Farmasi UBY S2 April 2016

dr Ediyono Sp P
Sub dep Paru RSAL Dr Ramelan
 Penyakit – penyakit Pernafasan
NO Kelompok Penyakit Penyakit
1 Infeksi 1. TBC
2. Bukan TBC ( ISPA, Bronkitis, Pneumonia, Abses )

2 Allergi Asma Bronkiale

3 PPOK ( Penyakit Paru Bronkitis Kronis, Emfisema
Obstruksi kronis )

4 Peny. Pleura Pleuritis, Efusi Pleura, Pneumotoraks, mesothelioma

5 Tumor, dll 1. Asal : PRIMER, SEKUNDER

2. Pertumbuhan : JINAK, GANAS
Bronkiektasis

6 Gawat Darurat Paru Batuk darah ( Hemoptoe ), Pneumotoraks,

PPOK Akut, Status Asmatikus, Oedem Paru,
gagal Nafas
7 Penyakit Paru Kerja Pneumokoniosis
GINA = Global Initatve For Asthma
2004

2015

www.ginasthma.org
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Prevalensi Asma

 Saat ini diperkirakan 300 juta penduduk dunia menderita

asma (Hari Asma sedunia 11 Mei 2010)
 Tahun 1993 di USA : 7,1 %

 Tahun 1993 di Inggris : 12 %

 Prevalensi Global :4- 8%
 Di Indonesia prevalensi asma sekitar : 5,4%
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Definition “ Asthma “
GINA 2006

 Asthma is a chronic inflammatory disorder of the airways

in which many cells and cellular elements play a role.
 The chronic inflammation is associated with airway
hyperresponsiveness that leads to recurrent episodes of
wheezing, breathlessness, chest tightness, and coughing,
particularly at night or in the early morning.
These episodes are usually associated with widespread, but
variable, airflow obstruction within the lung that is often
reversible either spontaneously or with treatment.
 Definition of asthma

Asthma 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.

GINA 2015 © Global Initiative for Asthma

 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
Allergens

IL-
3
-13
IL-10

/ IL
/ IL
TGF-β Y

-4
IL-5 / IL-13
Ig E
4

/ IL
IL-

-5

YY
Y
Ig G Ig A Basofil Eosinofil Mast cell
Allergo Journal,S. S1-S28.September 2005
Reaksi Hipersensitivitas
 Reaksi Hipersensitivitas Tipe I
a. Sensitization/IgE Production b. Subsequent Exposure to Allergen

B cell

Plasma cell
Mast Cell

Ig E

Ig E Ig E

Ig E
 Respon inflammasi dari Mast cell

Histamin,
serotonin,b
radikinin
 Sumber Alergen dan Komposisi Alergen

Jenis Alergen Sumber Ekstrak Komposisi Alergen

Hewan Rambut, serpih, saliva, Mengandung 10-20

urine alergen
Tungau debu rumah Biakan laboratorium Mengandung 10-40
alergen
Serbuk sari Tumbuhan Mengandung 30-50
alergen, komplek
Kecoak Seluruh badan, kulit > 29 antigen
yang dilepas
Jamur Biakan Laboratorium Antigen bervariasi

Alergi Dasar ed 1 Baratawidjaja KG, Rengganis I hal 9

 Cara masuknya Allergen

Inhalasi :
Debu rumah, tepung sari,
obat nyamuk, bau-bauan dll

Oral : Kulit :
Udang, Ikan laut, telur, Obat- 2 an, zat kimia,
susu, obat dll gigitan serangga dll

Kontak langsung :
Zat-zat kimia, obat-obatan,
debu dll
Allergic diseases …
Allergy, one feature with many faces

AIRWAYS

SKIN
Gejala- gejala Alergi

Mata merah,
Gatal, berair

Bersin,
Hidung buntu

Tenggorokan gatal,
serak, batuk
 Gejala Alergi

Sering bersin
 Pengaruh
Lingkungan
(mis. pajanan
Alergen)

Genetik Inflammasi Bronkokonstriksi Batuk intermiten,

Asma ( Radang )) bervariasi mengi dan sesak

Rangsang
spesifik
(alergen) dan
nonspesifik

Hipereaktivitas
bronkus
 Mast Cell degranulation

1. Alergi 2. Non Alergi

 Mast Cell degranulation

2. Non Alergi ( mekanisme non imun )

a. Liberator Histamin : Zat yang dapat

menyebabkan pelepasan histamin :
1. opiat ( codein, morfin )
2. pelemas otot
3. polimiksin
4. tiamin
5. murbei, tomat, putih telur, lobster
 Mast Cell degranulation

2. Non Alergi ( mekanisme non imun )

b. Faktor Fisik :
1. Cahaya  urtikaria solar.
2. Dingin  urtikaria dingin
3. Gesekan / tekanan
4. Panas
5. Getaran / vibrasi
 Mast Cell degranulation

2. Non Alergi ( mekanisme non imun )

c. Latihan Jasmani :
Exercise  asetilkolin  degranulasi mast cell.
d. Psikis
e. Penghambat ensim siklooksigenase :
- Aspirin
- NSAID
- Zat warna tartrazin
- Pengawet sodium benzoat
 Bahan mediator

