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

项目摘要 危重病后的喉功能损害和喉插管损伤未被充分认识。这种损害将成为一个流行病比例的问题，因为新冠肺炎导致插管ICU患者的数量急剧增加。到目前为止，已有85,000-170,000名新冠肺炎患者需要住进ICU并进行插管换气。由于当前的国家指南建议将新冠肺炎患者的气管切开推迟到插管21天，他们的喉部损伤风险呈指数级增加。这是令人担忧的，因为气管切开术通常在7-10天内进行，57%的患者在12小时后就发现喉部粘膜损伤。这些损伤是由气管导管对喉部结构的压力造成的，可以永久性地损害发声功能，造成声门关闭不全，并产生后部声门狭窄。它们都有严重的发病率和生活质量后遗症，并且没有最佳的治疗方法。发声功能障碍会导致沮丧、孤立、恐惧和自我认同的改变，以及生活质量下降、员工生产力下降，以及需要以类似于充血性心力衰竭、慢性阻塞性肺疾病和严重抑郁症等慢性病的比率提交残疾索赔。预计在ICU治疗新冠肺炎患者引起的嗓音障碍造成的生活质量后果将极其普遍和严重，造成沉重的个人和社会负担。 我们的长期目标是开发干预措施，以减少插管后喉部损伤的发生率和影响。新冠肺炎人群的高风险使我们必须了解喉部损伤的负担，并从这次大流行中吸取教训，将未来插管患者的风险降至最低。该项目的目标是：1.创建一个全国新冠肺炎重症监护病房幸存者队列，并量化感染和治疗对出院后喉功能、声音、沟通和生活质量的急性负担；2.量化队列内新冠肺炎感染和治疗对喉功能、语音、通信和生活质量的长期负担；3.确定潜在的干预目标，以预防和治疗插管后喉部损伤。 在我们以前工作的基础上，以及我们与40多个参与的学术机构开展的北美航空公司合作的力量和覆盖范围，我们将进行一项纵向的新冠肺炎重症监护病房幸存者队列研究。这项研究将收集500名患者的临床数据，以及使用喉镜获得的纵向结果，并验证患者报告的结果，评估语音(语音残疾指数-10)、沟通(交流参与项目库)和全球生活质量(12项SF健康调查)。 这项研究将广泛影响耳鼻咽喉、麻醉学和重症监护医学领域。它将提高我们对插管相关损伤的认识，使我们能够更好地预防和治疗它们，最终降低患者的发病率和这种疾病的社会负担。

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.