1. BRONCHIAL ASTHMA

2. Asthma is a chronic inflammatory disorder of the airways causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable airflow obstruction is often reversible either spontaneously or with treatment.

6. Indoor allergens

7. Pollen allergens

8. Pathogenesis of asthma

10. Mechanisms of inflammation in asthma The inflammation in asthma may be acute, subacute, or chronic. Eosinophil cell and mononuclear infiltration, airway edema mucus hypersecretion, desquamation of the epithelium, smooth muscle cells hyperplasia, and airway (bronchial tree) remodeling are present. Cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play role in the regulation of airway inflammation through the release of pro-inflammatory cytokines. Fibroblasts, epithelial and endothelial cells contribute to the chronicity of the disease. Adhesion molecules (eg, selectins, integrins) directs the inflammatory changes in the airway. Cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.

11. Mechanisms of airways obstruction in asthma Airflow obstruction can be caused by acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response . Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response . Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.

13. Mechanisms of bronchial hyperreactivity (hyperresponsiveness) in asthma The bronchial hyperreactivity (hyperresponsiveness) in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

14. Pathophysiology Airway inflammation and edema in period of asthma attack

16. PATHOLOGY In a patient who has died of acute asthma, the most striking feature of the lungs at necropsy is their gross overdistention and failure to collapse when the pleural cavities are opened. When the lungs are cut, numerous gelatinous plugs of exudate are found in most of the bronchial branches down to the terminal bronchioles. Histologic examination shows hypertrophy of the bronchial smooth muscle, hyperplasia of mucosal and submucosal vessels, mucosal edema, denudation of the surface epithelium.

20. Laboratory Findings Eosinophilia (> 250 to 400 cells/μL), > 4 %; Sputum: Grossly , it is tenacious, rubbery, and whitish; in the presence of infection, especially in adults, it may be yellowish. Many eosinophils, are found microscopically ; large numbers of histiocytes and polymorphonuclear leukocytes are also present. Eosinophilic granules from disrupted cells ( Creola bodies ) may be seen throughout the sputum smear. Elongated dipyramidal crystals (Charcot-Leyden) originating from eosinophils are commonly found. When bacterial respiratory infection is present, and particularly when there are bronchitic elements ( Coorshman spirales ), polymorphonuclear leukocytes and bacteries predominate.

21. Lab Studies Eosinophilia greater than 4% or 300-400/ μ L supports the diagnosis of asthma. Eosinophil counts greater than 8% may be observed in patients with concomitant atopic dermatitis, allergic bronchopulmonary aspergillosis. Total serum immunoglobulin E levels greater than 100 IU are frequently observed in patients experiencing allergic reactions, but this finding is not specific for asthma. A normal total serum immunoglobulin E level does not exclude the diagnosis of asthma.

22. Imaging Studies Chest radiography. In most patients, chest radiography findings are normal or indicate hyperinflation. Findings may help determine other pulmonary diseases such as chronic bronchitis (emphysema, pneumosclerosis, increase pulmonary roots), pneumonia. Sinus CT scan may be useful to determine acute or chronic sinusitis as a contributing factor. Other Tests: Allergy skin testing is a useful adjunct in individuals with atopy. Results help guide indoor allergen mitigation or help diagnose allergic rhinitis symptoms. In patients with reflux symptoms and asthma, 24-hour pH monitoring or FGDS can help determine if gastroesophageal reflux disease is a contributing factor.

24. Pulmonary function tests Static lung volumes and capacities - total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) are usually increased. Vital capacity (VC) may be normal or decreased. Dynamic lung volumes and capacities , an index of airways obstruction, are reduced in asthmatics and return toward normal after inhalation of an aerosolized bronchodilator. Assessment of etiologic factors Positive skin tests indicate the presence of IgE Ab to the test allergen and represent only the potential for allergic reactivity to the allergens (hypersensitivity to the allergen) .

