Manual Control of the Upper Esophageal Sphincter

描述（由申请人提供）：吞咽困难或吞咽困难是一种毁灭性的疾病，每年影响超过1000万美国人。未经治疗的吞咽困难可导致脱水、营养不良、吸入性肺炎和死亡。该项目的总体目标是通过临床和转化研究为深度吞咽困难患者开发创新的新治疗方案。虽然用于其他器官系统的医疗器械已经取得了很大的进步，但目前还没有可用的器械来辅助吞咽行为。目前的治疗选择包括吞咽疗法，饮食调整，非口服喂养和侵入性手术。尽管我们尽了最大的努力，但这些治疗在很大一部分人中失败了。该建议的特定假设是，长期深度口咽吞咽困难（OPD）可以通过手动打开上食管括约肌（UES）来治疗。将使用OPD的绵羊模型和手动打开UES的吞咽扩张装置来检验该假设。该提案的具体目的是确定：1）通过向前拉动环状软骨来最大程度地打开UES所需的力; 2）通过使用吞咽扩张装置手动打开UES来持续改善吞咽; 3）通过使用吞咽扩张装置造成的损伤或感染来证明环状软骨或邻近组织和器官系统的损伤;以及4）安全地移除吞咽扩张装置而不损伤环状软骨或邻近组织。在这些研究完成时，将严格确定手动打开UES治疗OPD是否安全有效。该提案的结果将通过增加对环状软骨如何响应治疗OPD所需的生物力学力的理解来影响研究领域，从而导致创新和优化设计的治疗。如果结果是积极的，这项研究将构成I期人体临床试验的基础。

DESCRIPTION (provided by applicant): Dysphagia, or difficulty swallowing, is a devastating disorder that affects over 10 million Americans each year. Untreated dysphagia can lead to dehydration, malnutrition, aspiration pneumonia, and death. The overall goal of this project is to develop innovative, new treatment options for patients with profound dysphagia via clinical and translational research. Although there have been great advances in medical devices for other organ systems, there is currently no device available to assist with the act of deglutition. Current therapeutic options include swallowing therapy, diet modification, non-oral feeding and invasive surgery. Regardless of our best efforts, these treatments fail in a significant percentage of individuals. The particular hypothesis of this proposal is that long-term profound oropharyngeal dysphagia (OPD) can be treated by manually opening the upper esophageal sphincter (UES). The hypothesis will be tested with an ovine model of OPD and a swallow expansion device that manually opens the UES. The specific aims of the proposal are to determine: 1) the force necessary to maximally open the UES by pulling the cricoid cartilage anteriorly; 2) sustained improvement in swallowing by manual opening of the UES with the swallow expansion device; 3) damage to the cricoid cartilage or adjacent tissue and organ systems as evidenced by injury or infection with use of the swallow expansion; and 4) safe removal of the swallow expansion device without damage to the cricoid cartilage or adjacent tissues. At the completion of these studies, it will have been rigorously determined whether manual opening of the UES is safe and efficacious for treating OPD. Results from this proposal will impact the research field through increased understanding of how the cricoid cartilage responds to the biomechanical force necessary to treat OPD, leading to innovative and optimally designed therapy. If the results are positive, this investigation will form the basis for Phase I human clinical trials.