Outline Consensus characteristics Consensus characteristics Allergens:role in asthma Allergens:role in asthma Immune/inflammatory basis Immune … Genetic basis Genetic basis Non-atopic (intrinsic) asthma Non-atopic (intrinsic) asthma Viral infection exacerbation of asthma Viral infection exacerbation of asthma Immune targets for therapy Immune targets for therapy Asthma -consensus Asthma -consensus characteristics characteristics Chronic inflammatory disorder of …

Allergens: role in asthma Allergens: role in asthma ? Allergen sensitization is linked to risk of ? Allergen sensitization is linked to risk of asthma asthma -Indoor allergens (house dust mites) - Indoor allergens (house dust mites) -Outdoor seasonal fungus ( Alternaria ) - Outdoor seasonal fungus ( Alternaria ) ? Asthma severity correlates with allergen ? Asthma severity correlates with allergen exposure exposure ? Reduced allergen exposure improves ? Reduced allergen exposure improves asthma asthma Allergens:role in asthma ? Antigen-specific IgE to aeroallergens ? Antigen-specific IgE to aeroallergens develops at ~2 develops at ~2 -3 years old in -3 years old in predisposed individuals ( predisposed individuals ( Atopy: genetic Atopy: genetic predisposition to form predisposition to form IgE) IgE) ? Allergen-induced asthma peaks in ? Allergen-induced asthma peaks in second decade second decade ? Sensitization to indoor and outdoor ? Sensitization to indoor and outdoor allergens should be evaluated in allergens should be evaluated in asthma patients asthma patients Review of Type I ( IgE) IgE) Hypersensitivity Hypersensitivity ? Sensitization ? Sensitization -IgE production - IgE production -Mast cell Fc receptors (FcR ? ) bind IgE - Mast cell Fc receptors (FcR ? ) bind IgE ? Allergen triggers mast cell degranulation ? Allergen triggers mast cell degranulation -Acute phase bronchospasm, edema - Acute phase bronchospasm, edema -Late phase inflammation - Late phase inflammation ? Chronic Tcell/eosinophil infiltrate ? APC T B Mast Cell EOS IgE Cytokines and mediators of allergy/inflammation FcR? R1 FcR? R1 IL-4 IL-6 IL-13 IL-4 IL-6 IL-5 TNF-? IL-3, IL-5, GM-CSF Cytokine Pathways in Asthma

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