Anatomical proximity of the inlet of the respiratory and digestive systems, along with the dual function of the pharynx as both airway and gastrointestinal passage, predisposes the lung to the dangers of aspiration during swallowing and retrograde transit of gastric content through the esophago-pharyngeal lumen. A large number of pulmonary and aerodigestive tract disorders, ranging from asthma, aspiration pneumonia, and other lung injuries to benign inflammatory lesions of the larynx and aerodigestive tract are attributed to the deleterious effects of the gastric content or its misdirection into the respiratory system The central theme of this program project therefore is mechanisms of upper gut and airway interaction with special emphasis on airway protection against aspiration. This theme is pursued in adult and infant humans and a feline model by systematic approach at 4 levels a) physiology b) pathophysiology c) diagnosis d) management. It uses the lessons learned from the studies of last funding period and is supported by the preliminary studies A total of 23 hypotheses will be tested in 6 specific aims. They systematically address different aspects of the central theme, answering different questions and providing a number of resolutions to a variety of important unresolved clinical uncertainties. The current proposal has three projects and an administrative core. In addition to long term professional relationship and research collaborations among the leadership of this project, each leader is an experienced investigator and has an established record of productivity and acknowledged contribution to their respective field. These fields include gastrointestinal physiology, neonatalogy, aerodigestive physiology, gastroenterology, otolaryngology, Gl motility and endoscopy. The degree of collaboration and cohesiveness of the three research teams is evidenced by the publication of the last funding period and the collaborative effort rendered by all in developing the current proposal and its preliminary data.

Public Health Relevance

A large number of pulmonary and aerodigestive tract disorders, ranging from asthma, aspiration pneumonia, and other lung injuries to benign inflammatory lesions of the larynx and aerodigestive tract are attributed to the deleterious effects of the gastric content or its misdirection into the respiratory system. The care of these patients is sub-optimal. This project attempt to develop better diagnostic and therapeutic modalities for these common but complex disorders.

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 #
8667102
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (J1))
Program Officer
Hamilton, Frank A
Project Start
2004-08-01
Project End
2019-06-30
Budget Start
2014-08-11
Budget End
2015-06-30
Support Year
6
Fiscal Year
2014
Total Cost
$1,219,162
Indirect Cost
$271,454
Name
Medical College of Wisconsin
Department
Internal Medicine/Medicine
Type
Schools of Medicine
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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