Control of breathing in Duchenne's muscular dystrophy

Abstract

Duchenne's muscular dystrophy is a progressive degenerative muscular disease which leads to death from respiratory insufficiency in over 80 percent of cases. Recent studies in neuromuscular diseases have suggested that respiratory failure may be of central origin in some of the genetically transmitted neuromuscular diseases. We therefore evaluated the control of breathing in nine patients with advanced Duchenne's muscular dystrophy and compared these patients to nine healthy controls matched on the basis of age, sex and arm span. The purpose of the study was to assess the sensitivity of respiratory centers to hypercapnia, hypoxia and hyperoxia in nine patients with advanced Duchenne's muscular dystrophy. We measured minute ventilation (V̇ E), tidal volume (V T), respiratory frequency (F), mean respiratory flow rate (V T:T i) and occlusion pressure (P 0.1) responses as indices of respiratory centers output during hypercapnia (Read's method) and isocarbic hypoxia (Weil's method). We also analysed V̇ e during the transient hyperoxia test (Dejours' method). The threshold and magnitude of responses to hypercapnia, hypoxia and hyperoxia were nearly similar in patients and in controls. Patients demonstrated subnormal response of V̇ e, V T:T i, V T. Occlusion pressures were nearly the same in normal subjects and in patients with severe muscle weakness. The patterns of responses to those stimuli were markedly different: patients demonstrated a tachypneic pattern of breathing whereas controls preferred to increase their tidal volume. Our study establishes that in patients with advanced Duchenne's muscular dystrophy, the integrity of the carbon dioxide (CO 2) and oxygen (O 2) drive of breathing is well preserved. However in these patients, the pattern of ventilatory response is different from normal. There is a preferential increase in respiratory frequency to hypercapnia and hypoxia stimuli. This tachyphea could well be a clinical manifestation of inspiratory muscle fatigue which resulted in the subnormal ventilatory responses of our patients with Duchenne's muscular dystrophy.