Pediatric Asthma

practical management overview

Darmawan B Setyanto
Dept of Child Health
Respirology Division
Darmawan B Setyanto, MD
Born: 11 April 1961

Education:
◼ Medical Doctor, Faculty of Medicine, University of Indonesia, 1986
◼ Pediatrician, Faculty of Medicine, University of Indonesia, 1997
◼ Respirology Consultant, 2005

Current position :
◼ Head of Respirology Division, Dept of Child Health, Faculty of
Medicine, University of Indonesia

Organization:
◼ Chairman of Respirology Coordination Working Unit, Indonesian
Pediatric Society 2008-2014
◼ IPS: Member of C Board, IPS Bulletin
◼ IMA, APSR, ERS, EAACI member
Pathogenesis
medical problem pathway
Medical problem pathway

 ANY FACTOR AFFECTING THE PHYSIOLOGIC

CONDITION (growth, development, process, or
function of the cell, tissue, organ, system, or
individual – DBS
insults
Medical problem pathway

The ability to survive

by eliminate, terminate,
defend, avoid, or adjust
to any kind of insults
(fight or flight)

adaptive
responses

insults
 2
Integumentary
system (skin)

Respiratory Neuro-musculo-
defense mechns skeletal system

Urinary Adaptive Endocrine

def mechn responses system

Gastro-intestinal Autonomic
defense mechns nerve system

1
Immune
system
Medical problem pathway

Diagnosis & Treatment

symptomatology

pathophysiology

pathology
pathogenesis adaptive
responses

insults
Classic clinical asthma
Dyspnea &
symptom
wheezing
Obstruction
pathophys
bronchospasm
smooth muscle
pathology

Adult
adaptive CLASSIC
response
asthma

Insult
Classic clinical asthma
Dyspnea &
symptom
wheezing
Obstruction
pathophys
bronchospasm
smooth muscle
pathology

adaptive
response
Some
children
Insult
NON-classic clinical asthma
symptom
Cough,
cough &
cough
pathophys
Airway
inflammation
pathology

adaptive
response
Other
children
Insult
 What is ‘INFLAMMATION’?
symptom
organism
body system
pathophys organ
tissue
cellular
pathology biochemical
Ongoing pathology
adaptive
response symptomatology

Insult
 Asthma pathogenesis
cough, dyspnea
symptom wheezing, …

Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...

Airway Inflammation oedema, Broncho-

pathology remodelling Th2, mast c, eos hypersecretion spasm

Enhancers: indoor AHR

adaptive allergen,mold,... Immune response: Autonomic
response Th2, IgE, IgG4, IgG1 imbalance
Inducers: ozone
rhinovirus, ... AHR:
Genetically airway hyper-
Insult susceptible responsiveness
Diagnosis
definition & classification
ATS 1987 asthma definition
A clinical syndrome characterised by increased
responsiveness of the tracheobronchial tree to a variety
of stimuli. The major symptoms of asthma are paroxysms
of dyspnoea, wheezing, and cough, which may vary from
mild and almost undetectable to severe and unremitting
(status asthmaticus).
The primary physiological manifestation of this hyper-
responsiveness is variable airways obstruction. This can
take the form of spontaneous fluctuations in the severity
symptomatology
of obstruction, substantial improvements in the severity
of obstruction following bronchodilators or cortico-
steroids, or increased obstruction caused by drugs or
other stimuli
pathophysiology
 Integumentary
system (skin)

Asthma = Autonomic system

Respiratory Neuro-musculo-
defense mechns skeletal system
mal-adaptive response
Urinary Adaptive Endocrine
def mechn responses system

Gastro-intestinal Autonomic Autonomic

defense mechns imbalance Nerve system

Immune
system
 GINA asthma definition
symptom Asthma is a chronic inflammatory disorder of the
airway in which many cells & cellular elements
play a role. The chronic inflammation is
pathophys associated with airway hyperresponsiveness
that leads to recurrent episodes of wheezing,
breathlessness, chest tightness & coughing,
pathology particularly at night or early in the morning.
These episodes are usually associated with
widespread, but variable airflow obstruction
adaptive within the lung that is often reversible either
response spontaneously or with treatment.

