The mechanics of symptom generation in dysphagia

Project: Research project

Description

Swallowing difficulties are common and result in a substantial reduction in quality of life with increased morbidity and mortality related to malnutrition and complications related to regurgitation and aspiration. Unfortunately, our understanding of 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 a new classification scheme for esophageal motor disorders, “the Chicago Classification.” Despite this improved understanding, there was still the lack of a true correlate for symptoms. Our work suggests that the measure of IBP was much more complex than previously appreciated. The IBP had distinct components modulated by additional physiological and mechanical properties of the wall invisible to the standard manometric assessment. Using impedance techniques combined with manometry and high-resolution planimetry, we can assess 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 will be influenced by different disease states and that these changes will manifest as impaired esophageal emptying and increased symptoms.
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 are extremely important. We have created new methodology and analysis paradigms utilizing combined manometry with impedance to define the pressure gradients during each phase of swallowing and flow through the EGJ and the volume of bolus retention associated with impaired function. We have also refined impedance planimetry techniques to study the response of the esophageal wall to 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. Our ultimate goal is to evolve the understanding of the pathogenesis of esophageal diseases 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.
StatusFinished
Effective start/end date8/15/146/30/19

Funding

  • National Institute of Diabetes, Digestive and Kidney Diseases (5R01DK079902-09)

Fingerprint

Deglutition Disorders
Mechanics
Pressure
Esophagogastric Junction
Deglutition
Electric Impedance
Manometry
Esophageal Diseases
Malnutrition
Compliance
Biomarkers
Quality of Life
Morbidity
Phenotype
Mortality