Manual Control of the Upper Esophageal Sphincter

描述(申请人提供)：吞咽困难，或吞咽困难，是一种破坏性的疾病，每年影响1000多万美国人。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性研究，为严重吞咽困难患者开发创新的新治疗方案。尽管用于其他器官系统的医疗设备已经有了很大的进步，但目前还没有可用的设备来帮助吞咽。目前的治疗方法包括吞咽疗法、改变饮食、非口腔喂养和侵入性手术。尽管我们尽了最大努力，这些治疗在相当大比例的个人中都失败了。这一建议的特殊假设是，长期深部口咽吞咽困难(OPD)可以通过手动打开上食道括约肌(UES)来治疗。这一假说将通过OPD的绵羊模型和手动打开UES的吞咽扩张装置进行验证。建议的具体目的是确定：1)通过向前拉动环状软骨来最大限度地打开UES所需的力量；2)通过使用燕子扩张器手动打开UES来持续改善吞咽情况；3)使用吞咽扩张器对环状软骨或邻近组织和器官系统造成损伤或感染；以及4)在不损害环状软骨或邻近组织的情况下安全地取出吞咽扩张器。在这些研究完成后，当局将会严格确定以人手开启UES对治疗门诊病人是否安全和有效。这项提议的结果将通过增加对环状软骨如何对治疗OPD所需的生物机械力做出反应的了解来影响研究领域，从而导致创新和优化设计的治疗方法。如果结果是肯定的，这项研究将形成第一阶段人类临床试验的基础。

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.