剂的相互作用更强(目标1)。在拟议的研究中，我们将从一项专家小组队列研究中得出新的发现，以解决知识差距并证明新的暴露评估方法的潜在有用性。这包括关于内毒素和空气污染联合暴露对哮喘健康重要性的新数据，以及暴露在PM中的新数据，PM的暴露因关键空气污染物特性及其氧化潜力而异。我们的长期目标是通过与实验毒理学建立更大的一致性来推进研究空气污染和健康的流行病学方法。 公共卫生相关性：通过确定内毒素和空气污染的联合暴露是否会影响哮喘儿童的呼吸健康结果，对这些对象的拟议研究得出的知识将对公共健康有益。我们将通过促进对颗粒性空气污染成分的理解来解决科学知识方面的主要差距，颗粒性空气污染成分是导致哮喘结果急剧变化与受管制细颗粒物总质量浓度之间关系的原因。我们建议使用重复测量个人接触不同氧化潜能颗粒物的方法，可能会影响未来进行空气污染和哮喘研究的方式。