Effects of Strength Training on Bulbar Function in Amyotrophic Lateral Sclerosis

描述（由申请人提供）：以进行性言语、吞咽和呼吸障碍形式出现的球功能障碍在肌萎缩侧索硬化症（ALS）中非常普遍，占疾病死亡率的95%。虽然进行性肌无力是ALS的主要体征，但运动和力量训练对该患者人群的影响仍存在争议。虽然由于担心肌肉负担过重可能导致身体衰退，ALS患者的运动在历史上一直不被鼓励，但最近的动物和人类数据表明，在疾病早期应用的中等强度运动可能在ALS中起神经保护作用。事实上，来自我们实验室的令人兴奋的初步数据表明，轻中度ALS患者的呼气肌力训练（埃姆斯特）方案对呼气力产生能力、吞咽期间的气道保护和咳嗽、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具有积极影响。本建议的中心目标是采用盲法、假对照、随机临床试验，研究为期8周的埃姆斯特治疗方案对轻度至中度ALS患者延髓功能的影响。这项建议的中心假设是，每天进行8周中等强度的埃姆斯特运动，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、吞咽和功能性口腔摄入功能。拟定研究旨在专门确定埃姆斯特对以下方面的影响：1）呼气力产生能力（最大呼气压）; 2）吞咽期间的吞咽生理学和气道安全性; 3）咳嗽功能; 4）功能性口服摄入、吞咽相关生活质量和自我报告的吞咽严重程度; 5）轻度至中度ALS患者的后续疾病进展。这些结果将为肌肉力量训练在改善ALS患者延髓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.