The mechanics of symptom generation in dysphagia

描述(申请人提供)：吞咽困难是非常常见的，无论原因如何，都会导致患者的生活质量大幅下降。不幸的是，我们对症状产生的病理生理学解释的理解很差。在考虑吞咽过程中食道症状的发生时，将注意力集中在团注内压(IBP)是合乎逻辑的，因为这是排空食道的主要力量。团注内压力取决于许多因素；然而，主要决定因素是EGJ顺应性，因为流出食道的流量高度依赖于EGJ直径。这一建议的假设集中在IBP和EGJ依从性之间的关系，因为它与吞咽困难和胸痛的症状有关。因此，本方案的目标是：1)明确IBP与EGJ顺应性之间的生理关系；2)确定症状严重程度与IBP异常之间的相关性；3)研究症状发生过程中食道敏感性与IBP的关系。为了实现上述目标，将进行一套全面的解剖学和生理学研究，重点测量EGJ的团注内压、蠕动完整性、食管壁厚度和顺应性，以阐明EGJ顺应性和团注内压在吞咽过程中产生食道症状中的作用。EGJ顺应性将使用阻抗平面法来确定，以创建EGJ几何图形的多维渲染，而团注内压力和蠕动完整性将使用固态HRM系统进行评估。阻抗平面仪也将被用来评估食道敏感性和生活质量，心理社会问卷也将被纳入分析，因为这些是症状感知的重要变量。我们已经验证了几种新的技术来测量团注运输的机械相关变量。这些生理和力学变量将被用来评估症状严重程度和食道排空机制之间的相关性。此外，还将开发统计模型来帮助预测EGJ遵从性对IBP的影响。这些机械变量的临床相关性将在一项评估治疗效果的研究中得到验证，该研究的重点是提高EGJ依从性和降低IBP对症状感知的影响。患者将在治疗前后进行食道敏感性分析，以控制分析中的这一变量。我们这项建议的最终目标是开发和验证新的分析范式，重点关注食道感觉和团注内压之间的机械关系。这些新的分析技术将改进相关食道运动疾病的诊断分类，并有助于确定哪些患者可能受益于专注于降低团注内压的治疗。与公共卫生相关：吞咽困难是极其常见的，吞咽困难的症状导致患者的生活质量大幅下降，无论原因如何。不幸的是，我们目前对这些症状的生理原因的了解受到缺乏准确描述食道排空机制的工具的限制。这项提案将利用新的分析技术来了解症状的原因，并确定可以采取什么措施来改善食道功能，从而减少症状。

DESCRIPTION (provided by applicant): Swallowing difficulties are extremely common and result in a substantial reduction in the quality of life for patients regardless of the cause. Unfortunately, our understanding regarding the pathophysiologic explanation for symptom generation is poor. In contemplating the occurrence of esophageal symptoms during swallowing it is logical to focus attention on intrabolus pressure (IBP), as this is the primary force that empties the esophagus. Intrabolus pressure is dependent on a number of factors; however, the primary determinant is EGJ compliance as flow out of the esophagus is highly dependent on EGJ diameter. The hypothesis for this proposal focuses on the relationship between IBP and EGJ compliance as it relates to symptoms of dysphagia and chest pain. Thus, the goals of this proposal are:1) to define the physiologic relationship between IBP and EGJ compliance, 2) determine the correlation between symptom severity and IBP abnormalities, and 3) study the relationship between esophageal sensitivity and IBP in symptom generation. In order to accomplish the above goals, a comprehensive set of anatomical and physiological studies focused on measuring intrabolus pressure, peristaltic integrity, esophageal wall thickness and compliance of the EGJ to elucidate the role of EGJ compliance and intrabolus pressure in generating esophageal symptoms during swallowing will be performed. EGJ compliance will be determined using impedance planimetry to create a multidimensional rendering of EGJ geometry, while intrabolus pressure and peristaltic integrity will be assessed using a solid-state HRM system. Impedance planimetry will also be used to assess esophageal sensitivity and quality of life and psychosocial questionnaires will also be incorporated into the analysis as these are important variables in symptom perception. We have validated several new techniques to measure the mechanically relevant variables of bolus transit. These physiologic and mechanical variables will be used to assess the correlation between symptom severity and the mechanics of esophageal emptying. In addition, statistical models will be developed to help predict the effect EGJ compliance has on IBP. The clinical relevance of these mechanical variables will be validated in a study assessing the effect of therapy focused on increasing EGJ compliance and reducing IBP on symptom perception. Patients will have esophageal sensitivity analysis before and after therapy to control this variable in the analysis. Our ultimate goal for this proposal is to develop and validate novel analysis paradigms that will focus on the mechanical relationship between esophageal sensation and intrabolus pressure. These new analysis techniques will improve diagnostic classification of relevant esophageal motor disease and also help determine which patients may benefit from treatment focused on reducing intrabolus pressure. PUBLIC HEALTH RELEVANCE: Swallowing difficulties are extremely common and symptoms of dysphagia result in a substantial reduction in the quality of life for patients regardless of the cause. Unfortunately, our current understanding regarding the physiologic cause of these symptoms is limited by a lack of tools to accurately describe the mechanics of esophageal emptying. This proposal will utilize new analysis techniques to understand the cause of symptoms and determine what can be done to improve esophageal function so that symptoms can be reduced.