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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK079902-05
Application #
8497451
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Hamilton, Frank A
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$252,410
Indirect Cost
$86,895
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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