Relationship of prenatal ambient air pollutants exposure with childhood asthma risk and underlying mechanism: Ma'anshan Birth Cohort study

产前环境空气污染物暴露和儿童哮喘发生风险的关联及其潜在机制：马鞍山优生优育队列

Authors：Yumei Zhong, Yun Zhou, Lijun Tang, Wenge Li, Yuxi Li, Hui Gao, Fangbiao Tao, Xiulong Wu

Source：Environmental Research

DOI: 10.1016/j.envres.2025.121283

Abstract

Introduction: Association between prenatal exposure to particulate matter speciation and childhood asthma was limited, and study of sensitive exposure window was needed.

Methods: Among 1807 children from Ma'anshan Birth Cohort, childhood asthma information was obtained by standardized questionnaire. Family address was collected at birth and in 7 years old and used to assess trimester-specific ambient air pollutants (AAPs) exposure. Restricted cubic spline and mixed effects logistic regression were applied to assess association of AAPs with childhood asthma, stratified by sex. Moreover, potential mechanism of AAPs-childhood asthma association was revealed by constructing adverse outcome pathway.

Results: There were significant correlations between AAPs. During the third trimester, exposure to PM2.5 exhibited a nearly J-shaped association with childhood asthma risk. When compared to the lowest tertile, childhood asthma risk increased by 59% (95% CI: 1.00-2.52) among children within the highest tertile of PM2.5 exposure (>76.65 μg/m3); and each unit increase in log2-transformed PM2.5 was associated with 102% (95% CI: 1.24-3.27) increase in childhood asthma risk. For chemical compositions of PM2.5, exposure to Cl-, NO3-, NH4+, and NO3- was also significantly associated with increased childhood asthma risk in the third trimester, especially in boys. Up-expression of IL-4 is molecular initiation event in the AAPs-asthma association, followed by decreased fibrinolysis, activated bradykinin, increased proinflammatory mediators, and recruitment of inflammatory cells, ultimately causing hyperinflammation.

Conclusions: Association of AAPs with asthma risk varied by trimester and sex, particularly PM2.5. Our findings enhance the public awareness of air pollution, heighten the importance of monitoring and control of AAPs.

Keywords: Air pollutants; Asthma; Birth cohort; Chemical composition; Inflammatory pathway.

摘要：

背景：产前暴露于细颗粒物特定组分与儿童哮喘的关联研究较为有限，需进一步研究探讨其暴露敏感窗口。

方法：在马鞍山优生优育队列的1 807名儿童中，通过标准化问卷收集儿童哮喘相关信息。分别在出生及7岁时收集参与者的家庭地址，用于评估孕期特异性环境空气污染物（AAPs）暴露水平。采用限制性立方样条曲线和混合效应Logistic回归模型被用来评估AAPs暴露与儿童哮喘发生风险之间的关联，并根据性别进行分层分析。此外，利用有害结局路径的构建来揭示AAPs暴露与哮喘关联的潜在机制。

结果：AAPs之间存在显著相关性。在孕晚期，暴露于PM_2.5与儿童哮喘风险表现出接近“J”型关系。与最低三分位数相比，暴露于最高三分位数PM_2.5（＞76.65 μg/m³）的儿童哮喘风险增加了59％（95％ CI＝1.00～2.52）；log₂转化的PM_2.5每增加一个单位，儿童哮喘风险增加102％（95％ CI＝1.24～3.27）。对于PM_2.5的化学组分而言，孕晚期暴露于Cl^-、SO₄^2-、NH₄⁺以及NO₃^-能显著增加儿童哮喘发生风险，上述关联在男孩中更强。IL-4的表达上调是AAPs暴露与哮喘关联的分子起始事件，这种上调会降低纤维蛋白的溶解作用，激活缓激肽，导致促炎介质的增加和炎症细胞的募集，最终引发过度炎症。

结论：产前AAPs暴露与儿童哮喘发生风险的关系存在孕期特异性和性别差异，特别是PM_2.5。我们的研究成果提高了公众对空气污染的认知，进一步说明加强监测和控制AAPs的重要性。

关键词： 空气污染物；哮喘；出生队列；化学成分；炎症途径