1. Asthma Sagal Yusuf #1447

2. General Outliune  Introduction  Definition  Types of Asthma  Epidemology  Pathogenesis

3. What is Asthma?  Chronic disease of the airways that may cause  Wheezing  Breathlessness  Chest tightness  Nighttime or early morning coughing  Episodes are usualy associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

5. Pathogenetic Types of Asthma:  Extrinsic (Allergic/Immune)  Typically develops in childhood (atopic)  70-80% child with asthma have other allergies  Eczema  Nasal allergies  Intrinsic (Non-Immune)  Develops after age of 30yrs  Not associated with allergies  Often chronic and year-round conditions

7. Pathogenesis  Allergens induce T H 2 phenotype in CD4 T cells of genetically susceptible individuals  T H 2 cells secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils), IL-10 (stimulates T H 2 cells and inhibits T H 1cells) and IL-13 (activates mast cells)  Re-exposure allergens leads to IgE-mediated activation of mast cells.

8. Early Phase  Starts in 30-60 mins of exposure and lasts up to 4-6 hours.  Antigen + IgE on the mast cell in mucosa  Release of preformed histamine granules and generation of leukotrienes C4, D4 and E4 lead to broncho-constriction, inflammation and edema (early-phase reaction)  Stimulation of sub-mucosal vagal fibers leads to reflex smooth muscle contraction

9. Late Phase  Starts after 4-6 hours  Eosinophils play important role of the inflammation by attracting cytotoxic molecules IL-5, PAF, epithelial cells.  Thus activate mast cells  broncho-constriction

12. TRIGGERING FACTORS  RESPIRATORY INFECTIONS  Changed Temperatures (Cold Air)  Fog  Wood smoke; tobacco smoke  OCCUPATION  Emotions  Allergens (dust, pollen, etc)  Stress  Laughter  Anxiety  Exercise (dry, cold weather especially )

13. Early Warning Signs  Cough  Mood Changes  Change in facial appearance  Breathing changes  Verbal complaints  Itchy chin or neck  Itchy, watery, or glassy eyes  Runny nose  Head stopped up  Sneezing  Dark Circles under eyes  Getting out of breath  Chest hurts

14. Asthma Flare Up  Cough  Wheeze  Shortness of breath  Chest tightness  Retractions

16. Clinical Asthma  Short, acute attacks:  Expiratory dyspnea  Wheezing  Dry cough  Curschman’s Spirals  Thick stringy mucus, casts  Charcot Leyden crystals  Creola bodies (clusters of surface airway epithelial cells)

17. Cells Involved  Mast cells,  Eosinophils,  T-lymphocytes,  Macrophages,  Neutrophils,  Epithelial cells

18. Curschmann’s Spirals  Spiral shaped mucus plugs from the subepithelial mucus gland duct or bronchioles

19. Charcot-Leyden Crystals  Microscopic crystals  Made up of eosinophilic membrane proteins (lysophospholipase)

20. Epidemology  ~300 million people with asthma around the world  Its projected that in 2025, another 100 million people will be affected  In the United States,  affects 25.7 million people, including 7.0 million children under 18  Asthma is a significant health and economic burden to patients  In 2010, 1.8 million people visited an ED for asthma-related care and 439,000 people were hospitalized because of asthma

21. Treatment  Steroids and other Anti Inflammatory Drugs  Lifesaving  Reducing swelling and mucus production in the airways  Creates less sensitivity and reaction to triggers  Bronchodilators  Relieve the symptoms of asthma by relaxing the muscles that tighten within the airways, thus opening the airways.  Rescue Inhalers: relieve the cough, wheezing and short breath  To control all asthma need to combine with other medications such as inhaled steroid for daily long term treatment

22. Continued…  Inhalers  Nebulizers  Mouth piece or mask - mist  IV  Oral

23. Tips for USMLE on Asthma  1. If question mentions Curschmann’s spirals, think asthma  2. If question mentions Charcot-Leyden crystals, think asthma  3. If question mentions creola bodies, think asthma  4. Status asthmaticus is an asthma attack that does not respond to pharmacologic agents and can be life threatening  5. If a 7-year-old boy suddenly complains to his mother that he can’t breath after playing with the new kitchen for the second time, think asthma

24. Famous Athletes with Asthma Paula Radcliffe --world record marathon runner David Beckham Jerome Bettis “The Bus” -- diagnosed 14yrs

25. References:  http://www.ginasthma.org/FAQs?faqid=2  http://www.score95.com/blog/blog/usmle-asthma/  http://www.asthma.org.uk/knowledge-bank-treatment- and-medicines-spacers  Kumar, Vinay, and Stanley L. 1915- Robbins. Robbins Basic Pathology. 8th ed. Philadelphia, PA: Saunders/Elsevier, 2007.