The effect of inhaled extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide on distal and central airway indices, assessed using Functional Respiratory Imaging in COPD (DARWiIN)

Background This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function. Methods Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV aw ) and resistance (siR aw ) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siV aw and siR aw changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siV aw and siR aw at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV 1 ) and COPD Assessment Test (CAT) were also assessed. Results There were no significant changes in pre-dose siV aw or siR aw at TLC from baseline to V3, although at FRC there was a significant decrease in mean siR aw in the distal airways (− 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siV aw and siR aw (siV aw : 39.8% and 62.6%; siR aw : − 51.1% and − 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siV aw : 77.9%; siR aw : − 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV 1 was 62.2 mL (p = 0.0690), and in CAT total score was − 3.30 (p < 0.0001). Conclusions In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021