Early Respiratory Care in Amyotrophic Lateral Sclerosis Patients at High Risk for Respiratory Failure

呼吸衰竭高危肌萎缩侧索硬化症患者的早期呼吸护理

• 批准号: 10318647
• 负责人: Jason Ackrivo
• 金额: $ 19.69万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10318647
• 关键词: ALS patients; Address; Alveolus; Amyotrophic Lateral Sclerosis; Applications Grants; Articular Range of Motion; Belief; Caregivers; Caring; Cause of Death; Cessation of life; Characteristics; Chest wall structure; Chronic; Clinical; Clinical Trials; Cohort Studies; Coughing; Data; Development; Diagnosis; Disease; Elasticity; Emotional; Enrollment; Event; Evolution; Exercise; Expert Opinion; Future; Goals; Guidelines; High Prevalence; Hypercapnic respiratory failure; Hypoventilation; Institutes; Intervention; Intervention Studies; Interview; Investigation; Knowledge; Longitudinal prospective study; Lung; Lung infections; Maintenance; Methodology; Modeling; Monitor; Morbidity - disease rate; Multicenter Studies; Muscle Weakness; Neurodegenerative Disorders; Neurologic; Newly Diagnosed; Observational Study; Outcome; Outcome Study; Outpatients; Patient Selection; Patients; Phenotype; Philadelphia; Physical therapy; Physicians; Pilot Projects; Population; Prevalence; Prospective Studies; Prospective cohort study; Protocols documentation; Publishing; Qualitative Methods; Randomized Clinical Trials; Randomized Controlled Trials; Research; Research Project Grants; Research Training; Respiratory Failure; Respiratory Therapy; Respiratory physiology; Resuscitation; Retrospective Studies; Risk; Sampling; Structure; Subgroup; Symptoms; Time; Uncertainty; Vital capacity; Work; amyotrophic lateral sclerosis therapy; arm; clinical effect; clinical practice; cohort; cost; design; effective intervention; high risk; improved; improved outcome; innovation; insight; lung volume; mortality; nervous system disorder; neuromuscular; novel; novel strategies; patient oriented; patient population; patient subsets; personalized approach; personalized medicine; pilot trial; predictive modeling; prospective; recruit; respiratory; respiratory morbidity; risk stratification; tool; trial design; ventilation; virtual

Project Summary/Abstract Respiratory failure commonly occurs in amyotrophic lateral sclerosis (ALS) and leads to significant morbidity and mortality. The onset of respiratory weakness heralds an increased risk of aspiration related to bulbar muscle weakness and ineffective cough, hypercapnic respiratory failure due to chronic hypoventilation, and pulmonary infections, ultimately leading to death. Despite the key role of respiratory failure in the morbidity and mortality associated with ALS, there remains uncertainty concerning optimum initiation and maintenance of respiratory care for this disease. ALS has a very heterogeneous clinical presentation and symptom progression, which causes variable evolution of respiratory involvement. Given the significance of respiratory morbidity with this disease combined with the unclear timing, identifying high-risk subgroups may facilitate studying outcomes of early respiratory interventions. Our group has published a clinical prediction tool which can predict a high risk of respiratory failure within six months in ALS. We have also published a latent class analysis to identify subphenotypes of ALS patients by their differing trajectories of forced vital capacity over time. Applying our clinical prediction tool and knowledge of phenotypes to a sample of ALS patients would identify a subgroup suitable for future clinical trials. However, given the emotional burden of ALS, patient perspectives on respiratory interventions are critical to successful implementation. To our knowledge, a prospective investigation on a cohort of ALS patients at high risk of respiratory failure has yet to be performed. The goals of this study are to use our clinical prediction tool to identify the prevalence of newly-diagnosed ALS patients at high risk of respiratory failure, to elucidate patient perspectives on early respiratory care, and to implement a pilot trial of lung volume recruitment in high-risk patients. This proposal will involve a multicenter study at three academic centers in Philadelphia. We will perform a prospective cohort study of patients with ALS, apply our clinical prediction tool, and monitor them for respiratory failure over one year. We will use semi- structured interviews to gather patient perspectives regarding circumstances under which they would accept early respiratory care in ALS. Third, we will perform a single-arm pilot intervention of lung volume recruitment in newly-diagnosed ALS patients at high risk of respiratory failure within six months. This project will provide essential preliminary data for a Research Project Grant application that will (1) conduct a randomized controlled trial of early respiratory therapy in high-risk ALS patients (2) elucidate physician and caregiver perspectives regarding respiratory care in ALS, and (3) identify which characteristics are associated with different trajectories of respiratory function, thus allowing for personalized medicine.

项目总结/摘要 呼吸衰竭通常发生在肌萎缩侧索硬化症（ALS），并导致显着的发病率 and mortality.呼吸无力的发作预示着与延髓相关的误吸风险增加 肌无力和无效咳嗽，慢性通气不足导致的高碳酸血症性呼吸衰竭，以及 肺部感染最终导致死亡尽管呼吸衰竭在发病率和 与ALS相关的死亡率，仍然存在关于最佳启动和维持的不确定性， 呼吸道疾病的治疗ALS具有非常异质性的临床表现和症状 进展，导致呼吸系统受累的变化。考虑到呼吸系统的重要性 这种疾病的发病率与不明确的时间相结合，确定高风险亚组可能有助于 研究早期呼吸干预的结果。我们的团队已经发布了一个临床预测工具， 可以预测ALS患者在六个月内呼吸衰竭的高风险。我们还发布了一个潜在类 分析，以确定ALS患者的亚表型，通过他们的不同轨迹的用力肺活量超过 时间将我们的临床预测工具和表型知识应用于ALS患者样本， 确定适合未来临床试验的亚组。然而，考虑到ALS的情感负担，患者 对呼吸干预的看法对成功实施至关重要。据我们所知， 对呼吸衰竭高危ALS患者队列的前瞻性研究尚未进行。 本研究的目的是使用我们的临床预测工具来确定新诊断的ALS的患病率 呼吸衰竭高危患者，阐明患者对早期呼吸护理的看法， 在高危患者中开展肺容量补充试点试验。该提案将涉及多中心 在费城的三个学术中心学习。我们将进行一项前瞻性队列研究， ALS，应用我们的临床预测工具，并监测他们的呼吸衰竭超过一年。我们将使用半- 结构化访谈，以收集患者的观点，了解他们在何种情况下会接受 ALS的早期呼吸护理第三，我们将进行肺容量招募的单臂试点干预 新诊断的ALS患者在六个月内呼吸衰竭的高风险。 该项目将为研究项目资助申请提供必要的初步数据，该申请将（1）进行 一项在高危ALS患者中进行早期呼吸治疗的随机对照试验（2）阐明了医生和 护理人员对ALS呼吸护理的看法，以及（3）确定哪些特征与ALS相关 呼吸功能的不同轨迹，从而允许个性化医疗。