室内燃煤细颗粒物与支气管哮喘发病关系及分子机制研究

The prevalence of asthma and asthma-related symptoms has increased dramatically over the last decade in China and western industrial countries．Indoor environmental quality has a significant impact on asthma attack. Zunyi district possesses abundant coal reserves, known as one of the cities most seriously polluted by high level of particulate matter air pollution in China. In Zunyi district, coal is still a major source of fuel for cooking and warming throughout the year, particularly in winter season. The use of coal for cooking and warming is considered an important factor associated with the prevalence of asthma and asthma-related symptoms. However, few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) from indoor coal combustion and a change in asthma and morbidity attack among local population. Our study will adopt a method that combines epidemiology and molecular biology. In a case-control study, both pilot epidemiological study and serological test on environmental risk factors for asthma and asthma-related symptoms in both rural and urban population will be conducted in Zunyi．The effects of environmental risk factors on asthma and morbidity attack and its immune mechanism will be investigated. A murine model of asthma will be established. Whether PM2.5 from indoor coal combustion enhances ovalbumin (OVA)-induced airway inflammation in asthmatic murine and its mechanisms will be first investigated. In vitro study，the gene expression of Toll-like receptors (TLRs) and NACHT-，LRR- and pyrin-domain containing protein 3 (NALP3) inflammasome in RAW264.7 cells of rats will be measured to investigate the role of TLRs and NALP3 inflammasome in the enhancement by PM2.5 from indoor coal combustion. Regulatory T cells (Treg cells) will be newly introduced into our epidemiological survey and animal experiments to explore the immunoregulatory role of PM2.5 from indoor coal combustion. In this study, asthma and asthma-related symptoms attack and its environmental risk factors will be probed; the mechanisms of PM2.5 from indoor coal combustion exacerbating asthmatic murine caused by OVA will be investigated as well. This study has important realistic and guide significance in strengthening PM2.5 indoor pollution prevention and disease protection among susceptible population.

居民哮喘及其相关过敏疾患发病率日益增高。室内空气质量对哮喘的发病起到重要作用。遵义地区煤炭资源丰富，80％以上的家庭烹饪和取暖时主要使用燃煤，室内燃煤产生的细颗粒物(PM2.5) 与支气管哮喘发病的关系及分子机制目前尚未见报道。本课题拟通过流行病学和分子生物学相结合的手段，在以燃煤为主的地区进行居民哮喘的危险因素调查和血清学检查，探讨导致居民哮喘及其发作的环境危险因素及其免疫机制。建立哮喘动物模型，首次探讨室内燃煤PM2.5对卵白蛋白诱导的哮喘小鼠气道炎症的作用及分子机制，阐明燃煤PM2.5对小鼠巨噬细胞中Toll样受体和NALP3炎症复合体表达的影响，并将调节性T细胞引入动物实验和流行病学调查中，展开燃煤PM2.5的免疫调节作用的研究。本研究探求人群哮喘和环境危险因素的关系及室内燃煤PM2.5对哮喘小鼠的损伤作用机制，对加强PM2.5污染防治及敏感人群的健康保护具有重要的现实和指导意义。

居民哮喘及其相关过敏疾患发病率日益增高。室内煤烟细颗粒物(PM2.5)污染等环境因素对哮喘的发病起到重要作用。室内燃煤产生的PM2.5与支气管哮喘发病的关系及分子机制目前尚未明了。本研究利用环境流行病学、整体动物实验、环境气象学相结合的研究方法, 研究室内煤烟PM2.5对哮喘、慢性阻塞性肺疾病（COPD）等慢性气道炎症性疾病发病及肺功能影响及其机制，本研究①率先监测酸雨城市-遵义市室内煤烟PM2.5颗粒物的浓度，发现燃煤家庭煤烟PM2.5颗粒物浓度是非燃煤家庭的1.2倍，室内浓度是室外浓度的1.4倍，冬季浓度约是夏季的1倍。发现煤烟PM2.5颗粒物浓度暴露引起居民肺功能（FVC, FEV1, FEV1/FVC和PEFR）水平明显下降，冬季影响较夏季明显。②调查遵义市11个街道办、1207名成年研究对象，发现遵义市冬夏两季成人哮喘患病率分别为1.8%和0.8%。成年哮喘患病率增加与室内燃煤、烹调油烟、被动吸烟和宠物饲养等环境危险因素有关。③通过建立动物哮喘模型，率先证实了室内燃煤 PM2.5 在 OVA 诱导哮喘大鼠肺组织结构改变、细胞因子表达异常、炎性细胞浸润增加中起促进作用，进而加重 OVA 诱导哮喘大鼠呼吸道炎性损伤及组织结构改变。④通过对遵义地区COPD疾病的病例对照流行病学调查，发现BMI<18.5或BMI>24、室内通风不好、燃煤、粉尘暴露、家族呼吸道病史、吸烟可能增加患COPD发生的风险，控制危险因素的暴露能够降低COPD的患病风险。⑤同时检测 ADAM33 基因Q-1、T1位点多态性在COPD患者中的分布频率，发现ADAM33 基因Q-1、T1位点多态性与黔北地区汉族 COPD尚无相关性，但T1（83bp、112bp）处两个杂合子在同一个样本中同时出现的概率较高（18/19），且位于编码区。⑥监测遵义市区公共场所室内空气污染物（吸入性颗粒物、甲醛等）的现状污染水平，证实了城市公共场所吸入性颗粒物、甲醛污染对呼吸健康有不利影响。⑦利用时间序列广义相加模型统计分析数据显示：酸雨灾区气象因素（气温、气压、湿度、降雨量）对居民心血管系统疾病急、门诊就诊人次呈明显负相关关系，本项目系统研究煤烟PM2.5颗粒物等多种因素在呼吸道疾患的引发及加重过程中起的相互作用，为评价环境中室内煤烟PM2.5颗粒物暴露对人体的安全性和环境研究治理提供科学依据。