Effects of Chronic Ozone Exposure on Lung Function

描述（由申请人提供）：大部分美国人口暴露于与急性呼吸系统健康影响相关的环境臭氧（03）水平;然而，对于长期暴露于此类环境浓度对人类呼吸系统健康的影响知之甚少。一项正在进行的研究，R 01 HL 60689（慢性臭氧暴露对肺功能的影响）正在研究长期暴露于环境O3对肺小气道功能（在呼气体积的75%下的用力呼气流量-FEF 75）的测量的影响。 臭氧暴露室研究表明，有些人根本没有反应，而在那些有反应的人中，反应模式往往是可重复的。这种多样性的个人之间的反应和个人内的反应的相对稳定性表明，有必要调查遗传因素作为暴露于环境O3和其他空气污染物的健康后果的决定因素。由于与暴露于环境和实验浓度的O3相关的人类健康影响与O3是一种强氧化剂的事实有关，因此研究遗传因素作为暴露于环境O3和其他空气污染物的健康后果的决定因素是很重要的。R 0160689的这种竞争性补充剂将检验总体假设，即导致宿主抗氧化防御降低的主要基因之间的多态性与人肺小气道的持续炎症和重塑相关，如较低水平的FEF 75所反映的。在300名受试者的队列中研究的基因是：超氧化物歧化酶2、谷胱甘肽-S-转移酶、谷胱甘肽过氧化物酶、过氧化氢酶、NADPH：氧化还原酶。还将在具有与抗氧化防御相关的不同遗传多态性的受试者中研究BAL和支气管活检中炎症的发生和程度之间的关系，所述受试者基于对环境O3的估计的终生暴露和FEF 75水平，被选择经历室暴露于O3的40名群组成员。还将研究细胞遗传学标记（微核）和DNA损伤（COMET）试验。 多元线性回归分析将用于评估遗传多态性对肺功能和气道炎症标志物的影响，以响应与估计的臭氧终生暴露有关的受控臭氧暴露。

DESCRIPTION (provided by applicant): A large part of the U.S. population is exposed to ambient ozone (03) levels that are associated with acute respiratory health effects; however, little is known about the effects on human respiratory health of long-term exposure to such ambient concentrations. An ongoing study, R0 1 HL60689 (Effects of Chronic Ozone Exposure on Lung Function) is investigating the effects of long-term exposure to ambient 03 on measures of lung small airway function (forced expiratory flow at 75 percent of expired volume-FEF75). Exposure chamber studies with ozone indicate that some individuals do not respond at all and that among those who do respond, the response patterns tend to be reproducible over time. This diversity of response among individuals and the relative stability of responses within individuals indicate the need to investigate genetic factors as determinants of health consequences of exposure to ambient O3 and other air pollutants. Since human health effects associated with exposure to ambient and experimental concentrations of O3 are related to the fact that O3 is a potent oxidizing agent, it is important to investigate genetic factors as determinants of health consequences of exposure to ambient O3 and other air pollutants. This competing supplement to R0160689 will test the overall hypothesis that polymorphisms among major genes that lead to decreased host antioxidant defense are related to ongoing inflammation and remodeling of the small airways of the human lung as reflected by lower levels of FEF75. The genes to be studied in the cohort of 300 subjects are: Superoxide Dismutase 2,Glutathione-S-Transferases, Glutathione Peroxidase, Catalase, NADPH:Oxidoreductase. The relation between the occurrence and magnitude of inflammation in BAL and bronchial biopsies in subjects with different genetic polymorphisms related to anti-oxidant defenses also will be studied among 40 members of the cohort who are selected to undergo chamber exposure to 03, based on estimated lifetime exposure to ambient 03 and level of FEF75. Markers of cytogenetic (micronuclei) and DNA damage (COMET) assay also will be investigated. Multiple linear regression analyses will be used to evaluate the influence of genetic polymorphism on lung function and markers of airway inflammation in response to controlled exposure to ozone in relation to estimated lifetime exposure to ozone.