© 2008 American Thoracic Society doi: 10.1164/rccm.200804-528ED
Enhancing the Benefits of Pulmonary RehabilitationDoing More for a Few or Doing a Little Less for Many?
Centre de Recherche de l'Hôpital Laval Québec Exercise training is the most effective intervention to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD). This intervention allows optimal bronchodilatory therapy to demonstrate its full potential to enhance exercise performance (1). But clinicians and scientists, probably for good reasons, are not happy with this; they want to achieve more with their patients. A variety of exercise performance–enhancing strategies have been tested in patients with COPD, including anabolic steroids (2), growth hormone (3), and nutritional interventions (4, 5). A general conclusion that can be drawn from these experiences is that, while it may be possible to make an impact on limb muscle function, it is much more difficult to show convincing benefits on whole body exercise performance and quality of life. However, when interpreting the current literature, it should be kept in mind that these studies were small and not designed to show such benefits. In this issue of the Journal (pp. 233–239), Deacon and colleagues publish what is arguably the most complete study to date (6), examining the comparative efficacy of creatine supplementation in conjunction with exercise training versus exercise training alone in patients with COPD. The primary outcome was the endurance time during incremental shuttle walking. Secondary endpoints included body composition, upper and lower limb muscle strength, and health status. Strengths of this study include a relatively large sample size, state-of-the-art creatine supplementation (7), and the fact that confirmation of increased muscle creatine levels was obtained by muscle biopsy in a subset of patients. Those of us interested in pulmonary rehabilitation are happy to see confirmation of the beneficial effects of exercise training. But despite its careful design, this study fails to show any impact of creatine supplementation as compared with exercise training alone in patients with COPD. The rationale underlying this study was strong. Phosphocreatine stores are lower and more rapidly depleted during exercise in patients with COPD compared with healthy subjects (8, 9). Creatine supplementation should help remedy this problem and should therefore enhance muscle performance, as previously demonstrated in athletes (7), and in conditions such as neuromuscular diseases and COPD (10, 11). So, how is that possible that such a hypothesis fails in a clinical trial? First of all, patients with COPD are not athletes. The main mechanism of action of creatine being to allow subjects to train harder, it may well be that patients with COPD are unable to achieve that level of training despite being aided by creatine. It is unfortunate that Deacon and her collaborators did not closely monitor training intensity, as it would have allowed them to reach a clear conclusion on this important issue. If creatine or other exercise performance-enhancing strategies are to be of any utility in improving physiologic outcomes related to training, they will have to show first that they improve tolerance to vigorous exercise. As pointed out by Deacon and colleagues, another likely explanation for their negative results is that any effects of creatine supplementation could have been obscured by the large improvement obtained with exercise training alone. Oftentimes patients with COPD are so deconditioned to start with that the magnitude of any additional interventions will be difficult to demonstrate on top of what is already achieved by exercise training alone. This is certainly an important lesson to consider in designing future clinical trials in this area. The exercise-enhancing effects of creatine supplementation have been mostly documented during highly specific muscle exercise tasks (12). Keeping this in mind, it is unlikely that creatine supplementation would improve performance during aerobic exercises because the normal phosphocreatine muscle content is sufficient to maintain ATP supply during the smooth transition from rest to exercise associated with this form of prolonged exercise. Thus, if creatine supplementation were to impart a potential benefit on energy provision, this would be during short-term and high-intensity exercise and not during aerobic exercise, such as a walking test. In this context the negative findings of Deacon and colleagues are not unexpected. Another potential pitfall of creatine supplementation is that there could be individual variability in the response to this therapy. For instance, elderly subjects may not be as responsive to this intervention as are younger individuals (12). This information indicates that creatine supplementation should not be viewed as a substitute for exercise training—good news for adepts of pulmonary rehabilitation. Could there be a fundamental flaw in the concept of having patients with COPD achieve, at all costs, high-intensity training? Undoubtedly, high-intensity training is superior to less intense training when it comes to physiologic endpoints (13). The demonstration of the physiologic benefits of exercise training was an essential step in convincing the medical community about the efficacy of this intervention. But that may not be the most relevant measure of efficacy of pulmonary rehabilitation. Obtaining physiologic benefits may not be what patients are looking for in pulmonary rehabilitation. It is still uncertain whether training harder will enhance the impact of pulmonary rehabilitation on quality of life, long-term adherence to exercise and general health status. In fact, current exercise training recommendations emphasize the role of moderately intense exercise to improve cardiovascular health and survival in the general population (14). Taking a step back in reflecting about the current challenges to pulmonary rehabilitation, one may wonder if the most important issue is to enable patients already involved in exercise training to train harder. Without minimizing the importance of this quest to optimize the results of pulmonary rehabilitation, we have to appreciate that only a small portion of patients with COPD actually engage in pulmonary rehabilitation. For instance, it was estimated in 2005 that only 1 to 2% of the Canadian population with COPD had access to pulmonary rehabilitation (15), a situation similar to what has been reported in other countries (16, 17). Research to improve these somewhat discouraging statistics is equally important for pulmonary rehabilitation to achieve its full potential from a public health perspective. FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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