A METABOLOMICS-BASED analysis of clinically stable asthma has identified biologically distinct patient subgroups despite similar symptom control, highlighting limitations in current approaches that rely primarily on symptoms and exacerbation history to assess disease stability.
In a prospective observational study, researchers investigated whether blood-based metabolomic profiling could uncover hidden biological differences among adults with apparently well-controlled asthma receiving maintenance inhaled corticosteroid therapy. The findings suggest that patients with comparable clinical control may still demonstrate substantial differences in airway structure, lung function, and immune activity.
Metabolomic Profiling Identified Three Distinct Asthma Endotypes
Using untargeted plasma metabolomic profiling with liquid chromatography–tandem mass spectrometry, investigators identified three distinct metabolite-derived asthma endotypes through consensus clustering analysis.
Although symptom burden and recent exacerbation history were similar across all groups, significant differences emerged in post-bronchodilator lung function, airway wall thickness, small-airway physiology, and peripheral immune cell signatures.
The first subgroup, termed “remodeling-prone” (C1), was characterised by increased relative abundance of glycerophospholipid-related metabolites. Patients in this cluster demonstrated lower post-bronchodilator FEV1 values, thicker airway walls, and elevated levels of innate lymphoid cells, suggesting ongoing structural airway changes despite apparent clinical stability.
The second subgroup, described as “biologically stable” (C2), showed preserved airway structure with thinner airway walls and higher post-bronchodilator FEV1 measurements. Researchers suggested this group may represent patients with genuinely controlled underlying disease biology.
The third subgroup, labelled “T2-high” (C3), exhibited metabolite signatures associated with type 2 inflammation. These patients had elevated fractional exhaled nitric oxide (FeNO) levels and increased blood eosinophil counts, although airway structure remained relatively preserved.
Findings Support Precision Medicine Approaches in Asthma Care
The authors noted that conventional asthma management strategies typically define disease control according to symptom severity and recent exacerbations. However, the current findings indicate that symptom-based assessments may fail to capture ongoing biological processes linked to airway remodelling or persistent inflammation.
The study adds to growing evidence supporting the use of precision medicine approaches in asthma care and suggests that metabolomic profiling could help identify patients at risk of disease progression despite apparently stable symptoms.
Researchers concluded that clinically stable asthma is biologically heterogeneous and that blood metabolomic profiling may provide a useful tool for identifying distinct disease endotypes. Further studies are needed to determine whether these metabolite-defined subgroups predict long-term outcomes or response to targeted therapies.
Reference
Pyung YJ et al. Metabolite-based endotypes of asthma reveal distinct clinical characteristics and immune cell signatures. Allergy. 2026; DOI:10.1111/all.70385.
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