LAUSR

BACKGROUND Chronic Obstructive Pulmonary Disease (COPD) is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal mortality. Overnight deterioration of inspiratory capacity (IC) and forced expiratory volume in 1 second (FEV1) have previously been documented. However, the precise nature of this deterioration and mechanisms by which evening bronchodilators may mitigate this have not been studied. RESEARCH QUESTION To determine the effect of evening dosing of dual, long-acting bronchodilators on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND). STUDY DESIGN A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilators (BD; aclidinium bromide/formoterol fumarate dihydrate, 400/12 mcg) or placebo (PL) on morning trough IC (12 hours post-dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics and IND (secondary outcomes). METHODS 20 participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures and diaphragm electromyography (EMGdi%max; IND) at 6 time points from 20h00-08h00 (i.e. 0-12 hours post-dose) and compared with sleeping IND. RESULTS Compared with PL, evening BD was not associated with increased morning trough IC 12 hours post-dose (p=0.48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 hours post-dose (AUC 0-12), and IC for 10 hours post-dose were improved (p<0.05). During PL, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with BD treatment (p<0.05) with no change in ventilation or breathing pattern. INTERPRETATION Respiratory mechanics significantly deteriorated at night during PL. While morning trough IC was unchanged, evening bronchodilator treatment was consistently associated with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo.