Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD

Chest. 2005 Mar;127(3):809-17. doi: 10.1378/chest.127.3.809.


Study objectives: Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-h improvements in airflow and lung hyperinflation reduction. We hypothesized that ventilatory mechanics improvements from tiotropium would permit enhanced ability to train muscles of ambulation and therefore augment exercise tolerance benefits of PR.

Design: In a randomized, double-blind, placebo-controlled trial (tiotropium, n = 47; placebo, n = 44), tiotropium (18 microg qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training three times a week; >/= 30 min per session) at 17 sites. Study drug was administered 5 weeks prior to, 8 weeks during, and 12 weeks following PR. The primary end point was treadmill walking (0% incline) endurance time at 80% of maximum speed attained in an initial incremental test. The transition dyspnea index (TDI), St. George's respiratory questionnaire (SGRQ), and rescue albuterol use were secondary end points.

Participants: Mean age of the 93 participants was 67 years, 57% were men, and mean FEV(1) was 0.88 L (34% predicted).

Results: Mean endurance time differences (tiotropium minus placebo) prior to PR, at the end of PR, and 12 weeks after PR were 1.65 min (p = 0.183), 5.35 min (p = 0.025), and 6.60 min (p = 0.018), respectively. Mean TDI focal scores at the end of PR were 1.75 for tiotropium and 0.91 for placebo (p > 0.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (p < 0.05). Relative to placebo, tiotropium improved SGRQ total scores by 3.86 at the end of PR and 4.44 at 12 weeks after PR (p > 0.05). Mean albuterol use declined following PR plus tiotropium, compared to PR alone (p </= 0.05 for 17 of 25 weeks).

Conclusions: Tiotropium in combination with PR improved endurance of a constant work rate treadmill task and produced clinically meaningful improvements in dyspnea and health status compared to PR alone. Improvements with tiotropium were sustained for 3 months following PR completion.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Cholinergic Antagonists / administration & dosage*
  • Cholinergic Antagonists / adverse effects
  • Double-Blind Method
  • Dyspnea / etiology
  • Exercise Test
  • Exercise Therapy*
  • Exercise Tolerance
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Quality of Life
  • Scopolamine Derivatives / administration & dosage*
  • Scopolamine Derivatives / adverse effects
  • Tiotropium Bromide
  • Vital Capacity


  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Scopolamine Derivatives
  • Tiotropium Bromide