GINA 2002 - 2012

Insult
GINA 2014 asthma definition
Asthma is a heterogenous disease, usually characterized
by chronic airway inflammation.
It is defined by the history of respiratory symptoms such
as wheeze, shortness of breath, chest tightness, and
cough that vary over time and intensity together with
variable expiratory airflow limitation

pathology
symptomatology
pathophysiology

NEW! GINA 2014-2019

 Integumentary
system (skin)

Asthma = Immune system

Respiratory Neuro-musculo-
defense mechns skeletal system
mal-adaptive response
Urinary Adaptive Endocrine
def mechn responses system

Gastro-intestinal Allergic Autonomic

defense mechns inflammation Nerve system
Immune
system
Asthma & 2 main symptoms

Congenital malformations
Cough
Rh-S ARI ARI

asthma
GER
TB TB
BPD
PCD GER
CHD
Wheeze Rh-S pneumonia
Asthma diagnosis, clinical

&/

Cough Wheeze
◼ Periodicity, episodicity (recurrent) !!!
◼ Variability (nocturnal, worsen at night)
◼ Reversibility (response to asthma drugs)
◼ Allergy history (patient, parents, family)
◼ Trigger factors (inhalant, ingestant, others)
 Asthma: chronic - acute
attack
attack
symptom
symptom

MPI
Asthma
time
MPI:
Chronic
minimalasthma: how frequent the symptom –
attack appear during certain time
persistent
inflammation
Acute asthma: how severe the symptom –
attack that appear
inflammation
 Chronic asthma classification
Frequency classification is made on initial visits and based
on anamnesis of long-term condition:

Frequency Asthma symptoms frequency description

<6x/year or time among symptoms ≥6
Intermittent
weeks
Mild-
>1x/month, <1x/weeks
persistent
Moderate-
>1x/week, but not daily
persistent
Severe- Asthma symptoms happened almost
persistent every day
1. Papadopoulus NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R et al. International consensus on (ICON) pediatric asthma. Allergy 2012.
4. Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T et al. Japanese Guideline for Childhood Asthma 2014. Allergol Inter 2014; 63:335-56.
Steps of asthma diagnosis
◼ Make a working diagnosis: Asthma
◼ Define the frequency classification
o Intermittent Made within 6 weeks,
o Mild persistent can be less than 6 weeks
if clinical information
o Moderate persistent is strongly confirmed.
o Severe persistent
◼ Assess the control
o Not controlled
Made after 6 weeks,
o Partly controlled experiencing initial
o Controlled with controller drug longterm treatment
o Controlled without drug
Pediatric asthma
principles of treatment
General principles
◼ Goals: good symptom control; minimize risk of
attack, airflow limitation, drug side effect
◼ Partnership
◼ Communication, information, education
◼ Control based management
◼ Patient preference

GINA 2018
Steps of asthma treatment

1. Avoidance of trigger(s)

2. Avoidance of trigger(s)

3. Avoidance of trigger(s)

a. Reliever
4. Drug(s)
b. Controller
Asthma treatment, step 1-3
symptom

pathophys

pathology
Avoidance
adaptive
response
Avoidance

Insult Avoidance
 Selesma 

Flu virus
Rhinovirus

Flu!
Chronic asthma
longterm treatment
Asthma treatment

Acute asthma
Asthma attack
Asthma exacerbation

Chronic asthma
Longterm treatment
Controlling asthma
Longterm treatment goals

No
Normal
symptoms
daily life
day or
activity
night

Minimum Prevent
drug drug’s
needs and side
no attack effect

Optimal growth and development

Steps of asthma treatment

1. Avoidance of trigger(s)

2. Avoidance of trigger(s)

3. Avoidance of trigger(s)

a. Reliever
4. Drug(s)
b. Controller
Asthma medication
Reliever • To relieve asthma symptoms - attack
drug • As needed medication
• If the symptom relieve, stoped
(pereda)

• To reduce airway inflammation, and

Controller control symptoms
• Long term medication, months - years
drug
• Evaluated regularly
(pengendali) • Dose adjusment: maintain, , 
 Asthma treatment, step 4b
cough, dyspnea
symptom wheezing, …
Controller
Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...

