PM2.5和极端温度对哮喘影响的协同作用及其机制研究

In recent years, extreme weather events (eg. heat waves, cold spells) are frequent in China. Air pollution becomes the public concern as well, with high concentrations of PM2.5. Both extreme temperature and PM2.5 have been associated with respiratory health impacts, however, there is little evidence on the interaction of extreme temperature and PM2.5 in their effects on asthma and its mechanism. This study aims to assess the effects of extreme temperature and PM2.5 on asthma by epidemiological design and toxicological experiment. Outpatients and emergency department visits for asthma in children aged 3-14 years, meteorological and air pollution data during 2010-2016 in Shanghai will be collected to evaluate the interaction effects of extreme temperature and PM2.5 on asthma. Childhood asthma patients will be followed up one year to count their acute attack and exacerbation after exposure to extreme temperature and elevated PM2.5. Animal experiments will be conducted in a cabin in which mice can be exposed to concentrated ambient PM2.5. Biomarkers of systemic immunity, inflammation and injuries, and respiratory oxidative stress will be analyzed to understand the toxic mechanisms of respiratory system injuries induced by ambient PM2.5 together with extreme temperature. The project will help explore the interaction of extreme temperature and high PM2.5 level in their effects on asthma, and contribute to appropriate strategies in respiratory health protection and policy making related to extreme weather and PM2.5.

近年来，我国热浪和寒潮等极端天气频繁发生，大气细颗粒物（PM2.5）污染态势严峻。极端温度（高温、低温）和PM2.5污染都会对呼吸系统造成健康损害，然而关于两者的协同作用对哮喘的影响及其机制研究在国内外还少见报道。本项目从人群流行病学和动物实验两方面研究极端温度和PM2.5对哮喘的综合影响。一方面开展时间序列和人群随访研究，拟收集近7年上海市儿童哮喘就诊资料，随访哮喘儿童的肺功能及哮喘发作情况，利用时间序列分析和混合效应模型等方法评价极端温度和PM2.5污染对哮喘的暴露反应关系。另一方面开展自然吸入式毒理学实验研究，探讨PM2.5暴露诱发哮喘急性加重的作用机制，研究生命早期PM2.5暴露对哮喘易感性的影响，揭示PM2.5和极端温度长期共同暴露对哮喘的协同作用机制。该研究可为预防和降低PM2.5和极端天气对哮喘人群的健康损害及相关政策制定提供科学依据。

哮喘的发生机制复杂，极端天气和PM2.5污染是否会对哮喘存在交互影响及其机制研究在国内外亦少见报道。本项目采用人群流行病学和动物实验相结合的研究方法，从群体水平、个体水平和干预研究等层次，分析了大气PM2.5和极端气温联合作用对哮喘的影响及作用机制。在群体水平，采用时间序列设计，利用广义相加模型建立了PM2.5和气温与哮喘门急诊的暴露-反应关系。在个体水平，采用定群研究，以225例哮喘儿童为研究对象，进行了1年多的追踪随访，随访结局包括哮喘急性发作和肺功能指标，使用广义估计方程和广义相加混合模型分析了PM2.5和气温对哮喘发作和肺功能指标的效应。另外，在人工气候环境暴露仓（Shanghai-METAS）中开展自然吸入式毒理学实验，探讨了PM2.5暴露和冷刺激对哮喘的交互作用及其作用机制。结果发现：1、PM2.5和气温对儿童哮喘就诊存在交互作用；2、气温较高季节，PM2.5浓度升高与哮喘急性发作明显相关，在低温下急性PM2.5暴露对哮喘患者的肺通气功能有显著影响；3、PM2.5暴露可诱发哮喘加重，减少PM2.5的暴露可以缓解肺部及白色脂肪炎症；4、PM2.5暴露和冷应激对哮喘发生具有显著的交互作用，生命早期两者共同暴露可增加成年后哮喘的易感性和严重程度；5、PM2.5暴露和冷应激可通过CD4+T细胞IL-4基因启动子的组蛋白乙酰化、Th2/Th1失衡、抑制Th17向Treg细胞的分化等机制对哮喘发生协同作用。本研究结果可为预防和降低PM2.5和极端天气对哮喘人群的健康损害及相关政策制定提供依据，对切实提高城市居民健康水平具有重要意义。