The purpose of this application is to investigate the pathogenesis and pathophysiology of exercise-induced asthma (EIA). To achieve these goals, we propose to: (1) determine if nitric oxide (NO) excretion is thermally sensitive; (2) Explore the source of NO; and (3) examine the role of vascular-permeability in EIA and its dependence upon NO and the leukotrienes. The first set of experiments will test the hypothesis that NO is generated by the airway epithelium as a function of the local temperature changes that develop during hyperpnea in order to regulatory respiratory heat exchange. It also seeks to determine if EIA is an exaggerated response to normal physiologic events or whether it derives from a combination of over production of mediators superimposed upon abnormal airway components. The second set explores the relative contribution of epithelial and vascular sources of NO in the exhaled air obstruction. The final experiments focus upon the physiologic events that lead to bronchial obstruction and test the premise that the airway narrowing in EIA derives from increased capillary permeability and that NO and the leukotrienes are involved in the process.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033791-18
Application #
6638247
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Noel, Patricia
Project Start
1984-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
18
Fiscal Year
2003
Total Cost
$302,000
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Yeh, Karen H; Skowronski, Mary E; Coreno, Albert J et al. (2011) Impact of obesity on the severity and therapeutic responsiveness of acute episodes of asthma. J Asthma 48:546-52
Nicolacakis, Katina; Skowronski, Mary E; Coreno, Albert J et al. (2008) Observations on the physiological interactions between obesity and asthma. J Appl Physiol 105:1533-41
McFadden Jr, E R (2008) Asthma-obesity relationship: association or causality? Curr Allergy Asthma Rep 8:85-6
McFadden, E R (2007) Exhaled nitric oxide in asthma: ""everything we have always wanted"" or ""not quite ready for prime time?"". Curr Allergy Asthma Rep 7:237-8
Stern, Thomas; Garg, Asha; Dawson, Neal et al. (2007) Validating a guidelines based asthma decision support system: step one. J Asthma 44:635-8
El-Ekiaby, Amr; Brianas, Lori; Skowronski, Mary E et al. (2006) Impact of race on the severity of acute episodes of asthma and adrenergic responsiveness. Am J Respir Crit Care Med 174:508-13
West, Erin; Skowronski, Mary; Ms, Albert Coreno et al. (2005) The effects of hyperpnea on exhaled nitric oxide synthesis in normal subjects. Chest 128:3316-21
Kotaru, Chakradhar; Coreno, Albert; Skowronski, Mary et al. (2005) Morphometric changes after thermal and methacholine bronchoprovocations. J Appl Physiol 98:1028-36
Coreno, Albert; Skowronski, Mary; West, Erin et al. (2005) Bronchoprotective effects of single doses of salmeterol combined with montelukast in thermally induced bronchospasm. Chest 127:1572-8
McFadden Jr, E R (2003) Acute severe asthma. Am J Respir Crit Care Med 168:740-59

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