Impact of bronchodilator therapy on diaphragmatic function in sleep in COPD

The impact of bronchodilation (BD) on diaphragm activation (electromyography, EMGdi) and force generation (transdiaphragmatic pressure, Pdi) during sleep in Chronic Obstructive Pulmonary Disease (COPD) is unknown. We examined the effect of nocturnal BD on inspiratory neural drive (IND) in supine wakefulness (W) and sleep (non-rapid eye movement stage 2, N2) at equivalent time-points overnight. 20 patients with COPD (FRC 147±32%pred; post-BD FEV1 56±16%pred) completed a double-blinded, placebo-controlled crossover study with two 2wk treatment arms (BD: aclidinium bromide/formoterol fumarate 400/12mcg, or Placebo, PL), polysomnography, and measurement of IND (EMGdi,%max) and Pdi(%max) during stable breathing in W at 2, 6 & 10h post-dose and in N2 directly before W testing at 6 & 10h post-dose. BD (vs PL) improved IC and FEV1 by up to 334±310mL and 184±170mL (p<0.05). In W, BD reduced EMGdi (-21%) and Pdi (-20%;p<0.05) for 2h post-dose. At 6h post-dose, BD decreased EMGdi (-35%,p<0.05) in N2. BD did not alter neuromuscular efficiency (EMGdi/Pdi) in W or N2. Within each treatment, sleep decreased EMGdi vs W up to 35% (p<0.05) but didn9t alter Pdi, such that EMGdi/Pdi decreased from W to N2 (p<0.05). Improved IND and respiratory mechanics (Pdi) after BD in wakefulness were associated with improvements in IND after BD during sleep. Neuromuscular efficiency was unchanged by BD despite the marked decrease in IND between W and N2 in both groups.