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Ambient PM2.5 species and ultrafine particle exposure and their differential metabolomic signatures
Environment International ( IF 10.3 ) Pub Date : 2021-02-24 , DOI: 10.1016/j.envint.2021.106447
Feiby L Nassan 1 , Cuicui Wang 1 , Rachel S Kelly 2 , Jessica A Lasky-Su 2 , Pantel S Vokonas 3 , Petros Koutrakis 1 , Joel D Schwartz 4
Affiliation  

Background

The metabolomic signatures of short- and long-term exposure to PM2.5 have been reported and linked to inflammation and oxidative stress. However, little is known about the relative contribution of the specific PM2.5 species (hence sources) that drive these metabolomic signatures.

Objectives

We aimed to determine the relative contribution of the different species of PM2.5 exposure to the perturbed metabolic pathways related to changes in the plasma metabolome.

Methods

We performed mass-spectrometry based metabolomic profiling of plasma samples among men from the Normative Aging Study to identify metabolic pathways associated with PM2.5 species. The exposure windows included short-term (one, seven-, and thirty-day moving average) and long-term (one year moving average). We used linear mixed-effect regression with subject-specific intercepts while simultaneously adjusting for PM2.5, NO2, O3, temperature, relative humidity, and covariates and correcting for multiple testing. We also used independent component analysis (ICA) to examine the relative contribution of patterns of PM2.5 species.

Results

Between 2000 and 2016, 456 men provided 648 blood samples, in which 1158 metabolites were quantified. We chose 305 metabolites for the short-term and 288 metabolites for the long-term exposure in this analysis that were significantly associated (p-value < 0.01) with PM2.5 to include in our PM2.5 species analysis. On average, men were 75.0 years old and their body mass index was 27.7 kg/m2. Only 3% were current smokers. In the adjusted models, ultrafine particles (UFPs) were the most significant species of short-term PM2.5 exposure followed by nickel, vanadium, potassium, silicon, and aluminum. Black carbon, vanadium, zinc, nickel, iron, copper, and selenium were the significant species of long-term PM2.5 exposure. We identified several metabolic pathways perturbed with PM2.5 species including glycerophospholipid, sphingolipid, and glutathione. These pathways are involved in inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Results were overlapped with the ICA.

Conclusions

We identified several significant perturbed plasma metabolites and metabolic pathways associated with exposure to PM2.5 species. These species are associated with traffic, fuel oil, and wood smoke. This is the largest study to report a metabolomic signature of PM2.5 species’ exposure and the first to use ICA.



中文翻译:

环境 PM2.5 物种和超细颗粒暴露及其差异代谢组学特征

背景

据报道,短期和长期暴露于 PM 2.5的代谢组学特征与炎症和氧化应激有关。然而,对于驱动这些代谢组学特征的特定 PM 2.5物种(因此来源)的相对贡献知之甚少。

目标

我们旨在确定不同种类的 PM 2.5暴露对与血浆代谢组变化相关的扰动代谢途径的相对贡献。

方法

我们对来自规范老化研究的男性血浆样本进行了基于质谱的代谢组学分析,以确定与 PM 2.5物种相关的代谢途径。暴露窗口包括短期(一、七和三十天移动平均线)和长期(一年移动平均线)。我们使用具有特定对象截距的线性混合效应回归,同时调整 PM 2.5、NO 2、O 3、温度、相对湿度和协变量,并针对多重测试进行校正。我们还使用独立成分分析 (ICA) 来检查 PM 2.5物种模式的相对贡献。

结果

2000 年至 2016 年间,456 名男性提供了 648 份血液样本,其中 1158 种代谢物被量化。在此分析中,我们选择了 305 种短期代谢物和 288 种长期暴露代谢物,它们与 PM 2.5 显着相关(p 值 < 0.01),纳入我们的 PM 2.5物种分析。男性平均75.0岁,体重指数为27.7 kg/m 2。只有 3% 是当前吸烟者。在调整后的模型中,超细颗粒 (UFP) 是短期 PM 2.5暴露中最重要的种类,其次是镍、钒、钾、硅和铝。黑碳、钒、锌、镍、铁、铜和硒是长期 PM 2.5的重要种类暴露。我们确定了几种受 PM 2.5物质干扰的代谢途径,包括甘油磷脂、鞘脂和谷胱甘肽。这些途径涉及炎症、氧化应激、免疫以及核酸损伤和修复。结果与 ICA 重叠。

结论

我们确定了与暴露于 PM 2.5物种相关的几种重要的受扰动的血浆代谢物和代谢途径。这些物种与交通、燃油和木材烟雾有关。这是报告 PM 2.5物种暴露的代谢组学特征的最大研究,也是第一个使用 ICA 的研究。

更新日期:2021-02-24
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