Dyspnea and Diaphragmatic Fatigue in Patients with Chronic Obstructive Pulmonary Disease. Responses to Theophylline

This study sought answers to 2 questions: (1) Is severe dyspnea to the point of exhaustion regularly accompanied by diaphragmatic fatigue in patients with moderately severe chronic obstructive pulmonary disease (COPD)? (2) When diaphragmatic fatigue occurs in such patients, does theophylline prevent or delay its onset? Eight eucapnic patients with moderately severe COPD were subjected to 2 different stresses to the point of severe dyspnea requiring cessation of the stress. The stresses were cycle exercise and inspiratory resistive breathing, the latter requiring a tidal Pdi equal to 60% of Pdimax. Despite incapacitating dyspnea, objective evidence of diaphragmatic fatigue was not encountered during cycle exercise. During inspiratory resistive breathing, diaphragmatic fatigue was encountered in all patients as defined by consistent inability to attain a target Pdi during final moments of the resistance run. Patients were uniformly extremely dyspneic at this point. In neither stressful maneuver did oral sustained-release theophylline show a convincing or significant advantage over placebo when administered in a randomized double-blind crossover protocol. These results suggest that the diaphragmatic fatigue encountered in this sort of COPD patient may be of predominantly central rather than peripheral (myogenic) origin and that theophylline may not be effective in this type of fatigue.