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 #
2P01DK068051-06
Application #
8742108
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (J1))
Project Start
Project End
Budget Start
2014-08-11
Budget End
2015-06-30
Support Year
6
Fiscal Year
2014
Total Cost
$421,658
Indirect Cost
$134,481
Name
Medical College of Wisconsin
Department
Type
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Shaker, Reza; Babaei, Arash; Naini, Sohrab R (2014) Prevention of esophagopharyngeal reflux by augmenting the upper esophageal sphincter pressure barrier. Laryngoscope 124:2268-74
Lang, Ivan M; Medda, Bidyut K; Babaei, Arash et al. (2014) Role of peripheral reflexes in the initiation of the esophageal phase of swallowing. Am J Physiol Gastrointest Liver Physiol 306:G728-37
Dua, Kulwinder S; Surapaneni, Sri Naveen; Kuribayashi, Shiko et al. (2014) Effect of aging on hypopharyngeal safe volume and the aerodigestive reflexes protecting the airways. Laryngoscope 124:1862-8
Hasenstab, Kathryn A; Jadcherla, Sudarshan R (2014) Respiratory events in infants presenting with apparent life threatening events: is there an explanation from esophageal motility? J Pediatr 165:250-255.e1
Babaei, Arash; Dua, Kulwinder; Naini, Sohrab Rahimi et al. (2012) Response of the upper esophageal sphincter to esophageal distension is affected by posture, velocity, volume, and composition of the infusate. Gastroenterology 142:734-743.e7
Dua, Kulwinder; Surapaneni, Sri Naveen; Kuribayashi, Shiko et al. (2011) Protective role of aerodigestive reflexes against aspiration: study on subjects with impaired and preserved reflexes. Gastroenterology 140:1927-33
Dua, Kulwinder; Surapaneni, Sri Naveen; Kuribayashi, Shiko et al. (2011) Pharyngeal airway protective reflexes are triggered before the maximum volume of fluid that the hypopharynx can safely hold is exceeded. Am J Physiol Gastrointest Liver Physiol 301:G197-202
Hernandez, Lyndon V; Dua, Kulwinder S; Surapaneni, Sri Naveen et al. (2010) Anatomic-manometric correlation of the upper esophageal sphincter: a concurrent US and manometry study. Gastrointest Endosc 72:587-92
Jadcherla, S R; Wang, M; Vijayapal, A S et al. (2010) Impact of prematurity and co-morbidities on feeding milestones in neonates: a retrospective study. J Perinatol 30:201-8
Jadcherla, Sudarshan R; Hogan, Walter J; Shaker, Reza (2010) Physiology and pathophysiology of glottic reflexes and pulmonary aspiration: from neonates to adults. Semin Respir Crit Care Med 31:554-60

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