• CLINICAL •

• ALPHARAPY • '

PEDIATRICS

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Asthma

Child hood asthma is the most common chronic disease in developed and developing countries.

There is no agreement about the definition of asthma, but it should include three important element, reversible airway obstruction, increased bronchial reactivity. and airway inflammation

--Before 15-20 years inflammation was not known as part of the pathophysiology, but now it is considered as an important part that all our treatment targeted against.

--about10 % of children are affected with asthma, more common in Males with ratio 2: 1.

--There isFamilial Tendency: if there is positive family history the chance of getting the disease in the siblings is 40 % but there is no mode of inheritance, its multi factorial.

--No exact etiology for asthma but there are 2 main components:

Environment and genetic but mostly combination.

Asthma:

** Affects ~5 million children <18 years in the US.

** ~3.5 million physician or outpatient hospital visits for US children <15 years in 1999

** 658,000 emergency department visits for asthma in US children <15 years in 1999.

** 190,000 hospitalisations for US children <15 years in 1999. ** >8.7 million prescriptions in the US for children <17 years. **176 deaths in US children ~14 years in 1999.

** Number 1 chronic illness causing school absences. (In the history

we must ask about how frequent the patient visits the Emergency Room and the frequency of school absence, this gives indication of asthma control. .

-- In spite nowadays we understand more about the pathophysiology, the mortality rate still the same or even increase.

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--An astlnnatic attack begins with triggering factor (e.g.URTI, perfume, smoking) that causes construction of the air way, increase mucous production, smooth muscle contraction, an interruption in the continuity of the epithelium and sub mucosal edema.

--Asthma is not a simple disease, the inflammation not well understood, many cytokines and many cells are involved in the disease process (eosinophills, mast cells, macrophages ... ), so one way of prophylaxis is to give leukotriene antagonist to stop release of cytokine, so if it is the only mechanism, any patient start with leukotriene antagonist should have no symptoms but patients still have symptoms.

--Most books says that there is increase in the incidence of asthma, a study in UK reveals that the prevalence = 10%, they repeat the study after 25 year in the same population, P = 20%. The explanation: most' probably an environmental factor OR increase awareness of physicians (criteria of diagnosis) but mostly environmental.

--More than 80% of patients they have symptoms before the age of 5 year. The most common triggering factor during infancy is DR TI, but later on it differs; exercise, pollens, and house dust mite are more common triggering factor than DRTI, but all can included in all ages.

--Triggering factors:

1. Infection

2. Pollens

3. House dust mites: found on beds, so we notice that the symptoms increases during the night, when they make studies to decrease the concentration of the mites by chemicals (expensive procedure), the patients condition improve temporarily but after 3 or 4 months the concentration

. .

mcreases agam.

4. Noxious agents

5. Exercise (in older children)

6. Smoking

7. Crying, Laughing ... etc

--In early morning ,at 4 am there is drop in the caliper of the air ways more sever in asthmatic than normal individual, so the symptoms increases in early morning.

--We don't have single test to diagnose asthma, it is clinical diagnosis. -About 10% of children present only with cough.

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--There is characteristic of cough in asthma: cough after exercise, at night, related to noxious agent. .. .if a child has cough with out variation, he is unlikely to be asthmatic.

--We can diagnose cough by giving bronchodilator after exercise or by spirometry (pulmonary function test) or peak expiratory flow rate pre and post exercise.

--Differential diagnosis:

1. Bronchiolitis :( very important during infancy) Lower RTI caused by RSV usually proceeded by URTI two to three days then the patient develops cough, respiratory distress, wheezes, and crepitation;

~ Unlikely to diagnose asthma from the first attack although they can present with sever attack of asthma from the first time and if you dig more deep in history ,mostly you will find neglected symptoms before. You have to have at least 3 recurrent attacks of cough and wheezes to .diagnose asthma so, if I see 5 to 6 month old infant (the peak age of Bronchiolitis) with an attack I will consider him as Bronchiolitis.

-years ago they think that we can't diagnose asthma in the first year of life, but in fact we can diagnose asthma before the age of 1 year. ~We can diagnose Bronchiolitis by nasopharyngeal swap looking for antigen.

~ There is relation between asthma & Bronchiolitis, at least 30% of patients with bronchiolitis well develop asthma in future, 50% will have recurrent wheeze, so as a general rule not every wheezes is asthma and not every asthma is wheezier. This correlation may be explained by: Asthma predisposes to infection OR (more likely) the virus makes certain changes in the epithelium and makes the mucosa irritable and hyper reactive to antigen.

2. Cystic Fibrosis: in developed countries (USA,UK) it is the second disease you have to consider as differential diagnosis of asthma , they may present with infection and wheezes so you ask about history, and do sweat chloride test (>60 meq/l is diagnostic ).

3. Foreign body aspiration: usually in toddler age group, unlikely to be presentation in the first year of life.

4. Gastroesophygeal reflux: common during infancy because of recurrent aspiration, they may present with cough.

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5. Immotile cilia syndrome: kartagener syndrome is part of immotile cilia syndrome. Kartagener syndrome characterize by situs inversus, SinuSItIS, bronchiectasis, and always have dextrocardia, but 50% of immotile cilia syndrome patients they don't have dextrocardia.

