Small Airways Disease as a Novel Target for Mepolizumab in Asthma. The SASAM Prospective Real-Life Study

Mepolizumab represents an effective strategy for severe eosinophilic asthma. Small airways disease (SAD) defines a peculiar asthma phenotype related to worse disease control. Limited and indirect findings are currently available on the effect of mepolizumab on SAD. Objectives: We investigated the impact of mepolizumab on SAD assessed through impulse oscillometry (IOS) and spirometry. As secondary outcomes, we tested the correlation between SAD and clinical, functional and inflammatory parameters. Methods: This is a prospective cohort study including severe eosinophilic asthmatics eligible for mepolizumab performed between 2021 and 2023. IOS (R5-R20) and spirometry (FEF25-75%, TLC%, RV/TLC%) parameters were assessed at baseline and over 1 year of mepolizumab. Other functional (FEV1%), clinical (ACT, number of asthma exacerbations/previous year, use of OCS) and inflammatory data (BEC and FeNO) were concomitantly collected for correlations. Results: A total of 18 patients (mean age 61.1 ± 12.0 y; 10 (55.5%) female) were included. Longitudinal data from 16 patients showed that R5-R20 significantly improved after 12-months treatment (p: 0.03), as well as FEF25-75% (p: 0.04) and TLC% (0.04). FEV1% and ACT showed a concomitant improvement (p: 0.03 and <0.01, respectively). All the steroid-dependent subjects discontinued OCS after 3 months and the percentage of subjects experiencing exacerbations significantly decreased (p: <0.01). As per drug effect, BEC consistently decreased (p: <0.01). The decrease in R5-R20 correlated with an improvement in FEF25-75% (r: -0.40 p: 0.048) and ACT at T12 (r: -0.59 p: 0.02). Conclusions: Twelve months treatment with mepolizumab improved R5-R20, suggesting its additional role as a targeted treatment for distal lung regions. This improvement also correlated with a clinically relevant amelioration of asthma symptoms.