A large number of pulmonary and aerodigestive tract disorders, ranging from aspiration pneumonitis, and lung abscesses to benign inflammatory lesions of the larynx and aerodigestive tract are caused by misdirection of gastric content into the respiratory system. The mechanisms of airway protection during retrograde transit of gastric content through the esophagopharyngeal lumen is not completely understood. In addition, although substantial information is available regarding the volume clearance of the aspirated material by the pulmonary structures, the defense mechanisms of the alveolar and bronchial linings against aspirated gastric acid remains unclear. Because of multisystem/organ involvement, systematic investigation of these mechanisms in health and disease conditions requires expertise from multiple disciplines. For this reason, during the past three years a concerted multidisciplinary, multidepartmental effort with participation of investigators from the Departments of Medicine, Otolaryngology, and Radiology was organized at the Medical College of Wisconsin Dysphagia Institute to systematically address these issues. The long-term objective of this program project is to provide the basis for preventive and/or therapeutic interventions in the future through the understanding of the central neural control and peripheral protective mechanisms against retrograde aspiration. All of the projects in this program share the common interest of identifying, characterizing, and quantitating the mechanisms that contribute to the protection of the airway against aspiration of gastric content in health and disease. The theme of this program project grant encompasses the function of the gastroesophageal junction as it relates to escape of gastric content into the esophagus, the significance of esophagopharyngeal, esophagolaryngeal, and pharyngolaryngeal reflexes in the closure mechanism of the tracheal inlet in response to gastroesophageal and esophagopharyngeal reflux and vomiting, and the role of bronchoalveolar defense mechanisms against acid alkaline and water exposure. The proposed program includes four projects and the administrative core. Projects 1 and 2 address the issue of extrapulmonary defense mechanisms against retrograde aspiration. Project 3 addresses the intrapulmonary defense mechanism against aspirated gastric content. Project 4 examines the mechanisms of airway protection during vomiting.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Program Projects (P01)
Project #
5P01DC003191-04
Application #
6516159
Study Section
Special Emphasis Panel (ZDC1-SRB-S (01))
Program Officer
Shekim, Lana O
Project Start
1999-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$418,495
Indirect Cost
Name
Medical College of Wisconsin
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Massey, Benson T; Simuncak, Chelsey; LeCapitaine-Dana, Nicole J et al. (2006) Transient lower esophageal sphincter relaxations do not result from passive opening of the cardia by gastric distention. Gastroenterology 130:89-95
Effros, Richard M; Peterson, Barry; Casaburi, Richard et al. (2005) Epithelial lining fluid solute concentrations in chronic obstructive lung disease patients and normal subjects. J Appl Physiol 99:1286-92
Effros, Richard M; Su, Jennifer; Casaburi, Richard et al. (2005) Utility of exhaled breath condensates in chronic obstructive pulmonary disease: a critical review. Curr Opin Pulm Med 11:135-9
Effros, Richard M; Dunning 3rd, Marshall B; Biller, Julie et al. (2004) The promise and perils of exhaled breath condensates. Am J Physiol Lung Cell Mol Physiol 287:L1073-80
Kawamura, Osamu; Easterling, Caryn; Aslam, Muhammad et al. (2004) Laryngo-upper esophageal sphincter contractile reflex in humans deteriorates with age. Gastroenterology 127:57-64
Effros, R M; Olson, L; Lin, W et al. (2003) Resistance of the pulmonary epithelium to movement of buffer ions. Am J Physiol Lung Cell Mol Physiol 285:L476-83
Effros, Richard M; Bosbous, Mark; Foss, Bradley et al. (2003) Exhaled breath condensates: a potential novel technique for detecting aspiration. Am J Med 115 Suppl 3A:137S-143S
Effros, Richard M; Biller, Julie; Foss, Bradley et al. (2003) A simple method for estimating respiratory solute dilution in exhaled breath condensates. Am J Respir Crit Care Med 168:1500-5
Effros, Richard M; Hoagland, Kelly W; Bosbous, Mark et al. (2002) Dilution of respiratory solutes in exhaled condensates. Am J Respir Crit Care Med 165:663-9
Crandall, Edward D; Effros, Richard M (2002) Historical perspectives on lung edema clearance. J Appl Physiol 93:1527-32

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