25. Diagnostics Determination of severity Determination of prognosis Monitoring of disease progression Basic indexes of spirometry FEV 1 – the Force expiratory volume for the first second; FVC – the Force vital capacity; FEV 1 /FVC (%) - the relation shown in percents

28. Step 3 - Moderate persistent bronchial asthma Daily symptoms Exacerbations affect activity and sleep Nocturnal symptoms occurring more than once a week FEV 1 rate 60-80% of predicted, with variability greater than 30% Step 4 - Severe persistent bronchial asthma Continuous symptoms Frequent exacerbations Frequent nocturnal asthma symptoms Physical activities limited by asthma symptoms FEV 1 rate less then 60-80% of predicted

29. Treatment of A sthma (1) Selective beta 2 agonist; long-acting agent for maintenance therapy 2 puffs (50 mcg) bid. Discuss: 1 puff (50 mcg) bid Salmeterol Comment Dose and Route Agent Selective beta 2 -agonists Quick & long-acting agent 2 puffs (4,5-9-12 mcg) bid Formoterol Selective beta 2 agonist; beta 1 (cardiac) effects at higher doses (inhalation preferred route) 100 mcg, 1-2 puffs q4-6h; not to exceed 12 puffs/d; may use 2-4 puffs q20min for 3 doses to treat an acute exacerbation. Nebulizer: Dilute 0.5 mL (2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h, diluted in 2-5 mL sterile saline or water Albuterol (Ventolin, Proventil)

30. Treatment of A sthma (2) 60 to 90 min may be required before peak bronchodilation is achieved. Nebulizer: 1-dose vial (20-40-80 mcg) q2h for acute exacerbations MDI: 2 puffs qid; not to exceed 12 puffs/d Ipatropium bromide (Atrovent) Anticholinergic Side-effects common. Therapeutic level 10-20mug/ml 5 – 10 ml 2,5 % IV 1 – 2 d, 5-6 mg/kg toad 0.3-0.6 mg/kg maint. infusion Aminophylline Nervousness, nausea, vomiting, anorexia, and headache. 150 – 300 mg td PO , IV twice per day or once daily 0.5 mg/kg Theophylline (Theo-Dur, Uniphyl) Methylxanthlnes Comment Dose and Route Agent

31. Treatment of A sthma (3) thrush ( Oropharyngeal candidiasis ) and dysphonia 125-250 mcg 2 puffs 3 to 4 times daily for adults Severe asthma: 250-500 mcg 2 puffs bid; adjust dose downward to response; not to exceed 2000 mcg/d Beclomethasone dipropionate (Beclofort, Becloson, Beclovent) Onset of action 6 hours 2 puffs tid/qid or 4 puffs bid; not to exceed 4 puffs qid for mild persistent or easily controlled moderately severe asthma Triamcinolone (Azmacort) Onset of action 2 hours 50 mcg MDI: 2 puffs bid for mild persistent asthma 125-250 mcg MDI: 2 puffs bid for moderate-to-severe persistent asthma Fluticasone (Flovent) Topical corticosteroids Comment Dose and Route Agent

32. Treatment of A sthma (4) thrush ( Oropharyngeal candidiasis ) and dysphonia IV 4-8 mg, IV infusion 12-16 mg/d Dexa methasone -------- PO 24-4 0 mg/d T riamcinolone acetonide IV infusion 4 mg/kg q6h Hydrocortisone Onset of action 6 hours PO 30-4 0 mg/d IV 30-60mg, IV infusion 90-120 mg/d Prednisolone Onset of action 6 hours IV 1-2 mg/kg q6-12h Methyl-prednisolone (Solu-Medrol) Systemic corticosteroids Comment Dose and Route Agent

33. Treatment of A sthma (5) IV, IM 750 mg q8h Cefuroxime ------------ PO 3000000 IU q12h Spiramicin (Rovamycin) Used only with clinical evidence of bacterial infection. PO, IV infusion 400 mg d Levofloxacin (Loxof) Antibiotics for treatment infective-dependent exasorbation --------- 2 mg 2 puffs qid (14 mg/d) Nedocromil sodium (Tilade) for maintenance therapy only and has no place in treatment of the acute attack 20 mg 2 puffs 4 times daily for 4 to 6 weeks Cromolyn sodium (Intal) Mast cell-stabilizing agents

34. Treatment options of bronchial asthma Step 1 – Intermittent bronchial asthma No daily medication needed . Occasional use of inhaled short acting beta 2 -adrenoceptor agonist bronchodilators (ventolin, salbutamol). Step 2 - Mild persistent bronchial asthma Regular inhaled anti-inflammatory agents. Inhaled short acting beta 2 -adrenoceptor agonists as required plus a low dose inhaled steroid (beclomethasone 200-500 mcg/d or fluticasone 1 00-250 mcg/d ). Alternatively sodium cromoglycate or nedocromil sodium 2-4 puffs tid/qid .

