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1 Respiratory Investigation Unit, Dept of Medicine, Queen's University, Kingston, Canada. 2 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. 3 UCP-X, Clinique de mail, Grenoble, France. 4 National Jewish Medical and Research Center, Denver, USA. 5 Krankenhaus Grosshansdorf, Grosshansdorf, Germany
CORRESPONDENCE: D.E. O'Donnell, 102 Stuart Street, Kingston, Canada K7L 2V6. Fax: 1 6135491459. E-mail: odonnell@post.queensu.ca
Keywords: Chronic obstructive pulmonary disease, chronic obstructive pulmonary disease treatment, dyspnoea, exercise tolerance, lung hyperinflation, tiotropium
Received: October 16, 2003
Accepted February 9, 2004
This study was supported by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. D.E. O'Donnell holds a career scientist award from the Ontario Ministry of Health.
The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease.
A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44±13% pred): 96 patients received 18 µg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared.
On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105±40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9±0.3 Borg scale units.
In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.
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