Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5-R20) and spirometry FEF25-75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV₁, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5-R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5-R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (<i>p</i> = 0.04), while predicted FEF25-75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (<i>p</i> < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (<i>p</i> < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (<i>p</i> = 0.01). Improvements in R5-R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.