Mechanisms of Upper Gut and Airway Interaction - PROGRAM PROJECT

描述（由申请人提供）： 尽管胃食管腔和咽喉腔在解剖学上是相邻的，但在正常情况下，气道不会被胃内容物吸入。这种保护的机制尚未完全理解，因此相关疾病的病理生理机制仍然不确定，因为缺乏适当的技术和仪器或合适的人类和动物模型来设计适当的实验。这些缺陷现在已经得到了弥补，我们的初步数据表明这些研究的可行性和安全性。我们已经确定了一个有缺陷的气道保护性反射的人模型，并开发了一个猫模型，用于研究在生理和病理生理条件下食管和气道之间的相互作用。我们还开发并成功测试了新的记录设备和实验技术，用于人类婴儿和成人以及我们的猫科动物模型。由于这些实验的性质需要来自多个学科的专业知识，我们组建了一个由医学，神经病学，生理学，放射学，儿科和耳鼻喉科等部门的专家组成的大型多学科研究团队，以开展本项目中的拟议研究。该团队有着长期的成功合作历史，发现和表征了几种迄今为止尚未描述的气道保护性反射，开发了更新的方法，并记录了上食管括约肌和声门保护功能的异常。该团队成员在追求共同目标的过程中相互作用和合作的程度，在过去几年中联合发表了许多研究成果，证明了这一点。强烈的兴趣和更好地理解上消化道和气道相互作用机制的明显需求，加上我们研究团队的协同作用和热情，为当前提案的发展提供了基本动力。该项目中的所有项目都有一个共同的主题，即识别、表征和量化食管和气道之间生理和病理生理相互作用的机制。拟议方案包括三个分项目和一个行政核心。项目1旨在研究猫模型中食管与气管支气管树之间的关系。项目2研究预防成人误吸的机制。项目3阐述了婴儿气道安全的发育生理学和病理生理学。

DESCRIPTION (provided by applicant): Despite the anatomical contiguity between the gastroesophageal and pharyngolaryngeal lumen, under normal condition the airway is protected from aspiration of gastric content. The mechanisms of this protection are not completely understood and as such the pathophysiologic mechanisms of related disorders remain uncertain because of either lack of proper techniques and instrumentations or suitable human and animal models for design of appropriate experiments. These shortcomings had now been remedied and our preliminary data suggests the feasibility and safety of these studies. We have identified a human model of defective airway protective reflexes and developed a feline model for studying interactions between esophagus and airway under physiologic and pathophysiologic conditions. We also have developed and successfully tested new recording devices and experimental techniques for use in both in human infants and adults as well as our feline model. Because the nature of these experiments requires expertise from multiple disciplines we have assembled a large multi-disciplinary research team comprised of experts from the Departments of Medicine, Neurology, Physiology, Radiology, Pediatric, and Otolaryngology to carry out the proposed studies in this project. This team has a long history of successful collaboration resulting in the discovery and characterization of several hitherto undescribed airway protective reflexes, development of newer methodology, and documentation of abnormalities of upper esophageal sphincter and glottal protective functions. The degree of interaction and collaboration among the members of this team pursuing their common goal is attested by their many joint publications of research outcomes over the past several years. The intense interest and the obvious need for better understanding of the mechanisms of upper gut and airway interaction coupled with the synergy and enthusiasm of our research team provided the basic impetus for the development of the current proposal. All of the projects in this program share the common theme of identifying, characterizing and quantitating the mechanisms that govern the physiologic and pathophysiologic interaction between the esophagus and the airway. The proposed program includes three subprojects and an administrative core. Project 1 is designed to investigate the relationship between the esophagus and tracheo-bronchial tree in a feline model. Project 2 studies the mechanism of prevention of aspiration in adult humans. Project 3 addresses the developmental physiology and pathophysiology of airway safety in infants.