Overnight deterioration of supine respiratory mechanics in COPD: impact of nocturnal aclidinium bromide/formoterol fumarate

Introduction: Patients with COPD report poor sleep quality and overnight dyspnea. We measured overnight respiratory mechanics in health and COPD and determined how these were impacted by nocturnal long-acting bronchodilation (aclidinium bromide/formoterol fumarate, AB/FF 400/12mcg). Methods: Subjects with moderate-to-severe COPD (n=20; FRC: 147.1±31.5%pred; post-BD FEV₁: 55.7±15.9%pred) completed two treatment arms (2 weeks/each) in a randomized, double-blinded crossover study: one arm=AB/FF BID, other arm=morning AB/FF + evening Placebo. Serial supine inspiratory capacity (IC), spirometry, and tidal transdiaphragmatic pressure (Pdi) and electromyography (EMGdi) were measured during a polysomnography visit at the end of each treatment arm in COPD and 20 age-matched healthy controls (CTRL). Results: Baseline IC was lower in COPD (82±23%pred vs CTRL 109±24%pred, p<0.05). End-expiratory lung volume increased (+434±386mL, p<0.05) and IC (-265±378mL, p<0.05) and FEV₁ (-211±186mL, p<0.05) decreased overnight in COPD, but not in CTRL (IC: +11±214mL, p=0.82; FEV₁: -89±312mL, p=0.27). There was no change in FEV₁/FVC. AB/FF increased IC (+334±310mL) and FEV₁ (+184±170mL, both p<0.05) vs Placebo, providing improvements (p<0.05) for 10hr post-dose. AB/FF decreased total lung resistance (-1.9±2.1cmH2O/L/sec, p<0.05) and Pdi (-2.5±3.2cmH2O, p<0.05), improving EMGdi:tidal volume (Vt) ratio (-9.9±10μV/L, P=0.021) without changing Vt or breathing rate. Conclusions: Overnight respiratory mechanics deteriorated progressively in COPD vs health. Nocturnal AB/FF provided sustained bronchodilatation and deflation, permitting equivalent ventilation with less inspiratory neural drive.