Asthma in children

chronic asthma & achieving control

Darmawan B Setyanto
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, CPD committee, Paediatrica Indonesiana, IPS Bulletin
◼ IMA: MKEK member
◼ APSR, ERS, EAACI member
 Prologue Dyspnea! Flow disturbance!
Wheezing! Bronchoconstriction!
What is Cough! Inflammation!
ASTHMA? Night waking! Airway
… hyperresponsiveness
…

Asthma is a chronic airway disease

due to chronic inflammation

What is the
TREATMENT? Bronchodilator! SABA!
Chronic asthma & Acute asthma
understanding the concept

Part 1

Pathogenesis and
treatment principles
Two era of astma

Bronchospasm Inflammation
era era

1. The Global Asthma Report 2018. Available from www.globalasthmareport.org

2. Pavord I et al. The Lancet Commissions. After asthma: redefining airways diseases. Lancet 2018; 391(10118):350–400.;
Medical problem pathway DBS

 ANY FACTOR AFFECTING THE PHYSIOLOGIC

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

The ability to survive

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

adaptive
responses

insults
Medical problem pathway DBS

Diagnosis & Treatment

symptomatology

pathophysiology

pathology
pathogenesis adaptive
responses

insults
 What is ‘INFLAMMATION’? DBS

symptom
organism
body system
pathophys organ
tissue
cellular
pathology biochemical
Ongoing pathology
adaptive
response symptomatology

Insult
Asthma pathogenesis DBS

cough, dyspnea
symptom wheezing, …

Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...
Inflammation
Airway oedema, Broncho-
pathology Inflammation
acute
remodelling hypersecretion spasm
chronic
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
 Integumentary DBS
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
History of asthma
through ages

bronchospasm

ATS definition 1987

A clinical syndrome characterized by increased responsiveness of the
tracheobronchial tree to a variety of stimuli. The major symptoms of
asthma are paroxysms of dyspnea, 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 of obstruction,
substantial improvements in the severity of obstruction following
bronchodilators or cortico-steroids, or increased obstruction caused by
drugs or other stimuli
 CIBA sympo 1958 asthma definition (classic) DBS

Autonomic nerve system imbalance

symptom [mal-adaptive response]

pathophys

pathology Asthma refers to the condition of subjects with

widespread narrowing of the bronchial airways,
adaptive which changes its severity over short periods of time
response either spontaneously or under treatment, and is not
due to cardiovasculardisease

Insult pathophysiology
 Integumentary DBS
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
History of asthma
through ages

bronchospasm inflammation

ATS definition 1987

A clinical syndrome characterized by increased responsiveness of the
tracheobronchial tree to a variety of stimuli. The major symptoms of
asthma are paroxysms of dyspnea, 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 of obstruction,
substantial improvements in the severity of obstruction following
bronchodilators or cortico-steroids, or increased obstruction caused by
drugs or other stimuli
 GINA 2014-2021 asthma definition
symptom
Asthma is a heterogenous disease, usually characterized by chronic
airway inflammation.
pathophys 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
pathology limitation. [2014-2019]
Airflow limitation may later become persistent. [2020]
adaptive
response
symptomatology pathophysiology
pathology
Chronic inflammation
Insult [allergic inflammation] NEW! GINA 2014-2021
 DBS pediatric asthma definition DBS

symptom Chronic lower airway disease with recurrent acute episodes of

symptomatology spectrum (symptoms --- attack --- life threat)
◼ Symptomatology: cough, wheeze, dyspnea & other respiratory
symptoms, with specific features (episodicity, variability, reversibility) …
pathophys ◼ … caused by lower airway bronchospasm & acute inflammation with
hypersecretion & wall oedema, which can lead to variable degree of
obstruction …
pathology ◼ … with underlying pathology: chronic inflammation & remodeling of
lower airway which many cells & cellular elements play a role …
◼ … as the result of mal-adaptive response of autonomic nerve system &
adaptive immune system due to …
response ◼ … chronic complex & accumulative interactions between internal insults
(genetic susceptibility) & external insults (infection, pollutant, allergen,
irritant, etc)

