1. Asthma is a chronic inflammatory disorder of the bronchi characterized by episodic and reversible bronchospasm caused by an exaggerated response to various stimuli like allergens. 2. It affects 10% of children and 5-7% of adults worldwide. The pathogenesis involves inflammation, airflow limitation, and airway hyperresponsiveness triggered by allergens, viruses, pollutants, and other factors. 3. New understanding of the role of leukotrienes, mast cells, eosinophils and cytokines in asthma pathology has led to more targeted drug therapies that inhibit these inflammatory pathways.

1. ?!*$# “ Twenty years from now you will be more disappointed by the things you didn't do than by those you did.” ...Catch the trade winds in your sails, explore, dream, discover & live….! ” - Mark Twain

2. Asthma Pathophysiology Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine

5. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 – 59% – 64% – 35% +163% – 7% Coronary Heart Disease Stroke Other CVD COPD All Other Causes

6. Pathogenesis: INFLAMMATION Airflow Limitation SYMPTOMS Cough Wheeze Dyspnoea TRIGGERS Allergens, Exercise, Cold Air, SO2 Particulates Airway Hyperresponsiveness Genetic* INDUCERS Allergens,Chemical sensitisers, Air pollutants, Virus infections

8. Pathogenesis - Atopic Asthma:

9. Mast cells in Asthma Pathogenesis:

10. Eosinophils in Asthma Pathogenesis:

12. Lung Hyperinflation in Asthma

13. Thick bronchi with Mucous plugs

14. Mucous plug in asthma:

16. Asthma Microscopic Pathology Obstructed Inflammed Bronchi

19. Asthma – TH2 lymphocytes immunostaining)

20. Eosinophils in Asthma:

21. Curschmann's spirals:

23. 5-LO inhibitors Antileukotrienes Arachidonic Acid Leukotrienes LTC4, D4, E4 Cyclooxygenase 5-Lipoxygenase Prostaglandins Prostacyclins Cell Damage Cell Membrane Phospholipids Steroids NSAID

26. Thank You… Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine

27. Asthma Pathology - Modern view Barnes PJ Leukotrienes C4, D4 & E4 Allergen Mucus hypersecretion Hyperplasia Vasodilatation New vessels Plasma leak Oedema Bronchoconstriction Hypertrophy/hyperplasia Cholinergic reflex Subepithelial fibrosis Sensory nerve activation Eosinophil Mast cell Th2 cell Neutrophil Macrophage/ dendritic cell Mucus plug Epithelial shedding Nerve activation

28. Mast cell Degranulation Barnes PJ Normal 5 Seconds 60 Seconds

29. Mast cell Degranulation Barnes PJ

30. Type I Hypersensitivity: Barnes PJ

31. Therapy - Pathology: Barnes PJ