大气复合污染致婴幼儿哮喘发病模式研究

Infant asthma is a chronic respiratory inflammatory disease that can severely affect the growth and development of infants. There are much uncentainty in the results of the researches studying the association between infant asthma pathogenicity and air pollutant exposure, especially in the pathogenic discipline and pathogenic pattern of infant asthma under composite air pollution exposure. Our study means to build a early-life cohort based on the theory of life course epidemiology. We will construct a "time of exposure-pollutant consistency-exposure parameter" valuation model supported by the 24-hour real-time test data gained from 16 monitoring points scattered in the urban area of Jinan, which are build in the Database of Real-time cloud data collection of Composite Air Pollution Level in the Urban Area of Shandong Province constructed by College of Public Health, Shandong University. It will be used to carry out an accurate measurement of the dynamic exposure level of composite air pollutants from which each infant subject suffered in different parts of gestation period and in the first 2 years of lifespan, thus we can confirm the pathogenic effect, pathogenic pattern and sensitive period of composite air pollution exposure leading to infant asthma. Besides we will construct a mouse wheezing/asthma model to validate the independent and combined pathogenesis effect and pathogenic sensitivity of composite air pollutants exposure in different periods of early life. Finally we expect to clarify the pathogenic pattern of infant asthma caused by composite air pollution, ascertain the intervention window of infant asthma prevention, and bring forth scientific methods to control the incidence rate of infant asthma and improve the constitution of children.

婴幼儿哮喘是一种严重影响婴幼儿生长发育的慢性气道炎症性疾病。关于空气污染物暴露与婴幼儿哮喘发病风险关系的研究结果存在诸多不确定性，尤其在大气复合污染状态下婴幼儿哮喘发病规律与发病模式尚不清晰。本研究拟依据生命历程流行病学理论构建生命早期研究队列；依托我院构建的“山东省城市大气复合污染实时云采集数据库”中济南市区16个监测点24h实时监测数据，构造“时间-污染物浓度-暴露参数”评估模型，精确测量每名研究对象的母亲孕期不同阶段及出生后两年内大气复合污染动态暴露剂量，确定生命早期不同时段暴露于大气复合污染对婴幼儿哮喘的致病作用、发病模式和敏感期；同时构建生命早期不同时段暴露于大气复合污染的致喘动物模型，验证不同生命时段大气复合污染暴露的独立和联合致喘效应及其致喘敏感性；阐明大气复合污染致婴幼儿哮喘发病模式，明确婴幼儿哮喘预防干预窗口，为控制婴幼儿哮喘发病率和提高儿童身体素质提供科学依据。

婴幼儿哮喘是一种严重影响儿童生长发育的慢性疾病，其发病率在逐年增高，关于大气复合污染对婴幼儿哮喘影响的发病模式尚不清晰。本研究在济南市构建生命早期研究队列，动态测量研究对象宫内及生后早期大气复合污染暴露剂量，探讨大气复合污染暴露对婴幼儿哮喘的致病作用和敏感暴露窗口；同时构建生命早期不同时段暴露于大气复合污染的动物模型，探讨大气复合污染致喘效应特点及其机制。研究发现：（1）出生队列人群2岁的哮喘和喘息累计发病率为1.29%，哮喘和喘息的恢复率在1.5周岁为95.23%，在2周岁为61.53%；（2）大气复合污染物之间存在明显共线性，主成分分析显示其主要存在两种主成分，主成分1为SO2、NO2、PM10、PM2.5，主成分2为O3,但模型显示仅主成分2暴露是婴幼儿生命早期哮喘的关键致喘物质，其发病风险增加了1.5倍；各种大气复合污染物对哮喘发生具有协同作用；（3）时依cox回归模型结果均提示暴露于较高水平的O3，婴幼儿哮喘的风险升高了7.4%；（4）分布滞后模型识别到出生后36周到91周是O3致婴幼儿哮喘的敏感期；（5）辛普森公式构造“时间-污染物浓度-暴露参数”模型评估室内外累积暴露量，发现出生后O3和SO2累积暴露量越高发生哮喘的风险越大（ORO3=8.86 ,ORSO2=7.62）；（6）动物模型结果显示，孕期和哺乳期不同时段暴露于大气复合污染物与单独暴露于O3均可致小鼠子代哮喘加重，联合染毒未显示复合物间的联合作用，孕期大气复合污染物暴露对子代哮喘的促进作用无累积效应，与人群研究结果一致。本研究阐明了大气复合污染致婴幼儿哮喘的发病模式，大气复合污染暴露对致哮喘有协同作用，O3是关键致病物质，该作用既有剂量反应关系又有风险因素累积效应，而发现存在的敏感期则明确了预防婴幼儿哮喘的预防干预窗口，相关数据为控制婴幼儿哮喘发病提供了科学依据。