DB Setyanto, 2010
Insult
 Asthma: chronic - acute DBS

attack
attack
symptom
symptom

MPI
Asthma
time
MPI:
Chronicminimal
asthma: how frequent the symptomatology [spectrum]
appear during certain time (long-term condition)
persistent
inflammation
Acute asthma: how severe the symptomatology [spectrum]
appear at a point of time (current condition)
inflammation
 Classification – chronic asthma
symptom Frequency classification is made on initial visits and based on
anamnesis of long-term condition:

pathophys Frequency Asthma symptoms frequency description

Intermittent <6x/year or time among symptoms ≥6 weeks
Mild-
pathology >1x/month, <1x/weeks
persistent
Moderate-
>1x/week, but not daily
adaptive persistent
response Severe- Asthma symptoms happened almost every
persistent 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.
Insult
 Classification – acute asthma DBS

symptom Current condition, based on clinical severity :

Life threatening attack
◼NO symptom
◼ With symptoms
pathophys
◼ Mild-to-moderate acute asthma Severe attack

◼ Severe acute asthma

pathology ◼ Impending respiratory failure Moderate attack

adaptive GINA terminology Mild attack

o Attack
response o Exacerbation Symptoms
o Flare up
NO symptom

Insult Clinical severity reflects inflammation severity

 Asthma control
the
symptomatology
are minimized
by therapeutic
interventions

The level of asthma control is the extent to

which the symptomatology of asthma can
the goals be observed in the patient, or have been
of therapy reduced or removed by treatment
are met GINA 2021

Pediatrics. 2017;139(1):e20163438
Asthma diagnosis: chronic, acute, control DBS

symptom
2. Acute asthma
It is about Current condition
SYMPTOMATOLOGY! Symptomatology severity
pathophys

------------------------------------ Asthma ----------------------------------

pathology

adaptive
1. Chronic asthma response
Long-term condition
Symptomatology frequency 3. Control of asthma
Recent condition
Symptomatology in the last month
Insult
Steps of asthma treatment symptom

1. Avoidance of trigger(s) pathophys

2. Avoidance of trigger(s) pathology

adaptive
3. Avoidance of trigger(s) response

a. Reliever
4. Drug(s)
b. Controller Insult
Asthma treatment

Acute asthma
to relieve symptoms,
attack, exacerbation

Chronic asthma
to control chronic
inflammation
Asthma medication for acute asthma DBS

Reliever • To relieve acute asthma symptoms – attack,

exacerbation
drug • Bronchodilator (SABA, SAMA) & acute anti-
inflammatory drug (systemic CS)
(pereda) • As needed, if the symptom relieve, stop

Controller* • To control chronic asthma inflammation

• Chronic anti-inflammatory (inhaled CS) & LABA
drug • Long term medication, months - years
• Evaluated regularly, dose adjustment: maintain,
(pengendali) increase, decrease

*Controller = maintenance = preventer = prophylactic medication

 Autonomic nervous system imbalance
Reliever

SABA

SAMA

SABA: short acting beta agonist

SAMA: short acting muscarinic antagonist
Acute asthma treatment, autonm imbalance relieverDBS
cough, dyspnea
symptom wheezing, … SABA SAMA
Reliever
Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...
Inflammation
Airway oedema, Broncho-
pathology Inflammation
acute
remodelling hypersecretion spasm
chronic
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
Acute asthma treatment, acute inflammation reliever
DBS

cough, dyspnea
symptom Systemic steroid wheezing, … SABA SAMA
Reliever Reliever
Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...
Inflammation
Airway oedema, Broncho-
pathology Inflammation
acute
remodelling hypersecretion spasm
chronic
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
Acute asthma reliever drug
Topical, Inhalation: Nebulizer or MDI+spacer
◼ Reliever inhalation drug, bronchodilator:
o β2 agonist: salbutamol, terbutaline, fenoterol, procaterol
o Anti-cholinergic: ipratropium bromide
o β2 agonist + anti-cholinergic
◼ Inhaled steroid ???
Systemic: enteral, parenteral
◼ Systemic steroid (oral, injection)
◼ Xanthin: aminophylline, theophylline
◼ Magnesium sulfate (MgSO4)
Steps of asthma treatment symptom

