Aim and objectives: Small Airway Disease (SAD) has gained relevance being this related to an asthma phenotype characterized by a higher degree of severity, a worse symptom control and an increased risk of exacerbations. Impulse Oscillometry (IOS) is the Gold Standard to directly assess the periphery of the lungs, with a R5-R20 >0.07 supportive of SAD. Mepolizumab represents an effective strategy for severe eosinophilic asthma, however, limited evidence is available about its benefits on SAD. First, we aimed to assess whether SAD may represent a treatment target for Mepolizumab and then if an improvement in SAD relates to standard functional and clinical endpoints.

Methods: Twelve subjects were included in a longitudinal observational study. IOS (R5-R20), functional (FEV1% pred.) and clinical (ACT score, exacerbation rate) endpoints were recorded at baseline (T0) and after 6 months of mepolizumab treatment (T6). Data series were tested for normality and expressed as mean±SD.

Results: SAD was present in 83% of subjects at baseline versus 58% at T6 (p=0.035). The R5-R20 value was reduced during mepolizumab (0.27±0.13 at T0 vs 0.19±0.17 - p= 0.03).
FEV1% pred. was 72.9±26% at baseline vs 85.9±35% at T6 (p=0.03). At baseline, 83% of subjects showed uncontrolled asthma (i.e ACT<20) compared to 42% at T6 (p=0.03) with an improvement exceeding the tool MCID (14.4±5.0 vs 19.3±3.7 -p=0.01). The percentage of subjects that experienced at least one exacerbation at baseline was 75 vs 16 after 6 months (p=0.004). 

Conclusions: Our findings support a significant benefit of Mepolizumab on SAD, paralleled by the considerable improvement in lung function and asthma control. Results should be confirmed in wider populations.