Airway Inflammation oedema, Broncho-

pathology remodelling Th2, mast c, eos hypersecretion spasm

Enhancers: indoor AHR

adaptive allergen,mold,... Immune response: Autonomic
response Th2, IgE, IgG4, IgG1 imbalance
Inducers: ozone
rhinovirus, ...
Genetically
Insult susceptible
Chronic asthma
controller drugs
 Controller drug

attack

symptom

MPI
Asthma
MPI: Trigger Trigger
minimal ‘light’, ‘heavy’,
persistent single combination
inflammation

inflammation
Longterm treatment steps
Define asthma severity (frequency) classification

Start longterm treatment according to asthma

severity

If a step in therapy has lasted for 6-8 weeks and

asthma still uncontrolled, then step up therapy

If a step in therapy has lasted for 8-12 weeks and

asthma is well controlled, then step down therapy
Controller drug
◼ Inhaled C-Steroid:
o fluticasone (Flixotide®, ……)
o budesonide (Pulmicort®, ……)
o mometasone
o triamcinolone
◼ LABA:
o salmeterol
o formoterol
◼ Combination: ICS + LABA (Symbicort®, Seretide®)
◼ Anti-leukotrien:
o montelukast
o zafirlukast
Steps in longterm treatment

ICS (inhaled corticosteroids, steroid inhalasi);

LTRA (Leukotriene Receptor Antagonist);
SABA (short acting beta agonist, β2-agonis kerja pendek);
LABA (long acting beta agonist, β2-agonis kerja panjang)
 Inhaled cortico-steroid - 1
◼ Suppress respiratory inflammation, important for long
term asthma management

◼ Administration of inhaled steroid with dose equal with

budesonide 100-200 ųg/day  decrease number of
asthma attacks and repair lung function in asthma
patient

◼ Some asthma patients need inhaled steroid with dose

400 ųg/day to control asthma and prevent attacks after
exercise

The Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2014. Available from: www.ginasthma.org
Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T et al. Japanese Guideline for Childhood Asthma 2014. Allergol Inter 2014;
63:335-56.
Inhaled cortico-steroid - 2
• Does not significantly affect body height and bone
density

• Growth monitoring (height percentiles and body

weight) must be conducted every year

• Side effects such as oral candidiasis and hoarseness

can be prevented with mouth wash every time after
inhaled steroid is given, and the resides is thrown
away.
Inhaled cortico-steroid - 3
◼ Designed & developed as ‘controller’

◼ Steroid as reliever – systemic administration (oral OR

injection)

◼ ICS as reliever – a very common (mis)practice

o Based on concept: wrong!
o Evidence based medicine??? --- there are!
o Later: logical mechanism explanation!
o High cost! --- really?
 ICS dose for pediatricasthma

The Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2014. Available from: www.ginasthma.org
The current trends
◼ The choice of inhaler device should be based on the
child’s age & capability
◼ The preferred device is p-MDI + spacer
◼ with facemask for <3y and mouth piece for 3-5y
GINA 2019
Nebulisation as alterntive to pMDI+spacer

Advantages
• Easy to use: no breath-holding required1
• Minimal patient cooperation1
• Less errors in drug delivery2
• Can be mixed with other compatible drugs1
• High doses can be administered1
• Can be used with supplemental oxygen1
• Inhaled solution rehydrates the airways3

1. Welch MJ, Clin Pediatr (Phila). 2008;47(8):744-56; 2. Welch MJ et al., Ped Allergy Immun Pulmo. 2010;23(2):113-20; 3. Moloney E,et al. Chest. 2002;121(6):1806-11
Presented at:
◼ CME IDAI Jabar Perwakilan Bekasi
◼ Aston Hotel Bekasi
◼ Sun, 28 Jul 2019
Asthma diagnosis flow
◼ Outline :

◼ More detailed in next slides

Asthma diagnosis flow upper part
Asthma diagnosis flow lower part
Asthma <5 years
◼ A special challenge.
◼ Wheezing in underfive has many more DD/.
◼ Most common cause: viral respiratory infection
◼ Asthma diagnosis is uncertain:
o Maybe not asthma
o Maybe asthma
o Asthma is likely
◼ The clinical pattern is changing dinamically
 Changing & dynamic pattern
Symptoms Symptoms Symptoms
(cough, wheeze, etc) (cough, wheeze, etc) (cough, wheeze, etc)

