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

Abstract

Patients with symptoms of GOLD stage I chronic obstructive pulmonary disease (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. The acute effects of nebulised ipratropium bromide 500 microg (IB) on resting pulmonary function and on dyspnoea and ventilatory parameters during symptom-limited constant work rate cycle exercise were measured. In a randomised double-blind crossover study, 16 patients with COPD (mean (SD) post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 90 (7)% predicted, FEV(1)/forced vital capacity (FVC) 59 (7)%) with a significant smoking history (mean (SD) 44 (16) pack-years) inhaled either IB or placebo on each of two separate visits. Pulmonary function tests and cycle exercise at 80-85% of each subject's maximal work capacity were performed 2 h after dosing. Compared with placebo, FEV(1) increased 5 (9)% predicted, residual volume decreased 12 (20)% predicted and specific airway resistance decreased 81 (93)% predicted (all p<0.05) after IB. At a standardised time during exercise, dynamic inspiratory capacity and tidal volume significantly increased in tandem by 0.12 and 0.16 litres, 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 intensity at higher submaximal ventilations correlated with the concurrent decrease in end-expiratory lung volume (p<0.05). In patients with symptoms of GOLD stage I COPD, IB treatment is associated with modest but consistent improvements in airway function, operating lung volumes and dyspnoea intensity during exercise. These results provide a physiological rationale for a trial of bronchodilator therapy in selected patients with milder but symptomatic COPD.