Steroid Resistant Asthma

Steroid Resistant Asthma - DMSeminar Therapy Dr.AjmalKhan...

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DM Seminar Steroid Resistant Asthma Definitions, echanisms and Approach to Mechanisms and Approach to Therapy Dr. Ajmal Khan
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troduction Introduction…. Asthma specific pattern of inflammation in airways Degranulated mast cells Infiltration of eosinophils Increased number of activated TH2 cells Current guidelines Anti inflammatory therapy with glucocorticoids Majority responds to inhaled corticosteroids bsets oorly responsive high doses of oral Subsets Poorly responsive high doses of oral prednisone
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lucocorticoid actions Glucocorticoid actions…. Inflammatory Cells Structural Cells y Eosinophils Numbers poptosis) Epithelial Cells Cytokine T lymphocyte (apoptosis) Cytokines Endothelial Cells Mediators Leak Mast Cells Numbers GCS Smooth Muscle ß2 Receptors Macrophages endritic lls Cytokines Numbers Mucus Gland Cytokine Mucus t i Dendritic cells Secretion
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efinition Definition…. . Failure to improve baseline FEV 1 by more than 15% after treatment with high doses of prednisolone (30– 40 mg daily) for 2 weeks Afflicts ~5% of asthma population Complete steroid resistance in asthma is rare 1:1000 educed responsiveness to steroids rticosteroid Reduced responsiveness to steroids corticosteroid dependent (CD) asthma, where large inhaled or oral oses of steroids are needed to control asthma doses of steroids are needed to control asthma adequately
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eatures Features…. Increased levels of T cell activation Failure of GCs to: Inhibit PHA induced T cell proliferation in vitro Decrease production of airway IL 2, IL 4, & IL 5 after GC therapy Reduce eosinophilia Suppress monocyte/macrophage secretion of IL 8 Inhibit cutaneous tuberculin delayed skin responses Increased IL 2 and IL 4 gene expression in the airways Enhanced AP 1 transcriptional activity in PBMC Increased GR expression in PBMC and airway cells
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ypes Types…. Type I Steroid Resistant Asthma Reduction in glucocorticoid receptor binding affinity Cytokine induced, reversible with deprivation of cytokines Mimicked by incubation of cells with high concentrations of IL 2 and IL 4 or by IL 13 alone J Allergy Clin Immunol 2002;109:649 57 Allergy Clin Immunol 2003;111:3 2 J Allergy Clin Immunol 2003;111:3 22 J Clin Invest 1994;93:33 9 Develop severe side effects, including adrenal gland suppression and cushingoid features from pharmacological doses
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ypes Types…. Type I Steroid Resistant Asthma rther divided into Further divided into Cytokine induced: Associated with genetic polymorphisms overproduction of cytokines (e.g., IL 4) or various key molecules involved in alteration of GC action Acquired: Allergen or infection induced cell activation or chronic exposure to medications such as beta agonists or corticosteroids
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ypes Types….
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This note was uploaded on 12/03/2011 for the course MEDICINE 350 taught by Professor Dr.aslam during the Winter '07 term at Medical College.

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Steroid Resistant Asthma - DMSeminar Therapy Dr.AjmalKhan...

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