Casaburi R, Kukafka D, Cooper CB, Witek TJ Jr, Kesten S.

Chest March 2005;127(3):809-817.

Study Objectives:

Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-hour 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 [mu]g qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training 3 times a week; = 30 minutes 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 minutes (P =.183), 5.35 minutes (P =.025), and 6.60 minutes (P =.018), respectively. Mean TDI focal scores at the end of PR were 1.75for tiotropium and 0.91 for placebo (P >.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (P <.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>.05). Mean albuterol use declined following PR plustiotropium, compared to PR alone (P =.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

PMID: 15764761 [PubMed - indexed for MEDLINE]

Commentary:

Bronchodilators are known to relieve symptoms of breathlessness in patients with COPD in part by reducing end-expiratory lung volume, both at rest and during exertion. This reduction leads to improvement in inspiratory capacity and respiratory muscle mechanics. This improvement in hyperinflation can in turn improve exercise tolerance. In the present study, the investigators evaluated whether the improvement in respiratory mechanics related to administration of the long-acting bronchodilator tiotropium bromide could enable patients to make greater gains in exercise tolerance in the context of pulmonary rehabilitation (PR). Inthis randomized, double-blind, placebo-controlled multisite trial of 93 patients with severe COPD, administration of tiotropium to patients undergoing PRledto asignificant increase in treadmill endurance time and constant work rate exercise (at 80% of the maximal speed attained during initial testing) as compared with PR alone (ie, the placebo group). Patients in both the tiotropium and placebo groups underwent the same training regimen: 8 weeks of treadmill exercise,= 30 minutes per training session). The increased endurance was associated with greater reductions in dyspnea and improvements in health status (assessed bythe St. George's Respiratory Questionnaire). The noted improvements persisted 3 months after completion of PR. Thus, it can be said that tiotropium not only reduces symptoms, improves bronchodilation, reduces COPD exacerbations, and improves hyperinflation, but also can augment the benefits achieved in pulmonary rehabilitation. The combination of tiotropium and PR should be considered for use for patients with significant airflow and exercise limitation despite the use of other medications, especially if they are planning to undertake PR.

CR