Frequency and Clinical Relevance of Residual Bronchodilator Responsiveness in Adults With Asthma

BACKGROUND: Bronchodilator responsiveness (BDR) reflects airflow variability in asthma and is typically assessed after withholding therapy. However, its relevance under ongoing maintenance therapy remains unclear. OBJECTIVE: To investigate the frequency and clinical relevance of residual bronchodilator responsiveness (rBDR) in patients with asthma receiving maintenance therapy. METHODS: In 248 adults with moderate-to-severe asthma receiving inhaled corticosteroids, with or without long-acting bronchodilators, rBDR was assessed according to European Respiratory Society / American Thoracic Society 2005 and 2022 criteria. Maintenance therapy was continued, while short-acting bronchodilators were withheld for at least 12 hours before spirometry. Type 2 biomarkers, lung function including small airway function, patient-reported outcomes, and exacerbation rates were analyzed according to rBDR status. RESULTS: rBDR was present in approximately 23% of patients and was consistent across both European Respiratory Society / American Thoracic Society criteria. Maintenance therapy did not differ by rBDR status. Patients with rBDR had higher type 2 biomarkers, despite high-dose inhaled corticosteroid, including sputum eosinophils and fractional exhaled nitric oxide, more frequent fixed airflow obstruction, and greater small airway dysfunction. They also exhibited increased clinical disease burden, with poorer asthma control and frequent exacerbations, independent of underlying lung function and type 2 inflammation. CONCLUSIONS: rBDR is frequent and identifies patients with refractory type 2 inflammation and poor disease control. rBDR integrates inflammatory activity and functional impairment into a simple, widely available measure and may serve as a practical marker to identify residual disease burden and guide treatment optimization in routine clinical care.