Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department of Medicine, The University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada.
Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-171 65, Sweden.
Environ Sci Technol. 2022 Jun 7;56(11):7107-7118. doi: 10.1021/acs.est.1c07268. Epub 2022 Jan 19.
Eicosanoids are potent regulators of homeostasis and inflammation. Co-exposure to allergen and diesel exhaust (DE) have been shown to lead to eosinophilic inflammation, impaired airflow, and increased airway responsiveness. It is not clear whether eicosanoids mediate the mechanism by which these exposures impair lung function. We conducted a randomized, double-blinded, and four-arm crossover study. Fourteen allergen-sensitized participants were exposed to four conditions: negative control; allergen-alone exposure; DE and allergen coexposure; coexposure with particle-reducing technology applied. Quantitative metabolic profiling of urinary eicosanoids was performed using LC-MS/MS. As expected, allergen inhalation increased eicosanoids. The prostacyclin metabolite 2,3-dinor-6-keto-PGF (PGF, prostaglandin F) increased with coexposure, but particle depletion suppressed this pathway. Individuals with a high genetic risk score demonstrated a greater increase in isoprostane metabolites following coexposure. Causal mediation analyses showed that allergen induced airflow impairment was mediated via leukotriene E and tetranor-prostaglandin D metabolite. Overall, DE exposure did not augment the allergen's effect on urinary eicosanoids, except insofar as variant genotypes conferred susceptibility to the addition of DE in terms of isoprostane metabolites. These findings will add to the body of previous controlled human exposure studies and provide greater insight into how complex environmental exposures in urban air may influence individuals with sensitivity to aeroallergens.
类二十烷酸是体内平衡和炎症的有效调节剂。过敏原和柴油废气（DE）的共同暴露已被证明会导致嗜酸性粒细胞炎症、气流受限和气道高反应性增加。目前尚不清楚类二十烷酸是否介导了这些暴露损害肺功能的机制。我们进行了一项随机、双盲、四臂交叉研究。14 名过敏原致敏参与者被暴露于四种条件下：阴性对照；单独过敏原暴露；DE 和过敏原共同暴露；共同暴露于颗粒减少技术。使用 LC-MS/MS 对尿类二十烷酸进行定量代谢谱分析。如预期的那样，过敏原吸入会增加类二十烷酸。前列腺素环氧化物代谢物 2,3-二去甲-6-酮-PGF（PGF，前列腺素 F）随着共同暴露而增加，但颗粒耗竭抑制了这一途径。具有高遗传风险评分的个体在共同暴露后，异前列烷代谢物的增加更为明显。因果中介分析表明，过敏原引起的气流受限是通过白三烯 E 和四氢前列腺素 D 代谢物介导的。总的来说，DE 暴露并没有增强过敏原对尿类二十烷酸的作用，除非变异基因型使个体易受 DE 影响，这在异前列烷代谢物方面表现得更为明显。这些发现将增加以前的人类对照暴露研究的数量，并提供更多关于城市空气中复杂环境暴露如何影响对空气过敏原敏感的个体的信息。
