Cough is the most common reason why sick patients visit physicians in the US. The long-range goal of this research is to delineate the neurogenic mechanisms by which cough is produced and regulated. The central hypothesis of this research is that the cough motor pattern is produced by an assembly of components that includes a novel regulatory element responsible for controlling the behavior of a reconfigured respiratory pattern generator. Moreover, the novel regulatory components that control laryngeal and tracheobronchial cough are not identical. The rationale for the proposed research is that once the functional organization of the brainstem cough pattern generation system is established, the mechanisms responsible for the production of pathological cough can be identified.
The specific aims of the project are: 1) Determine the role of modulation of the expiratory phase in the regulation of the tracheobronchial and laryngeal cough motor patterns, 2) Determine the functional organization of the central regulatory system for tracheobronchial and laryngeal cough, 3) Determine the role of brainstem expiratory motor pathways in the antitussive-sensitive regulatory system for tracheobronchial cough, 4) Determine the role of spinal expiratory motor pathways in the antitussive-sensitive regulatory system for cough. In the first aim, key regulatory mechanisms controlling the frequency and magnitude of repetitive tracheobronchial and laryngeal cough will be determined by altering of the excitability of each. Our preliminary data suggest a) that the frequency of repetitive coughing is primarily controlled by modulation of the duration of the latter part of the cough expiratory phase, and b) that separate regulatory mechanisms are responsible for the control of the frequency and intensity of repetitive coughing. In support of the second aim, preliminary findings suggest differential sensitivity of tracheobronchial and laryngeal cough to antitussive drugs and thus divergent central regulatory mechanisms for each. In the third aim, we test a model that predicts the presence of a tracheobronchial cough gating mechanism that is presynaptic to medullary and spinal expiratory motor pathways. This gating mechanism is sensitive to antitussive drugs. The sensitivity of rostral and caudal medullary expiratory neurons to antitussive drugs will be determined during breathing and cough to differentiate between inhibition or disfacilitation of these neurons by these compounds. In the fourth aim, antitussive drugs will be delivered intrathecally while monitoring expiratory motor drive during cough to determine the role of spinal pathways in the suppression of expiratory motor discharge. The results of these experiments will provide an important test of the proposed functional organization of the cough pattern generator. Furthermore, this project will test the proposed roles of medullary and spinal cellular elements that contribute to the generation and control of expiratory motor discharge during cough.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070125-02
Application #
6736973
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Twery, Michael
Project Start
2003-05-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$315,198
Indirect Cost
Name
University of Florida
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Poliacek, Ivan; Morris, Kendall F; Lindsey, Bruce G et al. (2011) Blood pressure changes alter tracheobronchial cough: computational model of the respiratory-cough network and in vivo experiments in anesthetized cats. J Appl Physiol 111:861-73
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Davenport, Paul W; Vovk, Andrea; Duke, Rita K et al. (2009) The urge-to-cough and cough motor response modulation by the central effects of nicotine. Pulm Pharmacol Ther 22:82-9
Pitts, Teresa; Bolser, Donald; Rosenbek, John et al. (2009) Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease. Chest 135:1301-1308
Fuller, D D; Doperalski, N J; Dougherty, B J et al. (2008) Modest spontaneous recovery of ventilation following chronic high cervical hemisection in rats. Exp Neurol 211:97-106
Poliacek, Ivan; Rose, Melanie J; Corrie, Lu Wen-Chi et al. (2008) Short reflex expirations (expiration reflexes) induced by mechanical stimulation of the trachea in anesthetized cats. Cough 4:1
Bolser, Donald C (2008) Older-generation antihistamines and cough due to upper airway cough syndrome (UACS): efficacy and mechanism. Lung 186 Suppl 1:S74-7
Jakus, Jan; Poliacek, Ivan; Halasova, Erika et al. (2008) Brainstem circuitry of tracheal-bronchial cough: c-fos study in anesthetized cats. Respir Physiol Neurobiol 160:289-300
Poliacek, I; Corrie, L W; Rose, M J et al. (2008) Influence of microinjections of D,L-homocysteic acid into the Botzinger complex area on the cough reflex in the cat. J Physiol Pharmacol 59 Suppl 6:585-96
Lane, Michael A; White, Todd E; Coutts, Marcella A et al. (2008) Cervical prephrenic interneurons in the normal and lesioned spinal cord of the adult rat. J Comp Neurol 511:692-709

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