Evening Bronchodilation Improves Respiratory Mechanics and Inspiratory Neural Drive in COPD
Introduction
Advanced chronic obstructive pulmonary disease (COPD) is often associated with night-time and early-morning respiratory symptoms such as dyspnea, cough, excessive production of phlegm, resulting in poor sleep quality, and increased risk of nocturnal death. Studies have demonstrated the link between this deterioration of respiratory mechanics with overnight worsening of inspiratory capacity (IC) and forced expiratory volume in 1 sec (FEV1). Bronchodilator therapy (BD) has been shown to improve the morning trough FEV1. However, the impact of BD therapy on respiratory mechanics throughout the night has not been studied.
Aim
The efficacy of evening BD therapy on overnight dynamic respiratory mechanics and inspiratory neural drive (IND) was evaluated in this study.
Method
Study Design
- A double-blind, randomized, placebo-controlled crossover study
Patient Profile
- Patients aged ≥40 years with moderate-to-severe COPD
- FEV1 30-79% predicted
- Functional residue capacity (FRC) >120% predicted
- >20 pack-year smoking history
Treatment Strategy
- IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography were measured at 6 time points from 0 to 12 h after the dose and compared with sleeping IND in the enrolled subjects.
- The cohort received morning long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 ?g) plus either evening BD or evening placebo.
End Points
Primary End Point
- Morning pre-dose trough IC
Secondary End Points
- Overnight IC
- Overnight FEV1
- Overnight FEV1/FVC ratio
- IND
- Neuromechanical dissociation (NMD)
- Respiratory pressures
Results
- Morning trough IC 12 hours post-dose did not differ between the BD and placebo groups (P = 0.48)
- Evening BD significantly improved nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 h after the dose, and IC for 10 h after the dose (P < 0.05).
- The improvements in IC and FEV1 were sustained for 10-hours post-dose.
- There were significant overnight increases in the secondary outcomes such as total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings compared with baseline evening values in placebo; however, BD therapy improved each of these outcomes (P < 0.05), with no change in ventilation or breathing pattern.
- Reduction in IND with BD was strongly associated with lung deflation.
Conclusions
- There is significant deterioration in the respiratory mechanics at night in the COPD patients.
- Evening bronchodilator treatment was clinically beneficial in these patients and resulted in sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo.
Chest. 2021 Jan;159(1):116-127. Doi: 10.1016/j.chest.2020.06.033.
