Functional respiratory imaging reveals early structural and functional airway responses to benralizumab in severe eosinophilic asthma

Background Benralizumab improves outcomes in severe eosinophilic asthma (SEA). We aimed to evaluate early effects of benralizumab on airway pathophysiology using functional respiratory imaging (FRI). Methods In this prospective, single-arm study, 20 adults with SEA underwent CT at baseline, 4 and 12 weeks. Coprimary endpoints were changes in specific airway volume (siVaw) and resistance (siRaw) at functional residual capacity (FRC) and total lung capacity (TLC) at 12 weeks. Imaging outcomes included mucus score/volume and air-trapping. Results At week 12, siVaw increased at FRC by 0.16 mL/L (27%; 95% CI 0.01% to 0.31%; p = 0.02) and at TLC by 0.14 mL/L (14%; 95% CI 0.03% to 0.25%; p = 0.02); siRaw at TLC decreased by -0.41 kPa & centerdot;s/L (-24%; 95% CI -0.80% to -0.01%; p = 0.04). siRaw at FRC increased (2.99 kPa & centerdot;s/L; 95% CI -4.57 to 10.54; p=0.42), with a significant relative change (293%; p=0.03) that lost significance after excluding outliers. siVaw at FRC increased early (week 4: 0.19 mL/L; 33%; 95% CI 0.03% to 0.34%; p = 0.01). At week 12, the mucus score decreased by 0.41 (95% CI -0.67 to -0.14; p<0.01), and air-trapping by 5.5% (95% CI -8.8 to -2.1; p < 0.01). Changes in siVaw and mucus correlated with improvements in forced expiratory volume in 1 s (r = 0.66 and -0.77; both p<0.01) and Saint George's Respiratory Questionnaire (mucus: r = 0.45; p = 0.05). Conclusions Benralizumab treatment in SEA was associated with early improvements in airway volume, resistance, mucus and air-trapping, correlating with better lung function and quality of life. These findings support FRI to monitor early treatment effects.