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بسم الله الرحمن الرحيم

بسم الله الرحمن الرحيم. بسم الله الرحمن الرحيم. BRONCHIAL ASTHMA. BY Mohamed Magdy Zedan Resident of Pediatric,Mansoura University Children Hospital. Definition :. It is a diffuse obstructive lung disease ,with 3 characteristics: High degree of reversibility

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بسم الله الرحمن الرحيم

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  1. بسم الله الرحمن الرحيم بسم الله الرحمن الرحيم

  2. BRONCHIAL ASTHMA BYMohamed Magdy ZedanResident of Pediatric,Mansoura University Children Hospital

  3. Definition: It is a diffuse obstructive lung disease ,with 3 characteristics: • High degree of reversibility (spontaneously or with treatment). • Airway inflammation ( corner stone of asthma). • Bronchial hyper-reactivity.

  4. Pathogenesis of Asthma:- Lies in 3 steps:- 1- Transformation of TH0 to TH2. 2- Genesis of atopic state. 3- Allergic reactions.

  5. (1) Transformation of TH0 to TH2 • T helper (CD4) lymphocytes are the maestro of the inflammatory process. • TH0 is switched either to TH2 ( under the effect of IL-4) or TH1 ( under the effect of IL-12 and IFN-gamma). • TH1 is responsible for cell mediated immunity (normal immune response) whereas TH2 is responsible for humeral immunity (allergic reactions). • The excess secretion of IL-4 results from disturbance in the long arm of chromosome no.5 , so the patient become phenotypically allergic (TH2 phenotype).

  6. (2) Genesis of Atopic State mInhaled allergen will be taken by APC that is homing in the airway. mOnce APC presents the allergen to TH2grelease of IL-4 &IL-5 a-IL-4 g formation of IgE from B-lymphocytes gfixed over the masts cells g early allergic reaction. b-IL-5ggrowth, maturation, recruitment of the eosinophils to the airway g late allergic reaction.

  7. (3) Allergic Reactions 1- Early allergic reaction:- mOccurs within 20 min from allergen exposure. mMediated by degranulation of the sensitized mast cells with release of different mediators. mResulting in g cough, bronchospasm, weal's and itching. 2- Late allergic reaction:- mOccurs within 6-8 hours from allergen exposure. mMediated by eosinophils. mResulting in chronic wheeze,hyperactive airway and nasal blockage.

  8. Diagnosis

  9. (1) Asthma Symptoms: mRecurrent cough, wheeze, chest tightness, dyspnea. mThese symptoms worsen at night and early morning and on exposure to a specific allergens. mThese symptoms are variable and reversible and they are associated with reversible wide spread airflow obstruction.

  10. (2) Asthma Exacerbations: [Asthma exacerbations are episodes of progressively worsening of asthma symptoms ,characterized by decrease in expiratory airflow. [These exacerbations usually reflects, a failure in long term management or exposure to a trigger. [Degree of asthma exacerbations is determined by: degree of wheeze, dyspnea and PEF value ( which is evaluated after the initial treatment with B2 –agonist every 20 min for one hour).

  11. Degree of Asthma Exacerbations: w Mild exacerbation: - PEF > 80% PB/predicted. - Breathlessness while walking. - Wheeze end-expiratory. w Moderate exacerbation: - PEF 50-80% PB/predicted. - Breathlessness while talking. - Wheeze throughout expiration.

  12. w Sever exacerbation: -PEF <50% BP/predicted. -Inability to give complete sentences in one breath -Marked wheeze throughout expiration and inspiration. -Pulse > 110 beats/min. w Life-threatening asthma: - PEF < 30% BP/predicted. - Inability to lie down. - Silent chest, cyanosis. - Bradycardia or hypo tension.

  13. (3) Clinical types of Asthma: • We have according to GINA guidelines 4 types Intermittent asthma and persistent asthma ( mild, moderate,sever). • Basis for classification are: frequency of symptoms and level of pulmonary function and performance.

  14. (4) Investigations 1- Chest x-ray. 2- CBC with differential: eosinophilia. 3- Serum IgG: total and specific. 4- Airway inflammatory markers: IL-2 receptors, ECP. 5- Pulmonary function test: FEV1 variability. 6- Skin test.

  15. (4) Differential Diagnosis of Bronchial Asthma ( wheezy infant) 1- Laryngeal obstruction. 2- F.B inhalation. 3- Recurrent aspiration: a- Gastro-esophageal reflux. b- Disorders of swallowing (Neuromuscular disease). 4- Host defense defect: a- Cystic fibrosis, ciliary dyskinesia. b- Immuno-deficiency. 5- Cardiac asthma. Continue E

  16. 6- Bronchiectasis. 7- Bronchiolitis oblitrans. 8-Developmental anomalies: a- Trachea-bronchial anomalies: 1- Tracheo-esophageal fistula. 2- Bronchomalacia. 3- Store-pipe trachea. 4- Bronchial compression: - Vascular ring. - Subclavian artery. - Bronchial or pericardial cyst. b- Congenital heart disease. c- Granulomas or polyps.

  17. ASTHMA MEDICATIONS

  18. Asthma medications have three categories: I- Quick-relief medications. II- Long term control medications. III- Allergen immunotherapy.