6. Vascular ring: it is congenital heart disease, the most common Vascular ring is double aortic arch that folds around trachea and esophagus, these patients may present with wheezes, but they don't respond to bronchodilator .with swallowed barium, you will see indentation in the esophagus but the definite diagnosis is by echo & MRI, the last procedure to do is angiograms because it is invasive.

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7. Psychogenic cough: diagnosed by exclusion, the cough disappears during

sleep.

--Recognition and Assessment of severe acute asthma: history, physical examination, investigation.

--Physical examination:

1. General appearance of the child: e.g. cyanosis indicates severe asthma, irritability, level of consciousness.

2. Vital signs: e.g. tachycardia (according to age :> 150 indicate severe asthma) &tacypnea (after the age of one year if the respiratory rate >50 indicate severe asthma)

3. Signs of dehydration: e.g, tacypnea, vomiting because of drugs

4. Signs of hypoxemia: e.g. cyanosis, O2 saturation <90%

5. Pulsus paradoxus: normally 'during inspiration there is drop in systolic blood pressure around 10 mmHg, if the drop is more than 20mmHg indicate severe asthma.

6. Wheezing: more with expiration, but in sever asthma it is inspiratory and expiratory.

7. Signs and symptoms of complicating features of asthma: e.g. pneumothorax is a singe of severe asthma.

Also, using accessory muscle indicate severe asthma.

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--Silent chest (severe astlnna) -7. poor air entry because of complete obstruction, sometimes you can't hear any sound even if you put the patient on ventilator, so you have to do manual respiration.

--If you count >7 ribs anteriorly, >9 ribs posteriorly on chest X-ray, it is indication of hyperinflation.

--any asthma for the first attack, you should do CXR but no need to repeat it every time.

--Indication for chest X-ray:

1. Signs of air leak.

2. Fever more than 38.9 or more (e.g. infection as a triggering factorpneumonia- ).

3. Post Intubations.

4. Presence ofRales&chracels.

5. Chest pain.

-- ABC (arterial blood gases): we should not do it in all patients because it is painful and invasive; we do it before putting the patient on ventilator. Children can tolerate high CO2 very well, so it is not indication to put a patient on ventilator if PC02 more than 60 nnnHg (e.g.65 or 70) because once the treatment begins, he will improve even if blood pH is 7.2.

--ABC: Usually not necessary in children who have responded partially to initial treatment and continue to improve.

An ABG should be obtained on patients:

1. with moderate - severe respiratory distress.

2. Not responding to therapy.

3. Serial ABG's may be necessary to evaluate progress/ deterioration.

--peak expiratory flow is another test used in older children; the patient takes deep inhalation then exhale into a peak flow meter with maximal effort. There are tables that give normal values according to the height of the patient. If the peak flow >80% of the normal, the patient is safe but if it is between 80% & 50%, you have to interfere by prednisolone, if <50% you have to admit the patient.

*2 types of peak flow meter: Portable peak flow meter (J'o;;<I) & Wright peak flow meter. {You have to read more about this subject}

Peak expiratory flow: is the maximum flow at the out set of forced expiration which is reduced in proportion to the severity of airway obstruction.

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Treatment:

1. Oxygen.

~ Hypoxemia is the usual fmding in severe asthma and is the main cause of morbidity and mortality. (All asthmatic patients are hypoxic)

-Oxygen should be given by mask: 8-10 L/min to keep the saturation above 95%.

+Oxygen administration never suppresses the respiratory drive in childhood asthma. so, no fear of giving 100% O2, but in COPD in adult if you give O2 there will be suppression, apnea and death may follow.

-Bronchodilator should be given through nebulizer,>8 lImin in order to give a small particle (0.3-3 nanograme) to enter the air way.

2. Nebulized salbutamol.

**the drug of choice is sympathomimetic drug ~ The dose according to age.

~ No rule of how frequent we give the drug, but we depend on the severity .e.g. continuous for 10 or 20 hours in severe asthma or hourly, every 20r 3 hours, ... etc.

-Beta-z-sympathomimetics are the mainstay of treatment.

"-'It can be given diluted or undiluted through a jet nebulizer driven by 8-10 L/min.

-The large volume and high gas flow through the nebulizer produce a small aerosol particle size, maximizing deposition of the drug in small airways.

-Side effect: l.tremor 2.tachycardia

3.hypokalemia (some times salbutamol used to treat hyperkalemia) so when you use continuous larg dose we should give K supplement more than usual e.g. 30meq/l instead of20 meq/l.

4.Metabolic acidosis (v. rare) the exact mechanism is unknown.

-Epinephrine can be used, but it is not selective.

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3. Corticosteroids.

~ Any acute asthma we should start with steroid. -Reduce the severity of acute severe astlnna.

-Reduce the inflammation in bronchial mucosa. (Anti inflammatory drug)

-Potentiate the relaxation of bronchial smooth muscle by Beta2 -agonists.

Reduce mucous production.

