The Effect of Long-Acting Dual Bronchodilator Therapy on Exercise Tolerance, Dynamic Hyperinflation and Dead Space during Constant Work Rate Exercise in COPD.

Abstract

PURPOSE\nWe investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere®) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (VD/VT) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in COPD.\n\n\nMETHODS\n48 COPD patients (62.9±7.6yrs; 33 male; GOLD spirometry stage 1/2/3/4, n=2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak work rate. Transcutaneous PCO2 (TcPCO2) measurement was used for VD/VT estimation.\n\n\nRESULTS\nBaseline post-albuterol FEV1 was 1.86±0.58L (63.6%±13.9 predicted). GFF increased FEV1 by 0.18±0.21L relative to PL (P<0.001). CWRET endurance time was greater after GFF vs. PL (383±184s vs 328±115s; difference 55±125s; P=0.013; C.I. 20-90s), a 17% increase. IC on GFF was above placebo IC at all time points and fell less with GFF vs. PL (P≤0.0001). Isotime tidal volume (1.54±0.50 vs. 1.47±0.45L; P=0.022) and ventilation (52.9±19.9 vs. 51.0±18.9 L/min; P=0.011) were greater, and respiratory rate was unchanged (34.9±9.2 vs. 35.1±8.0 br/min, P=0.865). Isotime VD/VT did not differ between groups (GFF 0.28±0.08 vs. PL 0.27±0.09; P=0.926).\n\n\nCONCLUSIONS\nGFF increased exercise tolerance in COPD patients and the increase was accompanied by attenuated dynamic hyperinflation without altering VD/VT. ClinicalTrials.Gov Identifier: NCT03081156.