CLINICAL STUDIES OF MIDDLE EAR PRESSURE DYSREGULATION

临床和实验证据表明，中耳（ME）压力调节机制的破坏与病理生理变化有关，包括明显的压力不足和粘膜炎症的发展，如果长期导致中耳炎伴积液（OME）。足量调节ME压力需要咽鼓管（ET）的间歇性瞬态开口提供足够数量的气体，以平衡与ME和血液之间梯度驱动交换相关的净玻璃。较差的ET功能导致了压力下的ME和真空机制下的ME，在本项目下进行的实验已经令人信服地证明了其有效性。事实上，在临床试验中证明，绕过ET向ME提供气体的OME治疗可以促进疾病的缓解。伴有易患OME的并发疾病的儿童和成人的ET功能测试显示，腔内充血发生变化，表现为肌肉辅助的输卵管扩张机制效率降低。其他针对OME及伴发OME患儿的研究显示，输卵管开口的主动机制存在原发性损伤。然而，ET功能测试对病程的预后价值有限，引发了关于ET功能障碍在OME发病机制中的作用的争议。最近在该项目下进行的研究表明，疾病进展与测试结果之间的不一致可能是由于当前的测试方案未能同时评估粘膜气体交换率变化对ET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试验参数的影响。由于组织病理学研究不能证明ET功能差的解剖学基础，新的MRI成像技术将用于尝试将体内ET结构和功能联系起来。该项目的目标是更好地了解OME发病机制中的ME压力失调，评估新开发的用于评估该功能的测试方案的预后价值，确定ET功能障碍的潜在原因，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..