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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.

肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，引起进行性肌肉