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Asthma and COPD

Hendarsyah Suryadinata
Divisi Respirologi dan Kritis Respirasi
Departemen Ilmu Penyakit Dalam
FK Unpad/RSUP Dr Hasan Sadikin
Bandung

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Definisi
GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Revised
2011. Available from: http://www.goldcopd.org
PPOK, suatu penyakit yang dapat dicegah
dan diobati, dikarakterisasi oleh limitasi
aliran udara persisten yang biasanya
progresif dan berhubungan dengan
peningkatan respons inflamasi kronik pada
saluran nafas dan paru terhadap partikel
atau gas beracun
Eksaserbasi dan penyakit komorbid
menambah berat penyakit pasien
REVISED 2011
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Perbandingan Anamnesis Asma dan PPOK
Asma PPOK
Onset Awal sering pada anak Usia pertengahan
Gejala
Bervariasi dari hari ke
hari; pada malam /
menjelang pagi
Progresif lambat
Riwayat Familial Lamanya merokok
Disertai Atopi, rinitis, eksim Sesak saat aktivitas
Reversibilitas
obstruksi
Reversible Irreversible
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Chronic Respiratory Disease is a Leading Cause
of Chronic Disease Deaths Worldwide
Adapted from: World Health Organization. Preventing chronic diseases: a vital investment. (2005) Available at:
http://www.who.int/chp/chronic_disease_report/contents/en/index.html (accessed June 2009).
LOGO
By 2020, COPD is projected to be the third leading
cause of chronic disease mortality worldwide
1
Diarrhoeal
Disease
1990
Perinatal Disorders Ischaemic heart
disease
Cerebrovascular
disease
Lower
Respiratory
Infections
COPD
Lower
respiratory
infections
COPD


Trachea,
bronchus and
lung cancers
Road traffic
accidents
2020
1. Murray CJL et al. Lancet 1997; 349:1498-1504
Bars are used to illustrate chronic disease ranking only and do not
represent actual values
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Penyakit Respirasi Tidak Menular:
Perkiraan Total Kematian di Indonesia pada 2008
Chart Title
COPD
Asthma
Cancer
http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html accessed on Apr 17th 2012
26.6%
62.4%
11%
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ASTHMA and COPD:
INFLAMMATORY GENE EXPRESSION

Acute and chronic inflammation of airways

Expression of many inflammatory proteins
-cytokines, enzymes, adhesion molecules, receptors

Inflammatory gene transcription






Corticosteroids inflammatory gene transcription
- and control asthma in most patients
- do not control inflammation in COPD
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Inflammatory mediators in
COPD Summary
Cell
Neutrophils
Macrophages
T-cell
Epithelial cell
IL-8, TGF- 1, IP-10, Mig, I-TAC, LTB4,
GRO- , MCP-1, MMP-9
Granzyme B, perforins, IFN-, TNF-
IL-8, IL-6, TGF-1 TGF-, IP-10, Mig, I-TAC,
LTB
4
, GRO-, MCP-1, ROS, MMP-9
Serine proteases, TNF-, ROS, IL-8, MPO, LTB
4

Selected Mediators
Barnes PJ, et al. Eur Respir J. 2003;22:672-888.
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Mast cell
CD4+ cell
(Th2)
Eosinophil
Allergens
Ep cells
ASTHMA
Bronchoconstriction
Airway hyperresponsiveness
Alv macrophage Ep cells
CD8+ cell
(Tc1)
Neutrophil
Cigarette smoke
COPD
Small airway fibrosis
Alveolar destruction
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LOGO
Symptoms Variable Persistent
Wheeze SOB on exertion
ASTHMA COPD
Onset Usually childhood Usually >45yr
Course Variable, remissions Progressive
rarely progressive
Smoking Sometimes Usually

Resp to steroids Good Poor
ASTHMA vs COPD: CLINICAL DIFFERENCES
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COPD IS NOT ASTHMA !
Asthma and COPD are:
Both common
Both increasing globally
Both involve chronic inflammation of respiratory tract
Both characterised by acute exacerbations
Both result in airflow limitation

