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Eur Respir J 2004; 24:86-94
Copyright ©ERS Journals Ltd 2004


Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease

D.E. O'Donnell, N. Voduc, M. Fitzpatrick and K.A. Webb

Respiratory Investigation Unit, Dept of Medicine, Queen's University, Kingston, Canada

CORRESPONDENCE: D.E. O'Donnell, 102 Stuart Street, Kingston, Ontario K7L 2V6, Canada. Fax: 1 6135491459. E-mail: odonnell@post.queensu.ca

Keywords: Chronic obstructive pulmonary disease, dyspnoea, exercise, inspiratory capacity, lung hyperinflation, salmeterol

Received: June 25, 2003
Accepted February 9, 2004

This study was supported by the Ontario Ministry of Health (Toronto, Canada) and GlaxoSmithKline (Oakville, Canada).

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator.

In a randomised double-blind crossover study, 23 patients with COPD (mean±sem forced expiratory volume in one second 42±3% of the predicted value) inhaled salmeterol 50 µg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate.

After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175±52%, inspiratory capacity (IC) increased by 11±2% pred and functional residual capacity decreased by 11±3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (V'O2) and carbon dioxide output. Salmeterol increased peak exercise endurance, V'O2 and ventilation by 58±19, 8±3 and 12±3%, respectively. Improvements in peak V'O2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT.

Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.




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