Delineating Physiologic Mechanisms of Swallowing impairment and Decline in ALS

描绘吞咽障碍和 ALS 衰退的生理机制

基本信息

批准号：
9286256
负责人：
Emily Kate Plowman
金额：
$ 35.33万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9286256
关键词：
Algorithms Amyotrophic Lateral Sclerosis Anatomy Aspirate substance Aspiration Pneumonia Biological Markers Caregiver Burden Cessation of life Clinical Clinical Assessment Tool Clinical Management Clinical Markers Clinical Research Clinical Trials Coughing Data Deglutition Deglutition Disorders Dehydration Denervation Dependence Detection Deterioration Development Disease Early Diagnosis Early identification Ensure Enteral Feeding Esophageal Evaluation Food Foundations Functional disorder Future Goals Gold Health Health Care Costs Impairment Individual Intake Intervention Isometric Exercise Knowledge Larynx Lead Lung Malnutrition Mediating Modeling Monitor Motor Muscle Weakness Myography Neurodegenerative Disorders Nutritional Oral Oral cavity Outcome Outcomes Research Patients Pattern Phenotype Physiological Population Practice Guidelines Procedures Public Health Quality of life Receiver Operating Characteristics Recommendation Reflex action Research Design Risk Safety Sensory Spinal Stomach Structure Techniques Testing Therapeutic Time Time Management Tongue Vestibule Work base clinical care clinical practice clinical predictors constriction design diagnosis evaluation disease diagnosis electric impedance evidence base functional decline improved indexing insight longitudinal dataset mortality motor impairment novel nutrition patient population predictive modeling predictive tools pressure pulmonary function response tool treatment effect treatment strategy

项目摘要

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive muscle weakness and impairments in swallowing (dysphagia). Dysphagia leads to malnutrition, dehydration, tracheal aspiration and pneumonia that contribute to 26% of ALS mortality. The current proposal is strongly motivated by fundamental knowledge gaps that have contributed to sub-optimal clinical care of individuals with ALS and a lack of formal practice guidelines in the management of progressive swallowing impairment in ALS. The overarching goal of this work is to improve clinical practice by 1) increasing our understanding of governing mechanisms and progression of dysphagia in ALS and 2) identification of sensitive biomarkers of swallowing dysfunction to build a clinical dysphagia risk index tool. We will perform serial instrumental swallowing evaluations in 100 individuals with ALS (50 bulbar-onset, 50 spinal-onset) from disease diagnosis to feeding-tube dependence and provide critical longitudinal data to help establish the first time-course model of ALS swallowing decline. Such a model is needed to guide best practice recommendations, optimal timing of interventions, for planning and design of future clinical trials, and for interpretation of experimental treatment effects. We will also test the discriminant ability and clinical utility of a set of promising clinical markers of swallowing decline that are pragmatically designed for easy dissemination into ALS clinical settings. Our long- term goal is to improve clinical care of swallowing disorders in ALS. The proposed study will deliver new insights into the pathophysiologic mechanisms of unsafe and inefficient swallowing in ALS to drive the development of future intervention strategies and lead to earlier and more accurate identification of swallowing impairment. Earlier identification and better treatment strategies for swallowing dysfunction in ALS will lead to improvements in oral intake, nutrition, pulmonary health and quality of life and ultimately reduce aspiration pneumonia associated mortality in this challenging population.

肌萎缩侧索硬化症 (ALS) 是一种致命的神经退行性疾病，会导致肌肉进行性进展吞咽无力和障碍（吞咽困难）。吞咽困难导致营养不良、脱水、气管破裂误吸和肺炎导致 26% 的 ALS 死亡率。当前的提案具有强烈的动机基础知识差距导致 ALS 患者的临床护理效果欠佳缺乏治疗 ALS 进行性吞咽障碍的正式实践指南。这项工作的总体目标是通过以下方式改善临床实践：1）增加我们对 ALS 吞咽困难的控制机制和进展，以及 2) 敏感生物标志物的鉴定吞咽功能障碍构建临床吞咽困难风险指数工具。我们将演奏系列乐器对 100 名 ALS 患者（50 名延髓发病，50 名脊柱发病）进行疾病诊断的吞咽评估饲管依赖性并提供关键的纵向数据以帮助建立第一个时程模型 ALS 吞咽能力下降。需要这样的模型来指导最佳实践建议、最佳时机干预措施，用于未来临床试验的规划和设计以及实验治疗的解释影响。我们还将测试一组有前途的临床标志物的判别能力和临床实用性吞咽能力下降的研究经过实用设计，易于传播到 ALS 临床环境中。我们的长期长期目标是改善 ALS 吞咽障碍的临床护理。拟议的研究将提供新的深入了解 ALS 中不安全和低效吞咽的病理生理机制，以推动制定未来的干预策略，并导致更早、更准确地识别吞咽障碍。 ALS 吞咽功能障碍的早期识别和更好的治疗策略将改善口腔摄入、营养、肺部健康和生活质量，并最终减少在这一具有挑战性的人群中，吸入性肺炎与死亡率相关。