Respiratory morbidity in neuromuscular diseases, with focus on Spinal Muscular Atrophy

Abstract

Patients with neuromuscular diseases (NMDs) suffer from respiratory muscle weakness, resulting in respiratory failure for which patients require mechanical ventilation. The weak cough in NMDs causes chest infections. There is limited evidence on the efficacy of interventions to prevent and treat these problems and knowledge about the natural history of respiratory problems in NMDs is incomplete. The first part of this PhD thesis describes the natural history in patients with the NMD spinal muscular atrophy (SMA), a severe hereditary NMD for which genetic treatments have been introduced recently. We showed that progressive respiratory muscle weakness followed by progressive lung function restriction characterizes SMA. More severely affected patients had more severe respiratory muscle weakness and lung function restriction. Hyperventilation was often observed in patients with SMA, which rapidly changed to insufficient ventilation the year before patients required mechanical ventilation. We observed no accelerated lung function decline prior to respiratory failure. The second part of this PhD thesis studies the evidence for supportive treatments in patients with NMDs. Patients with weak cough are supported with cough augmenting treatments such as air stacking or mechanical insufflation-exsufflation (MI-E). , thereby aiming to reduce the number of chest infections. A systematic review of the literature showed no evidence that daily MI-E treatment reduces the number of chest infections or hospital admissions. We retrospectively observed less chest infections and a major reduction of admission days in children the years following MI-E introduction. We prospectively studied the effect of air stacking and MI-E on lung function. We observed increased lung volumes immediately after air stacking or MI-E treatment. This effect was prolonged up to one hour after MI-E application. We investigated the role of scoliosis (surgery) on lung function and did not find evidence for stabilization of lung function after scoliosis surgery. Lung function testing plays an important role in the assessment of possible respiratory failure in children with NMDs. However, obtaining reliable test results is a major challenge. In the last part of this PhD thesis we studied the relation between oscillometry and lung function results. We observed a non-linear relation between oscillometry and lung function results in children with NMDs.