1. Avoidance of trigger(s) pathophys

2. Avoidance of trigger(s) pathology

adaptive
3. Avoidance of trigger(s) response

a. Reliever
4. Drug(s)
b. Controller Insult
Asthma treatment

Acute asthma
to relieve symptoms,
attack, exacerbation

Chronic asthma
to control chronic
inflammation
Chronic asthma treatment – control chronic inflammation DBS
Inhaled CS cough, dyspnea
symptom wheezing, …
Controller
Airway
pathophys Triggers: smoke, obstruction
dust, HDM, ...
Inflammation
Airway oedema, Broncho-
pathology Inflammation
acute
remodelling hypersecretion spasm
chronic
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
Asthma medication for chronic asthma DBS

Reliever • To relieve acute asthma symptoms – attack,

exacerbation
drug • Bronchodilator (SABA, SAMA) & acute anti-
inflammatory drug (systemic CS)
(pereda) • As needed, if the symptom relieve, stop

Controller* • To control chronic asthma inflammation

• Chronic anti-inflammatory (inhaled CS) & LABA
drug • Long term medication, months - years
• Evaluated regularly, dose adjustment: maintain,
(pengendali) increase, decrease

*Controller = maintenance = preventer = prophylactic medication

Chronic asthma treatment – mantain bronchodilatation DBS

Inhaled CS cough, dyspnea

symptom wheezing, …
Controller
Airway LABA
pathophys Triggers: smoke, obstruction
dust, HDM, ...
Controller
Inflammation
Airway oedema, Broncho-
pathology Inflammation
acute
remodelling hypersecretion spasm
chronic
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
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-leukotrient:
o montelukast
o zafirlukast
◼ Theophylline slow release (TSR)
 DBS
Acute asthma Chronic asthma
SABA SAMA Inhaled CS
To dilate To control
Reliever constricted Controller chronic
bronchi inflammation
1. Autonomic 1. Chronic
imbalance inflammation
Systemic CS LABA LAMA
2. Acute 2. Autonomic
inflammation To relieve imbalance To maintain
acute dilatation of
inflammation bronchi

*Controller = maintenance = preventer = prophylactic medication

Part 1 - summary
◼ Asthma old concept: bronchospasm, new concept: airway chronic inflammation,
causing AHR
◼ Bronchospasm due to autonomic nerve system imbalance; decrease sympathetic
(adrenergic) tonus, &/ increase parasympathetic (cholinergic) tonus
◼ Asthma, a chronic disease (chronic asthma inflammation) with acute exacerbation
(acute asthma inflammation)
◼ Medication: reliever to relieve acute asthma symptom, and controller to control
chronic asthma inflammation
◼ Reliever (pereda): SABA as the fast bronchodilator & systemic CS as the anti acute
inflammation
◼ Controller (pengendali): inhaled CS to control chronic inflammation & LABA to
maintain long bronchodilatation
◼ Most of asthma medication (reliever & controller) are in aerosol form, topical
delivery, best delivered by inhalation therapy, with many advantages
Chronic asthma treatment
the role of controller

Part 2

Why should be controlled?

Treat asthma using reliever only
symptom

pathophys

pathology
Ongoing pathology
adaptive
response

Insult
 Reliever VS Controller on mortality
▪ Most of patient increase SABA rather than using controller
when their asthma get worse1
▪ Regular or overuse SABA cause down-regulation and decrease
response of beta-receptor which will increase more SABA usage

2.5
250
Asthma Mortality/10,000 patient-year

Rate ratio of asthma mortality

2.0
200 SABA related
asthma mortality 1.5
ICS related
150
asthma mortality
1.0
100

50 0.5

0.0 0.0
0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 8 9 10 11 12

Canister (20,000 μg) SABA/month1 Canister ICS/year2

SABA, short-acting β2-agonist. ICS, inhaled corticosteroid;

1. Suissa S, et al. A Cohort Analysis of Excess Mortality in Asthma and the Use of Inhaled ~-Agonists. Am J Respir Crit Care Med
1994; 149:604–10
2. Suissa S, et al. Low-dose inhaled corticosteroid and the prevention of death from asthma. New Engl J Med 2000; 343:332–6;
Reliever only, facing patient to danger
Use of SABA puts patients at risk because:
o SABA’s do NOT address the underlying inflammation1,3
o SABA do not protect against future attacks1
o SABA use is an indicator of risk:
▪ ≥3 SABA canister/year associated with 2x likelihood of
hospitalization2,3*

Reliever alone is not enough!

