MAINTAINING LONG TERM CONTROL FOR

SCHOLL AGE CHILDREN WITH ASTHMA

Ni Putu Siadi purniti

Departemen/KSM ilmu kesehatan anak
FK unud/Rsup sanglah Denpasar
 OUTLINE
• Introduction
• Diagnosis of asthma
• Asthma long-term management
• Review response therapy
 introduction

• Asma is a heterogeneous 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 in intensity, together with variable
expiratory airflow limitation.
• Asthma is a common, affecting 1-18% of the population in different countries
• Symptoms and airflow limitation may resolve spontaneously or in response to medication
• Asthma is usually associated with airway hyperresponsiveness to direct or indirect stimuli,
and with chronic airway inflammation. These features usually persist, even when symptoms
are absent or lung function is normal, but may normalize with treatment

GINA, 2020
 Pathophysiology OF ASTHMA
Genetic factors

Remodeling

Environment Airway Airway Airflow Asthma

factors inflammation Hyperresponsivenes Limitation symptoms
• Allergen s • Smooth muscle • Wheezing
• Airway infection contraction • Increased
• Cigarette smoke Exacerbation factors • Mucus respiratory rate
• Air pollution secretion • Dyspnea
• Allergen
• Edema
• Airway infection
• Cigarette smoke
• Air pollution
• Weather change
• Physical training
• Psychological factor PNAA,2015
Pedoman Nasional Asma Anak
 Antigen

Pathogenesi
s of Asthma
Naïve Lymphocyte T IL-12 ( - )
Th-0
Dendritic cell
IL-12 ( + ) Th-2 response
(-)

IL-3
IL-4 IL-9 IL-55
Th-1 response IL-13 IL-4 IL-3 GM-CSF

(IFNɣ, lymphotoxin, IL-2)

IgE Mast cell Basophil Eosinophil

Inflammation mediators
(histamine, prostaglandin,
Cellular immunity and leukotriene, enzyme)
neutrophilic inflammation

Bronchus hyper-responsiveness
Asthma symptoms Airway obstruction

Pedoman Nasional Asma Anak

 Trigger Remodeling
Smooth muscle hypertrophy
Collagen deposition
Basal Membrane thickening

Bronchial inflammation

Airway Mucus and cell Edema Bronchospasm

and hyper responsiveness

remodeling
debris
Normal response
Subclinical
Obstruction

Healing Healing
(Total) (partial)

Pedoman Nasional Asma Anak

Figure 1. Schematic representation of
underlying inflammation, bronchial
Symptoms
hyperresponsiveness with consequent
airflow ... and Exacerbations

Airflow
Obstruction

Bronchial
Hyperresponsiveness

Inflammation
QJM, Volume 98, Issue 3, March 2005, Pages 171–182, https://doi.org/10.1093/qjmed/hci024
The content of this slide may be subject to copyright: please see the slide notes for details.
Asthma diagnosis criteria
Symptoms
Wheezing, cough, short of breath, chest
tightness, sputum production
Confirm limitation of expiratory airflow
Respiratory tract obstruction
Reversibility test (post bronchodilator)
Variability
Provocation test
Characteristics
- Usually more than 1 respiratory symptom
- Symptoms fluctuate and vary in intensity
- Symptoms are often worse at night or on waking
- Symptoms are often triggered
Low FEV1 (< 80%)
FEV1/FVC ≤ 90%
Increase FEV 1 > 12%
Difference in daily > 13%
Decrease FEV1 > 20%, or PEFR >15%
 Cough/wheezing/shortness of

DIAGNOSTIC breath/tightness/sputum

FLOWCHART
Suspected asthma
- Chronic and recurrent
- Symptoms fluctuates and vary in intensity
- Symptoms are often worse at night and or
waking
- Symptoms are often triggered

No
Yes

Spirometry/Peak Flow Meter (PFM)

- Think of another diagnosis
Available Not available - Consider examination:
• Tuberculin test
Reverbility >12% • Chest x-ray
ß2 agonist* • Reflux check
Or
Variability >13% 3-5 days • Thorax CT-scan/ sinus CT-scan

No No

Yes Repeat spirometry examination/PFM**

Management
Yes according to diagnosis
Yes
Asthma Response (+)

No
Yes
Added systemic steroid
Note:
3-5 days
* ß2 agonist is better administered in the form on inhalation
** Lung function test is reexamined after 4 weeks from prior lung
function test No
Determine the degree
Response (+)
of disease and attack
PNAA,2015
ASSESSING A PATIENT WITH ASTHMA
SYMPTOM CONTROL
AND RISK FACTOR COMORBIDITIES TREATMENT ISSUES
- Symptom control over - Rhinitis, chronic - Record the patient
the last 4 weeks rhinosinusitis, GERD, treatment, side effect
obesity, OSA, depression
- Check using their inhaler,
- Risk factor and poor and anxiety
technique
outcomes - Comorbidities contribute
- Ask about their goals and
- Lung function to respiratory symptoms, preferences for asthma
exacerbation, poor
periodically quality of life?
treatment
- Patient written asthma
action plain?
 ASTMA SEVERITY CRITERIA

Asthma severity Description of the frequency of

asthma symptoms
Infrequent Episode symptoms <6x/year (duration ≥ 6 weeks)
Mild persistent Episode symptoms > 1x/month, <1x/week
Moderate persistent Episode symptoms > 1x/week, but not every day
Severe persistent Episode symptoms almost every day

PNAA, 2015
 LABELING OF ASTHMA PATIENTS
Frequency Current situation
Infrequent Without symptoms
Mild persistent With symptoms
Moderate persistent Mild exacerbation
Severe persistent Moderate exacerbation
Severe exacerbation
Potentially life threatening
Level of asthma control
Uncontrolled
Partly controlled
Well controlled with medication
Well controlled without
medication
PNAA, 2015
 KLASIFIKASI ASMA MENURUT UMUR
• Asma bayi-baduta (bawah 2 tahun)
• Asma balita (bawah lima tahun)
• Asma usia sekolah (5-11 tahun)
• Asma remaja (12-17 tahun)
ASTHMA MANAGEMENT

Acute asthma Chronic asthma

Asthma attack Long term
Asthma exacerbation treatment
Controlling asthma
 GENERAL PRINCIPLES OF ASTHMA
MANAGEMENT
GOALS OF ASTHMA
MANAGEMENT
Long-term of asthma
management are:
- To achieve good control of
symptoms and maintain
normal activity levels
- To minimize the risk of
asthma-related mortality,
exacerbations, persistent
airflow limitation and side-
effects
THE PATIENT-HEALTH
PROFESSIONAL PARTNERSHIP
- Effective a partnership between
the person with asthma (or the
parent/carer) and their health
care providers
- Good communication
- The patient ability to obtain,
process and understand basic
health information to make
appropriate health decisions
MAKING DECISION ABOUT
ASTHMA TREATMENT
- Is a continuous cycle of
assessment, treatment, and
review of response in both
symptom control and future
risk (exacerbation and side-
effects)
- Decisions about asthma
treatment: the preferred option
based on Evidence based
- Also take into account any
patient characteristics or
phenotype that predict the
response to treatment
GINA, 2020
Asthma Medications

Reliever • To relieve asthma symptoms - attack

drug • As needed medication
• If the symptom relieve, stoped
(pereda)

• To control asthma inflammation

Controller • Long term medication, months - years
drug • Evaluated regularly,
• Dose adjusment: maintain, increase,
(pengendali) decrease
Asthma Medications
CONTROLLER
n Inhaled corticosteroids
n Leukotriene modifiers
n Combination: inhaled
LABA + corticosteroid
n Theophylline Slow Release
n Systemic corticosteroids
n Anti-IgE
RELIEVER
§ Short acting inhaled β2-
agonists
§ Systemic corticosteroids
§ Anticholinergic
§ Theophylline short acting
§ Short-acting oral β2-
agonists
BEFORE STARTING INITIAL CONTROLLER
TREATMENT

• Record evidence for the diagnosis of asthma

• Document symptom control and risk factors
• Assess lung function, when possible
• Train the patient to use the inhaler correctly, and check their
technique
• Schedule a follow up visit
CONTROLLER TREATMENT WERE STARTED

The differential diagnosis of asthma has been ruled out

Non-medical management has been carried out (trigger avoidance)

Asthma complicating factors such as allergic rhinitis, rhinosinusitis,

or GERD have been managed

The frequency classification of asthma is persistent asthma (mild,

moderate, severe)
GINA, 2020
Jenjang dalam pengendalian asma

6-8 minggu

8-12
minggu

Keterangan gambar: SI (steroid inhalasi); LTRA (Leukotriene Receptor Antagonist); SABA (short
acting beta agonist, agonis β2 kerja pendek); LABA (long acting beta agonist, agonis β2 kerja
panjang)
PNAA, 2015
Controllers therapy steps
• Initial step in long-term management is to define asthma
1 frequency classification
• If a step in therapy has lasted for 6-8 weeks and asthma still
2 uncontrolled, then step up therapy

• If a step in therapy has lasted for 8-12 weeks and asthma is well
3 controlled, then step down

• Stage change in management must considers triggers avoidance

4 and comorbid diseases management

• At step 4, if asthma still uncontrolled, add omalizumab to therapy

5
 Inhaled corticosteroid (ICS)
• The most effective drug in asthma treatment to suppress airway
inflammation:
- by suppressing the production of chemotactic mediators and
adhesion molecules
- by inhibiting the survival of these inflammatory cells in the
airway
• Growth monitoring must be monitored
• Side effect : oral candidiasis, can be prevented by rinsing after
administration of ICS
P. J. Barnes. Inhaled corticosteroid. Pharmacayticals
2010, 3,514-40
Leukotriene receptor antagonis (LTRA

