BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Authors: Fernando J Martinez; Alvar Agusti; Bartolome R Celli; MeiLan K Han; James P Allinson; Surya P Bhatt; Peter Calverley; Sanjay H Chotirmall; Badrul Chowdhury; Patrick Darken; Carla A Da Silva; Gavin Donaldson; Paul Dorinsky; Mark Dransfield; Rosa Faner; David M Halpin; Paul Jones; Jerry A Krishnan; Nicholas Locantore; Fernando D Martinez; Hana Mullerova; David Price; Klaus F Rabe; Colin Reisner; Dave Singh; Jørgen Vestbo; Claus F Vogelmeier; Robert A Wise; Ruth Tal-Singer; Jadwiga A Wedzicha Journal: Am J Respir Crit Care Med Date: 2022-02-01 Impact factor: 21.405