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Plasma metabolite profiles in children with current asthma
R S Kelly1, J E Sordillo2, J Lasky-Su1
1Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Insights
Asthma in children may be linked to specific metabolites, including those from the nicotinamide pathway and gut bacteria. Further research could reveal new diagnostic or therapeutic targets for childhood asthma.
Area of Science:
- Metabolomics
- Pediatric Asthma Research
- Biomarker Discovery
Background:
- Understanding asthma pathophysiology in children is crucial.
- Metabolomic profiling offers a potential avenue for deeper insights.
Purpose of the Study:
- To identify differences in plasma metabolites between children with and without current asthma.
- To explore the metabolome's potential in distinguishing asthma cases from controls in mid-childhood.
Main Methods:
- Untargeted mass spectrometry was used to analyze plasma metabolites in a pediatric cohort (Project Viva).
- Partial least squares discriminant analysis assessed the overall metabolic profile's discriminatory ability.
- Logistic regression identified individual metabolites associated with asthma status, with replication in the VDAART trial.
Main Results:
- No systematic metabolomic difference was observed between children with and without asthma.
- Several metabolites, including N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate, showed nominal associations with current asthma.
- Replication of associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate in an independent cohort confirmed their potential relevance.
Conclusions:
- Current asthma in children is nominally associated with altered levels of specific metabolites.
- These include metabolites from the nicotinamide pathway and gut microbiome.
- Findings suggest potential biomarkers for childhood asthma, warranting further investigation.
Background:
Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology.
Objective:
To identify differences in plasma metabolites between children with and without current asthma at mid-childhood.
Methods:
We used untargeted mass spectrometry to measure plasma metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual metabolites that were differentially abundant by case-control status. We tested significant metabolites for replication in 411 children from the VDAART clinical trial.
Results:
There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a pyrimidine metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04).
Conclusions And Clinical Relevance:
Current asthma is nominally associated with altered levels of several metabolites, including metabolites in the nicotinamide pathway, and a bacterial metabolite derived from the gut microbiome.
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