Indacaterol/Glycopyrronium improves pulmonary ventilation and ventilation inhomogeneity in the CLAIM Study

Background: Ventilation of the lungs is disturbed in COPD. Bronchodilator treatment reduces airway obstruction and improves airflow in the lung. Analysis of lung ventilation might help to further characterize COPD patients and assess treatment effects. Objectives: The objective was to analyze treatment effects of indacaterol/glycopyrronium (IND/GLY) on regional lung ventilation. 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 mg q.d.) for 14 days followed by placebo or vice versa. Regional lung ventilation was measured under free breathing conditions in three coronal slices and in left and right sagittal slices using phase-resolved functional lung (PREFUL)-MRI. Results: Analysis of coronal lung slices showed that treatment with IND/GLY increased total fractional ventilation (FV) in the lung by 12.4% vs. placebo (relative LS Mean difference, p=0.0114) at day 14. Increase in total FV was associated with a reduction of hypoventilated areas (volume defect percentage) by 16.6% (p=0.0002) and an increase in homogeneity of lung ventilation by 12.4% (p<0.0001) vs. placebo, measured as reduction of the variation coefficient of FV. Similar results were obtained for sagittal slices, thereby supporting the validity of these results for the entire lung. Conclusion: IND/GLY improved lung ventilation in hyperinflated COPD patients. Importantly, this was associated with a reduction of hypoventilated areas and increased homogeneity. Improved regional lung ventilation might contribute to the reduction in dyspnea reported earlier for the CLAIM study.