Childhood Asthma

It is a chronic inflammatory disorder (chronic Lower Respiratory Tract Disease),

clinically, characterized by:

1- Reversible airway obstruction or disease.

2-Increased bronchial reactivity, once there is stimulating antigen there is
abnormal response of the bronchial tree which leads to narrowing of the
airways.
3- Airway inflammation that's why we give anti-inflammatory either in
prophylaxis or in acute treatment .

Pathophysiology:

Airways narrowing are the main visible pathology in asthma that related to 3
events:
1. Inflammation and mucosal Oedema with thickened basement membrane .
2. Bronchial Smooth Muscle Spasm and Hypertrophy.
3. Mucous plugging.

** The pathophysiology is very complex. We have local causes(allergens,

irritants) then inflammatory cells involvement: Mast cells, eosinophils and
epithelial cells lead to tissue destruction also Sub-epithelial proliferation of
myofibroblasts, neural elements(sensory C-fibers), multiple interlukins
involvement, also we have increased mucous secretion then
decreased mucous transport all of them finally lead to bronchospam.
Inflammation is driven by Th2-predominant immune response.

** In longstanding asthma , there will be structural changes ( Airway

remodeling ) .
- Unfortunately even with drug antagonists sometimes still we can’t
control asthma. So if we have inadequate treatment there is possibility
of lung tissue damage or even death.

Symptoms : which suggest athma ;

1- COUGH: especially ;
* After exertion.
* After breathing cold air.
* At night.

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*if It was paroxysmal.
2- WHEEZING: especially ;
*if It was variable or intermittent.
* After exertion or at night.

Always cough cause wheezes at night and wheeze always considered

LRTI , so in children there is no single test to diagnose asthma.

Signs of "silent asthma" (when no wheezing is heard) include:

persistent cough at night, cough with exercise, cough with laughter, cough
when consuming cold foods or drinks, prolonged cough following or
accompanying a cold, feeling of "tight chest" or difficulty breathing.

Soft signs indicating that asthma is out of control include:

frequent overt wheezing episodes, increasing frequency of using rescue
medications (i.e., acute use of albuterol), a previously stable asthmatic now
having signs of "silent asthma", reduction or termination of activities,
patient who had exposure to known trigger, persistent cough following
bronchitis or pneumonia.

**There are many presentations of asthma, The most recognizable form is the
acute episode in which the patient presents with acute shortness of breath.
Depending on the underlying degree of inflammatory damage of the airways,
the episode may have been festering with persistent cough and occasional
bouts of shortness of breath for weeks.
Failure to attend to these soft signs of "asthma in transition" may lead to an
acute case of status asthmaticus. Hence, paying attention to signs of "silent
asthma" (asthma not in an acute phase), can prevent costly and life
threatening consequences.
Asthma may appear solely as an event associated with work or exercise. Most
asthma in childhood occurs as a result of encounters with respiratory viruses. If
the asthmatic is already unstable because of a poor maintenance regimen of
the existing chronic asthma, the acute phase will begin simultaneously with the
first signs of a "cold". If the asthma is managed well, then the cough and
wheezing may occur several days after cold symptoms. Hence, early
recognition of "asthma in transition" is a major point of cooperation involving
the physician and patient.

Asthma etiology:

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 1- The most important are HERITABLE and ENVIROMENTAL factors, they
contribute to its pathogenesis.
2- Also there are at least 20 distinct chromosomal regions with linkage to
asthma and asthma related traits have been identified.

