Lung deflation with indacaterol/glycopyrronium improves pulmonary microvascular blood flow in the CLAIM Study

Background: Lung and heart function are closely entangled. In particular, lung hyperinflation adversely affects cardiac function and pulmonary perfusion. The CLAIM study has shown that lung deflation with the fixed-dose LABA/LAMA combination Indacaterol/Glycopyrronium (IND/GLY) improves cardiac filling and cardiac output in hyperinflated COPD patients. Here, we report the impact of lung deflation on pulmonary microvascular perfusion and provide correlations with cardiac endpoints. Methods: The CLAIM study was a randomized, double-blind, single-center, placebo-controlled, 2 period cross-over trial. 62 hyperinflated patients (residual volume, RV > 135 % pred.) were enrolled to receive IND/GLY (110/50 mg q.d.) for 14 days followed by placebo or vice versa. Pulmonary blood flow (PBF) was measured using gadolinium-enhanced MRI at the end of each treatment period. Results: Lung hyperinflation as measured by elevated RV was inversely correlated with PBF (r=-0.40; p<0.0001). Lung deflation with IND/GLY significantly increased PBF by 11% compared to placebo (D=4.31 ml/min/100 ml lung volume; 95% CI: 1.32, 7.30; p=0.0056). This was consistently observed in almost all lobes of the lungs. PBF was significantly correlated with left-ventricular end-diastolic volume (r=0.34; p<0.0001) and cardiac output (r=0.48; p<0.0001). Conclusion: Pulmonary microvascular blood flow is correlated with pulmonary hyperinflation. Treatment with the dual bronchodilator IND/GLY reduces hyperinflation and improves microvascular blood flow in the lungs. This demonstrates a beneficial effect of lung deflation on the pulmonary microvasculature, which might contribute to improved cardiac output and reduction of symptoms.