© 2003 American Thoracic Society
Oxygen in the Rehabilitation of Patients with Chronic Obstructive Pulmonary DiseaseAn Old Tool Revisited
a Department of Internal Medicine University of Genoa Genoa, Italy Oxygen is one of the oldest drugs in respiratory and cardiovascular medicine. Among its benefits are a reduction of ventilatory demand and improvements in metabolism, muscle function, and cardiovascular function. As a result, oxygen can help relieve dyspnea and ameliorate the physical condition of patients with chronic obstructive pulmonary disease (COPD). Two basic studies in the early 1960s provided evidence for improved survival in patients with severe COPD treated with supplemental oxygen (1, 2). Since then, a growing interest has led the scientific community to explore new horizons in assisting patients with irreversible pulmonary disorders by supplemental oxygen with the intent of improving their quality of life. One approach is to combine oxygen and rehabilitation programs with the hope of achieving greater benefits from physical training. The results, however, were unexpectedly contradictory and partly disappointing. Whereas some investigators reported a substantial improvement in health status and physical condition, others failed to document clear benefits in terms of exercise performance. Apparently, this was independent of oxygenation in the patients. It is in this historic frame that the report of Emtner and coworkers (3) in this issue of the Journal (pp. 1034–1042) sheds new light on the usefulness of supplemental oxygen administered during physical training in patients with severe nonhypoxemic COPD. They examined the effects of a 7-week high-intensity training program while breathing air or 30% oxygen, and measured an array of physiologically and clinically relevant end-points. Oxygen supplementation allowed patients to train at higher intensity and for a longer time than a control group undergoing the same training program while breathing compressed air. As a result, physical performance and health status improved significantly more by training with oxygen than with air. Thus, it appears that patients affected by severe COPD may take remarkable advantage of rehabilitation programs if conducted with supplemental oxygen, even if they are not hypoxemic and do not desaturate during exercise. One of the key messages in the study of Emtner and coworkers (3) is that achievement of significant clinical benefits from training programs in patients with COPD requires the level of exercise to be as high as possible. The concept stems from the principle that only strenuous exercise drives metabolism and the skeletal muscles to better adapt to external demands. Applied to a disease where an organ, such as the lung, primarily limits physical activity, performing physical training at an intensity well beyond that permitted by the disease itself is expected to be highly favorable because it forces metabolism and the skeletal muscles to become less dependent on the amount of oxygen, thus decreasing ventilation. In this sense, the reasoning of the investigators to maximize training by using supplemental oxygen appears to be a winning move and perhaps one of the many key reasons that allowed the investigators to demonstrate what other investigators failed to achieve. Other merits of this study are the appropriateness of the double-blind design, which guarantees the reliability of results, the analysis of data from identical exercise task (isotime), which best allowed highlighting differences from the control group, and the inclusion of symptoms and health status scores as major end-points. Somewhat surprisingly, the mastery scale of the Chronic Respiratory Disease Questionnaire and the vitality scale of the Short Form-36 increased significantly in subjects training with oxygen, yet the values did not correlate with improvement of any index of physical performance. The lack of close relationship between physical performance and health status has been previously reported (4, 5), and probably arises because of the many confounding factors, such as the instrument used to assess the health-related quality of life, the multifactorial dimensions of dyspnea and a feeling of well-being, and the functional parameters chosen to measure physical performance. Yet, though unrelated to exercise parameters, the improvement in health status certainly represents a major clinical achievement of the use of supplemented oxygen during rehabilitation programs in COPD. Emtner and coworkers (3) identified a decrease in breathing frequency as one the main effects of oxygen supplementation during exercise. This observation is consistent with previous studies (6, 7). In contrast, tidal volume remained constant, suggesting that end-inspiratory and end-expiratory lung volumes shifted to lower lung volumes to a similar extent. This study does not apparently offer additional explanations on how and why respiratory rate decreased with oxygen. A hypothesis put forward in previous papers (6, 7) is that a decrease in ventilation during exercise, no matter how it is achieved with oxygen, is associated with less impingement of tidal expiratory flow on the maximal flow-volume loop. Consequently, operating lung volume is accommodated at a lower level and breathing frequency decreases. This reasoning is in line with the concept that lung hyperinflation on exercise may result from stimuli arising in airways undergoing dynamic compression on expiration (8). Interestingly, the response pattern to physical training in this study differs from that previously reported in mildly obstructed subjects, who tended to increase frequency and decrease tidal volume to prevent end-expiratory lung volume from increasing during exercise (9). From a physiological viewpoint, it would be interesting to see whether patients with mild COPD, not adapted to breathing under conditions of expiratory flow limitation at rest, might also benefit from oxygen supplementation during training sessions. Among other possible mechanisms through which oxygen might have contributed to a decrease in operating lung volumes and breathing frequency in the study of Emtner and coworkers (3) are bronchodilation (10) and decrease in alveolar volume (11). Whether bronchodilation may have occurred differently during training with oxygen or air cannot be determined because airway caliber was not measured during exercise. In any case, it must be noted that pharmacologic bronchodilation may increase exercise tolerance by reducing lung hyperinflation in some patients with COPD (12), although this may not be the case in patients with more severe disease, who tend to bronchoconstrict with a deep breath (13). A decrease in alveolar volume during oxygen breathing might have occurred because of absorption of oxygen out of the alveolar compartment and into the vascular compartment, without compensation by an opposite flow of nitrogen. Taking the challenge of Emtner and coworkers (3) that more clinical benefits for patients with COPD may be achieved only by pushing harder physical training programs, we envision that similar results might also be achieved with other methods, such as application of positive airway pressure, so long as exercise load is allowed to increase. In any case, the boundaries for assisting patients with severe and irreversible airway obstruction can somehow be broken, giving hope to make the disease more tolerable for patients. FOOTNOTES Conflict of Interest Statement: V.B. and R.P. have no declared conflict of interest. REFERENCES
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