<10 days, during ARI >10 days, during ARI >10 days, during ARI

<3 episodes/yr >3 episodes/yr >3 episodes/yr

Severe episode &/ Severe episode &/

night worsening (+) night worsening (+)

Between ARI episode Between ARI episode Between ARI episode

NO symptom occasional symptom symptom appear

History of allergy (-) History of allergy (+) History of allergy (+)

MAYBE NOT ASTHMA MAYBE ASTHMA ASTHMA IS LIKELY

Steps in longterm treatment

ICS (inhaled corticosteroids, steroid inhalasi);

LTRA (Leukotriene Receptor Antagonist);
SABA (short acting beta agonist, β2-agonis kerja pendek);
LABA (long acting beta agonist, β2-agonis kerja panjang)
Spectrum of asthma symptoms
Based on current state:
◼ NO symptoms
◼ With symptoms
◼ Mild-to-moderate acute asthma
◼ Severe acute asthma
◼ Impending respiratory failure
 Acute asthma classification
Based on severity of acute asthma 2,4
◼ Mild-to-moderate asthma attack
◼ Severe asthma attack
◼ Asthma attack with respiratory-failure risk

Acute asthma severity is used as basis

to determine acute asthma treatment.

2. The Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2014. Available from: www.ginasthma.org
4. Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T et al. Japanese Guideline for Childhood Asthma 2014. Allergol Inter 2014; 63:335-56.
 Asthma control classification
Based on control level 1,2,4
◼ Well-controlled asthma
o Without controller: in intermittent-asthma
o With controller: in persistent asthma
(mild/moderate/severe)
◼ Partly-controlled asthma
◼ Uncontrolled asthma
Control level is used to evaluate the success of asthma treatment
and to determine a step-up, maintenance or
step-down management that will be administered.
1. Papadopoulus NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R et al. International consensus on (ICON) pediatric asthma.
Allergy 2012.
2. The Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2014. Available from: www.ginasthma.org
4. Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T et al. Japanese Guideline for Childhood Asthma 2014. Allergol Inter
2014; 63:335-56.
When to initiate controllers?

Asthma differential diagnosis is ruled out

Non pharmacology management (triggers

avoidance) is already done
Asthma comorbid factors such as allergic
rhinitis, rhinosinusitis or GERD have already
been managed
Asthma frequency classification is persistent
asthma (mild, moderate, severe)
 Global Initiative for Asthma (GINA)
What’s new in GINA 2019?

GINA Global Strategy for Asthma

Management and Prevention
This slide set is restricted for academic and educational purposes only. No additions
or changes may be made to slides. Use of the slide set or of individual slides for
commercial or promotional purposes requires approval from GINA.

© Global Initiative for Asthma

The 12y history behind changes in GINA 2019
◼ In the meantime, GINA challenged conventional criteria for initiation
of ICS
– During preparation for 2014 GINA revision, we identified no evidence for the
recommendation to withhold ICS until symptoms were more than twice
weekly
– This was investigated in a post hoc analysis of START data (Pauwels, Lancet 2003).
This found that ICS halved the risk of serious exacerbations even in patients
with symptoms 0-1 days a week at entry (Reddel, Lancet 2017)
◼ GINA found no evidence to support a Step 1 SABA-only
recommendation
– The lack of evidence for SABA-only treatment contrasted with the strong
evidence for safety, efficacy and effectiveness of treatments recommended in
Steps 2-5
– In 2014, as an interim safety measure, GINA restricted SABA-only treatment to
patients with symptoms less than twice a month and no risk factors for
exacerbations
◼ 2018: Review of evidence for mild asthma, including SYGMA studies
– A careful review of GINA conflict of interest processes was undertaken first
 GINA 2018 – main treatment figure

Step 1 treatment is for

patients with symptoms
<twice/month and no risk
factors for exacerbations

Previously, no controller
was recommended for
Step 1, i.e. SABA-only
treatment was ‘preferred’

GINA 2018, Box 3-5 (2/8) (upper part)

