Exercise is an important trigger of asthma. The underlying pathogenesis of exercise-induced asthma remains unclear. Heat loss or evaporative loss triggers ensuing events within the airways, although conflicting data exists about the relative importance of each factor. Recent evidence shows that exercise shares common pathophysiological features with other triggers for asthma including mediator release during the acute asthmatic response, the presence of a late airway response in many individuals, and the inhibition of the acute asthmatic response by therapies targeted at inflammatory mediators. Our hypothesis is that the pathogenesis of exercise-induced asthma is due to mediator, cytokine and chemokine release from mast cells and other airway cells during the early bronchoconstrictor response, which is followed by infiltration of the airways with inflammatory cells, during the late asthmatic response.
The specific aims are: 1) to define the nature of the cellular inflammatory response in the airways and peripheral blood during the development of the acute asthmatic response to exercise; 2) to determine if the late airway response to exercise results from infiltration of the airways by inflammatory cells; 3) to understand the relationship between the severity of preexistent airway inflammation and the development of a late airway response to exercise; 4) to determine the role of leukotriene antagonists and corticosteroids in the management of the late phase of exercise-induced asthma. The experimental approach will be to assess the release of specific mediators (histamine, tryptase, leukotrienes), Th2 cytokines (IL-3, IL-4, IL-5, IL-13), and eosinophil and neutrophil promoting chemokines (MCP-3, RANTES, eotoxin, IL-8) during the genesis of the acute asthmatic response to exercise. The late asthmatic response will be characterized by determining the composition of inflammatory cells (Eosinophils, Th2 lymphocytes, Neutrophils, Monocytes, Basophils), Th2 cytokines, eosinophil and neutrophil chemokines, and mediators (ECP, MBP, leukotrienes, histamine, tryptase) within the airways during the late asthmatic response to exercise. Elucidation of the mechanisms of exercise-induced asthma will be important in the development of new therapies for asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL004231-04
Application #
6607567
Study Section
Special Emphasis Panel (ZHL1-CSR-F (O1))
Program Officer
Rothgeb, Ann E
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$125,080
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hallstrand, Teal S; Martin, Diane P; Hummel, Jeffery P et al. (2009) Initial test of the seattle asthma severity and control questionnaire: a multidimensional assessment of asthma severity and control. Ann Allergy Asthma Immunol 103:225-32
Carlsten, Chris; Aitken, Moira L; Hallstrand, Teal S (2007) Safety of sputum induction with hypertonic saline solution in exercise-induced bronchoconstriction. Chest 131:1339-44
Hallstrand, Teal S; Debley, Jason S; Farin, Federico M et al. (2007) Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction. J Allergy Clin Immunol 119:1092-8
Hallstrand, Teal S; Chi, Emil Y; Singer, Alan G et al. (2007) Secreted phospholipase A2 group X overexpression in asthma and bronchial hyperresponsiveness. Am J Respir Crit Care Med 176:1072-8
Hallstrand, Teal S; Moody, Mark W; Aitken, Moira L et al. (2005) Airway immunopathology of asthma with exercise-induced bronchoconstriction. J Allergy Clin Immunol 116:586-93
Hallstrand, Teal S; Moody, Mark W; Wurfel, Mark M et al. (2005) Inflammatory basis of exercise-induced bronchoconstriction. Am J Respir Crit Care Med 172:679-86
Hallstrand, Teal S; Fischer, Mary E; Wurfel, Mark M et al. (2005) Genetic pleiotropy between asthma and obesity in a community-based sample of twins. J Allergy Clin Immunol 116:1235-41
Hallstrand, Teal S; Calenoff, Emanuel; Becker, Jonathan W et al. (2004) The role of allergy in manifestations of respiratory disease in adult cystic fibrosis. Ann Allergy Asthma Immunol 92:228-33
Hallstrand, T S; Ochs, H D; Zhu, Q et al. (2004) Inhaled IFN-gamma for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-gamma deficiency. Eur Respir J 24:367-70
Hallstrand, Teal S; Sprenger, Jay D; Agosti, Jan M et al. (2004) Long-term acquisition of allergen-specific IgE and asthma following allogeneic bone marrow transplantation from allergic donors. Blood 104:3086-90

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