Different causes

Different inflammatory cells

Different mediators

Different inflammatory consequences

Different sites




Different response to treatment
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COPD AND ASTHMA
COPD
Neutrophils
Macrophages
CD8
+
cells
Minimal AHR
No atopy
No steroid
response
ASTHMA
Eosinophils
Mast cells
CD4
+
cells
AHR
Atopy
Steroid
response
Wheezy
bronchitis
~10%
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AIRWAY OBSTRUCTION IN ASTHMA AND COPD
ASTHMA

Bronchoconstriction
(multiple b/c mediators)
Mast cell activation

Oedema
(acute exacerbations)

Mucus plugging
(fatal asthma)

Structural changes
(irreversible)

COPD

Small airway fibrosis
(2
0
to inflammation)

Emphysema
(loss of alveolar attachments)

Mucous exudate

Oedema
(acute exacerbations)

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100
75
50
25
0
25 50 75
Age (years)
Normal
Asthma
ASTHMA
LUNG FUNCTION: NATURAL HISTORY
100
75
50
25
0
25 50 75
Age (years)
COPD
Death
Disability
Normal
COPD
Severe asthma
Symptoms
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Chronic Obstructive Pulmonary Disease
a slowly progressive disease - characterized by a gradual loss
of lung function
chronic bronchitis, chronic obstructive bronchitis, or
emphysema, combinations
n Chronic bronchitis
Inflammation of the bronchi, which
results in excess mucous, a
reduction of airflow and shortness
of breath
n Emphysema
A respiratory disease characterized by
breathlessness brought on by the
enlargement, or over-inflation of alveoli in
the lungs
LOGO
ASTHMA AND COPD
Macrophages

Neutrophils

Tc1 cells
Mast cells

Eosinophils

Th2 cells
Airway Inflammation
ASTHMA COPD
Inflammatory gene
expression
Steroid sensitive Steroid resistant
AIRFLOW LIMITATION
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Mast cell
Inhaled allergens
Y
Y
Bronchoconstriction
Eosinophils
IL-5
CCL11, CCL24, CCL26
CCL5, CCL13
CCR3
Histamine
Cys-LTs
PGD
2
IL-9
CELLS and MEDIATORS IN ASTHMA
Th2 cell
CCL17
CCL22
CCR4
Dendritic cell
Bronchoconstriction
B-lymphocyte
Y
Y Y
IL-4, IL-13
IgE
Epithelial cells
TSLP
SCF
Epithelial cells
Barnes PJ: JCI 2008
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Cigarette smoke
(and other irritants)
Macrophage
Epithelial cells
PROTEASES
Alveolar wall destruction
(Emphysema)
Mucus hypersecretion
Neutrophil elastase
MMP-9
Fibrosis
(Small airways)
TGF-
Fibroblast
Neutrophil
CXCL1
CXCL8
Tc1 cell

Monocyte
Th1 cell
CXCR3
CXCR2
CCR2
CCL2
CXCL9
CXCL10
CXCL11
INFLAMMATION IN COPD
Barnes PJ: JCI 2008
LOGO
COPD

Eosinophils (+)
Neutrophils +++
T-lymphocytes Tc1,Th1, Th17
TNF- +++
IL-8 +++
Oxidative stress +++
Steroid response -
SEVERE
ASTHMA
+
++
Tc1,Th1,Th17
++
++
+++

MILD
ASTHMA
+++
-
Th2
-
-
+
+++
COPD vs ASTHMA
LOGO
LOGO
Mekanisme Limitasi Aliran Udara
pada PPOK (Saluran nafas perifer)
Adapted from: Barnes P. NEJM 2000; 343; 269
LOGO
Asthma death
ASTHMA AND COPD PATHOLOGY
Severe COPD
Courtesy of Jim Hogg
Fibrosis
+ +++
BM
+++ -
Alveolar
disruption
+++
-
Inflammation
+++
+++
+++
ASM + +++
LOGO
Normal
COPD
PATHOLOGY OF COPD
Peripheral lung
Dr Manuel Cosio
Bronchiole
Alveolar
wall
Loss of
attachments
EMPHYSEMA
Fibrosis
Inflammation
Chronic obstructive bronchitis
Small airway inflammation
Correlated with diseased severity
Inflammatory cell numbers
Inflammatory cell exudate in lumen
Peribronchiolar fibrosis
Hogg JC et al: NEJM 2004
LOGO
Adapted from: Hansel T/Barnes P. An Atlas of COPD. 2004