© Global Initiative for Asthma, www.ginasthma.org

GINA 2019 – landmark changes
◼ For safety, GINA no longer recommends SABA-
only treatment for Step 1
– This decision was based on evidence that SABA-only
treatment increases the risk of severe exacerbations,
and that adding any ICS significantly reduces the risk
◼ GINA now recommends that all adults and
adolescents with asthma should receive
symptom-driven or regular low dose ICS-
containing controller treatment, to reduce the
risk of serious exacerbations
– This is a population-level risk reduction strategy, e.g.
statins, anti-hypertensives
 Box 3-5A Confirmation of diagnosis if necessary
Adults & adolescents 12+ years Symptom control & modifiable
risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Personalized asthma management: Patient goals
Assess, Adjust, Review response
Symptoms
Exacerbations
Side-effects
Lung function
Patient satisfaction Treatment of modifiable risk
factors & comorbidities STEP 5
Non-pharmacological strategies
Education & skills training High dose
Asthma medication options: ICS-LABA
Adjust treatment up and down for
Asthma medications STEP 4
Refer for
individual patient needs STEP 3 Medium dose phenotypic
assessment
STEP 2 ICS-LABA
Low dose ± add-on
PREFERRED STEP 1 therapy,
CONTROLLER Daily low dose inhaled corticosteroid (ICS), ICS-LABA e.g.tiotropium,
to prevent exacerbations As-needed or as-needed low dose ICS-formoterol * anti-IgE,
and control symptoms low dose anti-IL5/5R,
ICS-formoterol * anti-IL4R
Other Low dose ICS Leukotriene receptor antagonist (LTRA), or Medium dose High dose Add low dose
controller options taken whenever low dose ICS taken whenever SABA taken † ICS, or low dose ICS, add-on OCS, but
SABA is taken † ICS+LTRA # tiotropium, or consider
add-on LTRA # side-effects
PREFERRED As-needed low dose ICS-formoterol * As-needed low dose ICS-formoterol ‡
RELIEVER
Other As-needed short-acting β2 -agonist (SABA)
reliever option
* Off-label; data only with budesonide-formoterol (bud-form) ‡ Low-dose ICS-form is the reliever for patients prescribed
† Off-label; separate or combination ICS and SABA inhalers bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
© Global Initiative for Asthma, www.ginasthma.org allergic rhinitis and 1FEV >70% predicted
Chronic asthma
comorbid management
Asthma comorbid
◼ Rhinitis
◼ Rhinosinusitis
◼ GERD
◼ Food allergy
◼ Obesity
◼ Anxiety & depression
Resp inflammation syndrome
◼ Rhinitis, rhino-sinusitis, & asthma represent the
manifestation of one syndrome in different parts of
respiratory system – united airway concept - UAC
◼ Spectrum:
o Rhino-pharyngitis (common cold)
o Rhinitis (allergic) alone
o Rhino-sinusitis (infection, allergy)
o Asthma
o Rhinitis with airway hyper-reactivity
o Rhinitis, rhino-sinusitis, & asthma present
o Or any other combinations

Med J Aust 2006; 185:565-71

 Rhino-sino-bronchitis
◼ Particularly notable in children
◼ Respiratory allergy is not a disease confined to a
specific target organ, but a disorder of the
whole respiratory system
Thorax 2000; 55 (Suppl 2):S26-7

◼ Inflammation in CRIS (chronic resp inflamm

synd): allergy or infection or both
o Rhinitis – allergy or infection
o Rhino-sinusitis – allergy & infection, viral &/ bacterial
o Asthma – allergy
Med J Aust 2006; 185:565-71
Spectrum of respiratory inflammation
Rhinitis (infection, allergy, etc)

AIRWAY
Rhino-sinusitis
Air passage
Airflow Otitis media

(Tonsilo)-pharyngitis
Conducting
zone Laryngitis

(Rhino)-bronchitis

Respiratory Zone
Pneumonia
Diffusion
Integrated diagnosis of CRIS
◼ Allergic rhinitis should be considered a risk
factor for asthma along with other known risk
factors

Allergic
Asthma
rhinitis
Integrated treatment of CRIS
◼ A combined strategy should ideally be used to
treat upper and lower airway diseases in terms
of efficacy and safety
◼ The recommended clinical approach is to
manage the two disorders discretely but
simultaneously
◼ You should treat each disease separately; that
even though it’s one disease, you can’t just treat
the nose & not take care of the asthma, or vice
versa. Each one has to be treated appropriately