1. Humbert M, Andersson TLG, Buhl R, et al. Allergy 2008;63:1567–1580.

2. Schatz M, Zeiger RS, Vollmer WM, et al. J Allergy Clin Immunol 2006;117:995–1000.
3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019.
Available at: http://www.ginasthma.org/
Controller drug DBS

attack

symptom

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

inflammation
Goals of chronic asthma treatment

Normal daily life good control of 1. Symptom

activity symptoms control

Minimize risk of
Minimize 2. Risk
exacerbation &
medication side
fixed airway Reduction
effect
limitation

Pediatrics. 2017;139(1):e20163438 GINA 2021

Pediatric specific treatment goals PNAA 2016

No
Normal
symptoms
daily life
day or
activity
night

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

Optimal growth and development

When to initiate controllers? PNAA 2016

Asthma differential diagnosis is ruled out

Non pharmacological 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)
Earlier is better
8
7

Increase in % predicted FEV1

6
5
4
3
2
1
0
<2 yr 2-3 yr 3-5 yr >5 yr
Years from diagnosis to start of ICS

Agertoft L, Pedersen S. Respir Med 1994;88:373-381

Chronic asthma treatment steps PNAA 2016

Define chronic asthma severity (frequency) classification

Start long-term treatment according to chronic 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
Steps in chronic asthma treatment PNAA 2016

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)
Uncontrolled, despite 2-3 mo treatments
◼ Incorrect diagnosis

◼ Persistent exposures to insults

◼ Comorbidities, not recognized &/ or not well treated

◼ Incorrect inhaler techniques

◼ Poor adherence

GINA 2021
 Corticosteroids – the main drug of asthma

Glucocorticoid receptors
are widely distributed
in the airways and are
expressed on inflammatory
and structural cells.

Reduce the
inflammatory
ICS cells in asthmatic
airways
Proc Am Thorac Soc Vol 1. pp 345–351, 2004
DOI: 10.1513/pats.200409-045MS
Inhaled CS role
◼ ICS is designed & developed as ‘controller’

◼ Steroid as reliever – systemic administration (oral OR injection)

◼ ICS is the backbone of chronic asthma controller medication

Inhaled CS efficacy
◼ 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 higher dose of ICS to

control asthma and prevent attacks after exercise

GINA. Global strategy for asthma management and prevention 2020. 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.
ICS + LABAs improve asthma control

ICS LABAs
receptors

Inflammation Effect structural

changes Bronchoconstriction
Mucus glands
Mucus secretion
Cytokines Endothelial cells Mast cell
Plasma leak Cytokine release
Endothelial cells
Plasma leak

Sensory nerve
activation

1. Barnes P. Pharmaceuticals 2010; 3:514-540; 2. Barnes P. Eur Respir J 2002;19:182–191 53

ICS-LABA combination therapy
Improves Offers
adherence1,2 Convenience1,2

Achieves asthma
Control at lower
Dose of ICS2 Improves
asthma control2

Cost effective2 Exacerbations1

Hospitalisations1

ICS = inhaled corticosteroid; LABA – Long acting beta-agonist

1. Storrar W & Chauhan AJ. Prescribing in Practice April 2015;29-33; 2. Barnes P. Eur Respir J 2002;19:182– 54

191; 3. Berger W. Therapeutics and Clinical Risk Management 2008:4(2):363–379

Treatment with SFC vs. twice the dose of FP
◼ Both treatments increased morning peak expiratory flow (PEF) over 12
weeks but the change from baseline was greater with SFC compared with FP
(p=0.012)
19,3
FP
(n=153)

Δ 7.6 L/min
(95% CI 1.7, 13.5);
p=0.012

SFC 26,9
(n=150)

0 10 20 30 40
Adjusted mean (±SE) change from
Baseline In morning PEF (L/min)
This double-blind, parallel group, non-inferiority study compared lung function and asthma control, in children (4-11 years) receiving either
salmeterol/fluticasone propionate (SFC) 50/100 μg bd (n = 150) or fluticasone propionate (FP) 200 μg bd (n = 153) for 12 wks. PEF=peak
expiratory flow; . ICS = Inhaled corticosteroids

