Effect of dupilumab on small airway dysfunction in real-life severe asthma: Japanese multi-center prospective cohort

<bold>Background:</bold> Dupilumab, anti-IL 4 receptor α, reduces exacerbation and oral corticosteroid dose and improves quality of life, symptom control, and lung function. However, its effect on small airway dysfunction (SAD) is not fully understood. <bold>Aims:</bold> To assess the effect of dupilumab on SAD in severe asthma patients in a Japanese multi-center prospective cohort. <bold>Methods:</bold> The subjects included 99 severe asthma patients. Large airway function, including FEV1, and small airway function, including forced expiratory flow at 25%-75% of forced vital capacity (FEF25-75%), the difference between respiratory system resistance at 5 Hz and 20 Hz (R5−R20), respiratory system reactance at 5 Hz (X5), resonant frequency (Fres), and area of reactance (AX), were assessed after 24 weeks treatment with dupilumab. In addition, the patients were classified into normal lung function (defined as %FEV1 ≥ 80% and %FEF25-75% ≥ 65%), SAD (defined as %FEV1 ≥ 80% and %FEF25-75% < 65%), and both large and small airway dysfunction (LSAD) (defined as %FEV1 < 80% and %FEF25-75% < 65%). <bold>Results:</bold> Overall, %FEV1, %FEF25-75%, R5, and R20 significantly improved after 24 weeks of treatment. There were 37 patients with normal lung function, 20 with SAD, and 42 with LSAD. FEV1 improved in patients with normal lung function, whereas FEF25-75% improved in patients with SAD. There was no significant improvement in oscillometric parameters. In patients with LSAD, however, FEV1, FEF25-75%, R5, R20, R5−R20, X5, and AX significantly improved. <bold>Conclusions:</bold> SAD, as reflected by FEF25-75%, significantly improved by 24 weeks of dupilumab treatment. Oscillometric parameters for SAD only improved in patients with LSAD.