• Consists of
• Antagonis receptor cysteinyl-leukotrien 1 (CysLT1):
montelukast, pranlukast, zafirlukast à montelukast
safe for children
• Inhibitor 5-lipoksigenase: zileuton
• LTRA are less effective than ICS, particulary for
preventing exacerbations

Mark FitzFerald, M. H. R., MD (2012). "Global Strategy for Asthma Management and Prevention Update 2012." GINA.
 Phospholipid bilayer
Phospolipase A2

Figure 2. Cysteinyl leukotriene synthesis pathway

Cyclooxygenase Arachidonic acid and their effects in the airway. FLAP, 5-lipoxygenase-
5-Lipoxygenase/ FLAP
activating ...
Prostaglandin 5-HPETE
Thromboxanes 5-Lipoxygenase/
Leukotriene A4 FLAP
hydrolase
Leukotriene B4 Leukotriene A4
Leukotriene C4
Synthase

Leukotriene C4
g-Glutanyl
transpeptidase

Cysteinyl Leukotriene D4
leukotriene receptor
Dipeptidase

Leukotriene E4

• Bronchoconstriction
• Mucous Hypersecretion
• Inflammatory Cell recruitment
• Increased vascular permeability
• Proliferation of smooth airway

QJM, Volume 98, Issue 3, March 2005, Pages 171–182, https://doi.org/10.1093/qjmed/hci024

The content of this slide may be subject to copyright: please see the slide notes for details.
Long acting 𝜷𝟐 𝐀𝐆𝐎𝐍𝐈𝐒 (LABA)
• LABA always used together ICS (ICS-LABA)
• Improvements in symptoms and lung function with a reduced
risk of exacerbations
• ICS-LABA was non-inferior to the same dose of ICS alone
• Before step up always checking inhaler technique and
adherence, and treating modifiable risk factors
Bisgaard H. Budesonide/formeterol maintenance plus reliever
therapy: a new strategy in Pediatric Asthma. Chest 2006;130
 Inhaled
Figure 4. The relative effects
Corticosteroids
Inflammation ++ of leukotriene receptor
Bronchial hyperresponsiveness ++ antagonists, inhaled
Bronchodilation + (with prolonged corticosteroids and long acting
use) ...

Optimum Asthma
control

Inflammation + Inflammation 0
Bronchial hyperresponsiveness + Bronchial hyperresponsiveness +
Bronchodilation + (“airway stabilizing effect”)
Bronchodilation ++

Leukotriene Long Acting b2

receptor antagonists agonists
QJM, Volume 98, Issue 3, March 2005, Pages 171–182, https://doi.org/10.1093/qjmed/hci024
The content of this slide may be subject to copyright: please see the slide notes for details.
REVIEW RESPONSE
THERAPY
 Klasifikasi Derajat Kendali Asma
A. Penilaian Klinis (Dalam 6-8 minggu)
Terkendali dengan/tanpa
obat pengendali Terkendali sebagian
Manifestasi Klinis Tidak terkendali
(Min. satu)
(Bila semua kriteria terpenuhi)
Gejala Siang Hari Tidak pernah (< 2 kali/minggu) > 2 kali/minggu
Aktivitas Terbatas Tidak ada Ada Tiga atau lebih
kriteria terkendali
Gejala Malam Hari Tidak ada Ada sebagian*†
Pemakaian Pereda Tidak ada (< 2 kali/minggu) > 2 kali/minggu

B. Penilaian risiko perjalanan asma (risiko eksaserbasi, ketidakstabilan, penurunan fungsi paru, efek samping)

Asma yang tidak terkendali, sering eksaserbasi , pernah masuk ICU karena asma, FEV1 yang rendah, paparan
terhadap asap rokok, mendapat pengobatan dosis tinggi

Pedoman Nasional Asma Anak

Inhalation device choice
Age Short acting Steroid
b2-agonist LABA
<3 yr MDI-hc-fm MDI-hc-fm
Nebulizer Nebulizer
3-6 yr MDI-hc-mp/fm MDI-hc-mp/fm
Nebulizer Nebulizer
>6 yr MDI-hc-mp MDI-hc-mp
DPI Nebulizer
Nebulizer
hc: holding chamber; fm: face mask; mp: mouth piece 37
Controller drug
• Inhaled corticosteroid
- Budesonide (Pulmicort)
- Fluticasone (Flixotide)
- Cyclosonide
- Beclometason
• Combination ICS + LABA
- Budesonide + formeterol (Symbicort)
- Fluticasone + salmeterol ( Seretide)
• Anti-leukotriene
- montelukast (Singulair)
- Zafirlukast
TAKE HOME MASSAGE
• Asthma is a heterogenous disease, usually characterized by
chronic airway inflammation
• 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, and
may later become persistent
• The long-term goals of asthma management are to achieve good
symptom control, to minimize future risk of morbidity and
mortality and side effects of treatment
• Review response of therapy: symptoms, exacerbations, side
effects, lung function, and patient and parent satisfaction
Thank you