55
The same results were first published in de Blic J et al. Pediatr. Allergy Immunol. 2009; 20:763-771. This graph has been independently
created by GSK from the original.
Treatment with SFC vs. twice the dose of FP
% Asthma patients “well controlled” in 7 % Asthma patients “totally controlled” in
of 8 weeks assessed during Week 5-12 7 of 8 weeks assessed during Week 5-12

OR 1.16 (95% CI, 0.7 to 1.9; p=0.535)

50 50
43%
40%
40 40

% of patients
% of patients

OR 1.31(95% CI, 0.7 to 2.4; p=0.389)

30 30

19%
20 20
15%

10 10

0 0
SFC FP SFC FP
(n=150) (n=153) (n=150) (n=153)

This double-blind, parallel group, non-inferiority study compared lung function and asthma control, in children (4-11 years) receiving either salmeterol/fluticasone
propionate (SFC) 50/100 μg bd (n = 150) or fluticasone propionate (FP) 200 μg bd (n = 153) for 12 wks. PEF=peak expiratory flow; . ICS = Inhaled corticosteroids;

56
The same results were first published in de Blic J et al. Pediatr. Allergy Immunol. 2009; 20:763-771.
Inhaled CS safety
• 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.
 Respiratory Medicine (1994) 88, 373-38 1

Before time 0 no children received any ICS. At time 0 one group (216 children= ●)
started continuous treatment with inhaled budesonide. The other group (62
children= ■ ) continued the treatment given before time 0. No significant changes
in height SDS were seen within or between the two groups.
 PLOS ONE | DOI:10.1371/journal.pone.0133428 July 20, 2015

Conclusion
Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS
users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in
the context of average adult height in England (175 cm for men and 161 cm for women), represents a
0.7% reduction compared to non-ICS users.
Asthma control measurement
symptom
SUBJECTIVE MEASURES
(1) detailed history taking,
(2) use of composite asthma control scores, and pathophys
(3) measurement of quality-of-life (in research settings).

pathology
OBJECTIVE MEASURES
(1) assessment of respiratory function, adaptive
(2) evaluation of airway hyperresponsiveness, and response
(3) measurement of biomarkers.

Pediatrics. 2017;139(1):e20163438
Insult
Asthma control assessment – SUBJ no 1
Asthma Symptom Control Level of Asthma Control
In the past 4 weeks, has the patient had:
▪ Daytime asthma symptoms
□ Yes □ No Not
>2x/week Well Partly
controlled controlled controlled
▪ Any night waking due to
□ Yes □ No
asthma?
▪ SABA reliever for symptoms
>2x/week?*
□ Yes □ No None of 1-2 of 3-4 of
these these these
▪ Any activity limitation due to
□ Yes □ No
asthma?

* Based on SABA reliever. Excludes reliever taken before exercise

GINA. Global Strategy for Asthma Management and Prevention, 2020. Available from:
www.ginashtma.org
Assessment of asthma control varies with age
GINA recommendations for assessment of asthma
control vary with age

Children aged Children aged 6–11 years

≤5 years and adolescents

0 1 2 3 4 5 6 7 8 9 10 11 12 years Adolescent

Asthma symptom c-ACT in children ACT in children

control tests can aged 4–11 years aged ≥12 years
be useful

ACT, Asthma Control Test; c-ACT, Children’s Asthma Control Test; GINA, Global Initiative for Asthma

62
Global Initiative for Asthma. Global strategy for asthma management and prevention. 2018. Available from: https://www.ginasthma.org.
Asthma control
assessment –
SUBJ no 2
c-ACT: assessing asthma control in children aged 4–11 years
Questions completed by the child
1. How is your asthma today?
SCORE

0 1 2 3
Very bad Bad Good Very good
2. How much of a problem is your asthma when you run, exercise or play sports?

0 1 2 3
It’s a big problem, I can’t do what It’s a problem and It’s a little problem It’s not a problem
I want to do. I don’t like it. but it’s ok.
3. Do you cough because of your asthma?

0 1 2 3
Yes, all of the time. Yes, most of the time. Yes, some of the time. No, none of the time
4. Do you wake up during the night because of your asthma?

