Despite the anatomical contiguity between the gastroesophageal and pharyngolaryngeal lumen, under normal condition the airway is protected from aspiration of gastric content. The mechanisms of this protection are not completely understood and as such the pathophysiologic mechanisms of related disorders remain uncertain because of either lack of proper techniques and instrumentations or suitable human and animal models for design of appropriate experiments. These shortcomings had now been remedied and our preliminary data suggests the feasibility and safety of these studies. We have identified a human model of defective airway protective reflexes and developed a feline model for studying interactions between esophagus and airway under physiologic and pathophysiologic conditions. We also have developed and successfully tested new recording devices and experimental techniques for use in both in human infants and adults as well as our feline model. Because the nature of these experiments requires expertise from multiple disciplines we have assembled a large multi-disciplinary research team comprised of experts from the Departments of Medicine, Neurology, Physiology, Radiology, Pediatric, and Otolaryngology to carry out the proposed studies in this project. This team has a long history of successful collaboration resulting in the discovery and characterization of several hitherto undescribed airway protective reflexes, development of newer methodology, and documentation of abnormalities of upper esophageal sphincter and glottal protective functions. The degree of interaction and collaboration among the members of this team pursuing their common goal is attested by their many joint publications of research outcomes over the past several years. The intense interest and the obvious need for better understanding of the mechanisms of upper gut and airway interaction coupled with the synergy and enthusiasm of our research team provided the basic impetus for the development of the current proposal. All of the projects in this program share the common theme of identifying, characterizing and quantitating the mechanisms that govern the physiologic and pathophysiologic interaction between the esophagus and the airway. The proposed program includes three subprojects and an administrative core. Project 1 is designed to investigate the relationship between the esophagus and tracheo-bronchial tree in a feline model. Project 2 studies the mechanism of prevention of aspiration in adult humans. Project 3 addresses the developmental physiology and pathophysiology of airway safety in infants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK068051-05
Application #
8111993
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Hamilton, Frank A
Project Start
2007-09-15
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$1,163,469
Indirect Cost
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
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
Jadcherla, Sudarshan R (2017) Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review. Dysphagia 32:15-26
Jiao, Hongmei; Mei, Ling; Liang, Chenyang et al. (2017) Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube-fed patients. Laryngoscope :
Lang, Ivan M; Medda, Bidyut K; Shaker, Reza et al. (2017) The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS? Pediatr Res :
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
Lang, Ivan M; Haworth, Steven T; Medda, Bidyut K et al. (2016) Mechanisms of airway responses to esophageal acidification in cats. J Appl Physiol (1985) 120:774-83
Lang, Ivan M (2016) The Physiology of Eructation. Dysphagia 31:121-33
Jadcherla, Sudarshan R; Hasenstab, Kathryn A; Sitaram, Swetha et al. (2016) Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants. Am J Physiol Gastrointest Liver Physiol 310:G1006-14
Lang, Ivan M; Medda, Bidyut K; Jadcherla, Sudarshan R et al. (2016) Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus. Am J Physiol Gastrointest Liver Physiol 311:G827-G837
Jiao, Hongmei; Mei, Ling; Sharma, Tarun et al. (2016) A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena. Am J Physiol Gastrointest Liver Physiol 311:G84-90

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