Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study

Background: Reduction of hyperinflation and improvement of heart function, regional lung ventilation and pulmonary microvascular blood flow after indacaterol/glycopyrronium (IND/GLY) treatment was demonstrated in COPD.

Objectives: The objective of this analysis was to analyze treatment effects of indacaterol/glycopyrronium (IND/GLY) on pulmonary ventilation/perfusion match (VQM) and regional ventilation dynamics.

Methods: CLAIM was a randomized, double-blind, single-center, placebo-controlled, 2 period cross-over trial. 62 hyperinflated COPD patients were enrolled to receive IND/GLY (110/50 µg q. d.) for 14 days followed by placebo or vice versa. Regional lung ventilation dynamics and perfusion was measured in three coronal slices using phase-resolved functional lung (PREFUL)-MRI. The regional MRI flow-volume curves during continuous tidal volume breathing were rated from 0% to 100% by a correlation metric (CM) based on an intra-subject healthy reference. A threshold of 20 ml/min/100 ml (perfusion) and 90% (CM) were used to calculate VQM.

Results: Treatment with IND/GLY increased CM in the lung by a relative LS Mean difference vs. placebo of 6.2% (p < 0.0001) at day 14. Furthermore, the treatment was associated with an increase of perfusion by 8.2% (p = 0.0489) and an increase in VQM by 9.7% (p < 0.0001) vs. placebo. VQM changes correlate with the changes of LV EDV (p = 0.015), FEV1 (p < 0.0001) and FVC (p = 0.004).

Conclusion: IND/GLY leads to improved VQM and regional ventilation dynamics in hyperinflated COPD patients. This in turn likely leads to better oxygenation resulting in improved microvascular function, which results in improved ventricular filling.