Early benefit of mepolizumab on small airways in severe asthma: insights from the IMPOSE study

Background Severe eosinophilic asthma adversely affects small airway function, but effective therapeutic options are limited. The IMPOSE trial (www.clinicaltrials.gov identifier number NCT05147155) assessed the early and sustained effects of mepolizumab on small airways in patients with severe eosinophilic asthma using impulse oscillometry (IOS). Methods The study comprised 130 participants: 40 with uncontrolled severe asthma initiating mepolizumab, 40 with well-controlled severe asthma and 50 healthy controls. Lung function was assessed with IOS, spirometry and plethysmography at baseline and at 1, 3 and 6 months post-treatment. Clinical outcomes included asthma control, quality of life and medication adherence. Results Small airway function significantly improved within 1 month of mepolizumab initiation, shown by reductions in resonance frequency (fres), indicating decreased small airway resistance undetectable by spirometry. By 6 months, sustained improvements in forced expiratory flow at 25-75% of forced vital capacity, total lung capacity % of predicted value, fres, area under the reactance curve and the difference in resistance between 5 and 20 Hz (R5-20) were evident, accompanied by better asthma control and quality-of-life scores. Negative correlations between change in resistance at 5 Hz and change in R5-20 with change in Asthma Control Test score at 6 months suggested that decreased small-airway resistance and heterogeneity correlated with improved asthma control. These benefits were particularly prominent in patients without fixed airway obstruction. Notably, even patients with irreversible airflow limitations saw improvements in small airway dysfunction, suggesting that mepolizumab may provide benefits even in cases of irreversible airway changes. Conclusions This study is the first to demonstrate that mepolizumab has a rapid and sustained therapeutic effect on small airways in severe eosinophilic asthma, as shown by IOS. IOS proves to be a valuable tool for monitoring the effects of biologic treatments on small airway function, revealing insights beyond those provided by spirometry.