Dr.Nuryunita Nainggolan,Sp.

P
AEROSOL
Aerosol : suspensi padat atau cairan
dalam bentuk gas
Aerosol yg ada di alam : asap, kabut
dan debu
Penggunaan aerosol sebagai obat
inhalasi (aerosol terapeutik)
Alat penghantar aerosol
TERAPI INHALASI
TERAPI INHALASI:
CARA PEMBERIAN OBAT DALAM
BENTUK AEROSOL LANGSUNG KE
TARGET ORGAN DI SALURAN NAPAS




Partikel yang terbentuk(berkisar antara 100
mikron sampai 0,01 mikron) akan mencapai
saluran napas bersama proses respirasi
sesuai dengan ukuran partikel yang
terbentuk (hukum Brown)

UKURAN PARTIKEL
> 5 micron
PHARYNX, LARYNX, UPP RESP TRACT
2-5 micron
TRACHEO BRONCHIAL
< 2 micron
ALVEOLAR
DISTRIBUSI PARTIKEL
AEROSOL
DITENTUKAN OLEH BESAR
KECILNYA PARTIKEL SERTA
KONSENTRASI OBAT YANG
TERLARUT DALAM CAIRAN YANG
DISEMPROTKAN
PARTIKEL YANG<0,5 MIKRON AKAN
TEREKSHALASI SEWAKTU
EKSPIRASI
KEUNTUNGAN PEMBERIAN
OBAT SECARA INHALASI

- bekerja langsung pada saluran
napas
- onset kerja cepat
- dosis rendah
- efek samping minimum

CARA DALAM TERAPI
INHALASI :
1. MDI - METERED-DOZE INHALER
GAS TO AEROSOL (gasuap)
POWDER TO AEROSOL(tepunguap) DPI (dry
powder inhalation)
2. MDI dengan alat bantu spacer (ruang
antara)
3. NEBULIZER
LIQUID TO AEROSOL(cairanuap)
4. Inhalasi dengan tekanan positif intermitten
(IPPB)

GAMBAR SPACER/NEBUHALER
TIPE NEBULIZER

http://www.aanma.org/childcare/cc_usingnebulizer.htm
Jet
Nebuliser
Ultrasound
Nebuliser
MACAM-MACAM OBAT INHALASI
1. Bronkodilator :
- 2 agonis : terbutalin, salbutamol, fenoterol dll
- Anti kolinergik : ipratropium bromide, tiotropium
2. Mukolitik
3. Anti inflamasi : budesonide, flutikason, beklometason
dll
4. antibiotik



WHEN WE USE AEROSOL (Inhalation
therapy) IN COPD ?
Chronic Obstructive Pulmonary Disease
(GOLD, PDPI)

A preventable and treatable disease state
characterised by airflow limitation that is not
fully reversible.
The airflow limitation is usually progressive and
associated with an abnormal inflammatory
response of the lungs to noxious particles or
gases, primarily caused by cigarette smoking


Cigarette smoke
(and other irritants)
PROTEASES
Neutrophil elastase
Cathepsins
MMPs
Alveolar wall destruction
(Emphysema)
Mucus hypersecretion
CD8
+
lymphocyte
Alveolar macrophage
Epithelial
cells
Fibrosis
(Obstructive
bronchiolitis)
Fibroblast
Monocyte
Neutrophil
Chemotactic factors
Inflammatory Cells Involved in COPD
Source: Peter J. Barnes, MD
TERAPI UTAMA

BRONKODILATOR

ANTI INFLAMASI

TERAPI INHALASI
Key Indicators for Considering
a Diagnosis of COPD
Dyspnea that is Progressive (worsen over time)
Usually worse with exercise
Persistent (present every day)
Described by patients as: increased effort to
breath, heaviness, air hunger or gasping
Chronic cough May be intermittent and may be
unproductive
Chronic sputum production Any pattern of chronic sputum production
may indicate COPD
History of exposure to risk
factors, especially
Tobacco smoke
Occupational dusts and chemicals
Smoke from home cooking and heating
fuels
Rabe KF et al. GOLD 2007. Am J Respir Crit Care Med 2007;176:532-555

