Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases
Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases
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DOI：
10.1016/j.envint.2018.06.025
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发表时间：
2018-10-01
影响因子：
11.8
通讯作者：
Probst-Hensch, Nicole
中科院分区：
文献类型：
--
作者：
Jeong, Ayoung;Fiorito, Giovanni;Probst-Hensch, Nicole
背景资料：流行病学证据表明，呼吸道和心血管疾病的常见风险因素，包括空气污染暴露，表明参与常见的改变分子途径。目的：目标是找到可能与空气污染物和健康结果相关的中间代谢物或代谢途径（“中间相遇”），从而阐明机制并加强因果关系。我们在两项独立的病例对照研究中应用了一种名为“中间相遇”的统计方法来研究非靶向代谢组学，这些研究嵌套在成人发作哮喘（AOA）和心脑血管疾病（CCVD）的队列中。结果：一个新的发现是AOA与超细颗粒（UFP;每增加5000个颗粒/cm（3），比值比为1.80 [1.26，2.55]）有很强的相关性。此外，我们已经确定了几种可能介导空气污染对健康结果影响的代谢途径。其中，亚油酸代谢途径的紊乱与空气污染暴露、AOA和CCVD.Conclusions：我们的研究结果表明，慢性空气污染暴露可能导致共同的途径紊乱，从而增加AOA和CCVD的风险。
Background: Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways.Objectives: The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes ("meeting-in-the-middle"), thus shedding light on mechanisms and reinforcing causality.Methods: We applied a statistical approach named `meet-in-the-middle' to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways.Results: A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000 particles/cm(3)). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD.Conclusions: Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD.