Depart.

of Internal Med/Pulmonogy
Univ./UII

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Hematopoietic stem cells give rise to two major progenitor cell lineages, myeloid and lymphoid progenitors
Regenerative Medicine, 2006. http://www.dentalarticles.com/images/hematopoiesis.png
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Inflammation ASTHMA COPD

CELLS Mast cells

Neutrophils
Eosinophils CD8 T cells
CD4 T cells Macrophages++
macrophages

MEDIATORS LTD4,histamineIL- LTB4’

4,IL-5, IL-8, TNFa,
ROS +/reactie ROS+++
oxidative stress

EFFECTS All airways Periph airways

Little fibrosis Lung destruction
Ep shedding Fibrosis +
Sq metaplasia

Response steroids +++ ±

 Example of Oxygen atom

Terpapar Ozone
(mis: O3)

Atom O2 stabil dgn 8 e- Kehilangan e- diambil O3

Mengambil e- dari antioksidan

Antioksidan kelebihan 1 e-

Atom O2 stabil
R O S ; Reactive Oxidative Stresschainr
reaksi berantaighy

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 MODERN VIEW OF ASTHMA
Allergen

Macrophage Mast cell

Th2 cell Neutrophil

Eosinophil
Mucus plug
Epithelial shedding
Nerve activation

Subepithelial
fibrosis
Plasma leak
Sensory nerve
Oedema activation
Mucus Cholinergic
Vasodilatation
hypersecretion reflex
New vessels
hyperplasia Bronchoconstriction
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Hypertrophy/hyperplasia
TREATING ASTHMA

with Bronchodilators alone

is like
Painting over rust !!!
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 Traditonal view : ABC
 Modern view :CBA

 A:Aminofilin
 B:Beta 2 Agonist/Bronkodilator
 C:Cortikosteroid

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 Pencegah/Controller(Pengontrol)
 Kortikosteroid inhalasi dan sistemik
 Sodium kromoglikat
 Nedokromil sodium
 Metilsantin
 Agonis beta-2 kerja lama inhalasi dan oral
 Leukotriens modifier
 Antagonis H-1

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 ß2-Agonists
Virus?
Adenosine
Exercise
Fog BRONCHOCONSTRICTION

Mast cell Airway smooth muscle

Antigen
Macrophage Eosinophil

AIRWAY
HYPERRESPONSIVENESS
Virus?
-lymphocyte

Barnes PJ
Corticosteroids
Complementary actions of long-acting b2-agonist(LABA) and 13
corticosteroids on the pathophysiology of asthma.
2 Agonist Bronchodilator
Response
Anticholinergic

Asthma Response COPD Response

Panel B 14
Panel A
 Wall thickening
– inflammation -
- mucus gland
hypertrophy

↑ Secretions
Bronchus
Wall thickening
– inflammation
– repair
ASTMA -- remodeling
Loss of alveolar
Bronchiole attachments

Wall thinning -
inflammation -
elastolysis
PPOK Coalescence ↓
Elasticity
Alveoli 15
PATIENT HISTORY

 Has the patient had an attack or recurrent episodes of

wheezing?
 Does the patient have a troublesome cough, worse
particularly at night, or on awakening?
 Does the patient cough after physical activity (eg.
Playing)?
 Does the patient have breathing problems during a
particular season (or change of season)?

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 Do the patient’s colds ‘go to the chest’ or take
more than 10 days to resolve?
 Does the patient use any medication (e.g.
bronchodilator) when symptoms occur? Is
there a response?
If the patient answers “YES” to any of the
above questions, suspect asthma.

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 Physical Examination
Wheeze -
Usually hear without a stethoscope

Dyspnoea -
Rhonchi hear with a stethoscope
Use of accessory muscles

Remember -
Absence of symptoms at the time of examination does not
exclude the diagnosis of asthma
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Spirometry for COPD/ASTHMA Diagnosis and Classification of Severity

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 Terapi Masa Depan
Tujuan
penatalaksanaan
Asma asma :
TOTAL KONTROL

Intermiten Persisten
Tidak Terkontrol
terkontrol

LABACS Maintain

Tidak Terkontrol
terkontrol

Tingkatkan
dosis
Boushey H. Is Asthma Control Achieveable ?, European Respiratory Journal , Dec 2004 20
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 Smooth
Airway
muscle
inflammation
dysfunction
LABA CS

 Bronchoconstriction Inflammatory cell infiltration/activation 

  Bronchial hyper-reactivity Mucosal oedema  

Cellular proliferation 
 Hyperplasia
Inflammatory mediator release Epithelial damage 

Basement membrane thickening 

Symptoms/exacerbations

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 ICS “underused”utilization

ASMA
USA Eropa Asia Pasifik
12
Intermiten 18
10
11
Ringan 30
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16
Sedang 26
18
18
Berat 26
20

0 5 10 15 20 25 30 35
% responden dalam tiap kategori beratnya asma

INHALASI STEROID
Is a “drug of choice” for astma
Inflamasi “ON” : Inflamasi “OFF”:
Steroid berikatan dengan
Sel inflamasi
reseptor Kortikosteroid
Lipocortin
menghambat enzim
Enzym- Phospholipase A2 Masuk ke inti sel

Arachidonic Acid Cascade Produksi Lipocortin

Pelepasan mediator

Inflamasi saluran napas

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 Bagan Terapi Asma Saat Ini

Tingkat 4: PERSISTEN BERAT Turunkan dosis

Pengontrol Terapi harian multi obat ketika terkontrol
(Controller) •Steroid inhalasi (ICS)
•Long Acting 2 -agonist (LABA) Inhalasi 2-agonis prn
Pelega (Reliever) •Oral steroid

Menghindari faktor pencetus

Tingkat 3: PERSISTEN SEDANG
Terapi harian
•Steroid inhalasi (ICS)
Inhalasi 2-agonis prn
•Long Acting 2 -agonist (LABA) • Penyesuaian dosis
setelah 3 bulan terkontrol
Menghindari faktor pencetus • harus tetap
dimonitor/evaluasi
Tingkat 2: PERSISTEN RINGAN

Terapi harian
•Steroid inhalasi (ICS) Inhalasi 2-agonis prn

Menghindari faktor pencetus

Tingkat 1: INTERMITEN

Naikkan dosis jika

Tidak perlu Inhalasi 2-agonis prn tidak terkontrol

Menghindari faktor pencetus

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Management of Asthma
Exacerbations
 Inhaled beta2-agonist to provide prompt
relief of airflow obstruction
 Systemic corticosteroids to suppress and
reverse airway inflammation
 For moderate-to-severe exacerbations, or
 For patients who fail to respond promptly and
completely to an inhaled beta2-agonist

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Risk Factors for
Death From Asthma
 Past history of sudden severe exacerbations
 Prior intubation or admission to ICU
for asthma
 Two or more hospitalizations for asthma
in the past year
 Three or more ED visits for asthma
in the past year

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Home Management of Exacerbations:
Instructions for Incomplete
Response

 Take 2 to 4 puffs beta2-agonist every

2 to 4 hours for 24 to 48 hours PRN
 Add oral corticosteroid for 3 to 10 days, at
least until symptoms and peak flow are stable
 Contact clinician urgently (same day) for
instructions

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Home Management of Exacerbations:
Instructions for Poor Response

IMMEDIATELY
 Take up to three treatments of 4 to 6 puffs
beta2-agonist every 20 minutes PRN
 Start oral corticosteroid
 Contact clinician
 Go to emergency department or
call ambulance or 9-1-1
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Admit to Hospital Intensive
Care
• Inhaled beta2-agonist hourly or
continuously + inhaled anticholinergic
• IV corticosteroid
• Oxygen
• Possible intubation and mechanical
ventilation

• Admit to hospital ward

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 Step Up dan Step Down Therapy of
Asthma
Outcome: Asthma Control Outcome: Best
Possible Results

Controller:
 Daily inhaled
corticosteroid
Controller:  Daily long –  When
acting inhaled asthma is
Controller:  Daily inhaled β2-agonist controlled,
Controller: Daily inhaled corticosteroid reduce
 plus (if needed) therapy
None corticosteroid  Daily long-
acting inhaled -Theophylline-SR
β2-agonist -Leukotriene
 Monitor
-Long-acting inhaled
β2- agonist
-Oral corticosteroid

Reliever: Rapid-acting inhaled β2-agonist prn STEP Down

THE END 37
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