Spirometry is needed to establish a diagnosis of
COPD.
SYMPTOMS
Cough
Sputum production
Shortness of breath
RISK FACTORS
Tobacco
Occupational hazards
Indoor/outdoor
pollution
+
Spirometry
FEV
1
/FVC < 0.70
COPD is diagnosed based on symptoms, risk
factors and spirometry
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive
Lung Disease (GOLD) 2010. Available from www.goldcopd.org
The GOLD document
Chapter 1. Definition and overview
Chapter 2. Diagnosis &
assessment
Chapter 3. Therapeutic options
Chapter 4. Manage stable COPD
Chapter 5. Manage exacerbations
Chapter 6. COPD comorbidities
Management stable of COPD
Pharmacological
Patient First choice First alternatives Other alternatives
A SABA or SAMA prn
LABA or LAMA or
SABA and SAMA
Theophylline
B LABA or LAMA LABA and LAMA
SABA and/or SAMA
Theophylline
C
ICS + LABA or
LAMA
LABA and LAMA
PDE4-inh
SABA and/or SAMA
Theophylline

D
ICS + LABA or
LAMA
ICS & LAMA or
ICS+LABA and LAMA
or
ICS+LABA & PDE4-
inh or LABA and LAMA
or
LAMA and PDE4-inh
Carbocysteine
SABA and/or SAMA
Theophylline
Source: GOLD guideline 2011 Update

MANAGE COPD
EXACERBATION
Wedzicha, JA, Seemungal T. Lancet 2007;370:786-96.
CAUSES AND EFFECTS OF EXACERBATIONS

An exacerbation of COPD is:
an acute event characterized by a
worsening of the patients respiratory
symptoms that is beyond normal day-
to-day variations and leads to a
change in medication.
GOLD 2011
Manage Exacerbations
GOLD 2013; www.goldcopd.org

Types of exacerbation
Mild
Worse symptoms possibly requiring more reliever
Moderate
Sustained worsening of symptoms (2-3 days) eg
Cough and sputum production
Breathlessness and wheeze
Needs treatment with antibiotics and/or corticosteroids
Unscheduled hospital visit
Severe
As for moderate but requires hospitalization

More than 80% exacerbation can be
managed in outpatient.

3 Medications in exacerbation:
- Bronchodilators Short Acting
- Corticosteroids
- Antibiotics
ERS-ATS COPD Guidelines
Management of COPD
exacerbation
outpatient treatment
Patient education
Check inhalation technique
Consider use of spacer devices
Bronchodilators
Short-acting
2
-agonist and/or ipratropium MDI with spacer or hand-held nebuliser as needed
Consider adding long-acting bronchodilator if patient is not using it
Corticosteroids (the actual dose may vary)
Prednisone 3040 mg per os q day for 10 days
Consider using an inhaled corticosteroid
Antibiotics
May be initiated in patients with altered sputum characteristics
Choice should be based on local bacteria resistance patterns
Amoxicillin/ampicillin, cephalosporins
Doxycycline
Macrolides
If the patient has failed prior antibiotic therapy consider:
Amoxicillin/clavulanate
Respiratory fluoroquinolones
ERS-ATS COPD Guidelines
Management of COPD
exacerbation
Treatment for hospitalised patient
Bronchodilators
Short acting
2-
agonist (albuterol, salbutamol) and/or
Ipratropium MDI with spacer or hand-held nebuliser as needed

Supplemental oxygen (if saturation <90% )
Corticosteroids
If patient tolerates, prednisone 3040 mg per os q day for 10 days
If patient can not tolerate oral intake, equivalent dose i.v. for up to 14 days
Consider use inhaled corticosteroids by MDI or hand-held nebuliser
Antibiotics (based on local bacteria resistance patterns)
May be initiated in patients that have a change in their sputum characteristics (purulence and/or volume)
Choice should be based on local bacteria resistance patterns
Amoxicillin/clavulanate
Respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin)
If Pseudomonas spp. and/or other Enterobactereaces spp. are suspected, consider combination therapy

ERS-ATS COPD Guidelines
Management of COPD
exacerbation
Treatment in patients requiring special or intensive care unit
Supplemental oxygen
Ventilatory support
Bronchodilators
Short-acting
2-
agonist (albuterol, salbutamol) and ipratropium MDI with spacer, two puffs every 24 h
If the patient is on the ventilator, consider MDI administration, consider long-acting -agonist

