Middle Ear Pressure Regulation in Health and Disease

描述（由申请人提供）：健康和疾病中的ME压力调节：我们提出一个转化临床研究计划，将我们之前的中耳压力调节工作从动物基础研究扩展到临床环境。该方案的综合主题是中耳压力失调，作为一种由构成或情境因素引起的疾病，这些因素增加了中耳气体需求，减少了气体供应或两者兼而有之。我们的总体假设是：中耳炎伴积液，即中耳炎症伴积液，相关疾病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进行治疗。本临床研究项目由四个子项目组成，由三个核心单元支持。子项目1“气体供应、需求和中耳气体平衡”开发了评估鼓膜完好的耳朵中耳咽管功能的新方案，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，并测量通过耳咽管的气体交换率。中耳粘膜和鼓膜用于改进现有的中耳压力调节模型。子项目2，“耳咽管生长发育：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相关性。子项目3，“腭裂患者中耳压力失调：形式-功能相关”，对腭裂儿童中耳压力调节进行了功能-解剖描述，并确定婴儿期功能失调标志物是否能预测老年疾病的患病率。子项目4“中耳造瘘管置入后的中耳压力失调”定义了积液性中耳炎造瘘管置入后压力调节的变化，并确定这些指标是否预测TT挤压后的疾病复发。核心A“行政/支持”为方案提供指导和整合，管理所有研究的财务方面，监督有关人权的所有事项，并为所有子项目提供护理、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”通过对中耳压力调节、耳咽管结构-功能和中耳对压力不平衡的反应进行一致的数学描述来整合程序的所有方面，用于解释子项目1至4的数据。子项目1和核心B、C水平整合预测中耳压力失调及其疾病表达的模型精度反馈。这个独特的临床研究项目将继续我们作为美国唯一的研究中心的传统，全面而深入地研究：1)中耳压力调节，2)压力失调在疾病发病机制中的作用，3)与未来疾病经验相关的特定测试的预后能力，以及4)被确定为潜在压力失调因素的治疗。

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.