Gastroesophageal reflux disease (GERD) accounts for more patient encounters in gastroenterology practices than any other disease entity. GERD epidemiology is linked to both an aging population and the obesity epidemic;related health care expenditures have increased precipitously paralleling these factors. However, the increase in GERD diagnoses is also related to broadened diagnostic criteria and the lack of accurate verifying physiological criteria, trends contributing to both erroneous diagnosis and excessive treatment. One root cause of GERD is impairment of the reflux barrier at the esophagogastric junction (EGJ) leading to more episodes of reflux, greater refluxate volume, and loss of the ability to selectively vent gas from the stomach without accompanying fluid. This can cause esophagitis or a host of nonspecific symptoms. Clinically, suspected GERD is often """"""""diagnosed"""""""" based on symptomatic responses (or failure to respond) to proton pump inhibitors (PPIs). However, there is no consistent abnormality of gastric acid secretion in GERD and this management strategy has led to the substantial and costly overuse of these medications. Furthermore, because PPIs almost certainly heal esophagitis (eliminating a major diagnostic criterion), the utility of endoscopy as a diagnostic test is compromised leading to frustration among both patients and physicians in the frequent scenario of therapeutic failure. Symptoms may persist because reflux persists, albeit with less acidity...or because they are unrelated to GERD. Clearly, we need better diagnostics. This proposal will evaluate the use of two novel technologies (3D- high resolution manometry (3D-HRM) and EndoFLIP(R)) to objectify GERD diagnostics. Both have the potential to quantify the root-cause mechanical and physiological EGJ compromises. 3D-HRM is next- generation manometry technology designed to precisely define defective EGJ contractile morphology. EndoFlip(R) is pioneering technology to quantify EGJ distensibility abnormalities in GERD, initially described by this research group. Our underlying hypothesis is that GERD management can be improved with these cutting-edge diagnostics that are essential both to select patients for novel therapies targeting mechanical EGJ dysfunction and to calibrate the application of these novel therapies.

Public Health Relevance

Gastroesophageal reflux disease (GERD) is an increasingly common medical condition affecting about ten percent of the adult US population and linked to both aging and obesity. One root cause of GERD with unique treatment implications is degradation of the reflux barrier function of the esophagogastric junction (EGJ), but there are currently no diagnostic tests that accurately assess this. This proposal will evaluate two novel technologies to improve diagnostic assessment of the EGJ and rationalize specific therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK056033-12
Application #
8536256
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
2001-04-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
12
Fiscal Year
2013
Total Cost
$320,079
Indirect Cost
$110,191
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
Taft, T H; Riehl, M; Sodikoff, J B et al. (2016) Development and validation of the brief esophageal dysphagia questionnaire. Neurogastroenterol Motil 28:1854-1860
Nativ-Zeltzer, N; Logemann, J A; Zecker, S G et al. (2016) Pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography-a normative study of younger and older adults. Neurogastroenterol Motil 28:721-31
Sodikoff, J B; Lo, A A; Shetuni, B B et al. (2016) Histopathologic patterns among achalasia subtypes. Neurogastroenterol Motil 28:139-45
Teitelbaum, Ezra N; Sternbach, Joel M; El Khoury, Rym et al. (2016) The effect of incremental distal gastric myotomy lengths on EGJ distensibility during POEM for achalasia. Surg Endosc 30:745-50
Kia, Leila; Pandolfino, John E; Kahrilas, Peter J (2016) Biomarkers of Reflux Disease. Clin Gastroenterol Hepatol 14:790-7
Carlson, Dustin A; Kahrilas, Peter J (2016) How to Effectively Use High-Resolution Esophageal Manometry. Gastroenterology 151:789-792
Kahrilas, Peter J (2016) Turning the Pathogenesis of Acute Peptic Esophagitis Inside Out. JAMA 315:2077-8
Nicodème, F; Soper, N J; Lin, Z et al. (2015) Calculation of esophagogastric junction vector volume using three-dimensional high-resolution manometry. Dis Esophagus 28:684-90
Kahrilas, P J; Keefer, L; Pandolfino, J E (2015) Patients with refractory reflux symptoms: What do they have and how should they be managed? Neurogastroenterol Motil 27:1195-201
Ravi, Karthik; Friesen, Laurel; Issaka, Rachel et al. (2015) Long-term Outcomes of Patients With Normal or Minor Motor Function Abnormalities Detected by High-resolution Esophageal Manometry. Clin Gastroenterol Hepatol 13:1416-23

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