Corticosteroids
If patient tolerates oral medications, prednisone 3040 mg per os q day for 10 days
If patient can not tolerate, give the equivalent dose i.v. for up 14 days
Consider use inhaled corticosteroids by MDI or hand-held nebuliser
Antibiotics (based on local bacteria resistance patterns)
Choice should be based on local bacteria resistance patterns
Amoxicillin/clavulanate
Respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin)
If Pseudomonas spp. and or other Enterobactereaces spp. are suspected consider combination therapy

BRONCHODILATORS
Short acting inhaled B2 agonis are usually
the preferred bronchodilators for treatment of
acute exacerbations of COPD (Evidence A)
Increase doses or frequency
Combine B2 agonists and anticholinergics
Use spacers or air driven nebulizers
Consider adding intravenous aminophyline ,if
needed
GLUCOCORTICOSTEROIDS
Systemic glucocorticosteroid are beneficial in
the management of acute COPD.They
shorten recovery time and help to restore
lung function more quickly (evidence A)
Oral or IV glucocorticosteroid are
recommended as an addition to
bronchodilator therapy in the hospital
management of acute exacerbation of COPD
(evidence A)
ANTIBIOTICS
Antibiotics are only effective when patients
with worsening dyspnea and cough also
have increased sputum volume and
purulence (evidence B)

SFC(salmeterol-fluticasone) reduces
breathlessness in COPD from 1 day onwards
0
0.5
1.0
1.5
2.0
2.5
Placebo
(n=181)
Salmeterol 50g bd
(n=160)
SFC 50/250g bd
(n=165)
I
m
p
r
o
v
e
m
e
n
t

i
n

b
r
e
a
t
h
l
e
s
s
n
e
s
s

s
c
o
r
e

1.7 1.2
*
* p<0.001 vs placebo and salmeterol. Differences vs placebo and
salmeterol exceed the clinically relevant difference threshold of 1
unit for this index. Patients were allowed as-needed salbutamol
and stable regimens of theophylline could be continued
Mahler Am J Respir Crit Care Med 2002
SFC improves FEV
1
in COPD
from 1 week onwards
Mahler Am J Respir Crit Care Med 2002
p<0.001 SFC, salmeterol and FP vs placebo
p=0.012 SFC vs salmeterol
p=0.038 SFC vs FP
0
Salmeterol
SFC
Placebo
FP
0 2 4 6 8 12 16 20 24
Time (weeks)
200
150
100
50
50 M
e
a
n

c
h
a
n
g
e

i
n

p
r
e
d
o
s
e

F
E
V
1

(
m
l
)

The goal of treatment in COPD
exacerbations is to minimize the
impact of the current exacerbation
and to prevent the development of
subsequent exacerbations

COPD EXACERBATION RECOVERY

-14 -7 0 7 14 21 28 35
0
1
2
3
30
35
40
45
50
Days
H
o
u
s
e
b
o
u
n
d

%

o
f

p
a
t
i
e
n
t
s

S
y
m
p
t
o
m

c
o
u
n
t

OPEN CIRCLES CLOSED CIRCLES
Donaldson GC, et al. AJRCCM 2005;171:446-52.
Significance of treatment delay
and recovery time
Prodrome
Exacerbation
Onset
Treatment Delay Treated Recovery Time
Total Recovery Time
Initiation of
Treatment
Wilkinson et al. Am J Respir Crit Care Med. 2004;169:1298-1303.
Symptom onset and early start of therapy


P<0.001
Wilkinson et al. Am J Respir Crit Care Med. 2004;169:1298-1303.
Patients who receive prompt therapy after symptom onset are likely to
recover more rapidly than are patients whose treatment is delayed
24
18
12
6
0
0 7 14
Delay between onset and treatment (day)
S
y
m
p
t
o
m

r
e
c
o
v
e
r
y

t
i
m
e

(
d
a
y
s
)

Question: Patients who have
frequent exacerbations
have......

