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AsthmaInflammation & Remodeling of AirwaysAnthony ShoukatHalima Zia Zahida YaseenAsthmaAsthma is pulmonary disorder which is characterized by inflammation and remodeling of airway that leads to reversible airway obstruction

Background and typesBackgroundEnvironmental factors & genetic factorsDisease of Civilization Dust, cool air and pollen etc.Late night, early morning and after exercise10% of US (total population)

TypesExtrinsic AsthmaIntrinsic AsthmaMolecular Pathology of AsthmaImmune systemEvolutionary response -> allergensMast cell, eosinophil, basophiles & macrophages etc. in lung airway

Hygiene Hypothesis

Differentiation of T Helper cellsTh1/Th2 PolarizationMolecular Mechanism of T Helper cells Inflammatory Action in Asthma

Dendritic Cells => IL-10 => Th2Th2 Cells response in two ways:1st Way:Cytokines including IL-4, IL-5 and IL-13. IL-4 and IL-13 Cytokines stimulates B-Cells and Plasma cells => IgE IgE stimulate mast cells maturationMaturation of mast cells => mediators (Histamine and Leukotriene)2nd Way: IL-5 & IL-4 => mast cells => histamine, chymase, tryptase, cysteinyl & leukotriene. IL-5 from these lymphocytes stimulates eosinophil. They released (ECP), (MBP), Eosinophil Peroxidase and Eosinophil-derived Neurotoxin. All of above collectively => hyperactivity & production of transmural edema.

Dendritic Cells -> IL-12 => Th1. Th1 cells -> Interferon (IFN-), IL-2 and Lymph toxin Neurophil Cells secrete Protease, Reactive oxygen species (ROS) and other inflammatory mediators Antioxidant agent Dismutase => Mast cells Neural Pathway and Inflammatory Pathway Inflammatory response mainly comes from mast cells.Neural Pathway Noradrenergic and No cholinergic (NANC) systemGoblet Cell HyperplasiaCollagen and elastic fibers => fibrosis and elastosis Hypertrophy and hyperplasia Transforming Growth Factor- (TGF-) Mitogenic mediators like Epithermal and Fibroblast Growth Factors (EGF-FGF)Molecular Mechanism of T Helper cells Inflammatory Action in Asthma

Genes involve in inflammatory action and remodeling of AirwaysIL-17Kawaguchi et al =>His161Arg substitutionIL-21C5250TP13KSHIPPTENINPP4a

Genes involve in inflammatory action and remodeling of AirwaysADAM33 DPP10

References:William, B.C. & Gregory, J. T. (2010). Essential Concept of Molecular Pathology. London UK: Elsevier Inc.Introductory material is retrieved from Wikipedia.Thomas, J. K., Barbara A. O & Richard A. G.(2006). Kuby: Immunology. US: Freeman, W. H. & Company Amrendra, K., & Balaram, G.,(2009). Genetics of asthma: a molecular biologist perspective. Clinical and Molecular Allergy :1476-7961Image Linkshttp://www.drugs.com/health-guide/images/205198.jpghttp://www.nature.com/nrg/journal/v5/n5/images/nrg1326-i1.jpghttp://www.nhlbi.nih.gov/health/health-topics/images/asthma.jpg