Untargeted metabolomics on plasma from children with asthma, comparing exacerbation-prone to non-exacerbation-prone

ABSTRACT: Background: Some children with asthma remain poorly controlled and have recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and limited understanding of potential underlying mechanisms. Objective: We sought to quantify small molecules in the plasma of children with exacerbation- prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation- prone asthma. Methods: Plasma metabolites were extracted from four pediatric asthma cohorts (n=215 total, n=41 with exacerbation-prone asthma) and detected using a ZIC-HILIC column coupled to a Q Exactive HF mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects on high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. Metaboanalyst was used to identify pathways of interest. Concentrations were calculated by reference standardization to NIST SRM 1950. Results: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. Conclusions: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Asthma

SUBMITTER: Joshua Chandler  

PROVIDER: ST002251 | MetabolomicsWorkbench | Mon Jul 25 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench