Impact of anti-eosinophilic biologic strategies on bronchial hyperreactivity in severe asthma

Mepolizumab and Benralizumab represent two anti-eosinophilic biologic strategies (A-EBS) for the treatment of severe uncontrolled eosinophilic asthma. Bronchial hyperreactivity (BH) is a hallmark of asthma, whereas A-EBS impact on BH is not fully clarified. We aimed to evaluate the change in BH, estimated through bronchodilator response (BDR), after 1 year of A-EBS in severe asthmatics. 27 patients (Mepolizumab n=16 and Benralizumab n=11) were included in this prospective cohort study. Lung function parameters were collected at baseline and 20 minutes after intake of salbutamol 400 mcg, both at the beginning (T0) and after one year of an A-EBS (T12). Blood Eosinophil Count (BEC), Fraction Exhaled Nitric Oxide (FeNO) and Asthma Control Test (ACT) were also recorded. Data were expressed as median (IQR) and analyzed with the Mann-Whitney test. Statistical significance was set at a p-value<0.05. No statistical significance was found for the adjusted ΔFEV1% change between T0 and T12 [0.09% (0.16-0.02) vs 0.1% (0.19-0.05); p=0.336]. ACT was 16 (18.5-12.5) at T0 vs 21 (24-19) at T12; p<0.0001. BEC was 1040/µL (1035-410) at T0 vs 65/µL (132.5-0) at T12; p<0.0001. FeNO was 40 ppb (67.5-17) at T0 vs 26 ppb (62-18.5) at T12; p=0.441. We found no significant change in BHR after one year of A-EBS, although a significant improvement in ACT and BEC reduction. Interestingly, FeNO values, despite lowered, were not significantly reduced, showing a persisting share of airway inflammation. In light of these data, we hypothize that BHR might be related to inflammatory mechanisms linked to additional cytokines and barrier alarmins, beyond IL-5.