In patients with moderate to severe chronic obstructive pulmonary disease (COPD), pharmacologic intervention with indacaterol/glycopyrronium (IND/GLY) is associated with improvements in regional ventilation and pulmonary microvascular blood flow (PMBF), according to findings published in the American Journal of Respiratory and Critical Care Medicine.
The Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated COPD Patients study (CLAIM; ClinicalTrials.gov Identifier: NCT02442206) was a double-blind, randomized single-center 2-period crossover clinical trial conducted at the Fraunhofer Institute of Technology and Experimental Medicine in Hannover, Germany.
Investigators sought to determine the effect of lung deflation with IND/GLY on regional pulmonary ventilation and PMBH by using magnetic resonance imaging (MRI) in patients with COPD and hyperinflation. They used gadolinium-enhanced MRI and phase-resolved functional lung MRI to measure PMBH and regional ventilation, respectively, in patients with COPD who received IND/GLY and compared these values with measures in those who received placebo.
A total of 62 patients were randomly assigned to receive once-daily IND/GLY (110/50 µg) for 14 days, followed by placebo for 14 days, or vice versa. All of the treatment periods were separated by a 14-day washout. Overall, 60 patients were included in the per-protocol analysis.
Based on MRI measurements, significant improvements were reported in total PMBH (P =.006) and regional PMBH with the exception of the middle lobe of the right lung (P values for individual lobes ranged between .004 and .022) with IND/GLY vs placebo.
Regional ventilation also improved significantly with IND/GLY, as demonstrated by the following findings: a 12.4% increase compared with placebo (P =.011); a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (with the cutoff defined as 0.075 regional ventilation; P =.0002); and a 15.7% decrease in the coefficient of variation of regional ventilation compared with placebo (P <.0001).
Being a single-center study performed in an exclusively white population with COPD and hyperinflation represent the major limitations of the study. These factors may restrict the generalizability of the data to the wider population of individuals with COPD.
The investigators concluded that IND/GLY-mediated deflation is possible in patients with COPD, accompanied by a notable increase in PMBH, thus underscoring the potential association of increased hyperinflation with reduced PMBH and implying a negative effect of lung hyperinflation on PMBH. Additional research is warranted to explore whether improved PMBH and regional ventilation lead to better gas exchange and improved ventilation/perfusion matching in this patient population.
Disclosures: The study was funded by Novartis Pharma GmbH, Germany.
Vogel-Claussen J, Schönfeld C-O, Kaireit TF, et al. Effect of indacaterol/glycopyrronium on pulmonary perfusion and ventilation in hyperinflated COPD patients (CLAIM): a double-blind, randomised, crossover trial [published online January 14, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201805-0995OC