Small airway abnormalities in asthmatic patients with persistent airflow limitation

Background: A subset of patients with asthma develops persistent airflow limitation (PAL) despite optimal treatment. The role of small airways dysfunction (SAD) in this phenotype, and its relationship with symptoms, remains incompletely understood. Objectives: To assess small airways function in asthmatic patients with PAL and compare it with patients with fully reversible asthma and with COPD; and to explore correlations between small airway indices and patient-reported outcomes. Methods: We enrolled 60 patients (20 with asthma and PAL, 20 with fully reversible asthma, 20 with COPD) matched for age, sex, and pre-bronchodilator FEV1. Small airways function was evaluated using impulse oscillometry (IOS; R5–R20) and single-breath nitrogen washout test (SBNWT; dN2). Patients completed a daily symptom diary (dyspnea, cough, sputum, and rescue medication use) over four weeks. Results: Compared with fully reversible asthma, asthmatic patients with PAL showed significantly higher dN2 and R5–R20 values, though less pronounced than in COPD. SAD (R5–R20 > 0.07 kPa·L−1·s) was present in all COPD patients, 79% of PAL patients, and 37% of reversible asthma patients (p < 0.001). In PAL, R5–R20 correlated strongly with dyspnea scores (r = 0.64, p < 0.001). In reversible asthma, R5–R20 correlated with cough and rescue medication use, whereas in COPD, symptoms were primarily related to residual volume. Conclusions: Small airways dysfunction is highly prevalent in asthmatic patients with PAL and significantly contributes to daily symptom burden. Its intermediate severity between COPD and reversible asthma suggests that SAD plays a central role in the pathogenesis of fixed obstruction, suggesting a potential role for targeted diagnostic and therapeutic strategies.