Early Intervention in

Childhood Asthma

Hendra Santoso
Bali, Indonesia
Definisi
Asma didefinisikan sebagai suatu penyakit
inflamasi kronis saluran pernapasan bagian
bawah dan diperankan olehnbanyak sel, seperti
sel mast, eosinofil, limfosit T, neutrofil dan sel
epitel. Pada mereka yang peka , reaksi inflamasi
ini menyebabkan episode mengi berulang, sesak
napas, rasa dada tertekan, dan batuk, terutama
pada malam hari dan/atau dini hari. Episode ini
biasanya berhubungan dengan obstruksi saluran
pernapasan yang luas, namun bervariasi dari
yang ringan sampai yang berat, sebagian besar
bersifat reversibel baik spontan maupun dengan
pengobatan.
Incidence of asthma in children is between
5%-10%
 30% develop symptoms before 1 year old

 50% before 2 year of age

 80% at the time they start school

Most children with asthma ( 70%)

experience remission before puberty
For the rest, further progression and a longer
period of troublesome symptoms
Important to identify and treat early to
prevent irriversible airway remodelling
Poor control of pediatric asthma will:
 worsen the disease as it progresses

 May be at risk for increased morbidity and /

or mortality
In acute attack of asthma, the “ longer it lasts
the worse it gets, and the worse it gets, the
longer it last ”
Early intervention is essential to eliminate this
process
Late intervention progress changes in
pulmonary function, increase the need for
corticosteroid, and emergency department /
hospital visits
Pathophysiology

Lung function is difficult to measure in

infants and young children
Elastic recoil is low in young children and
increases with age
Asthma results a failure for the increase in
elastic recoil and provide persistent
hyperinflation
Lung volume
 According Poiseuille’s law

8 nl
Resistance of airflow in the bronchioles = _____
r4

 Resistance varies inversely with the fourth

power of the radius of the bronchioles
 If the radius of the bronchioles is halved, the
resistance to airflows increased 16-fold
Airway resistance
 Term Newborn: 25 cm H O / l / sec
2

 Fall until 2 cm H2O / l / sec in adult

Immune system and risk for asthma

During pregnancy, high Th2 cytokines are

required to prevent premature labour
After birth, Th2 will decrease for a balance of
Th1 / Th2 type responses
Non atopic children will have rapid transition
Atopic children, the transition is delayed and
Th2 type increases
Differences of INF- in atopic and non
atopic children
So, Inflammation is vulnerable in young
children and might result in persistent
airflow limitation
Most children above 5 year of age will
have
a. Dramatic increase in anatomic size of the airways
b. Increase INF-
c. Less susceptible to viral respiratory infection
The above factors causes the outgrow
of asthma in these children
Distribution of asthma in 401 subjects at age 35 years

asthma at age 35 (%)

No recent
At age 7 Total
asthma(%) infrequent frequent persistent

Mild wheezy
bronchitis 42 (65%) 8 (12%) 10 (15%) 5 (8%) 65
episode <5,  RSV

Wheezy bronchitis
54 (63%) 10 (12%) 9 (10%) 13 (15%) 86
episode > 5,  RSV

Asthma (not  RSV) 29 (30%) 20 (20%) 18 (18%) 31 (32%) 98

Severe asthma
7 (10%) 10 (15%) 8 (12%) 41 (63%) 67
(at age 10 )

Total 132 48 45 91 401

Goals of asthmatic therapy
 Abolish symptoms
 Prevent chronic and troublesome
symptoms
 Maximize lung function (age > 6 years old)
 Maintain normal activity
 Prevent recurrent exacerbation
 Provide optimal pharmacotherapy with the
least amount of adverse effects
Managing acute asthma

In accordance with the NAEP report 2 (1997),

management of acute asthma can be
considered in 3 settings:
 The home
 The office
 The hospital
Home treatment
a. Patient education
 To teach the nature, aggravating factors, and
prognosis of asthma
 Avoidance of trigger factors
 To know the action of medication, how to
administer, and the side effects
 Manage proper use of inhalation devices
 To recognize acute exacerbation, when to treat
and when and where to get medical help
 Diary card monitoring, peak flow meters
b. Preventive and environment control
measure
 Avoid house dust mite, household pets,
pollen and molds, eliminate/avoid food
allergens
 Parents should not to smoke in the house
or car with their child
 Avoid mosquito recoil repellent
c. Pharmacotherapy

