What does this research mean for the field?

Normal-weight and obese children with asthma exhibit divergent metabolic mechanisms, with normal-weight asthma characterized by enhanced TCA cycle activity and sphingomyelin-linked inflammation, and obesity-related asthma driven by oxidative stress from chronic inflammation. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to identify the metabolic mechanisms driving obesity-related asthma in children of varying body weights.

May 17, 2026Open Access

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A Multi-Omics Approach Uncovers Divergent Mechanisms of Asthma in Normal Weight and Obese Children

Key Points

This study aims to identify the metabolic mechanisms driving obesity-related asthma in children of varying body weights.
Participants included 95 normal weight asthmatic and 67 non-asthmatic children, and 99 overweight/obese asthmatic and 100 non-asthmatic children aged 6–17 years.
Plasma metabolomic and lipidomic profiling was performed, followed by orthogonal partial least squares discriminant analysis (OPLS-DA) to assess differences within BMI groups.
Gaussian Graphical Models were used to map metabolic-clinical interactions.
In OPLS-DA models, normal weight asthmatic children showed a R2Y of 0.72 compared to 0.65 in overweight/obese, indicating stronger separation from controls.
Asthma was linked to distinct lipid changes: TCA intermediates and sphingomyelins in normal weight and phosphatidylcholines in obese children.
Connections were found between altered sphingomyelins and interleukins, with associations to increased leptin in normal weight asthmatics.

Abstract

Background: Children with obesity-related asthma exhibit poorer symptom control and more frequent exacerbations than their normal-weight peers, but the underlying metabolic mechanisms are unclear. This study aimed to identify drivers of obesity-related asthma through untargeted plasma metabolomic and lipidomic profiling. Methods: Plasma was obtained from normal weight (NW) asthmatic (n = 95) and non-asthmatic (n = 67) and overweight/obese (OO) asthmatic (n = 99) and non-asthmatic (n = 100) children (6–17 years). We assessed metabolic and lipidomic differences between asthmatics and controls within each BMI group using orthogonal partial least squares discriminant analysis (OPLS-DA), examined overlap with the adult Qatar Biobank cohort, and mapped metabolic–clinical interactions using Gaussian Graphical Models. Results: In the fitted OPLS-DA models, separation between asthmatic and control groups was stronger in the NW group (R2Y = 0.72/0.52) than in OO (R2Y = 0.65/0.63) children. Asthma was associated with altered tricarboxylic acid (TCA) intermediates, ether-linked phosphatidylethanolamines, and sphingomyelins (SM) in NW, and with phosphatidylcholines, lysophosphatidylcholines, and phosphatidylethanolamines in OO. Integrating metabolomic, lipidomic, and clinical data revealed connections between altered SMs and interleukins, and TCA intermediates and electrolytes, all associated with elevated leptin in NW. An increased residual volume to total lung capacity ratio in OO was associated with phospholipid shifts. The overall dynamics in lipid metabolism with asthma, conditioned on BMI, was also observed in the adult Qatar Biobank cohort. Conclusions: Among NW children with asthma, we found enhanced TCA cycle activity and inflammation linked to altered SM metabolism, whereas in OO, the findings suggest oxidative stress arising from chronic obesity-related inflammation. These data reveal BMI-specific metabolic mechanisms of pediatric asthma that might inform precision approaches to disease management.

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A Multi-Omics Approach Uncovers Divergent Mechanisms of Asthma in Normal Weight and Obese Children

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