Related Experiment Video
Updated: Aug 29, 2025
Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations
Kirsten A Cottrill1, Susan T Stephenson1, Ahmad F Mohammad1
1Department of Pediatrics, Emory University, Atlanta, Ga.
Insights
Researchers identified 32 unique plasma metabolites differing in children with exacerbation-prone asthma. These findings suggest potential biomarkers for identifying children at high risk for asthma exacerbations.
Area of Science:
- Pediatric Pulmonology
- Metabolomics
- Biomarker Discovery
Background:
- Childhood asthma often remains poorly controlled despite inhaled corticosteroid treatment.
- Recurrent exacerbations in children lack reliable predictors and understanding of underlying mechanisms.
- Current management strategies have limitations in identifying exacerbation-prone asthma.
Purpose of the Study:
- To quantify plasma small molecules in children with exacerbation-prone asthma using metabolomics.
- To investigate differences in the plasma metabolome between exacerbation-prone and non-exacerbation-prone pediatric asthma.
- To identify potential metabolic pathways associated with severe asthma exacerbations in children.
Main Methods:
- Mass spectrometry-based metabolomics was employed to analyze plasma samples from 215 children across 4 cohorts.
- 32 unique, cohort-independent metabolites were identified using MetaboAnalyst software.
- Metabolite concentrations were compared to healthy children and analyzed for pathway enrichment, focusing on arginine, lysine, and methionine pathways.
Main Results:
- 32 unique plasma metabolites were found to differ between children with exacerbation-prone and non-exacerbation-prone asthma.
- Most identified metabolites were decreased in both asthma groups compared to healthy children, with a more pronounced reduction in exacerbation-prone asthma.
- Arginine, lysine, and methionine metabolic pathways were significantly impacted in children with exacerbation-prone asthma.
Conclusions:
- Perturbations in specific plasma metabolites, particularly those in arginine, lysine, and methionine pathways, are associated with exacerbation-prone asthma in children.
- These identified plasma metabolites show promise as potential biomarkers for exacerbation-prone asthma.
- Further validation studies are necessary to confirm the utility of these metabolites in clinical practice.
Background:
The asthma of some children remains poorly controlled, with 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 only a limited understanding of the 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 4 pediatric asthma cohorts (215 total subjects, with 41 having exacerbation-prone asthma) and detected with a mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects receiving high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. MetaboAnalyst software was used to identify pathways of interest. Concentrations were calculated by reference standardization.
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.
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