PHRM 514 - Asthma - Fall 2012 (1)

Allergen induced bronchoconstriction early phase

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Allergen Induced Bronchoconstriction: Early Phase Allergic Reaction 1. Antigens taken up by antigen-presenting cells 2. Antigens presented to T-lymphocytes and response is activated 3. Antigen interacts with IgE on mast cells ü. Pro-inflammatory cytokines and chemokines, histamine, and inflammatory mediators released ü. Eosinophils, neutrophils, alveolar macrophages recruited and activated 4. Bronchoconstriction results n. Lasts ~1 hour after antigen exposure Leader WG. Asthma. In: Chisholm-Burns MA, Schwinghammer TL, Wells BG, et al., eds. Pharmacotherapy: Principles and Practice. 2nd ed. New York: McGraw Hill Medical; 2010:265-267.
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Allergen Induced Bronchoconstriction: Late Phase Allergic Reaction n 4 to 9 hours after exposure to antigen 1. Activated airway cells release inflammatory cytokines and chemokines 2. Milder bronchoconstriction as well as airway hyper-responsiveness and inflammation occur Leader WG. Asthma. In: Chisholm-Burns MA, Schwinghammer TL, Wells BG, et al., eds. Pharmacotherapy: Principles and Practice. 2nd ed. New York: McGraw Hill Medical; 2010:265-267.
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Airway Hyperresponsiveness n Exaggerated bronchoconstrictor response n Occurs in response to stimuli Kelly HW, Sorkness CA. Asthma. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy a pathophysiologic approach. 8th ed. New York: McGraw Hill Medical; 2011:439-448.
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Additional Contributors to Airway Narrowing n Airway edema n Airway smooth muscle contraction n Airway thickening n Mucus hypersecretion Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma. http://www.ginasthma.org/. Updated 2011. Accessed October 10, 2012.
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What is Asthma? National Heart, Lung, and Blood Institute Diseases and Conditions Index. http://www.nhlbi.nih.gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html. Updated February 1, 2011. Accessed October 16, 2011.
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Airway Remodeling n Airway narrowing may only be partially reversible n Permanent structural changes n Progressive loss of lung function ¡ Airway smooth muscle n Increases due to hypertrophy and hyperplasia n Contributes to increased thickening of airway wall ¡ Blood vessels n Proliferate, dilate, and may contribute to increased airway wall Increases thickness ¡ Mucus hypersecretion n Due to increased number of goblet cells and increased size of submucosal glands Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma. http://www.ginasthma.org/. Updated 2011. Accessed October 10, 2012. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. http://www.nhlbi.nih.gov/guidelines/asthma/ asthgdln.pdf. Published August 28, 2007. Accessed October 16, 2011.
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Airway Inflammation n Central and peripheral airways inflamed n All cells of airway involved ¡ Epithelial cells ¡ Eosinophils ¡ Lymphocytes ¡ Mast cells ¡ Alveolar macrophages ¡ Neutrophils ¡ Fibroblasts and myofibroblasts
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Allergen Induced Bronchoconstriction Early Phase Allergic...

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