Perturbations of the arginine metabolome following exposures to traffic-related air pollution in a panel of commuters with and without asthma

Abstract Background Mechanisms underlying the effects of traffic-related air pollution on people with asthma remain largely unknown, despite the abundance of observational and controlled studies reporting associations between traffic sources and asthma exacerbation and hospitalizations. Objectives To identify molecular pathways perturbed following traffic pollution exposures, we analyzed data as part of the Atlanta Commuters Exposure (ACE-2) study, a crossover panel of commuters with and without asthma. Methods We measured 27 air pollutants and conducted high-resolution metabolomics profiling on blood samples from 45 commuters before and after each exposure session. We evaluated metabolite and metabolic pathway perturbations using an untargeted metabolome-wide association study framework with pathway analyses and chemical annotation. Results Most of the measured pollutants were elevated in highway commutes ( p p Conclusions We detected numerous significant metabolic perturbations associated with in-vehicle exposures during commuting and validated metabolites that were closely linked to several inflammatory and redox pathways, elucidating the potential molecular mechanisms of traffic-related air pollution toxicity. These results support future studies of metabolic markers of traffic exposures and the corresponding molecular mechanisms.