Triggering factors:

* Infections: URTI is the most common triggering factor in the 1st year of life.
most of the time children have long history of cough but suddenly they have
acute attack or acute exacerbation of symptoms.
* Pollens: common in spring season this is related to different pollens like
flowers or olives especially in Jordan, that's why sometimes prophylactic
treatment is initiated.
* House dust mites: present in every house and its hard to get rid of them coz
they found on corners, pillows, beds etc...
* Noxious agents: like air-refreshers and perfumes. Diurnal variation:
* Smoking. There is more narrowing in
* Exercise: almost in older children. asthmatics airway compared to
* Crying, Laughing: also can trigger asthma. normal person between day and
night . Explained by the diurnal
rhythm of hormones mainly
corticosteroids.
Diagnosis:
In order to diagnose asthma in young children there is certain criteria:
> 4 episodes/yr of wheezing lasting more than 1 day affecting sleep in a child
with one MAJOR or two MINOR criteria.
MAJOR CRITERIA: Risk Factors for persistent
- Parents with asthma. wheezing and predisposing to
- Physician diagnosed atopic dermatitis. asthma:
MINOR CRITERIA: - frequent wheezing in 1st year of
- Physician diagnosed allergic rhinitis. life.
- Eosinophilia (> 4%). - Maternal history of asthma or
smoking
- wheezing apart from colds. - eczema.
- High IgE levels.
Investigations:

Include- CBC, ABG with moderate to severe RD, and PULMONARY FUNCTION
TEST.
Asthmatics have tachypnea >>>>co2 washing out >>>>and finally alkalosis
which indicates good respiratory muscles function, but this is not in all patients

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some of them as he gets exhausted and the CO2 rises he will have respiratory
acidosis then inadequate perfusion and oxygenation resulting in hypoxia and
metabolic acidosis together with respiratory acidosis.

So ABG is indicated in:

* Patients with moderate to severe respiratory distress.
* Patients not responding to therapy.
NOT EVERY WHEEZE IS
ASTHMA AND NOT EVERY
CLINICAL FINDINGS: ASTHMA HAS WHEEZE.
* History of episodic symptoms of airway obstruction.
Around 10% of children
* Physical examination: wheeze and hyperinflation. they present with cough
*Libratory: exhaled nitric oxide(eNO),spirometry. only, they don’t have
*** And we should exclude other possibilities. history of wheeze, present
just by cough.

Differential Diagnosis:

1-Broncholitis : age of 2-3 years. Patient present with crackles, hyperinflation,

Rhonchi. Mainly diagnosed by nasopharyngeal aspirate and treated by
supportive treatment .
2- Cystic fibrosis: common in developed countries.
3- Foreign body aspiration: usually preceded by choking, mainly in ages
between 1-3 years.
4- gastroesophygeal reflux: especially in 1st year of life, also associated with
multiple aspirations.
5- Immotile cilia syndrome: definite diagnosis is done by taking a biopsy from
the epithelium.
6- Vascular ring: double aortic arch that rings around the esophagus and
trachea. We do barium swallow to find indentations in the esophagus. Or by
using MRI, or an ECHO.
7- Psychogenic cough: which disappears during sleep.

** An acute asthma exacerbation is a biphasic process. Understanding the

inflammatory process of asthma came about when it was observed that 4 to 8
hours following allergen exposure, wheezing would occur that was not
responsive (or less responsive) to beta agonists but it was ablated by cromolyn
and corticosteroids.
However, beta agonists could easily neutralize the immediate reaction,
occurring within minutes of the allergen exposure. This created a picture of a
biphasic reaction to allergen (or infection) induced wheezing.

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The first phase was described as the immediate (bronchospastic) phase and
the second phase as the late phase inflammatory response.
In the early phase of allergic inflammation, preformed mediators such as
histamine and rapidly formed mediators such as leukotrienes are released and
cause bronchospasm. Other mediators signal ; the late phase inflammatory
cells , These cells (e.g., eosinophils) recruit other cells such as epithelial cells to
participate in the resultant inflammatory damage of the airways and
subepithelial structures. These events eventually result in extensive
restructuring of the normal histology of the airways. This damage is not
restored by beta-2 bronchodilators.
An important immunologic occurrence is the activation of the Th2 helper cell,
which is pivotal in the progression of the allergic immunologic process. The
other helper designated Th1 cell does not enhance the allergic inflammatory
process.
acute exacerbations are treated with quick relief (or rescue) medications,
which is most commonly prn albuterol and optional short bursts of systemic
corticosteroids.