35. Treatment options of bronchial asthma Step 3 - Moderate persistent bronchial asthma Middle dose inhaled steroids. Inhaled short acting beta 2 -adrenoceptor agonists as required plus an inhaled steroid (beclomethasone 500-1000 mcg/d or fluticasone 250-500 mcg/d). Or inhaled steroid (fluticasone 250-500 mcg/d) and long acting beta 2 -adrenoceptor agonist (salmeterol 50-100 mcg/d), especially for nighttime symptoms (Seretid 25/125 1-2 puffs q12h); fluticasone 250-500 mcg/d and formoterol 4,5-9 mcg/d (Foracort 9/125 1-2 puffs q12h) sustained-release theophylline.

36. Treatment options of bronchial asthma Step 4 - Severe persistent bronchial asthma High dose inhaled steroids and regular bronchodilators. Inhaled short acting beta 2 -adrenoceptor agonists as required with an inhaled steroid (beclomethasone 800-2000 mcg/d, fluticasone 500-1000 mcg/d) plus a sequential therapeutic trial of one or more of: inhaled long acting beta 2 -adrenoceptor agonist (salmeterol or formoterol) - Seretid 25/250 mcg (50/250mcg) 1-2 puffs q12h; or Foracort 12/250 mcg 1-2 puffs q12h; sustained release theophylline 150-300 mg/d, inhaled ipratropium bromide 20 mg 1-2 puffs q12h. Addition of regular oral steroid therapy: regular prednisolone, dexamethasone or triamcinolone tablets in the lowest dose necessary to control symptoms in a single daily dose.

38. An Acute Attack of Asthma The symptoms of asthma consist of a triad of dyspnea, cough, and wheezing . Respiration becomes audibly harsh, wheezing in both phases of respiration becomes prominent, expiration becomes prolonged, and patients frequently have tachypnea, tachycardia, and mild systolic hypertension. The patient prefers to sit upright or even leans forward, uses accessory muscles of respiration, is anxious, and may appear to struggle for air. Chest examination shows a prolonged expiratory phase with relatively high-pitched wheezes throughout inspiration and most of expiration. They have "squared off" thorax. Although coarse rhonchi may accompany the wheezes, fine crackles are not heard unless pneumonia, atelectasis, or cardiac decompensation is also present. The cough during an acute attack sounds "tight" and is generally nonproductive of mucus. Tenacious mucoid sputum is produced as the attack subsides.

39. Staging Of The Severity Of An Acute Asthma Attack ↓↓↓ ↑↑ ↓↓ 10% N Severe respiratory distress, lethargy, confusion, prominent pulsus paradoxus 30-50 mm Hg, use of accessory muscles IV (respi-ratory failure) ↓↓ N or ↑ ↓ 25% N Marked respiratory distress, cyanosis, use of accessory muscles, marked wheezes or absent breath sounds; check for pulsus paradoxus 20-30 mm Hg III (severe) ↑ ↓ N or ↑ 50% N Respiratory distress at rest. hyperpnea, use of accessory muscles. marked wheezes, air exchange N or ↓ II (moderate) N or ↓ N or ↑ N or ↑ 50-80% of N Mild dyspnea, diffuse wheezes, adequate air exchange I (mild) PaO 2 (Room air) PaCO 2 pH FEV 1 or FVC Symptoms and Signs Stage

45. Status asthmaticus occurs the severe attack, especially if it has been prolonged (> 12 h), or severe obstruction persisting for days or weeks. Fatigue and severe distress are evident in rapid, shallow, ineffectual respiratory movements. There may be a loss of adventitial breath sounds, and wheezing becomes very high pitched. Further, the accessory muscles become visibly active, and a paradoxical pulse often develops. Cyanosis becomes evident as the attack worsens. The end of an episode is frequently marked by a cough that produces thick, stringy mucus, which often takes the form of casts of the distal airways (Curschmann's spirals).