Metabolomics identifies disturbances in arginine, phenylalanine, and glycine metabolism as differentiating features of exacerbating atopic asthma in children

• Type of Material: Article
• Authors: Kirsten A. Cottrill, Emory University; Joshua Chandler, Emory University; Seibi Kobara, Emory University; Susan T. Stephenson, Emory University; Ahmad F. Mohammad, Emory University; Mallory Tidwell, Children's Healthcare of Atlanta; Carrie Mason, Children's Healthcare of Atlanta; Morgan Van Dresser, Children's Healthcare of Atlanta; James Patrignani, Emory University; Rishikesan Kamaleswaran, Emory University; Anne Fitzpatrick, Emory University; Jocelyn Grunwell, Emory University
• Language: English
• Date: 2023-08-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacig.2023.100115
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology: Global
• Volume: 2
• Issue: 3
• Grant/Funding Information: Supported by National Institutes of Health grants R01 NR018666, K24 NR018866, T32 HL116271, and UL 1TR002378.
• Keywords: inflammation; glycine; asthma control; Arginine; status asthmaticus; phenylalanine; asthma exacerbation; asthma in children; metabolomics
• Research Categories: Environmental Sciences; Biology, Molecular

Abstract

Background: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population. Objective: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles. Methods: A total of 98 children aged 6 through 17 years with exacerbating asthma (n = 69) and stable asthma (n = 29) underwent clinical characterization procedures and submitted plasma samples for metabolomic analyses. High-confidence metabolites were retained and utilized for pathway enrichment analyses to identify the most relevant metabolic pathways that discriminated between groups. Results: In all, 118 and 131 high-confidence metabolites were identified in positive and negative ionization mode, respectively. A total of 103 unique metabolites differed significantly between children with exacerbating asthma and children with stable asthma. In all, 8 significantly enriched pathways that were largely associated with alterations in arginine, phenylalanine, and glycine metabolism were identified. However, other metabolites and pathways of interest were also identified. Conclusion: Metabolomic analyses identified multiple perturbed metabolites and pathways that discriminated children with exacerbating asthma who were hospitalized for status asthmaticus. These results highlight the complex biology of inflammation in children with exacerbating asthma and argue for additional studies of the metabolic determinants of asthma exacerbations in children because many of the identified metabolites of interest may be amenable to targeted interventions.