  19. I- Quick-relief medication (Rescue medications) A- Inhaled short acting B2 agonist: - Albuterol (ventolin) or salbutamol (farcolin), it is supplied as MDI (metered dose inhaler, 100mcg/puff) or nebulizer solution (5mg/ml). - Most effective and safe bronchdilator. - Onset of action: 5-10 min following inhalation, with 4-6 hours of action.

  20. -Dose:0.15 mg/kg (minimum dose 2.5 mg = ½ ml & maximum dose of 5 mg = 1 ml). - Side effects: a- Tremors. b- Tachycardia and palpitation (as a result of hypotension caused by V.D) c- Hpokalemia ( due to stimulation of Na/k pump) d- Tolerance ( if given in large , frequent doses)

  21. B- Anticholinergics • Ipratropium bromide (atrovent), it is supplied as MDI or nebulizer solution ( 250 mcg/ml). • Producebronchodilatation , by antagonizing the activity of acetylcholine at the level of M3. • Not sufficiently effective alone, used in addition to B2 agonist in sever exacerbation. • Dose :- one unit dose ( 1ml / 6 hours ).

  22. C- Systemic Corticosteroids • Used when the patient not respond rapidly to bronchodilators. • Mode of action: They reduce bronchial inflammation & hyper- reactivity , through: 1- Anti-inflammatory effects: - Inhibit PGs & LTs synthesis. - Inhibit the release of inflammatory mediators. - Inhibit the release of proteolytic enzymes. - Reduce capillary permeability. Continue E -

  23. 2- Anti-allergic effects: - Inhibit cellular immunity. - Inhibit antibody formation. - Inhibit release of proteolytic enzymes. 3- Potentiation of endogenous catecholamines: - Increase number of beta cells. - Decrease neuronal uptake of catecholamines. • Dose:-Hydrocortisone (6mg/kg/6h , 1ml = 20 mg ) Methylprednisolone (1-2mg/kg/dose). - Onset of action: Maximal response occur after 6 hours, but they start to reverse the tolerance to B2 agonist within one hour.

  24. D- Systemic bronchodilator therapy (aminophylline) l Mode of action: 1- Inhibit phosphodiesterase g Increase c-AMP g a- Bronchodilatation. b- Decrease release of bronchoconstrictor sub. From mast cells. 2- Block adenosine receptors g a- Bronchodilatation. b- Decrease release of histamine from mast cells. 3- Increase sympathetic Bronchodilatation,by :- a- Stimulate release of catecholamines. b- Inhibiting COMT. 4- Increase diaphragmatic contraction & decrease respiratory muscle fatigue.

  25. lDose: 6 mg/kg by I.V infusion. lAdverse effects: 1- C.N.S : Insomnia, irritability and convulsions. 2- C.V.S : Palpitation, tachycardia and arrhythmias. 3- G.I.T : Nausea, vomiting, diarrhea & intestinal bleeding. 4- Rapid I.V. Injection of aminophylline cause hypo tension,syncope,arrhythmias and convulsions.

  26. D- Subcutaneous epinephrine lMode of action: a- Stimulation of B2 receptors ] Bronchodilatation. b- Stimulation of α receptors ] decrease mucosal edema. lDose: 0,01 mg/kg (maximum dose of 0.3 mg) every 20 minutes to a maximum 3 doses.

  27. II- Long-term control medication (maintenance medications) 1- Inhaled corticosteroids. 2- Leukotriene modifiers. 3- Sodium cromoglycate and nedocromil. 4- Long-acting B2 agonists as : a- Formoterol (Foradil). b- Salmeterol (Serevent). 5- Methylxanthines.

  28. I-Inhaled corticosteroids: mAction:- - Improve airflow obstruction. - Improve lung functions. - Improve daytime and nighttime symptoms. - Improve airway hyper responsiveness and airway remodeling - They reduce frequency of exacerbations. mSide effects: - Sore throat,hoarseness of voice,candidate infection. - Decrease bone density and growth.

  29. m Available inhaled steroids : - Beclomethasone dipropionate (Becotide). - Budesonide (pulmicort). - Fluticasone propionate (flixotide)

  30. II- Leukotriene modifiers m Two subclasses: a- 5-lipoxygenase inhibitors. b- Leukotriene receptor antagonist: - Montelukast. - Zafirlukast. mActions: a- Inhibition of exercise induced and aspirin induced asthma. b- Bronchodilatation. c- Decrease need of steroid use in acute asthma. d- Decrease nocturnal and daily asthma exacerbations. e-Decrease mucus production. mDose: one chewable tab (5mg) once daily at bedtime.

  31. III- Allergen immunotherapy Indications: 1- Unavoidable exposure to allergen to which the patient is sensitive,such as house dust mites or pollens. 2- Symptoms occur allover the year. 3- Difficult in controlling symptoms with pharmacological management. Mechanism of action: Shift of TH2 asthma phenotype to TH1 normal immune- response. Method: -Choose the proper patient with IgE mediated asthma. -Use one or maximum 3 allergens in the course. -The course usually 3-5 years on maintenance doses.

  32. THANK YOU

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