大气细颗粒物暴露可导致肺功能下降或者发展为慢性阻塞性肺病，其致病规律与机制仍不清楚，本项目拟采用分子流行病学研究方法，利用已经建立的武汉珠海社区队列，系统测定室内外空气PM2.5浓度计算队列成员PM2.5外暴露量，测定尿中金属、多环芳烃代谢产物，结合饮食分析推算PM组分内暴露量；随访武汉珠海队列，行肺功能测定和COPD诊断，采用时间序列和生存分析等方法分析空气PM2.5及其组分的内外暴露量、暴露时间与肺功能下降及COPD发病的暴露剂量-效应关系，计算肺功能下降及COPD发病归因于PM2.5的率；分析PM2.5暴露与免疫炎性反应等通路因子/蛋白变化、DNA甲基化改变的关联，以及与肺功能下降及COPD发病的关系，探讨免疫炎性反应等和DNA甲基化改变在PM2.5致肺功能下降及COPD发病中的作用，筛选肺功能下降及COPD的效应标志物。为进一步阐明COPD发生机制和制订预防对策提供科学依据。

Exposure to ambient particulate matter may lead to decline in lung function or development of chronic obstructive pulmonary diseases (COPD). The regular pattern and pathogenic mechanism of PM2.5 induced lung function decline and CODP remain unclear. This project will be conducted on established WHZH cohort through molecular epidemiological methods. The personal external exposure to PM2.5 and its components will be estimated through systemic measurements of indoor and outdoor ambient PM2.5. The personal internal exposure to the components of PM will be estimated through the levels of urinary metal and polycyclic aromatic hydrocarbon metabolites and exclude the amount from foods. We will follow the WHZH cohort, determine lung function for each participant and make diagnosis of COPD. The dose-response relationship between internal and external exposure to PM2.5 or its components and alter in lung function or incidence of COPD will be analyzed by time series and survival analysis. Attributable risk of lung function decline or COPD to PM2.5 or its components will be calculated. The association of PM2.5 exposure with changes of cytokines/proteins of inflammatory immune response or DNA methylation, and further association with lung function decline or COPD will be conducted. The role of mechanism of cytokines/proteins or DNA methylation during PM2.5 exposure and lung function decline or COPD will be discussed. The possible biomarkers for lung function decline or COPD will be selected through the analysis. This study will provide scientific basis for the mechanism of COPD development and prevention.