Passive stretch of the chest wall in patients with Congential Muscular Dystrophy

描述（由申请人提供）： 继发于 VI 型胶原蛋白缺乏的先天性肌营养不良症 (CMD) 是一种独特的遗传性神经肌肉疾病，从出生起就会出现运动功能逐渐丧失、骨骼畸形和衰弱性挛缩的症状。呼吸衰竭是该疾病发病和死亡的主要原因。由于 CMD 尚无现有治疗方法，大多数受影响的儿童会出现呼吸衰竭，需要在生命的第一个和第二个十年之间进行无创通气。有证据表明，在肌营养不良症中，肺容量的进行性减少不成比例地大于呼吸肌无力程度的预期。胸壁僵硬和肺弹性下降共同降低了呼吸系统的顺应性，被认为是导致肺容量不成比例减少的重要原因。我们的研究旨在检验这样的假设：在患有 CMD 的受试者中，通过肺部过度吹气疗法每日被动拉伸胸壁可以减缓肺容量的年下降速度，延缓呼吸衰竭的发生并改善生活质量。我们将证明：1) 通过测量每个受试者的呼吸压力与容积关系，可以通过过度吹气达到最大肺膨胀并估计相应的压力，2) 患有 CMD 的受试者将能够在 5 个月的时间内坚持每天两次、每次 15 分钟的过度吹气方案，以及 3) 通过对干预组中的 17 名受试者和观察组中的 17 名受试者进行为期一年的研究，证明肺活量下降率的差异两组之间的差异将产生 > 0.5 的效应大小。该应用的结果将为未来开展一项随机对照试验铺平道路，该试验通过肺部过度充气对神经肌肉疾病患者进行每日被动拉伸胸壁。

DESCRIPTION (provided by applicant): Congenital muscular dystrophy (CMD) secondary to collagen VI deficiency is a distinct genetic neuromuscular disorder presenting from birth with progressive loss of motor function, skeletal deformities and debilitating contractures. Respiratory failure is the principal cause of morbidity and mortality from the disease. As CMD has no existing treatment, the majority of affected children develop respiratory failure and require non-invasive ventilation between the first and second decades of life. There is evidence that in muscular dystrophy the progressive decrease in lung volume is disproportionally greater than anticipated for the degree of respiratory muscle weakness. Chest wall stiffness and decreased lung elasticity which collectively diminish compliance of the respiratory system are believed to be important contributors to the disproportionate decrease in lung volume. Our research aims at testing the hypothesis that in subjects with CMD, daily passive stretch of the chest wall through lung hyperinsufflation therapy could slow down the annual rate of decline in lung volume, delay the onset of respiratory failure and improve quality of life. We will demonstrate that 1) By measuring in each subject the respiratory pressure volume relationship, maximum lung inflation by hyperinsufflation could be attained and the corresponding pressure estimated, 2) Subjects with CMD will be able to adhere to a twice-a-day 15 minute hyperinsufflation regimen over a period of 5 months and 3) Demonstrate that by studying for a period of one year 17 subjects enrolled in the intervention group and 17 in the observational group, the difference in the rate of decline of vital capacity between the 2 groups will yield an effect size of > 0.5. The results of this application will pave the way for the development of a future randomized control trial of daily passive stretch of the chest wall through lung hyperinsuflation in patients with neuromuscular disorders.