Effects of Chronic Ozone Exposure on Lung Function

描述（由申请人提供）：美国大部分人口暴露于与急性呼吸道健康影响相关的环境臭氧（03）水平；然而，人们对长期暴露于这种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r01 HL60689（慢性臭氧暴露对肺功能的影响）正在调查长期暴露于环境03对肺小气道功能测量的影响（呼气流量为呼气容量的75% - fef75）。臭氧暴露室研究表明，有些人根本没有反应，而那些有反应的人，随着时间的推移，反应模式往往是可重复的。个人之间反应的多样性和个人内部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臭氧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臭氧有关的人类健康影响与臭氧是一种强氧化剂这一事实有关，因此必须调查遗传因素作为暴露于环境臭氧和其他空气污染物的健康后果的决定因素。R0160689的竞争性补充将测试导致宿主抗氧化防御下降的主要基因多态性与持续的炎症和人类肺部小气道重塑有关的总体假设，这与较低水平的FEF75有关。300名受试者队列中待研究的基因有：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。在具有与抗氧化防御相关的不同遗传多态性的受试者中，BAL炎症的发生和程度与支气管活检之间的关系也将在40名队列成员中进行研究，这些成员被选择接受室内暴露于03，基于估计的终生暴露于环境03和FEF75水平。细胞遗传学标记（微核）和DNA损伤（彗星）测定也将进行研究。将使用多元线性回归分析来评估基因多态性对肺功能和气道炎症标志物的影响，这些指标与受控臭氧暴露有关，与估计终生臭氧暴露有关。

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.