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重度吞咽困难患者开发创新的新治疗方案。虽然在其他器官系统的医疗设备方面已经取得了很大的进步，但目前还没有设备可以帮助吞咽。目前的治疗选择包括吞咽治疗、饮食改变、非口服喂养和侵入性手术。尽管我们尽了最大的努力，这些治疗在很大程度上还是失败了。这个建议的特殊假设是，长期的深度口咽吞咽困难（OPD）可以通过手动打开食管上括约肌（UES）来治疗。该假设将通过绵羊OPD模型和手动打开UES的吞咽扩张装置进行测试。该建议的具体目的是确定：1)通过前拉环状软骨来最大限度地打开UES所需的力；2)使用吞咽扩张装置手动打开UES，持续改善吞咽；3)使用吞扩器造成环状软骨或邻近组织和器官系统损伤或感染；4)在不损伤环状软骨或邻近组织的情况下安全取出咽扩张器。在这些研究完成后，将严格确定手动打开UES对于治疗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方法。如果结果是积极的，这项调查将成为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.