Combination therapy for exercise intolerance in COPD.

C hronic obstructive pulmonary disease (COPD) is a miserable disease; exercise intolerance is one of its most troubling symptoms. Moreover, it has recently been discovered that poor exercise tolerance is highly predictive of poor survival. Those who care for these patients are therefore highly motivated to seek ways to ameliorate exercise intolerance. In recent years progress has come from what, at first glance, would seem to be an unlikely quarter. Although research expenditures for this disease are heavily weighted towards cell and molecular biology pursuits, physiological research (considered ‘‘old fashioned’’ in some quarters) has provided solid insights into rational treatment for exercise intolerance. A key insight is that dynamic hyperinflation is a major mechanism limiting exercise tolerance in patients with COPD. This occurs when the increased metabolic requirements of exercise demand higher levels of pulmonary ventilation. This, in turn, requires that both tidal volume and respiratory rate increase. The patient with COPD is asked to exhale a larger volume in a shorter time, which becomes an impossible task given flow limitation imposed by the increased expiratory airflow resistance. At some point the exhalation cannot be completed in the allotted expiratory time, full exhalation cannot be accomplished, and end expiratory volume increases. Eventually, dynamic hyperinflation leads to end inspiratory lung volumes that approach a limiting value (total lung capacity). As the inspiratory reserve volume shrinks, additional inspiratory volume cannot be achieved without greatly increased elastic work of breathing, since the lung is increasingly on a shallow portion of its pressure-volume curve. Severe dyspnoea results and exercise terminates when this sensation becomes unbearable.