** Recognition and assessment of severe acute asthma :

- HISTORY: in history ask if the child was in NICU or any previous
admissions.
- PHYSICAL EXAMINATION: the general appearance of the child is very
important, if he can’t talk or speak, vital signs, signs of dehydration,
wheezing which is usually an expiratory sound, deteriorated level of
consciousness.
*Tachypnea : which is >40 in children under 2 yrs.
*Tachycardia : in general any HR >140.
*Cyanosis : O2 saturation <90%.
*A pCO2 of 40 or greater on a blood gas.
*Silent chest : late sign of severe asthma indicates very low air entry.
* Persistent respiratory distress and poor aeration despite aggressive beta-2
agonists .
*Barrel chest shape : bad sign in uncontrolled asthma.
*Pulsus paradoxus : which is a drop in the systolic pressure during inspiration
>20mmHg.
*Pneumothorax : indicates severe asthma. All asthmatics have hyperinflation
and horizontal ribs in CXR.

Management of acute attack :

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 Asthma management plans depend on the severity of the asthmatic. Higher
severity levels warrant greater use of corticosteroids and prophylactic
medications such as leukotriene inhibitors and inhaled corticosteroids.

** The NIH guidelines categorizes severity levels into "steps" as follows:

Step 1 (mild intermittent): Day symptoms two days per week or less and night
symptoms two nights per month or less. Chronic peak flow is 80% of expected
or higher.
*This step requires no daily medications. ALL of the other categories (i.e., any
category with the word "persistent"), requires a chronic controller anti-
inflammatory medication.

Step 2 (mild persistent): Day symptoms greater than two times per week, but
less than once per day or night symptoms greater than nights per month.
Chronic peak flow is still 80% of expected or higher.
*This step recommends a low dose inhaled corticosteroid. Alternatively,
a cromolyn medication or a leukotriene receptor antagonist may be used.
Theophylline is another option, but only in children older than 5 years.

Step 3 (moderate persistent): Day symptoms occur daily or night symptoms

occur more than once per week. Chronic peak flow is 60% to 80% of expected
value.
* This step recommends a low dose inhaled corticosteroid plus a long acting
beta-2 agonist (salmeterol or formoterol). Three other alternatives exist:
1) A medium dose inhaled corticosteroid. 2) A low dose inhaled corticosteroid
plus an LTRA. 3) A low dose inhaled corticosteroid plus theophylline.

Step 4 (severe persistent): Continual day symptoms or frequent night

symptoms. Chronic peak flow is less than or equal to 60% of expected value.
*This step recommends a high dose inhaled corticosteroid, plus a long
acting beta-2 agonist.

………………………………….
Here , wht the Doctor talked about management in the lecture :
** Oxygen
Any patients with acute attack we give him O2 by mask 8-10 L/min to keep the
saturation above 95%.
It has side effects can lead to Retinopathy, Prematurity, Bronchopulmonary
dysplasia.
That’s why in NICU O2 is monitored and not allowed to increase >98%.

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Don’t forget that prolonged 100% O2 can cause lung tissue damage.

** Nebulizer Salbutamol
it is a beta-2 agonist , given after O2 an acute attack at least 8 L/min given by
mask.
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 effects: hypokalemia, hyperglycemia, tachycardia, palpitation and tremor.

Bronchodilators can be administered via several routes , In general, inhaled

medications have a faster onset, greater potency and less side effects.

** Corticosteroids
(prednisolone – O.
methylprednisolone - O, IV.
dexamethasone - O, IV).
- most important drug in asthma, it takes long time to work 4-6 hrs.
– reduce the severity of acute severe asthma.
– reduce the inflammation in bronchial mucous.
– potentiate the relaxation of bronchial smooth muscle by beta-2 agonists.
– reduce mucous production.
– decrease recruitment and activation of inflammatory cells.
– decrease microvascular permeability.
– Up regulates B2 receptors.

Occasional bursts of systemic corticosteroids have no significant long term

side effects, but chronic or long term use of systemic steroids have major side
effects.

The above 3 drugs should always be given in any acute asthma

if there is no response we give :

**Ipratropium Bromide
- anti-cholinergic bronchodilator with no systemic atropine like effects and no
inhibition of mucociliary clearance.
– has a good synergy with beta-2 agonist and can be mixed with salbutamol in
nebulizer.

