Role of altered response to volumetric distension in esophageal disease

项目总结 吞咽困难是非常常见的，并导致生活质量的大幅下降 与营养不良有关的发病率和死亡率以及与反流和 渴望。不幸的是，我们对吞咽困难和GERD的病理生理学的理解 主要集中在环状肌肉的活动上，而忽视了 促进正常排空的食管壁。我们最初的工作探索了团注之间的关系 压力(IBP)和食管胃交界处(EGJ)顺应性作为流出阻力的指标。这部作品 强调了IBP和EGJ开放之间的直接关系，是发展 一种新的食道运动障碍分类方案，“芝加哥分类”。尽管如此，情况还是有所改善 理解重点是团注运输动态，仍有以 缺乏与症状的真正相关性或不良后果的预测模型。鉴于这些限制，我们 使我们的重点转向更直接地评估墙的膨胀性和墙的反应 食管体到体积的扩张将改变正常的团注运输。我们假设这个机械装置 食管壁的特性可能会通过扰乱正常的低压状态来改变团注的运输 是无症状的药丸通过食道运输所必需的。 为了验证壁力学是食道疾病的主要决定因素的假设，我们 必须开发新的方法和新技术来直接测量机械墙的状态。vbl.使用 结合阻抗技术和测压技术，我们现在能够评估IBP和直径的变化 跨越时空连续体(4D-IM)。这种方法将使我们能够研究推注的运输机制。 通过测压量化的等长环状肌肉收缩，使我们能够评估 食道通过等张松弛和被动扩张来容纳传播的推注，而 食道通过被动后坐和强直性收缩推动推进剂的能力。此外，我们还有 还改进了翻转技术，以评估食管壁对容量扩张的反应 翻转参数分析。食管壁对丸剂滞留或反流的反应是最大的 食道在预防吸入并发症、反流性损伤或相关症状中的重要作用 以增强保留力。我们最近报道，对容量扩张的正常反应与 反复顺行收缩(RAC)，这种反应在特定的疾病状态下会改变。我们的 首要目标将是研究以墙为目标的干预前后明确定义的患者群体 扩张性以确定扩张性和对容量扩张的反应是否异常 对结果的重要预测因素。这项工作将建立在芝加哥分类法之前的成功基础上 通过定义疾病活动性的新生物力学生物标记物和治疗干预的新靶点。

PROJECT SUMMARY Swallowing difficulties are extremely common and result in a substantial reduction in the quality of life and increased morbidity and mortality related to malnutrition and complications related to regurgitation and aspiration. Unfortunately, our understanding regarding the pathophysiology of dysphagia and GERD has been hampered by focusing predominantly on circular muscle activity and ignoring the biomechanical properties of the esophageal wall that promote normal emptying. Our initial work explored the relationship between intrabolus pressure (IBP) and esophagogastric junction (EGJ) compliance as a metric for outflow resistance. This work highlighted the direct relationship between IBP and EGJ opening and was the foundation for the development of a new classification scheme for esophageal motor disorders, “the Chicago Classification.” Despite this improved understanding focused on bolus transit dynamics, there are still significant unresolved issues centered on the lack of a true correlate for symptoms or a predictive model for adverse outcomes. Given these limitations, we have evolved our focus toward a more directed assessment of how wall distensibility and the response of the esophageal body to volumetric distention will alter normal bolus transit. We hypothesize that the mechanical properties of the esophageal wall will likely alter bolus transport by disturbing the normal low pressure state that is required for asymptomatic bolus transit through the esophagus. In order to test our hypothesis that wall mechanics are a major determinant of esophageal diseases, we have had to develop new approaches and new technology to directly measure mechanical wall state. Using impedance techniques combined with manometry, we are now capable of assessing IBP and diameter changes across a space-time continuum (4D-IM). This approach will allow us to study the mechanics of bolus transport beyond the isometric circular muscle contraction quantified by manometry and allow us to assess the ability of the esophagus to accommodate the propagating bolus via isotonic relaxation and passive distention and the ability of the esophagus to propel the bolus via passive recoil and auxotonic contraction. Additionally, we have also modified FLIP techniques to assess the response of the esophageal wall to volumetric distention using FLIP-panometry analysis. The response of the esophageal wall to bolus retention or reflux is one of the most important functions of the esophagus in preventing complications of aspiration, reflux injury, or symptoms related to bolus retention. We recently reported that the normal response to volumetric distention is associated with repetitive antegrade contractions (RACs) and that this response was altered in specific disease states. Our overarching goal will be to study well-defined patient populations before and after interventions targeting wall distensibility to determine whether abnormalities in distensibility and response to volumetric distention are important predictors of outcome. This work will build upon the previous success of the Chicago Classification by defining new biomechanical biomarkers of disease activity and new targets for therapeutic intervention.