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.

项目总结