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Also if there is no response we give:

**Aminophylline
as dr said the use of this drug is controversial, because the therapeutic levels
are narrow as it causes many side effects like convulsions. So plasma levels
should be monitored.

**IV Salbutamol
unfortunately this drug not found in Jordan.

**Magnesium Sulfate
it is bronchodilator with unclear MOA but maybe due to:
1- inhibition of Ca++ mediated smooth muscle contraction.
2- Direct inhibition of smooth muscle contraction.
Can be given IV or Nebulized.

**Ketamine
- it is sedative and analgesic drug can be used in asthma.
– has sympathomimetic action.
-Side effects : arrhythmia, laryngospasm, increased secretions.
Contraindicated in pts with neurological problems and hyperkalemia .

**very very rare if there is no response we put patients on

MECHANICAL VENTILATORS:
- 10-33% of all PICU admissions for status asthmaticus require MV.
– Mortality rates for those pts requiring MV up to 5%.

## As we said before , most patients are dehydrated due to:

1- increase insensible loss.
2- Increase metabolism. **Most of the time when we give the pt
3- Decrease intake. O2 and IV fluid rarely we give sodium
4- Vomiting. bicarbonate. Always keep PH>7.2.
So we should give IV fluids.
**No role for antibiotics in asthma except
if there is infection.

**No place for sedation or anti-histamine.

## Non-Conventional interventions:
- Manual chest compression.
- Inhalation anaesthetics.
- Nitric Oxide: strong bronchodilator.
- Bronchoscopy: if there is severe collapse.

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- Heliox: O2 and Helium.
- ECMO: extracorporeal membrane oxygenation (artificial lung).only if the
cause is reversible like infection.
- CPAP.

## CONTROLLERS MEDICATIONS:
1- inhaled corticosteroids. ***before discharge we should
2- leukotriene modifiers. advise the pt to avoid all the
triggering factors, educate
3- Long acting inhaled beta-2 agonists.
patients and parents and
4- theophylline: long acting{slow release}. planning for management at
5- cromones: useless in children. home.
6- long acting oral beta-2 agonist.
7- Systemic glucocorticosteroids.

** The type of medication used to treat asthma reflects the mechanism of

airway obstruction: bronchospasm versus inflammation. the logic for
appropriate use of individual medications for asthma can be understood by
recalling the biphasic reaction .
now it is possible to create an asthma treatment program. Genetics aside,
elimination of triggers and aggravators of asthma such as allergens, cigarette
smoke, and environmental and industrial pollutants, can prevent acute
exacerbations of asthma and serve as the first line of defense. Conditions such
as weather changes and respiratory infections fall outside of the readily
controllable factors.

** Co-morbid conditions such as allergic rhinitis, sinusitis, eczema, and

gastroesophageal reflux have profound influence on asthma. Their presence
makes asthma extremely difficult to control.
The main goal is to keep the patient functional and free of side effects from
medications. With this approach, asthmatics have been able to participate in a
normal life style.

Prevalence:

- It varies from country to another, in Jordan around 10% of the population

suffered from one event of asthma.
- It is more common in males.

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 - There is familial tendency, if one of the parents has asthma it will increase the
incidence in the siblings. There is no definite mode of inheritance it is a
multifactorial.

REAL FACTS ABOUT ASTHMA IN CHILDHOOD:

- It is number one of chronic illness causing school absence.
- Affects around 5 million children <18 years in US.
- 658,000 emergency department visits for asthma in US children <15 years in
1999.

NATURAL HISTORY OF ASTHMA:

* 27% never reported wheezing.
* 21% reported wheezing at only one assessment.
*10% had intermittent wheezing
* 14% had wheezing that persisted throughout the study.
* 15% had remission during adolescence and no further wheezing.
* 12% had remission with subsequent relapse.

ASTHMA EDUCATION:
Self managed education associated with:
- Improvement in air flow.
- Improvement in self efficacy scales.
- Reduction in school absence.
- Reduction in emergency room visits.

