Exertional dyspnea relief following bronchodilation in COPD: Role of neural respiratory drive

We hypothesized that exertional dyspnea relief following acute bronchodilation in COPD reflects the awareness of reduced neural respiratory drive. In a randomized double-blind crossover study, 20 patients (13 men) aged 68.0±1.5 yrs (mean±SE) with GOLD stage II-IV COPD (FEV₁=50±3% predicted) performed four 3-min stair stepping tests at 14, 16, 20 and 24 steps/min (externally paced) after inhalation of nebulized placebo or Combivent^® (500 µg ipratropium bromide/2.5 mg salbutamol). Assessments of dyspnea, ventilation (V_E), breathing pattern, dynamic operating lung volumes, crural diaphragm EMG activity (EMGdi; an index measure of neural respiratory drive), and transdiaphragmatic pressure swings (Pdi,swing) were compared between treatments at each step rate. Compared to placebo, Combivent^®improved dyspnea, breathing pattern, inspiratory capacity, inspiratory reserve volume (IRV), EMGdi and Pdi,swing at any given step rate and V_E during exercise. By contrast, the relationship between exercise-induced changes in 1) EMGdi and Pdi,swing and 2) each of dyspnea, IRV and EMGdi were relatively preserved during exercise following treatment with Combivent^® vs. placebo. Exertional dyspnea relief following bronchodilation in COPD can be largely explained by the awareness of reduced neural respiratory drive (EMGdi) needed to achieve a given V_E in the setting of more favorable dynamic operating lung volumes.