Effects of Strength Training on Bulbar Function in Amyotrophic Lateral Sclerosis

描述（由申请人提供）：在肌萎缩性侧索硬化症（ALS）中，以进行性语言、吞咽和呼吸障碍的形式出现的球功能障碍非常普遍，占疾病死亡率的95%。虽然进行性肌肉无力是ALS的主要症状，但运动和力量训练对这类患者的影响仍存在争议。由于担心肌肉过度负担可能导致身体机能下降，ALS患者历来不鼓励进行运动，但最近的动物和人类数据表明，在疾病早期进行中等强度的运动可能对ALS起到神经保护作用。事实上，我们实验室令人兴奋的初步数据表明，轻中度ALS患者的呼气肌力量训练（EMST）方案对呼气力产生能力、气道保护和吞咽时的咳嗽、吞咽运动学、自我报告的吞咽严重程度和吞咽相关的生活质量有积极影响。本提案的中心目标是通过一项盲法、假对照、随机临床试验，研究为期8周的EMST治疗对轻度至中度ALS患者球功能的影响。该建议的中心假设是，每天进行8周的中等强度抵抗性EMST运动将积极参与呼气和颏下肌肉组织，阻止废用性萎缩，延长ALS患者的气道保护、吞咽和功能性口服摄入功能。本研究旨在明确EMST对以下方面的影响：1)呼气力产生能力（最大呼气压力）；2)吞咽生理及吞咽时气道安全；3)止咳功能；4)功能性口服摄入量、吞咽相关生活质量和自述吞咽严重程度；5)以及轻至中度ALS患者随后的疾病进展。该结果将为肌肉力量训练在改善ALS患者球功能方面的潜在作用提供有价值的见解，并将有助于指导这种毁灭性疾病的未来研究和治疗方向。

DESCRIPTION (provided by applicant): Bulbar dysfunction in the form of progressive speech, swallow and respiratory impairment are highly prevalent in Amyotrophic Lateral Sclerosis (ALS) and together account for 95% of disease mortality. Although progressive muscle weakness is the primary sign of ALS, the effects of exercise and strength training in this patient population i controversial. While exercise in persons with ALS has historically been discouraged due to fear that muscle overburden may execrate physical decline, recent animal and human data suggest that moderate intensity exercise applied early in the disease may serve a neuroprotective role in ALS. Indeed, exciting preliminary data from our laboratory indicate that a regimen of expiratory muscle strength training (EMST) in persons with mild-moderate ALS has a positive effect on expiratory force generating abilities, airway protection and cough during swallowing, swallow kinematics, self-reported swallow severity and swallow- related quality of life. The central goal o this proposal is to investigate the effects of an eight-week regimen of EMST on bulbar function in persons with mild to moderate ALS using a blinded, sham-controlled, randomized clinical trial. The central hypothesis of this proposal is that eight-weeks of daily moderate intensity resistance EMST exercise will actively engage the expiratory and submental musculature, deter disuse atrophy and prolong function of airway protection, swallowing and functional oral intake in persons with ALS. The proposed study is designed to specifically determine the effect of EMST on: 1) expiratory force generating ability (maximum expiratory pressure); 2) swallow physiology and airway safety during swallow; 3) cough function; 4) functional oral intake, swallow-related quality of life and self-reported swallow severity; 5) and subsequent disease progression in persons with mild to moderate ALS. The results will provide valuable insight into the potential role of muscle strength training for improving bulbar function in persons with ALS and will help guide the future direction of research and treatment for this devastating disorder.