Abstract
BackgroundMechanisms 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. ObjectivesTo 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. MethodsWe 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. ResultsMost of the measured pollutants were elevated in highway commutes (p < 0.05). From both negative and positive ionization modes, 17,586 and 9087 metabolic features were extracted from plasma, respectively. 494 and 220 unique features were associated with at least 3 of the 27 exposures, respectively (p < 0.05), after controlling confounders and false discovery rates. Pathway analysis indicated alteration of several inflammatory and oxidative stress related metabolic pathways, including leukotriene, vitamin E, cytochrome P450, and tryptophan metabolism. We identified and annotated 45 unique metabolites enriched in these pathways, including arginine, histidine, and methionine. Most of these metabolites were not only associated with multiple pollutants, but also differentially expressed between participants with and without asthma. The analysis indicated that these metabolites collectively participated in an interrelated molecular network centering on arginine metabolism, underlying the impact of traffic-related pollutants on individuals with asthma. ConclusionsWe 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.
Highlights
Asthma is the most prevalent chronic respiratory disease worldwide, accounting for over 495,000 global deaths annually (Roth et al 2018)
We found a similar number of significant features associated with the pollutants in both the subgroup with and without asthma (Eq 2), 40.1% of which were shared by both subgroups, while 36.6% were observed only in the subgroup with asthma and 23.3% observed only in the subgroup without asthma
Crossover small panel study design and High-resolution metabolomics (HRM) analytical platform, we detected numerous significant metabolic perturbations associated with in-vehicle exposures during commuting and verified metabolites that were closely linked and connected in several inflammatory and redox pathways
Summary
Asthma is the most prevalent chronic respiratory disease worldwide, accounting for over 495,000 global deaths annually (Roth et al 2018). The impact of urban air pollution on asthmatic population has been a long-standing environmental health concern (Cohen et al 2017; Soriano et al 2017). Traffic related air pollution (TRAP), in particular, comprises over 25% of urban air pollution and has been linked in observational and controlled studies to asthma exacerbation and hospitalizations (Health Effects Institute 2010). Less is known about the specific components of TRAP that may be causally responsible for these findings. Traffic emissions are highly heterogeneous, consisting of hundreds of organic and inorganic chemicals. The lack of sensitive and specific biomarkers has hindered research into the etiological basis and acute health risk associated with exposure to TRAP in individuals with asthma
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