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/cm³). 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.

中文翻译：

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代谢途径的扰动介导空气污染物与哮喘和心血管疾病的关联

 背景

流行病学证据表明，呼吸系统疾病和心血管疾病存在常见的危险因素，包括空气污染暴露，这表明常见的改变的分子途径涉及其中。

 目标

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”），从而揭示机制并加强因果关系。

 方法

我们在两项独立的病例对照研究中，对成人发病哮喘 (AOA) 和心脑血管疾病 (CCVD) 队列中的非目标代谢组学应用了一种名为“中间相遇”的统计方法。我们比较了结果，以确定常见的和疾病特异性的改变的代谢途径。

 结果

一项新发现是 AOA 与超细颗粒有很强的相关性（UFP；每增加 5000 个颗粒/cm ³优势比为 1.80 [1.26, 2.55]）。此外，我们还发现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，亚油酸代谢途径的扰动与空气污染暴露、AOA 和 CCVD 相关。

 结论

我们的结果表明，长期暴露于空气污染可能导致常见通路扰动，导致 AOA 和 CCVD 风险增加。