Central
nervous
system
Vagus nerve
Airway epithelium
Parasympathetic
ganglion
ACh
ACh
ACh
Inflammatory
cell mediators
Submucosal
gland Cholinergic
receptors
Irritants
(e.g. cigarette smoke, bacteria, viruses)
Airway smooth muscle
constriction
Mucus
Hypersecretion
Patofisiologi PPOK : Sistem Saraf Vagus
LOGO
Normal
Inspiration
Expiration
AIR TRAPPING IN COPD
alveolar attachments
small
airway
Inflammation
COPD
loss of alveolar attachments
loss of elasticity (emphysema)
airway closure
thickened airway
Hyperinflation: air trapping
TLC
Residual volume
FRC
Inspiratory capacity
Exertional
dyspnoea
Exercise
tolerance
BRONCHODILATORS
LAMA: tiotropium bromide, ..
LABA: salmeterol, formoterol, .
Normal
Hyperinflation
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Konsep Perjalanan Penyakit
Time (age)
Disease
Onset
S
e
v
e
r
i
t
y

Advanced
Disease
Radiographic Abnormalities
Pathological (Structural) Evidence
Biochemical and Cellular
Events
Clinical Manifestations
(Patient-Centered Outcomes)
Physiological (Functional)
Abnormalities
Induction Latenc
y
Exposure
Genetic
Predisposition
LOGO
Underdiagnosis PPOK
Terdapat persepsi bahwa pasien tidak
terdiagnosa karena pasien tidak datang berobat
ke dokter. Pada kenyataannya banyak yang
terlewatkan
1
Petty TL. J Resp Dis 1997;18:3659;
2
Mannino DM et al. MMWR Surveill Summ 2002;51:116.
1016 juta terdiagnosa
16 juta tidak terdiagnosa
versus
LOGO
Underdiagnosis dan Misdiagnosis:
Persepsi Pasien
Pasien mungkin saja
salah mengartikan atau
menganggap remeh
gejala seperti lelah,
sesak dan batuk
Sebagai akibatnya,
mereka mungkin tidak
menyampaikan gejala-
gejala ini pada
dokternya




Mannino DM and Braman S. Proc Am Thoracic Soc 2007;4:5026
Saya selalu batuk setiap
bangun pagi di pagi hari,
tapi ini hanya batuk
perokok. Hal ini normal
dan tidak berbahaya bagi
kesehatan

Saya tidak
memerlukan
pengobatan untuk
pernafasan saya
karena ini bukan hal
serius

Membawa
barang belanjaan
menjadi lebih
berat dari
biasanya.
Saya sudah
semakin tua
dengan fisik
yang melemah

LOGO
Severe COPD
Progresivitas PPOK
Mild COPD
LOGO
Penilaian PPOK
Penilaian gejala
Penilaian derajat hambatan aliran udara
menggunakan spirometri
Penilaian risiko eksaserbasi
Penilaian faktor komorbid
GOLD Updated 2013
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TREATMENT & PROGNOSIS

The approach to the treatment of asthma and
COPD is different. The essential difference is
that the treatment of asthma is driven by the need to
suppress the chronic inflammation, whereas in
COPD, treatment is driven by the need to reduce
symptoms.

The better prognosis and the better response to
corticosteroids described in patients with fixed
airflow limitation associated with asthma compared
with COPD.

LOGO
I: Mild II: Moderate III: Severe IV: Very Severe

FEV
1
80% pred

FEV
1
<80% 50%
pred

FEV
1
<50% 30%
pred

FEV
1
<30% pred
or
FEV
1
<50% pred +
chronic respiratory
failure

Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting bronchodilators
(when needed); Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
Add long-term oxygen
if chronic respiratory
failure. Consider
surgical treatments

COPD Guidelines
Treatment Progression
LOGO
Kombinasi Penilaian PPOK
R
i
s
k


(
G
O
L
D

C
l
a
s
s
i
f
i
c
a
t
i
o
n

o
f

A
i
r
f
l
o
w

L
i
m
i
t
a
t
i
o
n
)

R
i
s
k


(
E
x
a
c
e
r
b
a
t
i
o
n

h
i
s
t
o
r
y
)

