Chest
Volume 121, Issue 2, February 2002, Pages 597-608
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A Systematic Review of the Effects of Bronchodilators on Exercise Capacity in Patients With COPD

https://doi.org/10.1378/chest.121.2.597Get rights and content

One of the major goals of bronchodilator therapy in patients with COPD is to decrease airflow limitation in the airways and, as a consequence, improve dyspnea and exercise tolerance. The focus of this systematic review is to assess the effects of treatment with β-agonists, anticholinergics, and theophyllines on dyspnea, and steady-state and incremental exercise capacity. Thirty-three, double-blind, randomized, placebo-controlled studies written in English were selected. This review shows that approximately half of the studies showed a significant effect of bronchodilator therapy on exercise capacity. Anticholinergic agents have significant beneficial effects in the majority of studies, especially when measured by steady-state exercise protocols. There is a trend toward a better effect of high-dose compared to low-dose anticholinergics. Short-acting β2-mimetics have favorable effects on exercise capacity in more than two thirds of the studies; surprisingly, the situation is less clear for long-acting β2-agents. The majority of the results of the published reports on theophyllines and their effects on exercise are negative. Direct comparisons of different classes of bronchodilators have not been made in a sufficient number of studies for a rational preference. The addition of a second bronchodilator has no proven advantage for improving exercise test results, but this has not been studied extensively and not in sufficiently large studies. The majority of studies reporting a measure of dyspnea found improvements, even in the absence of improvement in exercise capacity.

Section snippets

Exercise Tests

To assess exercise capacity, different protocols are used depending on the aim of the study. The tests can be classified as steady-state tests and incremental tests, both measuring a different aspect of exercise capacity (Table 1). The term steady state is employed to indicate a more or less constant work rate during the test. Incremental exercise tests assess maximal exercise capacity in terms of peak exercise level, whereas steady-state tests explore the maximal capacity that can be endured

Materials and Methods

A systematic review of the literature searched with MEDLINE was performed including articles up to September 1999. Only randomized, controlled, double-blind trials written in English, were selected. Firstly, a database including all articles about obstructive lung diseases (key words: COPD, lung diseases, obstructive, plus all subheadings) was constructed. From this database, all articles that investigated patients with asthma were excluded (key-word strategy: database minus [asthma minus

Anticholinergics

Seventeen studies examining the effects of anticholinergics on exercise in patients with COPD were identified (Table 2). Ten studies applied ipratropium, 6 studies applied oxitropium, and 1 study applied atropine. At present, no tiotropium study is available. Twelve of 17 studies used a single-dose protocol; 16 of these studies primarily focusing on exercise testing showed a significant effect on FEV1(Table 2).

Discussion

We identified 33 double-blind, randomized, controlled studies investigating the effects of bronchodilators on exercise capacity in patients with COPD. Only a few studies have been published with a head-to-head comparison between different types of bronchodilators. Bronchodilators are frequently prescribed to patients with COPD in order to improve exercise intolerance. Nevertheless, our systematic review shows that approximately half of the studies with bronchodilators do not show a significant

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      Our study has documented that a 5-day treatment with formoterol 12 μg twice daily increased the walked distance by 53.6 m at the end of the 6-MWT and 59.9 m at the end of the 12-MWT. This is, in our opinion, an important finding because, at least for the 6-MWT, none of the studies that have explored the effects of bronchodilators in COPD reached the minimal clinical significance limits and, consequently, the relevance of the observed effect to the patient remains debatable.8 It must be pointed out that Redelmeier et al.16 suggested that subjects have to improve their walking distance by 54 m after a 6-MWT in order to appreciate this increase as a beneficial effect, whereas Troosters et al.17 reported a mean increase of 52 m in a study of the short- and longer-term benefits of pulmonary rehabilitation delivered over a 6-month period.

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    Dr. Liesker received research stipendium from AstraZeneca BV, Zoetermeer, the Netherlands.

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