The care of patients suffering from aerodigestive disorders attributed to reflux of gastric content (supraesophageal is sub-optimal. This shortcoming is for the most part due to incomplete understanding of the reflux related physiology and pathophysiology of the Pharyngo-esophageal junction and the esophagus as well lack of reliable diagnostic and effective therapeutic modalities for these common and complex conditions. Consequently the cost of current fragmented care of these patients is estimated at $54 billion annually in addition to patient suffering and diminished quality of life. There are two specific aims in this proposal:
Specific Aim A: Pathophysiology of pharyngo-esophageal junction and esophageal mechanisms preventing pharyngeal reflux of gastric content. The overall goal is to define and characterize the manometric characteristics of UES incompetence associated with objectively documented pharyngeal reflux. Studies of this aim include patients suffering from both pharyngeal reflux (regurgitation) and SE-GERD healthy controls and GERD patients without regurgitation and SE-GERD and vyill: 1. Characterize and compare the UES pressure response to liquid refluxate. 2. Determine the contribution of sub-sphincteric striated esophagus to UES pressure barrier. 3. Characterize the reflux- induced esophageal motor activity. 4. Determine and characterize the mechanisms of esophago- pharyngeal reflux.
Specific Aim B. Development of physiology- and pathophysiology-based diagnostic test and therapeutics Studies of this aim will: 1. Determine the reproducibility of manometric criteria for UES incompetence in prevention of pharyngeal reflux developed based on our preliminary data and studies of specific aim A. 2. Determine the ability of externally applied cricoid cartilage pressure in preventing pharyngeal reflux. 3. Determine and characterize the effect of externally applied cricoid cartilage pressure on related functions such as belch and swallow.

Public Health Relevance

There is no reliable diagnostic and effective therapeutic modalities for patients suffering from airway disorders attributed to reflux of gastric. The cost of current fragmented care of these patients is estimated at $54 billion annually. The overall goal of this project is to develop the manometric criteria for diagnosing UES incompetence associated with pharyngeal reflux and test the ability of externally applied cricoid cartilage pressure in preventing pharyngeal reflux.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK068051-07
Application #
8904656
Study Section
Special Emphasis Panel (ZDK1-GRB-6)
Project Start
Project End
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
7
Fiscal Year
2015
Total Cost
$388,218
Indirect Cost
$134,481
Name
Medical College of Wisconsin
Department
Type
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Jadcherla, Sudarshan R; Prabhakar, Varsha; Hasenstab, Kathryn A et al. (2018) Defining pharyngeal contractile integral during high-resolution manometry in neonates: a neuromotor marker of pharyngeal vigor. Pediatr Res 84:341-347
Lang, Ivan M; Medda, Bidyut K; Shaker, Reza et al. (2018) The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS? Pediatr Res 83:731-738
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Hasenstab, Kathryn A; Sitaram, Swetha; Lang, Ivan M et al. (2018) Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants. Dysphagia 33:63-75
Jadcherla, Sudarshan R (2017) Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review. Dysphagia 32:15-26
Mei, Ling; Jiao, Hongmei; Sharma, Tarun et al. (2017) Comparative effect of the sites of anterior cervical pressure on the geometry of the upper esophageal sphincter high-pressure zone. Laryngoscope 127:2466-2474
Kern, Mark K; Balasubramanian, Gokulakrishnan; Sanvanson, Patrick et al. (2017) Pharyngeal peristaltic pressure variability, operational range, and functional reserve. Am J Physiol Gastrointest Liver Physiol 312:G516-G525

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