The mechanics of symptom generation in dysphagia

描述（由申请人提供）：吞咽困难非常常见，无论原因如何，都会导致患者生活质量大幅下降。不幸的是，我们对症状产生的病理生理学解释的理解很差。在考虑吞咽期间食管症状的发生时，将注意力集中在团内压（IBP）上是合乎逻辑的，因为这是排空食管的主要力量。团内压取决于许多因素;然而，主要决定因素是EGJ顺应性，因为流出食管的流量高度依赖于EGJ直径。该建议的假设重点是IBP和EGJ依从性之间的关系，因为它与吞咽困难和胸痛症状有关。因此，本提案的目标是：1）定义IBP和EGJ顺应性之间的生理关系，2）确定症状严重程度和IBP异常之间的相关性，3）研究食管敏感性和IBP在症状产生中的关系。为了实现上述目标，将进行一组全面的解剖学和生理学研究，重点是测量团内压力、蠕动完整性、食管壁厚度和EGJ顺应性，以阐明EGJ顺应性和团内压力在吞咽期间产生食管症状中的作用。EGJ顺应性将使用阻抗平面测量法确定，以创建EGJ几何结构的多维渲染，而团内压力和蠕动完整性将使用固态HRM系统进行评估。还将使用阻抗平面测量法评估食管敏感性和生活质量，并将心理社会问卷纳入分析，因为这些是症状感知的重要变量。我们已经验证了几种新技术来测量团注传输的机械相关变量。这些生理和机械变量将用于评估症状严重程度与食管排空机制之间的相关性。此外，将开发统计模型，以帮助预测EGJ依从性对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，该研究的重点是增加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管敏感性分析，以控制分析中的该变量。我们这项建议的最终目标是开发和验证新的分析范式，将重点放在食管感觉和团内压力之间的机械关系。这些新的分析技术将改善相关食管运动疾病的诊断分类，并有助于确定哪些患者可能受益于以降低团内压为重点的治疗。公共卫生相关性：吞咽困难是非常常见的，吞咽困难的症状会导致患者生活质量的大幅下降，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理解受到缺乏准确描述食管排空机制的工具的限制。该提案将利用新的分析技术来了解症状的原因，并确定可以采取哪些措施来改善食管功能，从而减轻症状。

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.