SEVEN YEAR-OLD BOY WITH COUGH

1. SEVEN YEAR-OLD BOY WITH COUGH Stanley Lipper M.D. Graphics, Arrangements, PresentationDr. Viera Lima

2. Presenting complaint A seven year-old boy is brought to your office by his mother. She has observed over the last 2 days that he has developed a persistent cough and an audible wheeze at night and in the early morning. This is especially noticeable on exercise.

3. Past medical history In the past year she has noticed that he often coughs and exhibits shortness of breath with exercise. With viral illnesses, he coughs for 2 weeks and he also wheezes. He hashadno hospitalizations or trips to the emergencywithchest symptoms. He has only been treated with antibiotics and cough syrups. He complains of year-round nasal stuffiness, some sneezing and rubbing of the nose and eyes.

4. Family history The child’s father smokes in the home and his mother suffers from hay fever. He has no siblings. There are no pets.

5. Physical examination The child appears lethargic. He is afebrile and exhibits tachypnea and tachycardia. On chest auscultation, there are sibilant rhonchi (wheezes) and he is using accessory breathing muscles. His height and weight are normal for age.

6. Special investigations Chest X ray is normal. Hemoglobin is normal and there is a mildly elevatedwhite cell count with a peripheral eosinophilia. Abundant eosinophils are present in the sputum. Spirometry is normal with FEV1 93% of predicted value and FEV1/FVC ratio of 0.80. Skin tests are positive for dust mites, catdanderand seasonal molds.

7. WHAT IS YOUR DIAGNOSIS?

8. ASTHMA • Clinicopathological Correlation • Objectives • Discuss a typical example of childhood asthma. • Become familiar with Type 1, atopic hypersensitivity in this clinical setting. • Understand the pathogenesis of this disease. • 4. Become familiar with the morphological changes in this disease.

9. Definition of asthma A chronic inflammatory disorder of the airways that causes episodic wheezing, breathlessness, chest tightness and cough associated with partially reversible bronchospasm, (bronchoconstriction) and airflow obstruction/limitation in susceptible individuals.

10. Airway Hyperresponsiveness Asthmatic airways constrict in response to various triggering stimuli such as environmental allergens, cold air, exercise and viral respiratory infections.

11. Asthma Triggers Various triggers in susceptible individualsresult in acute and chronic airway inflammation and bronchial hyperresponsiveness which might progress to airway remodeling unless treatedeffectively.

12. Asthma Triggers (allergens): "Seasonal" pollens. Year-round dust mites, molds, pets, and insect parts. Foods, such as fish, egg, peanuts, nuts, cow's milk, and soy. Additives, such as sulfites. Work-related agents, such as latex.

13. Asthma Triggers (irritants): Respiratory infections, such as those caused by viral "colds," so-called non atopic asthma (rhinovirus, parainfluenza virus). Drugs, such as aspirin, other NSAIDs (nonsteroidal anti-inflammatory drugs), and Beta Blockers (used to treat blood pressure and other heart conditions). Tobacco smoke. Outdoor factors, such as smog, weather changes, and diesel fumes. Indoor factors, such as paint, detergents, deodorants, chemicals, and perfumes.. GERD (gastro-esophageal reflux disorder). Exercise, especially under cold dry conditions. Work-related (occupational) factors, such as chemicals, dusts, gases, and metals. Emotional factors, such as laughing, crying, yelling, and distress. Hormonal factors, such as in premenstrual syndrome.

14. PATHOGENESIS OF ALLERGIC ASTHMA 1. Atopy: immediate hypersensitivity reaction - allergen reacting with IgE antibody bound to mast cells in previously sensitized individual. 2. Genetic predisposition: susceptible individuals with bronchial hyperresponsiveness have a genetic predisposition to type 1 (atopic) hypersensitivity and are prone to acute and chronicairway inflammation.

15. Role of inflammation Many cell types and inflammatory mediators Model for allergic asthma 1. Inhaled allergen encounters an airway dendritic cell, eliciting a TH2 response producing interleukins which stimulate B cells causing IgE Ab production. This reacts with mast cell IgE Fc receptor and interleukins are produced causing eosinophil recruitment (priming or sensitization). TH2 cells also produce interleukins and granulocyte monocyte colony stimulating factor (GM-CSF) which recruit eosinophils.

16. Role of inflammation 2. Re-exposure to allergen: immediate reaction triggered by Ag induced cross linking of IgE bound to IgE receptors on presensitized mast cells. They release mediators that open tight junctions between epithelial cells so that Ags can enter the mucosa and activate mucosal mast cells and eosinophils which release additional mediators. Mediators induce bronchospasm, increase vascular permeability and mucus production and recruit additional mediator-releasing cells from blood (neutrophils, eosinophils, basophils, lymphocytes, monocytes). Fresh round of mediator release from leukocytes, endothelium and epithelial cells. Eosinophils release major basic protein, eosinophil cationic protein which damage epithelium and cause airway constriction.

17. Morphology 1.Overdistention because of overinflation: occlusion of bronchi and bronchioles by thick, tenacious mucus plugs. Plugs contain whorls of shed epithelium (Curschmann spirals). Many eosinophils and Charcot-Leyden crystals (eosinophil membrane protein). 2. Airway remodeling: thickened bronchial epithelial BM, edema and inflammatory infiltrate in bronchial walls, eosinophils and mast cells, hypertrophy of submucosal glands, hypertrophy of bronchial wall muscle. Curschmann spiral Charcot-Leyden crystal

18. Bronchus Eosinophils in wall of bronchus Wall of bronchus with thick BM, smooth muscle hypertrophy

19. Clinical Course Classic asthma attack lasts several hours and is followed by coughing up of copious mucus. In some patients, symptoms persist at a low level all the time. In its mostsevere form, status asthmaticus occurs with cyanosis and even death. Hyperinflated lungs in status asthmaticus Cut surface essentially appears normal

20. Suggested Reading Material Robbins Pathologic Basis of Disease, 7th Edition. 723-727