 The parents must understand for early

diagnosis and intervention for an acute
attack of asthma

 -agonists are the most potent and rapid

acting agents and if necessary add
corticosteroid
 Home Treatment
Initial Treatment
Inhaled short-acting 2 agonist: up to three
treatments of 2-4 puffs by MDI or nebulizer
at 20 minute intervals

Good Response Incomplete Response Poor Response

Mild Episode Moderate Episode Severe Episode
PEF >80% predicted PEF 50-80% predicted PEF <50% predicted
No wheezing or Persistent wheezing Marked wheezing and
shortness of breath and shortness of shortness of breath
• May continue 2 breath • Add oral steroid
agonist every 3-4 • Add oral steroid • Repeat 2 agonist
hours for 24-48 • Continue 2 agonist immediately
hours
• For patients on
inhaled steroids
Contact clinician Proceed to emergency
(ICS), double the
urgently department
dose for 7-10 days
Adapted from Lemanske FR et al, Textbook of Allergy 1998, 887-900
 Emergency department and hospital based
management of asthma exacerbation
Initial Assessment
History, physical examination, PEF or FEV1, oxygen saturation, and
other tests as indicated

FEV1 or PEF 50% FEV1 or PEF <50% Respiratory Arrest

(Severe Exacerbation)
Inhaled 2 agonist by Intubation and
MDI or nebulizer, Inhaled high-dose 2 mechanical
Oxygen to achieve O2 ventilation with
agonist and
100% O2
saturation 90% anticholinergic by
Oral systemic nebulization Nebulized 2 agonist
corticosteroids if no Oxygen and anticholinergic
immediate response systemic cortico- Intravenous
or if patient recently steroid corticosteroids
took oral steroid

Repeat Assessment Admit to Hospital

Intensive Care
Hospital management
 Special care for infants and young children with
severe asthma attack is to balance fluid and acid-
base
 Giving sodium bicarbonate to correct metabolic
acidosis seems rational
 Fluid deficits should be restored, but no more than
1-1.5 times of the fluid requirements
 Electrolytes and osmolality must be carefully
monitored
 Oxygen should be administered immediately and
oxygen saturation should be monitored
 Pharmacotherapy
-agonists for acute asthma

Short acting -agonists is the treatment of

choice for acute asthma
In emergency department and in hospital
ward children received continuous nebulized
albuterol (CNA) improved more rapidly, and
recovered from respiratory failure faster than
intermittent nebulization
-agonists delivered by MDI plus spacer is as
effective as by nebulizer
Ipratropium bromide

A study of 120 children with acute moderate / severe

asthma, ipratropium bromide 250 gr every 30 min
for 3 doses added to albuterol have greater
improvement in FEV1 compared to albuterol or
ipratropium bromide alone and produced no adverse
effect
Repeated doses of nebulized ipratropium bromide
added to high dose salbuterol is safe and may
reduced hospitalizations
In adult ipratropium bromide has better efficacy than
in children with asthma
Corticosteroid in acute asthma

Oral prednisone 2 mg/kg given within 4 hours

of arrival at the emergency department /
doctor’s office, will need less hospitalization
Oral prednisone (2 mg/kg) is used also to
treat asthmatic patients in hospital
Intravenous corticosteroid is unnecessary in
patient who are not vomiting
Methylxanthines in acute asthma

NAEP expert panel report did not recommend the

use of aminophylline in emergency department
And did not make recommendation use
aminophylline in the hospital
In a hospital comparative study, CNA produced
improved SaO2, PEFs and early discharge than
aminophylline
Theophylline has a narrow therapeutic range,
and requires monitoring serum concentrations
Long term asthma treatment

Early intervention should be performed into 2

approaches :
1. early intervention after the onset of the
disease
2. anti inflammatory drugs should be started
in milder asthma
According to NAEP 2, asthma is classified into
4 levels of severity :
Mild intermittent, mild persistent, moderate
persistent and severe persistent
The effect of drug therapy on long term
outcome of child hood asthma
175 asthmatic children, mild intermittent asthma
treated with as needed -agonists
Mild persistent asthma treated with cromolyn /
nedrocromyl and moderate / severe persistent
asthma with low dose / high dose ICS
Result, ± 50 % treated with anti-inflammatory drugs
and only 17 % of the as needed -agonists improved
and move to milder group
The condition of the as needed -agonists group
remained the same or worsened compared to anti-
inflammatory drugs
Adapted from Kőnig et al, J Allergy Clin Immunol 1996; 198: 1103-11
 Risk and benefit of anti-inflammatory drugs
Early intervention negates the need for increased doses of ICS

