Effects of inhaled bronchodilators on dynamic lung mechanics during exercise in COPD: protocol for a randomised,...

Activity-related dyspnoea in moderate-severe COPD is centrally related to heightened wasted ventilation in the physiological dead space colliding with constraints to tidal expansion due to acute-on-chronic gas trapping. Both phenomena are ultimately related to small airway dysfunction. However, it remains unknown whether the positive effects of pharmacological deflation on exertional dyspnoea in COPD can be ascribed to improved small airway conductance, enhancing ventilation-perfusion matching and neuromechanical coupling.

We postulate that inhaled bronchodilators will enhance small airway function at rest and during exercise, improving gas exchange efficiency, lung mechanics and exertional dyspnoea in hyperinflated patients with COPD.

A double-blind, placebo-controlled study involving 25 symptomatic patients (modified Medical Research Council score ≥2) showing functional residual capacity >120% pred and/or >upper limit of normal will receive nebulised salbutamol sulphate (2.5 mg) plus ipratropium bromide (0.5 mg) or normal saline. On different days, patients will undergo a constant-load test at 75% peak to symptom limitation. Single- and multiple-breath N₂ washout and impulse oscillometry (IOS) will assess resting small airway function. Key exercise measurements will include 1) alveolar and physiological dead space by volumetric capnography, 2) operating lung volumes, 3) oesophageal catheter-based respiratory manometry and inspiratory neural drive via diaphragm electromyography, 4) exercise IOS, and 5) exertional dyspnoea (0-10 Borg scale).

Confirmation of the study's hypotheses will shed new light on the mechanisms of dyspnoea improvement after inhaled bronchodilators in patients with COPD. Moreover, it will provide a novel integrative platform for assessing the effects of therapeutic approaches targeting their small airways.