MECHANISMS OF AXON GUIDANCE IN LARYNGEAL REINNERVATION FOLLOWING INJURY OF THE RECURRENT LARYNGEAL NERVE

喉返神经损伤后喉部神经再生中轴突引导的机制

• 批准号: 10177279
• 负责人: Michael Pitman
• 金额: $ 23.38万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177279
• 关键词: Acute; Admission activity; American; Anesthesiology; Businesses; COVID-19; Chronic Disease; Chronic Obstructive Airway Disease; Chronology; Clinical Data; Cohort Studies; Collaborations; Communication; Congestive Heart Failure; Controlled Environment; Critical Care; Critical Illness; Cues; Data; Development; Disease; Dysphonia; Epidemic; Exanthema; Exhibits; Fright; Frustration; Functional disorder; Future; Goals; Growth; Growth Cones; Guidelines; Health Surveys; Hospitals; Hour; Impairment; In Vitro; Incidence; Infection; Injury; Institution; Intervention; Intubation; Knowledge; Laryngeal Injury; Laryngeal Mucosa; Laryngeal muscle structure; Laryngoscopy; Larynx; Learning; Medicine; Mental Depression; Modeling; Modification; Molecular; Morbidity - disease rate; Motor Neurons; Muscle; NTN1 gene; Nerve Regeneration; Operative Surgical Procedures; Otolaryngology; Outcome; Outcome Measure; Paralysed; Pathway interactions; Patient Outcomes Assessments; Patients; Pattern; Play; Population; Process; Productivity; Public Health; Quality of life; Rattus; Receptor Signaling; Recurrent Laryngeal Nerve; Research; Risk; Signal Transduction; Stenosis; Structure; Survivors; Synkinesis; System; Testing; Tracheotomy procedure; Trauma; Tube; United States; Up-Regulation; Voice; Voice Disorders; Work; axon growth; axon guidance; burden of illness; cohort; coronavirus disease; disability payment; endotracheal; experimental study; functional disability; glial cell-line derived neurotrophic factor; in vivo Model; indexing; infection burden; loved ones; nerve injury; nerve supply; neuronal survival; optimal treatments; pandemic disease; pressure; prevent; receptor; receptor expression; regenerative; reinnervation; restoration; risk minimization; ventilation; vocal cord

Project Summary Laryngeal functional impairment after critical illness and laryngeal intubation trauma are underrecognized. This impairment will become an issue of epidemic proportions as the number of intubated ICU patients has dramatically increased due to COVID-19. To date, 85,000-170,000 patients with COVID-19 have required ICU admission with intubation for ventilation. Their laryngeal injury risk is exponentially increased due to the current national guidelines which recommend delaying tracheotomy for COVID-19 patients until they have been intubated >21 days. This is alarming as tracheotomies are usual performed at 7-10 days and 57% of patients evidence laryngeal mucosal injury after just 12 hours. These injuries, caused by pressure of the endotracheal tube on laryngeal structures, can permanently compromise vocal function, create glottic incompetence and generate posterior glottic stenosis. All have major morbidity and quality of life sequelae and no optimal treatments exist. Voice dysfunction leads to frustration, isolation, fear, and altered self-identity, as well as impaired quality of life, lost worker productivity, and the need to file disability claims at rates similar to those of chronic diseases like congestive heart failure, chronic obstructive pulmonary disease and severe depression. Quality of life consequences from voice disorders due to treatment of COVID-19 patients in the ICU is expected to be extremely prevalent and severe, resulting in a high personal and societal burden. Our long-term goal is to develop interventions to reduce the incidence and impact of post-intubation laryngeal injury. Heightened risks in the COVID-19 population make it imperative that we understand the burden of laryngeal injuries and learn from this pandemic to minimize risks for future intubated patients. The aims of this project are: 1. Create a national cohort of COVID-19 ICU survivors and quantify the acute burden of infection and treatment on laryngeal function, voice, communication and quality of life after hospital discharge, 2. Quantify the longer-term burden of COVID-19 infection and treatment on laryngeal function, voice, communication and quality of life within the cohort, 3. Identify potential intervention targets to prevent and treat post-intubation related laryngeal injuries. Building on our previous work and the power and reach of the North American Airway Collaboration which we developed, with over 40 participating academic institutions, we will conduct a longitudinal COVID-19 ICU survivor cohort study. The study will gather clinical data on 500 patients as well as longitudinal outcomes obtained using laryngoscopy and validated patient reported outcome measures evaluating voice (Voice Handicap Index-10), communication (Communication Participation Item Bank) and global quality of life (12-Item SF Health Survey). This research will broadly impact the fields otolaryngology, anesthesiology and critical care medicine. It will advance our knowledge of intubation related injuries and allow us to better prevent and treat them, ultimately decreasing patient morbidity and the societal burden of this disease.

项目摘要 喉头疾病和喉部插管创伤后的喉功能障碍不足。随着插管ICU患者的数量已大大增加，这种障碍将成为流行比例的问题。迄今为止，有85,000-170,000名Covid-19患者需要进行通风插管的ICU入院。由于当前的国家准则建议，他们的喉损伤风险被指数增加，该指南建议将气管切开术延迟，直到插管> 21天。这令人震惊，因为在7-10天时进行气管群，而57％的患者仅在12小时后证明喉粘膜损伤。这些伤害是由气管管在喉结构上的压力造成的，可以永久损害声音功能，产生发光症，并产生后骨狭窄。所有人都有重大的发病率和生活质量后遗症，并且没有最佳治疗方法。语音功能障碍会导致挫败感，孤立，恐惧和自我认同，以及生活质量受损，工人生产力失去的障碍以及与慢性疾病，如充血性心力衰竭，慢性阻塞性肺部疾病和严重抑郁症等慢性疾病相似的率提出残疾索赔。由于ICU中COVID-19患者治疗COVID患者而导致的语音障碍质量后果预计非常普遍且严重，导致个人和社会负担很高。 我们的长期目标是制定干预措施，以减少喉咙后喉损伤的发病率和影响。 Covid-199人群的风险增加使我们必须了解喉部受伤的负担，并从这种大流行中学习，以最大程度地减少未来插管患者的风险。该项目的目的是：1。创建一个全国性的Covid-19 ICU幸存者，并量化对喉部功能，语音，语音，沟通和生活质量的急性负担，住院后的生活质量，2。量化COVID-19的长期负担，COVID-19的长期负担和治疗范围内的功能和质量相关，以防止laryngeal功能和质量识别，以防止，以防止laryngeal，识别识别，以防止，以防止，以防止，以防止，识别识别，3.。喉损伤。 我们将建立在我们先前的工作以及我们开发的北美气道合作的力量和范围的基础上，并通过40多个参与学术机构进行了纵向Covid-19 ICU幸存者队列研究。该研究将收集有关500名患者以及使用喉镜检查获得的纵向结局的临床数据，并经过验证的患者报告了评估语音（语音障碍指数10），沟通（通信参与项目库）和全球生活质量（12- ITEM SF SF HEALTY调查）的结果指标。 这项研究将广泛影响耳鼻喉科，麻醉学和重症监护医学。它将提高我们对插管相关伤害的了解，并使我们能够更好地预防和治疗它们，最终减少患者的发病率和这种疾病的社会负担。