CLINICAL STUDIES OF MIDDLE EAR PRESSURE DYSREGULATION

临床和实验证据表明，中耳(ME)压力调节机制的紊乱与病理生理变化有关，包括明显的低压和粘膜炎症的发展，如果持续下去，就会导致渗出性中耳炎(OME)。要充分调节ME压力，需要咽鼓管(ET)的间歇性瞬时开口提供足够数量的气体，以平衡ME和血液之间的梯度驱动交换相关的净玻璃。较差的ET功能导致ME低压和OME，这一机制在本计划下进行的实验中得到了令人信服的验证。事实上，临床试验表明，OME的治疗方法可以绕过ET，向ME供应气体，以促进疾病的缓解。对易患OME的儿童和成人的ET功能测试显示，管腔内充血的变化表现为肌肉辅助的输卵管扩张机制的效率降低。其他关于OME和伴发OME的儿童“t风险”的研究表明，输卵管开口的主动机制存在主要损害。然而，就病程而言，ET功能测试的预后价值是有限的，这引发了关于ET功能障碍在OME发病机制中的作用的争议。根据该计划进行的最新研究表明，疾病进展和测试结果之间的不一致可能是由于当前测试方案未能同时评估不同的跨粘膜气体交换速率对ET施加的功能需求。该项目的总体目标是开发临床适用的ME压力调节测试，同时评估这些需求和供应功能。还评估了与粘膜愈合相关的测量测试参数的效果。由于组织病理学研究不能证明ET功能不良的解剖学基础，因此将使用新的MRI成像技术来尝试将体内ET的结构和功能联系起来。该项目的目标是更好地了解ME压力失调在OME发病机制中的作用，评估新开发的用于评估这一功能的测试方案的预后价值，确定ET功能障碍的潜在原因(S)，并利用这些知识建议OME的新治疗策略。

Clinical and experimental evidences show that disruption of the mechanism for middle ear (ME) pressure regulation is associated with pathophysiological changes including the development of significant under- pressures and mucosal inflammation that if prolonged results in otitis media with effusion (OME). Adequate regulation of ME pressure requires that the intermittent transient openings of the Eustachian tube (ET) provide a sufficient quantity of gas to balance the net glasses associated with the gradient driven exchange between the ME and blood. Poor ET function causes ME under-pressures and OME by the hydrops ex vacuo mechanism, the validity of which has been convincingly demonstrated in experiments conducted under this program. Indeed, treatments for OME that bypass the ET to supply the ME with gas were shown in clinical trials to promote disease resolution. ET function tests in children and adults with concurrent diseases that predispose them to OME show changes in intraluminal congestion that present as a decreased efficiency of the muscular assisted mechanism of tubal dilation. Other studies in children "t risk" for OME and with concomitant OME, show a primary impairment of the active mechanism for tubal openings. However, the prognostic value of ET function tests with respect to disease course is limited, provoking controversy as to the role of ET dysfunction in the pathogenesis of OME. Recent studies conducted under this program show that the discordance between disease progression and test results may be explained by the failure of current test protocols to assess concurrently the functional demand placed upon the ET by the varying rates of transmucosal gas exchange. The overall objective of this project is to develop clinically applicable tests for ME pressure regulation that assess simultaneously these demand and supply functions. Also evaluated is the effect of measured test parameters associated with mucosal healing. Because histopathological studies cannot demonstrate an anatomic basis for poor ET function, new MRI imaging techniques will be used in an attempt to relate in vivo ET structure and function. The goals of this project are to develop a better understanding of ME pressure-dysregulation in the pathogenesis of OME, to evaluate the prognostic value of newly developed test protocols for assessing that function, to identify the underlying cause(s) of ET dysfunction, and to utilize this knowledge in suggesting new treatment strategies for OME..