The mechanics of symptom generation in dysphagia

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): 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 pathophysiologic explanation for symptom generation is poor. During our first funding cycle, we 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 regarding bolus transit dynamics, there were still significant unresolved issues focused on the lack of a true correlate for symptoms. Our previous work did suggest that the measure of IBP was much more complex than previously appreciated. It appeared that IBP had distinct components that were modulated by additional physiological and mechanical properties of the esophageal wall invisible to the standard manometric assessment. Using impedance techniques combined with manometry and high-resolution planimetry, we are now capable of assessing IBP within the framework of 4 specific phases of swallow function [1-esophageal accommodation, 2-esophageal compartmentalization, 3-esophageal stripping and 4- ampullary emptying]. We hypothesize that abnormalities in IBP at different stages of the swallow will be influenced by different disease states and that these changes will manifest as impaired esophageal emptying and increased symptoms. In order to better understand the complex relationship between IBP and the esophageal body, new techniques that focus on defining IBP along the continuum of the 4 phases of swallowing would be extremely important. We have created new methodology and analysis paradigms utilizing combined manometry with impedance that can accurately define the pressure gradients during each phase of swallowing with the added benefit of defining flow through the EGJ and the volume of bolus retention associated with impaired esophageal body function. Additionally, we have also refined impedance planimetry techniques to study the response of the esophageal wall to volumetric distention to study the mechanical response to IBP and the threshold for stimulating esophageal contractility. These tools and techniques have been developed at Northwestern and provide the needed detail to test our hypotheses focused on the role of abnormal esophageal wall mechanics in generating symptoms and complications. Our ultimate goal is to evolve the understanding of the pathogenesis of esophageal diseases beyond the current standards of motility patterns and to incorporate biomechanical principles into the management and treatment paradigms of these disorders. This work will build upon the previous success of the Chicago Classification by defining new important biomarkers of disease activity and clinically relevant phenotypes of dysphagia.