~ Decreases recruitment and activation of inflammatory cells +Up-regulates B2 receptors.

-Decreases micro vascular permeability

-Decreases mucus production

~given orally, IV, nebulizer.

-fhe patients of severe asthma with history of I CU' admission we give them prednisolone to keep it at home, once the portable peak flow drop below 80%, they take prednisolone 2 to 3 days.

** It is a must to give B2-agonist and steroid with O2 to each asthmatic patient.

4. Ipratropium bromide.

~It is an anticholinergic bronchodilator with no systemic atropine-like effects and no inhibition of mucociliary clearance.

+-it has good synergy with beta2 agonist.

-Ipratropium can be given alone or mixed with salbutamol in the nebulizer.

5. Aminophylline. -phshpodiestrase inhibitor

-American center dose not believe on Aminophylline but it is still used in

ICU. (Continuous infusion Img/kg/hur)

-Aminophylline is a standard therapy for acute severe asthma, although the evidence for its effectiveness is conflicting.

-Jt may have beneficial non bronchodilator effect; such as improvement in respiratory muscle strength (mainly the diaphragm) and also may have delayed anti-inflammatory effect.

-Plasma level must be monitored (narrow therapeutic index).

6. IV -salbutamol.

-Jt appears as effective as inhaled route but it is not certain that LV. infusions offer extra benefit in a child receiving maximal inhaled therapy.

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~lt is used (the only indication) when the child's tidal volume is so reduced that it limits aerosol drug delivery to the small airways.

**we are listing the drugs in order before we put the patient on ventilator **.

7. MagneSium 804

~bronchodilator - mech. unclear but may be due to: -inhibition of Ca++-mediated smooth muscle contraction

-direct inhibition of smooth muscle contraction

+given IV, onset minutes, duration about 2 hrs

-eide effects-

a )facial flushing/warmth, malaise

b )hypotensionlbradycardia only with rapid infusion' -dosing - 30-70 mg/kg IV over 20-30 min: (max=2g) =bronchodilation proportional to serum levels

8. Ketamin.

-used by anesthetics and not used except in leu

+relaxes smooth muscle directly, also increases chest wall compliance -sympathomimetic properties

~has been used in unintubated asthmatics to avoid intubations successfully (if no response to all above drugs we will intubate).

-side effects:

A)arrhythmias

B )increased secretions C) laryngospasm

D) hallucination

+use benzodiazepines to decrease emergence reactions ..... dose: 0.5-2.5mg/kg IV

9. Mechanical ventilation +the last treatment of astlnna

~ 10-33% of all PICU admissions for status asthmaticus require MV -rnortalityrates for those requiring MV in children = up to 5% ~MV usually for hours to few days.

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10. Part of the treatment is IV fluid

-Most patients are dehydrated due to:

1. t Metabolism

2. t Insensible loss 3.,} Intake

4. Vomiting

5. Dehydration t viscosity of secretions and worsen already poor cardiac output.

--Correct Metabolic Acidosis:

~ t Lactic acid production by respiratory muscles.

~,} Utilization of lactate by underperfused liver and skeletal muscles. -Bsagonist (IV) direct effect on muscle tissue.

~ Keep pH > 7.2. (Not necessarily in severe asthma to have ideal pH)

11 Antibiotics

+No role for routine use.

-Indications:

-Sputum/tracheal aspirate predominantly PMNs.

-Evidence of pneumonia.

12.Sedative.

-sedation is contra indication in asthma. +ketamine is ideal when we do intubations =benzodiazepams

=propofcl

+avoid opiates (e.g. fentanyl) may cause histamine release, worsen symptoms

--Risk factors for persistent wheezing and predisposing to asthma

1. Frequent wheezing in the first year of life.

2. Eczema.

3. Maternal history of asthma.

4. Elevated IgE levels.

5. Maternal smoking.

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--Non Conventional Interventions

1. Manual chest compression

2. Inhalation anesthetics

3. Nitric oxide

4. Bronchoscopy

5. Heliox: 02 and helium

6. ECMO: ( extra corporeal membrane oxygenation)

7. CP AP/non-invasive positive pressure ventilation

--Prevention of subsequent attacks of asthma

1. Avoidance of triggering factors. (E.g. pits, smoking, perfumes)

2. Environmental control.

3. Prompt recognition and treatment of exacerbation factors.

4. Patient and parent's education.

5. Monitor PEFR at home.

6. Development plan for management at home.

7. Development good communication 'and good relationship between the physician and the patient.

--Prophylactic therapy

1. Inhaled Corticosteroids (the drug of choice in prophylaxes &severe asthmaj.the main concern of the parents about using Corticosteroids is growth.

2. Long acting Salbutamol

3. Leukotriens Antagonist

4. Sodium cromoglygate: little use.mot effective

5. N odocromil.

*The first three is the most important

Notes:

+an asthmatic patient may have barrel chest, increase anterio-posterior diameter.

--Cushing's disease is one of the side effects of Corticosteroids. =sometimes we need to use oral Corticosteroids in severe asthma. -- Spacer used to deliver drugs.

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