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BYMohamed Magdy ZedanResident of Pediatric,Mansoura

University Children Hospital

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Definition:

It is a diffuse obstructive lung disease ,with 3 characteristics:

(1) High degree of reversibility

(spontaneously or with treatment).

(1)Airway inflammation ( corner stone of asthma).

(2)Bronchial hyper-reactivity.

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Pathogenesis of Asthma:-

Lies in 3 steps:-

1- Transformation of TH0 to TH2.

2- Genesis of atopic state.

3- Allergic reactions.

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(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).

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(2) Genesis of Atopic State

Inhaled allergen will be taken by APC that is homing in the airway.

Once APC presents the allergen to TH2 release of IL-4 &IL-5

a-IL-4 formation of IgE from B-lymphocytes fixed over the masts cells early allergic reaction.

b-IL-5growth, maturation, recruitment of the eosinophils to the airway late allergic reaction.

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(3) Allergic Reactions 1- Early allergic reaction:-Occurs within 20 min from allergen exposure.Mediated by degranulation of the sensitized mast cells

with release of different mediators.Resulting in cough, bronchospasm, weal's and itching.

2- Late allergic reaction:-Occurs within 6-8 hours from allergen exposure.Mediated by eosinophils.Resulting in chronic wheeze,hyperactive airway and

nasal blockage.

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(1) Asthma Symptoms:

Recurrent cough, wheeze, chest tightness, dyspnea.

These symptoms worsen at night and early morning and on exposure to a specific allergens.

These symptoms are variable and reversible and they are associated with reversible wide spread airflow obstruction.

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(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).

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Degree of Asthma Exacerbations:

Mild exacerbation: - PEF > 80% PB/predicted. - Breathlessness while walking. - Wheeze end-expiratory.

Moderate exacerbation: - PEF 50-80% PB/predicted. - Breathlessness while talking. - Wheeze throughout expiration.

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Sever exacerbation: -PEF <50% BP/predicted. -Inability to give complete sentences in one

breath -Marked wheeze throughout expiration and

inspiration. -Pulse > 110 beats/min.Life-threatening asthma: - PEF < 30% BP/predicted. - Inability to lie down. - Silent chest, cyanosis. - Bradycardia or hypo tension.

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(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.

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(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.

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(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

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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.

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Asthma medications have three categories:

I- Quick-relief medications.

II- Long term control medications.

III- Allergen immunotherapy.

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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.

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- 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)

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B- Anticholinergics

- Ipratropium bromide (atrovent), it is supplied as MDI or nebulizer solution ( 250 mcg/ml).

- Produce bronchodilatation , 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 ).

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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 -

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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.

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Mode of action: 1- Inhibit phosphodiesteraseIncrease c-AMP a- Bronchodilatation.b- Decrease release of bronchoconstrictor sub. From mast cells.2- Block adenosine receptors 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.

D- Systemic bronchodilator therapy (aminophylline)

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Dose: 6 mg/kg by I.V infusion.

Adverse 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.

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D- Subcutaneous epinephrine

Mode of action: a- Stimulation of B2 receptors Bronchodilatation.

b- Stimulation of α receptors decrease mucosal edema .

Dose: 0,01 mg/kg (maximum dose of 0.3 mg) every 20 minutes to a maximum 3 doses.

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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.

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I-Inhaled corticosteroids:Action:- - Improve airflow obstruction.

- Improve lung functions.

- Improve daytime and nighttime symptoms.

- Improve airway hyper responsiveness and airway

remodeling

- They reduce frequency of exacerbations.

Side effects: - Sore throat,hoarseness of voice,candidate infection.

- Decrease bone density and growth.

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

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II- Leukotriene modifiers Two subclasses: a- 5-lipoxygenase inhibitors. b- Leukotriene receptor antagonist: - Montelukast. - Zafirlukast.Actions: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.Dose: one chewable tab (5mg) once daily at bedtime.

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III- Allergen immunotherapyIndications: 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.

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