BACKGROUND: Asthma control is commonly defined by symptom burden and recent exacerbation history. However, symptom-based clinical stability does not necessarily reflect biological quiescence, and heterogeneity in lung function and airway structure may persist despite apparent clinical control. This study aimed to determine whether blood-based metabolomic profiling can discriminate biologically distinct subgroups within a clinically stable asthma population. METHODS: We conducted a prospective observational study of adults with clinically stable asthma, defined by sustained symptom control and absence of recent exacerbations under maintenance inhaled corticosteroid-based therapy. Untargeted plasma metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry, and metabolite-derived subgroups were identified by consensus clustering. Lung function, airway structure, small-airway physiology, and peripheral immune cell profiles were compared across clusters, with associations assessed using regression analyses. RESULTS: . Cluster 3 (C3; T2-high) exhibited metabolite patterns associated with type 2 inflammatory features, including higher FeNO levels and blood eosinophil counts, while maintaining preserved airway structure. CONCLUSIONS: Metabolomic profiling reveals biologically distinct subgroups among clinically stable asthma, indicating that symptom-based stability does not necessarily reflect biological homogeneity.
Pyung et al. (Wed,) studied this question.