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.

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 th 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK079902-06
Application #
8760020
Study Section
Special Emphasis Panel (ZRG1-DKUS-N (03))
Program Officer
Hamilton, Frank A
Project Start
2007-12-01
Project End
2018-06-30
Budget Start
2014-08-15
Budget End
2015-06-30
Support Year
6
Fiscal Year
2014
Total Cost
$336,038
Indirect Cost
$118,538
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Carlson, D A; Lin, Z; Kou, W et al. (2018) Inter-rater agreement of novel high-resolution impedance manometry metrics: Bolus flow time and esophageal impedance integral ratio. Neurogastroenterol Motil 30:e13289
Carlson, Dustin A; Beveridge, Claire A; Lin, Zhiyue et al. (2018) Improved Assessment of Bolus Clearance in Patients With Achalasia Using High-Resolution Impedance Manometry. Clin Gastroenterol Hepatol 16:672-680.e1
Carlson, D A; Kathpalia, P; Craft, J et al. (2018) The relationship between esophageal acid exposure and the esophageal response to volumetric distention. Neurogastroenterol Motil 30:
Xiao, Y; Carlson, D A; Lin, Z et al. (2018) Jackhammer esophagus: Assessing the balance between prepeak and postpeak contractile integral. Neurogastroenterol Motil 30:e13262
Kahrilas, Peter J; Bredenoord, Albert J; Carlson, Dustin A et al. (2018) Advances in Management of Esophageal Motility Disorders. Clin Gastroenterol Hepatol 16:1692-1700
Carlson, D A; Kahrilas, P J; Tye, M et al. (2018) High-resolution manometry assessment of the lower esophageal sphincter after-contraction: Normative values and clinical correlation. Neurogastroenterol Motil 30:
Kou, Wenjun; Pandolfino, John E; Kahrilas, Peter J et al. (2018) Studies of abnormalities of the lower esophageal sphincter during esophageal emptying based on a fully coupled bolus-esophageal-gastric model. Biomech Model Mechanobiol 17:1069-1082
Taft, T H; Carlson, D A; Triggs, J et al. (2018) Evaluating the reliability and construct validity of the Eckardt symptom score as a measure of achalasia severity. Neurogastroenterol Motil 30:e13287
Taft, Tiffany H; Kern, Emily; Starkey, Kristen et al. (2018) The dysphagia stress test for rapid assessment of swallowing difficulties in esophageal conditions. Neurogastroenterol Motil :e13512
Carlson, Dustin A; Kou, Wenjun; Lin, Zhiyue et al. (2018) Normal Values of Esophageal Distensibility and Distension-Induced Contractility Measured by Functional Luminal Imaging Probe Panometry. Clin Gastroenterol Hepatol :

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