Mepolizumab improves small airway function in severe eosinophilic asthma

Background: Mepolizumab is an anti-IL5 monoclonal antibody approved for severe eosinophilic asthma (EA) primarily to reduce exacerbations. In clinical trials, mepolizumab is associated with modest improvements in symptom control and FEV1. The time course of changes in small airway function are unknown. Aim: To describe changes in ventilation inhomogeneity as a marker of small airway function after commencing mepolizumab. Methods: Prospective cohort of adults with severe EA commencing mepolizumab according to standard criteria. Measurements at baseline and one month after the first injection included the Asthma Control Questionnaire (ACQ5), spirometry and multiple breath nitrogen washout to measure global (Lung Clearance Index, LCI) and regional indices of ventilation inhomogeneity attributed to the acinar (Sacin) and conducting (Scond) airways. All other asthma therapy remained unchanged. Paired t-tests and Pearson’s correlation were used. Results: 12 patients (7 male) mean (SD) age 64 (13) years, were studied. Eosinophil count at baseline was 1.45 (3.15) x109/L. At one month, ACQ5, post bronchodilator FEV1, FEV1/FVC ratio, LCI and Sacin improved significantly (Table 1). The change in ACQ5 was only associated with the change in Sacin (r=0.49, p=0.05). Conclusion: Improved symptom control was seen rapidly after commencing mepolizumab in patients with severe EA. The early improvement in small airway function may be a significant contributor to the therapeutic response.