Small airway dysfunction as a functional barrier to spirometry-defined clinical remission in severe asthma treated with biologic therapies

Background and objective Small airway dysfunction (SAD) is a frequent yet underrecognized feature of severe asthma that may influence treatment outcomes and remission. This study evaluated the prevalence of SAD using impulse oscillometry (IOS) and spirometry, and its impact on clinical remission on biologic therapy. Methods Severe asthma patients were assessed for SAD by IOS, spirometry, and combined modalities. Baseline characteristics, biomarkers, and clinical outcomes were compared between patients with and without SAD. Changes after 1 year of biologic therapy were analyzed, and associations between SAD and clinical remission criteria (CR) were evaluated. Results SAD was most frequently detected by IOS (66.9%), followed by spirometry (54.9%). Patients with SAD were significantly older and had higher rates of allergic rhinitis, diabetes, and hypertension (all P < 0.05). Baseline pulmonary function showed greater airflow limitation and peripheral airway resistance in the SAD group (P < 0.001). Biologic therapy significantly improved asthma control, reduced exacerbations, and enhanced FEV 1 (P < 0.001). Blood eosinophil count (BEC) decreased significantly in both mean and median values, whereas FeNO and IgE did not show significant overall change. However, categorical analysis revealed significant shifts in all 3 biomarkers, with the greatest improvement in BEC. Despite these benefits, CR was achieved in only 17.3% of patients and was significantly less frequent among those with SAD (P ≤ 0.01). Post-biologic BEC levels were significantly lower in patients with SAD defined by spirometry or combined modalities. Conclusion SAD is common in severe asthma and is associated with older age, metabolic and allergic comorbidities, and worse baseline lung function. While biologic therapy yields substantial clinical and functional improvement, the persistence of SAD predicts a lower likelihood of CR and distinct biomarker dynamics, underscoring the importance of assessing small airway function in personalized asthma management.