Now , I will give you 2 cases from Dr Samah tables and ask about the severity,
control and treatment of each one.

** We diagnose and manage asthma according to NIH Asthma Guidelines , you

can find them on this site : “ www.nhlbi.nih.gov “ .

**I will put the tables here but they aren't clear, so you can find the tables on the
website :

- The First Table talks about the classification of the severity of asthma until the
age of 11 . (There are other tables for the ages ≥12 years .)
- The second table is talking about the assessment of control of asthma .
- The third table talks about the steps of treatment .

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**Table 1

**table 2

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 **table 3 :

CASE 1
A 6 year-old male presented to our clinic :

- Cough and wheezing every day.

- Wakes up at night at least 2-3 times a week .
- Tried to relieve symptoms using salbutamol inhaler several times/week
- Some limitation of activity .

* First , what’s the severity of the case?

According to the 1st table it’s “persistent moderate” .

In general , level of severity (whether intermittent or persistent ) is

determined by both :

1. Impairment :
- Symptoms.
- Night time awakenings .

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 - Short-acting β2-agonists used for system control .
- Interference with normal activity .
- Lung function
2. Risk .

** if we are confused whether it’s mild or moderate for example , you take the
higher level of severity always .

“It’s not required from you , when you take a history of asthma that you
determine the level of severity . but you should know the difference between the
intermittent and the persistent ( memorize the intermittent and anything else will be
persistent ) and you should include the criteria of severity in your history”.

*Second , What medications would you use for long term management ?

According to table1 , moderate persistent come with step 3 management Which

is ( according to table 3 ) : Either : 1 Low dose ICS + LABA LTRA or theophyline or 2
Medium dose ICS alone .

** LABA : long acting β2-agonists . ** LTRA : Leukotriene receptor antagonist.

I prefer using the medium dose ICS because we try to avoid using LABA until we
need it as we try to minimize the number of medications and decrease the incidence of
poor control . There are practical and scientific points in determining what we use .

- Scientific point : they prefer option 1 to minimize the S.E of ICS that can
happen with medium to high dose .
- Practical point : they prefer option 2 which is starting with higher dose because
we hate for the kid to experience poor control and experience the symptoms coming back.

So , it’s physician dependant strategy but both are right .

** it’s not required to know what medications is given in each step but you
should know that in any persistent level of asthma , we should start with a controller
medicine ( the best is ICS) .

Third , in the Follow up Visit :

patient persist to have symptoms 3-4 times/week , wakes up at night 1

time/week.

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 What is the level of Control ?

According to table 2 , it’s “ not well controlled “ . So , we step up the treatment

so that it become Step 4 … which is according to table 3 : Either : 1 Medium Dose ICS +
LABA . or 2 Medium dose ICS + LTRA or theophyline .

Before stepping up the treatment we should make sure that the patient is 1 using
the medication appropriately ,2 is compliant , and 3 the environment is free of triggering
factors .

“”” Why the doctor is giving us this ?? because 6th year students were asked in
OSCI exam : ( patient → symptoms daily , used β2-agonist several times/day , he wakes
up every night, he goes to the ER every 2 weeks , Exacerbation 4 times/year ) , is the
asthma is controlled or not ?

They are not asked about the level of control , it’s just controlled or not but they
didn’t know what that means so “ it’s a shame “ ..

We say “ asthma is controlled “ when it is : - Symptoms free or – at least become

intermittent ”””.

CASE 2
A 5 year-old female presented with :

- Cough once weekly

- No night time symptoms
- No activity limitation
- Symptoms improve with salbutamol when used 1-2 times/month .

- The level of severity : Intermittent.

- Step Of treatment : Step 1 : SABA Per needed . ( short acting β2-agonists).
The End
Resources : past lectures , case – based book
Original lectures By : MOATAZ ABU RABEAH & MARWAN ALKRENAWI (Shifa' )
/ Bara' Alzu'bi ( Hope )

Collected and Edited by : Nadeen Ta'ani / HOPE 2010

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