Abstract
INTRODUCTION: Eosinophil depletion with benralizumab reduces exacerbations and improves disease control and FEV(1) in patients with severe eosinophilic asthma. However, few studies have investigated the effect of biologics on small airways dysfunction (SAD) even though the latter correlates better with poor asthma control and type 2 inflammation. METHODS: 21 GINA-defined severe asthma patients who were treated with benralizumab and who had baseline oscillometry-defined SAD were included in this study. Here, SAD was diagnosed only if patients satisfied both R5-R20≥0.10 kPa/L/s and AX≥1.0 kPa/L. The mean duration of follow-up between pre-benralizumab versus post-benralizumab clinical measurements was 8 months. RESULTS: Mean values for FEV(1)% and FVC% but not FEF(25%-75%) significantly increased following benralizumab, along with significant reductions in Asthma Control Questionnaire (ACQ). There were no significant improvements in R5-R20, X5 or AX, while the mean (SEM) PBE count fell to 23 (14) cells/µL. In a responder analysis, n=8/21 and n=12/21 patients experienced improvements exceeding biological variability of 0.04 kPa/L/s and 0.39 kPa/L in R5-R20 and AX, respectively, in severe asthma. N=10/21, n=10/21 and n=11/21 patients experienced improvements in FEV(1), FEF(25-75) and FVC exceeding biological variability of 150 mL, 0.210 L/s and 150 mL, respectively. In contrast, n=15/21 patients experienced an improvement in ACQ greater than minimal clinical important difference of 0.5 units. CONCLUSION: Eosinophil depletion with benralizumab improves spirometry and asthma control but does not improve spirometry-measured or oscillometry-measured SAD in severe asthma in a real-life setting.