Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF2α, 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

中文翻译：

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质谱分析揭示了健康人在控制接触生物柴油废气后单羟基脂肪酸和相关脂质的血浆水平发生变化

实验性人体接触研究是研究急性吸入颗粒物和其他空气污染成分对健康造成的不利影响的有效工具。在这项随机和双盲交叉研究中，我们研究了健康人在受控生物柴油废气暴露后对生物活性脂质代谢物水平的全身影响，并将其与单独暴露情况下的过滤空气进行了比较。来自 14 名健康志愿者的血浆中的类二十烷酸和其他 oxylipins 以及内源性大麻素和相关脂质在基线和暴露 1 小时后的三个后续时间点（2、6 和 24 小时）进行量化。开发了基于液相色谱 (LC) 与串联质谱 (MS/MS) 方法相结合的方案，以检测生物柴油废气暴露后循环水平的时间变化。尾气是由柴油发动机产生的，柴油发动机使用未稀释的油菜籽甲酯燃料。在分析的 51 种脂质代谢物中，PGF2α、9,10-DiHOME、9-HODE、5-HETE、11-HETE、12-HETE 和 DEA 对生物柴油废气暴露表现出显着的响应，而不是过滤空气。其中，24 小时的 9-HODE 和 5-HETE 在 10% 的错误发现率截止（p < 0.003）中幸存下来。因此，大多数响应性脂质代谢物是单羟基脂肪酸。我们得出的结论是，使用 LC-MS/MS 检测循环生物活性脂质代谢物对生物柴油废气暴露的变化是可能的，重点是具有炎症相关特性的代谢物以及对心血管健康和疾病的影响。这些观察结果有助于未来对空气污染影响的调查，