Middle Ear Pressure Regulation in Health and Disease

描述(申请人提供)：ME压力调节在健康和疾病中：我们提出了一个转化性临床研究计划，将我们之前在中耳压力调节方面的工作从动物基础研究扩展到临床环境。该项目的综合主题是中耳压力失调，这是一种由结构性或情境性因素引起的疾病，这些因素增加了中耳的气体需求，减少了气体供应，或者两者兼而有之。我们的全球假设是：渗出性中耳炎，即中耳渗出性炎症，以及相关疾病的表达是由中耳压力失调引起和维持的，预防或解决这些病理需要专门针对该病因的治疗。这项临床研究计划由四个子项目组成，由三个核心单位提供支持。子项目1“气体供应、需求和中耳气体平衡”开发了新的方案，用于评估鼓膜完整的耳朵的咽鼓管功能，确定这些测试的结果是否可以预测病毒性上呼吸道感染期间中耳炎和其他中耳并发症的发生率，并测量咽鼓管、中耳粘膜和鼓膜之间的气体交换率，以用于完善现有的中耳压力调节模型。子项目2“咽鼓管生长发育：解剖/功能”描述了中耳压力调节随年龄的变化，并确定是否存在压力失调的预测性解剖学相关性。子项目3“腭裂患者的中耳压力失调：形式-功能相关”开发了对腭裂儿童中耳压力调节的功能解剖学描述，并确定婴儿时期中耳压力失调的功能标记物是否预测以后疾病的流行。子项目4，“鼓室置管后中耳压力失调”定义了渗出性中耳炎鼓室置管后中耳压力调节的变化，并确定这些指标是否预测TT挤出后的疾病复发。核心A“行政/支助”为方案提供指导和整合，管理所有研究的财务方面，监督与人权有关的所有事项，并为所有次级项目提供护理、数据输入和统计服务。核心B，“测试和成像”，监督测试仪器的建造和维修，现场测试新开发的功能测试和成像协议，并执行子项目1至4所要求的测试。核心C，“建模”通过开发中耳压力调节、咽鼓管结构功能和中耳对压力不平衡的响应的一致数学描述，集成了计划的所有方面，用于解释来自子项目1至4的数据。子项目1、核心B和C与关于预测中耳压力失调及其疾病表现的模型准确性的反馈横向整合。这一独特的临床研究计划将延续我们作为美国唯一一个全面和深入研究以下内容的研究中心的传统：1)中耳压力调节，2)压力失调在疾病发病机制中的作用，3)针对未来疾病经验的特定测试的预后能力，以及4)那些被确定为潜在压力失调的因素的治疗。

DESCRIPTION (provided by applicant): ME PRESSURE-REGULATION IN HEALTH AND DISEASE: We propose a translational Clinical Research Program that extends our previous work on middle ear pressure regulation from basic studies in animals to the clinical environment. The integrating theme for the Program is middle ear pressure dysregulation as a disease caused by either constitutive or situational factors that increase middle ear gas demand, decrease gas supply or both. Our global hypotheses are: otitis media with effusion, i.e. middle ear inflammation with effusion, and related disease expressions are caused and maintained by middle ear pressure dysregulation and treatments to prevent or resolve those pathologies need to specifically address that etiology. This Clinical Research Program consists of four subprojects supported by three Core units. Subproject 1, "Gas Supply, Demand and Middle Ear Gas Balance" develops new protocols for assessing Eustachian tube function in ears with an intact tympanic membrane, determines if the results of those tests predict the incidence of otitis media and other middle ear complications during a viral upper respiratory tract infection, and measures the rate of gas exchange across the Eustachian tube, middle ear mucosa and tympanic membrane for use in refining existing models of middle ear pressure-regulation. Subproject 2, "Eustachian Tube Growth and Development: Anatomy/Function" describes the changes in middle ear pressure-regulation with age and determines if there are predictive anatomical correlates of pressure dysregulation. Subproject 3, "Middle Ear Pressure Disregulation in Cleft Palate Patients: Form-Function Correlates" develops a functional-anatomical description of middle ear pressure-regulation in cleft palate children and determines if functional markers of disregulation in infancy predict disease prevalence at later ages. Subproject 4, "Middle Ear Pressure Disregulation after Tympanostomy Tube Insertion" defines the changes in pressure-regulation after tympanostomy tube insertion for otitis media with effusion and determines whether those measures predict disease recurrence after TT extrusion. Core A, "Administration/Support" provides direction and integration for the Program, manages the financial aspects of all studies, oversees all matters concerning human rights and provides nursing, data entry and statistical services to all subprojects. Core B, "Testing and Imaging" oversees the construction and servicing of the test instruments, field tests newly developed function testing and imaging protocols and performs the testing required by subprojects 1 through 4. Core C, "Modeling" integrates all aspects of the Program by developing consistent mathematical descriptions of middle ear pressure-regulation, Eustachian tube structure-function and the middle ear response to pressure imbalances for use in interpreting the data from subprojects 1 through 4. Subproject 1 and Cores B and C are horizontally integrated with feedback regarding model accuracy for predicting middle ear pressure dysregulation and its disease expressions. This unique Clinical Research Program will continue our tradition of being the only research center in the United States for the comprehensive and intensive study of: 1) middle ear pressure-regulation, 2) the role of pressure dysregulation in disease pathogenesis, 3) the prognostic capabilities of specific tests with respect to future disease experience, and 4) the treatment of those factors identified as underlying pressure dysregulation.