Cromolyn / nedrocromyl Inhaled corticosteroid (ICS)

sodium
Low dose ICS for persistent moderate
asthma
Non steroid anti-
High dose ICS for severe persistent asthma
inflammatory drugs
In severe asthma ICS is more superior than
For mild and cromolyn
moderate asthma
Aggressive therapy is needed to gain rapid
showed equal control of asthma
efficacy as ICS
Safety of ICS is very good but not excellent
Have excellent safety as cromolyn
records One daily morning dose will reduce the side
effects of ICS
99 % of Fluticasone / mometasone, 90%
budesonide, 80%-90% triamcinolone and
60%-70% BDP is inactivated in the liver
So Fluticasone / mometasone has superior
safety than BDP
 Alternatives or add-on therapy to ICS
Long acting -agonists
Salmeterol and formoterol
Has delayed onset of action
but the duration is much
longer than short acting -
agonists
As monotherapy, long term
use will develop tolerance and
the bronchodilator effect may
diminished with time
Combination salmeterol and
ICS will be more efficacious
and less side effect than
increasing ICS alone
Sustained release theophylline
Is effective as monotherapy for
chronic asthmatic symptom
Has bronchodilator, anti-allergic,
and anti-inflammatory compound
Improve asthma control more
significantly than the regular use
of oral or inhaled albuterol
Has behaviour side effects much
like caffeine
Leukotrienes antagonists has been
discussed earlier in this session
Conclusion
The goal of childhood asthma management is to
recognize and to intervene it early
In acute asthma inhaled 2-agonists are the
bronchodilator of first choice
Systemic corticosteroid should be given in patients
who do not respond completely to initial therapy
Aminophyline has no benefit as add-on therapy in
acute asthma and may increase adverse effects
In managing asthma long term, use anti-
inflammatory therapy (cromolyn or inhaled steroid) in
a step wise manner
Starting anti-inflammatory drugs early, will result a
better long-term outcome
Clinical feature before treatment in children over 5 years old

Symptoms Night time symptoms Lung function

Mild intermittent Symptoms < 2 times/week < 2 times/month FEV1 / PEF >80% pred
Asymp / NPEF between exacerb PEF variability < 20%
Exarb brief (few hours-few days)
Intensity may vary

Mild persistent Symptoms > 2 times/wk - <1 time/day FEV1 / PEF >80% pred
Exarcerb may affect activity >2 times/month Pef variability 20 – 30%

Moderate persistent Daily symptoms >1 time/week FEV1 / PEF 60 - 80% pred
Daily use of inhaled B2 agonist PEF variability >30%
Exacerb affect activity
Exarb 2 times/wk ; may last days

Severe persistent Continual symptomt Frequent FEV1 ? PEF <60% pred

Limited physical activity PEF variability > 30%
Frequent exarcebations

From National Asthma Education and Prevention Program NIH publication No 97-
4051, july 1997
Long-term Medications For Asthma in Children Over 5 Years Old
Mild Intermittent * No daily medication needed

Mild persistent * Daily medication :

Antiinflammatory : Cromol;yn/ nedocromil or inhaled steroid (low doses)
Begin will a trial of cromolyn or nedocromil. Sustained release theophyline
to serum concentration of 5-15 ug/ml and leukotriene antagonist may also
be
considered
Moderate persistent Daily medication
Antiinflammatory : inhaled corticosteroid (medium dose) and if necessery add
a long-acting bronchodilator, either long-acting inhaled 2 agonist, sustained
release theophylline, or leukotriene antogonist

Severe persistent Daily medications

* Antiiflammatory : inhaled corticosteroid and
* Long acting bronchodilator: either long-acting 2 agonist, sustained release
theophylline, or leukotrine antogonist and
* Prednisone tablet (2 mg/kg/day, max 60 mg/day

From National Education and Prevention Program NIH publication No 97-4051, july 1997