> 2
1
0
(C)
(D)
(A)
(B)
mMRC 0-1
CAT < 10
4
3
2
1

mMRC > 2
CAT > 10
Symptoms
(mMRC or CAT score)
GOLD Updated 2013
LOGO



Bronkodilator merupakan dasar pengobatan PPOK dan BD kerja
panjang lebih disukai daripada yang kerja singkat (anti
kolinergik/muskarinik antagonis atau beta2 agonis)
Kortikosteroid inhalasi dapat ditambahkan pada bronkodilator kerja
panjang untuk pasien dengan risiko tinggi eksaserbasi
Monoterapi jangka panjang dengan kortikosteroid oral atau inhalasi
tidak direkomendasikan pada PPOK
Phospodiesterase-4 inhibitor roflumilast mungkin dapat bermanfaat
untuk mengurangi eksaserbasi pada pasien FEV
1
< 50% predicted,
bronkitis kronik, dan eksaserbasi sering.

Tatalaksana PPOK Stabil
GOLD Updated 2013
LOGO
1
0
mMRC 0-1
CAT < 10
4
mMRC > 2
CAT > 10
3
2
1
SAMA prn
or
SABA prn
LAMA
or
LABA
LAMA
or
ICS + LABA
A B
D C
LAMA
and/or
ICS + LABA
LAMA or
LABA or
SABA and
SAMA
LAMA and
LABA or
LAMA and
PDE4-inh. or
LABA and
PDE4-inh.
ICS + LABA +
LAMA or
ICS + LABA +
PDE4-inh or
LAMA + LABA
or
LAMA + PDE4-
inh.
LAMA and LABA
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
A B
D
C
First Choice Alternative
Choice
Tatalaksana PPOK Stabil
GOLD Updated 2013
> 2
LOGO
LAMA
or
LABA
ICS + LABA +
LAMA or
ICS + LABA +
PDE4-inh or
LAMA + LABA
or
LAMA + PDE4-
inh.
> 2
1
0
mMRC 0-1
CAT < 10
4
mMRC > 2
CAT > 10
3
2
1
SAMA prn
or
SABA prn
A B
D C
LAMA or
LABA or
SABA and
SAMA
LAMA and LABA
A B
D
C
First Choice
LAMA or
LABA or
SABA and
SAMA
LAMA and LABA
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
A B
D
C
Alternative
Choice
Tatalaksana PPOK Stabil
GOLD Updated 2013
LAMA and
LABA or
LAMA and
PDE4-inh. or
LABA and
PDE4-inh.
LAMA
or
ICS + LABA
LAMA
and/or
ICS + LABA
LOGO
Step 1 Step 2 Step 3 Step 4 Step 5
Low-dose ICS plus
sustained-release
theophyline
Sustained release
theophyline
Low-dose ICS plus
leukotriene modifier
Anti-IgE treatment Leukotriene modifier
Medium- or
high-dose ICS
Leukotriene modifier
Oral
glucocorticosteroid
(lowest dose)
Medium- or
high-dose ICS
plus long-acting

2
-agonist
Low-dose ICS
plus long-acting

2
-agonist
Low-dose inhaled
ICS
Add one or more Add one or more Select one Select one
Controller
options
As needed rapid-acting
2
-agonist
As needed rapid-
acting
2
-agonist

Asthma education
Environmental control
Asthma Guideline
In most cases, preferred controller option is an ICS/LABA combination
GINA 2010
LOGO
Konsekuensi Sistemik
co, pengecilan otot, penyakit kardiovaskular, perubahan berat badan,
depresi, osteoporosis, kematian
Perjalanan Penyakit PPOK
Udara Terperangkap
Limitasi Aliran Udara
Hiperinflasi
Kondisi Menurun Inaktivitas
Berkurangnya Kemampuan
Exercise
Eksaserbasi
PPOK
Kesulitan Bernafas
Kualitas hidup
Decramer M et al. COPD 2008;5:235-256.
LOGO
Boschetto, Respirology 2112;17;422-431.
LOGO
CONCLUSIONS
Asthma and COPD are usually different:
different inflammatory cells
different inflammatory mediators
different response to therapy
natural history
attend co-morbidity



Some similarities however:
both disorders of airways obstruction
both inflammatory

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