1. Lower quality of life
2. Increased inflammation
3. Faster disease progression
4. Increased likelihood of hospitalisation
5. Increased risk of recurrent exacerbations
6. Increased mortality
7. All of the above
Frequent exacerbations drive
disease progression
Adapted from Wedzicha JA and Seemungal TA. Lancet 2007;370:786-796.;
and Donaldson GC and Wedzicha JA. Thorax 2006;61:164-168.
PATIENTS WITH
FREQUENT EXACERBATIONS
Increased risk of
recurrent exacerbations

Increased
inflammation

Lower quality of life

Increased mortality

Increased likelihood
of hospitalisation

Faster disease
progression

Health status and exacerbation frequency
0
20
40
60
80
100
Total Symptoms Activities Impacts
S
G
R
Q

s
c
o
r
e

*p < 0.001
02 exacerbations
38 exacerbations

*
*
*
*
Seemungal et al. Am J Respir Crit Care Med. 1998 ;157(5 Pt 1):1418-22
Baseline SGRQ score
Exacerbation in
following year
GOLD II GOLD III GOLD IV
None 38 51 59
1 42 53 62
2+ 54 58 63
P-value p<0.001 p<0.001 p=0.182
Hurst JR et al. N Engl J Med 2010;363:1128-1138, Supplementary appendix
Relationship between baseline GOLD stage and
SGRQ score and exacerbations in following year

Exacerbations worsen the QoL of COPD patients




Question: Exacerbations are
responsible for how much of
decline in lung function
1. 0-25%
2. 25-50%
3. 50-75%
4. > 75%
0.75
0.80
0.85
0.90
0.95
0 1 2 3 4
Years
F
E
V
1

(
l
)

Donaldson et al Thorax. 2002 ;57(10):847-52
FEV
1
decline over 4 years and
exacerbation frequency
Frequent exacerbators
Infrequent exacerbators
25% of FEV
1
DECLINE ATTRIBUTED TO EFFECT
OF EXACERBATIONS
PREVENT EXACERBATIONS
0
20
40
60
80
0 6 12 18 24 30 36 42 48
P
r
o
b
a
b
i
l
i
t
y

o
f

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

(
%
)
Tiotropium Control
14% Reduction
in Risk
Hazard ratio = 0.86,
(95% CI, 0.81-0.91)
p < 0.001 (log-rank test)
UPLIFT STUDY EFFECT ON EXACERBATIONS
Tashkin et al; NEJM; 2008; 359; 1543-1554
0.02 9% SFC vs FP
0.002 12% SFC vs salmeterol
<0.001 25% SFC vs placebo
SFC significantly reduces
exacerbations over 3 years
p-value Treatment effect
A
n
n
u
a
l
i
s
e
d

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

r
a
t
e

25% (p<0.001)
0
0.2
0.4
0.6
0.8
1.0
1.2
Placebo Salmeterol FP SFC
1.13
0.97
0.93
0.85
Calverley N Eng J Med 2007
Inhalation Therapy in COPD
Bronkhodilator

SABA- Short Acting B2 Agonist:
Terbutaline (Bricasma)
Fenoterol (Berotec)
Salbutamol (Ventolin)
Procaterol ( Meptin )
LABA - Long Acting B 2 agonist
Salmeterol
Formoterol
Indacaterol (Onbrez)


SAMA Short Acting Anti muscarinic :
Ipratropium bromide (Atrovent)
LAMA -Long acting Antimuscarinic:
Tiotropium bromide (Spiriva)

ICS/ Inhalasi Kortikosteroid
Fluticasone Propionate (Flixotide)
Budesonide :
(Pulmicort, inflammide,obucort)

Kombinasi (ICS+LABA)
Salmeterol+ Fluticasone (Seretide)
Form0terol+ Budesonide (Symbicort)

Kombinasi lain
Salbutamol + Ipratropium (combivent)



Conclusions
Detection of COPD exacerbations and
prompt management and prevention are
important in improving health status and
reducing hospital admissions
Exacerbation frequency is associated with
important impacts on health and future risk
in COPD
Short acting inhaled B2 agonis are
usually the preferred bronchodilators for
treatment of acute exacerbations of
COPD (Evidence A)
Medications in COPD exacerbation:
- Inhlalation Bronchodilators Short Acting
- Corticosteroids
- Antibiotics



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