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
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
Mei, Ling; Dua, Arshish; Kern, Mark et al. (2018) Older Age Reduces Upper Esophageal Sphincter and Esophageal Body Responses to Simulated Slow and Ultraslow Reflux Events and Post-Reflux Residue. Gastroenterology 155:760-770.e1
Jiao, Hongmei; Mei, Ling; Liang, Chenyang et al. (2018) Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube-fed patients. Laryngoscope 128:1310-1315
Agrawal, D; Kern, M; Edeani, F et al. (2018) Swallow strength training exercise for elderly: A health maintenance need. Neurogastroenterol Motil 30:e13382
Levy, Deborah S; Osborn, Erika; Hasenstab, Kathryn A et al. (2018) The Effect of Additives for Reflux or Dysphagia Management on Osmolality in Ready-to-Feed Preterm Formula: Practice Implications. JPEN J Parenter Enteral Nutr :
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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