0 1 2 3
Yes, all of the time. Yes, most of the time. Yes, some of the time. No, none of the time

64
Liu AH et al. J Allergy Clin Immunol. 2007;119:817–825.
c-ACT: assessing asthma control in children aged 4–11 years
Questions completed by the care-giver

5. During the last 4 weeks, how many days did your child have any daytime asthma symptoms? SCORE

5 4 3 2 1 0
Not at all 1–3 days 4–10 days 11–18 days 19–24 days Every day

6. During the last 4 weeks, how many days did your child wheeze during the day because of asthma?

5 4 3 2 1 0
Not at all 1–3 days 4–10 days 11–18 days 19–24 days Every day

7. During the last 4 weeks, how many days did your child wake up during the night because of asthma?

5 4 3 2 1 0
Not at all 1–3 days 4–10 days 11–18 days 19–24 days Every day

A score of 19 means the child’s asthma may be uncontrolled

Liu AH et al. J Allergy Clin Immunol. 2007;119:817–825. 65

Chronic asthma management cycle
▪ Symptoms
▪ Exacerbations
▪ Side effects
▪ Lung function
▪ Patient (& parents)
satisfaction
▪ Confirmation of diagnosis if necessary
▪ Symptom control & modifiable risk factors
(incl lung function)
▪ Comorbidities
▪ Inhaler technique & adherence
▪ Patient (& parents) goals

▪ Treatment of modifiable risk

When should be reviewed?
▪ 1st time after controller
started: 2 – 4 weeks
▪ Then every 1-3 months
▪ Then every 3-12 months
▪ After an exacerbation:
within 1 week
factors and comorbidities
▪ Non-pharmacological strategies
▪ Education & skill training
▪ Asthma medications
GINA. Global Strategy for Asthma Management and Prevention, 2020.
Available from: www.ginashtma.org
 Global Initiative for Asthma (GINA)
What’s new in GINA 2019?

GINA Global Strategy for Asthma

Management and Prevention
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© Global Initiative for Asthma

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
o 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
o This is a population-level risk reduction strategy, e.g. statins, anti-
hypertensives
GINA 2019 – landmark changes
Box 3-5B Confirmation of diagnosis if necessary

Children 6-11 years Symptom control & modifiable

risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Child and parent goals
Personalized asthma management:
Assess, Adjust, Review response

Symptoms
Exacerbations
Side-effects
Lung function
Treatment of modifiable risk factors
Child and parent
& comorbidities STEP 5
satisfaction
Non-pharmacological strategies
Refer for
Education & skills training
Asthma medication options: phenotypic
Asthma medications STEP 4 assessment
Adjust treatment up and down for
± add-on
individual child’s needs STEP 3 Medium dose therapy,
STEP 2 ICS-LABA e.g. anti-IgE
Low dose Refer for
PREFERRED STEP 1
CONTROLLER Daily low dose inhaled corticosteroid (ICS) ICS-LABA, or expert advice
to prevent exacerbations (see table of ICS dose ranges for children) medium dose
and control symptoms ICS

Other Low dose ICS Leukotriene receptor antagonist (LTRA), or Low dose High dose ICS- Add-on anti-IL5,
controller options taken whenever low dose ICS taken whenever SABA taken* ICS+LTRA LABA, or add- or add-on low
SABA taken*; or on tiotropium, dose OCS,
daily low dose ICS or add-on LTRA but consider
side-effects
RELIEVER As-needed short-acting β2 -agonist (SABA)

* Off-label; separate ICS and SABA inhalers; only one study in children
Can we cure it? DBS
Part 2 - summary
◼ Asthma can not be treated using reliever (SABA) only
◼ Underlying chronic inflammation should be targeted using inhaled CS
◼ Cortico-steroid will up-regulate (increase) β-agonist receptor
◼ Two main target of chronic asthma treatment are symptom control &
risk reduction
◼ Control of asthma is the goal of asthma treatment, and should be
assessed regularly, to adjust the treatment, and review the response
◼ Inhaled CS is the most potent controller
◼ Earlier is better, to start the controller
◼ Growth is not or minimally affected by long-term ICS
◼ Asthma can not be cured but can be controlled