Evaluation of acute bronchodilator reversibility in patients with symptoms of GOLD stage I COPD

Background: Symptomatic patients with GOLD stage I COPD can have significant abnormalities of ventilatory mechanics with greater exertional symptoms and exercise limitation than age-matched healthy subjects. In such patients, the impact of bronchodilator therapy remains unknown and is difficult to evaluate. Methods: We measured the acute effects of nebulized ipratropium bromide 500μg (IB) on resting pulmonary function and on dyspnoea and ventilatory parameters during symptom-limited constant work-rate cycle exercise. In a randomized, double-blind, crossover study, 16 patients with COPD [post-bronchodilator forced expiratory volume in one second (FEV 1 )=90±7 %predicted, FEV 1 /forced vital capacity (FVC)=59±7%; mean±SD] with a significant smoking history (44±16 pack-years) inhaled either IB or placebo (PL) on each of two separate visits. Pulmonary function tests and cycle exercise at 80-85% of each subject9s maximal work capacity were performed 2-hours after dosing. Results : After IB compared with PL: FEV 1 increased 5±9 %predicted; residual volume decreased 12±20 %predicted; and specific airway resistance decreased 81±93 %predicted (all p<0.05). At a standardized time during exercise: dynamic inspiratory capacity and tidal volume significantly increased in tandem by 0.12 and 0.16 L, respectively (each p<0.05); dyspnoea fell by 0.9±1.8 Borg units (p=0.07) and dyspnoea/ventilation ratios fell significantly (p<0.05). The fall in dyspnoea at higher submaximal ventilations correlated with the concurrent decrease in end-expiratory lung volume (p<0.05). Conclusion: In symptomatic GOLD stage I COPD, IB treatment was associated with modest but consistent improvements in airway function, operating lung volumes and dyspnoea intensity during exercise. Our results provide a physiological rationale for a trial of bronchodilator therapy in selected patients with milder but symptomatic COPD.