Histamin, PG. Pengaruh MEDIATOR pada saluran nafas

Lekotrin

Sel Goblet Hipersekresi sekret

Mukosa sal nafas Edema Mukosa

Otot Polos Kerusakan epitel

Bronkokonstriksi

Obstruksi Saluran nafas Dyspnea  wheezing

 Berbagai faktor pencetus asma
Infeksi
bakterial

Infeksi
Virus
Paparan Serangan
alergen asma
spesifik
Polusi
udara
Aktivitas
fisik
Uap
Udara dingin iritan
Hubungan antara inflamasi akut, kronik dan airway
remodelling
Airway inflammation

Inflamasi Inflamasi Airway

Akut kronik remodeling

Gejala Eksaserbasi Obstruksi

bronkokonstriksi Non spesifik Persisten aliran udara
 Manifestasi klinis asma
Airway inflammation

Acute Airway
Exacerbation
Symptoms remodeling

Bronchodilators Anti inflammatory ??

(Relievers) (Controller)
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
Faktor Risiko Asma
Figure 1-2. Factors Influencing the Development
and Expression of Asthma

 HOST FACTORS
 Genetic, e.g.,
• Genes pre-disposing to atopy
• Genes pre-disposing to airway
hyperresponsiveness
 Obesity
 Sex

 Figure 1-2. Factors Influencing the Development
and Expression of Asthma
 ENVIRONMENTAL FACTORS
 Allergens
• Indoor: Domestic mites, furred animals (dogs, cats, mice), cockroach
allergen, fungi, molds, yeasts
• Outdoor: Pollens, fungi, molds, yeasts
 Infections (predominantly viral)
 Occupational sensitizers
 Tobacco smoke
• Passive smoking
• Active smoking
 Outdoor/Indoor Air Pollution
 Diet
House Dust Mites ( Tungau )
( Dalam bahasa jawa : Tengu )

Tungau debu rumah

 Tungau debu rumah

 Termasuk spesies laba-laba

 Terdapat pada debu rumah & tempat tidur

 Penyebab utama alergi

 Tidak dapat dilihat dengan mata telanjang

 Populasi banyak di “ permukaan kasur ( kapuk ) , busa

 Makanan dari serpihan kulit manusia

Early postnatal allergen
exposure…

Pets

House dust mites

Environmental substances
= allergens (proteins…)

1. Inhalant allergens
house dust mites, pollen
pets, moulds

2. Food allergens
egg, cow’s milk, soy, wheat ( < 3 yrs)
peanuts, fish, shrimp (> 3 yrs)
Cockroaches
 Cockroaches
Many people with
asthma are allergic
to the dried
droppings and
remains of
cockroaches.
Faktor Pencetus Asma
Bahan alergen makanan
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Asthma phenotypes
1. Allergic asthma: inchildhood , family history of allergic disease
such as eczema, allergic rhinitis, or food or drug allergy.
2. Non-allergic asthma: some adults have asthma that is not
associated with allergy.
3. Late-onset asthma: asthma for the first time in adult life.
4. Asthma with fixed airflow limitation: asthma develop to airway
wall remodeling.
5. Asthma with obesity: some obese patients with asthma have
prominent respiratory symptoms.
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Diagnosis Asma Bronkiale
1. Anamnesa

2. Pemeriksaan Fisik

Tidak semua pemeriksaan perlu dilakukan bila dg pemeriksaan sudah dapat

ditegakkan diagnosa
 Diagnosis of asthma – symptoms

 Increased probability that symptoms are due to asthma if:

 More than one type of symptom (wheeze, shortness of breath,
cough, chest tightness)
 Symptoms often worse at night or in the early morning
 Symptoms vary over time and in intensity
 Symptoms are triggered by viral infections, exercise, allergen
exposure, changes in weather, laughter, irritants such as car
exhaust fumes, smoke, or strong smells

GINA 2015 © Global Initiative for Asthma

Sesak pada malam hari

Salah satu ciri asma

 Sesak pada waktu malam hari
Obstruksi Saluran Nafas pada
asma
Asma Asma

Normal Obstruksi Obstruksi

Gangguan Ventilasi

Pemeriksaan Spirometri (Faal Paru

 Pemeriksaan FAAL PARU ( Fungsi Ventilasi )

Parameter Faal Paru

Untuk Obstruksi

1. FEV 1 ( VEP 1 ) = Volume ekspirasi paksa detik pertama :

Jumlah volume udara yang bisa dikeluarkan secara paksa
dalam 1 detik pertama setelah inspirasi maksimal.

2. A P E = Arus Puncak Ekspirasi

PEFR (Peak Expiratory Flow Rate)
 Pemeriksaan FAAL PARU Spirometri

Ada Obstruksi Sal. Nafas,

Normal
Bila : FEV 1 (Volume ekspirasi paksa 1
detik pertama ) menurun < 80 % predicted
Obstruksi
 Pemeriksaan FAAL PARU Spirometri

Parameter yang diperiksa pada spirometri :

1. FEV 1 ( VEP 1 ) = Volume ekspirasi paksa detik pertama :

Jumlah volume udara yang bisa dikeluarkan secara paksa
dalam 1 detik pertama setelah inspirasi maksimal.
2. FVC ( Forced Vital Capaciti ) / KVP ( kapasitas vital paksa )

Pemeriksaan bergantung pada :

a. Kemampuan penderita
b. Kooperatif penderita
c. Pemeriksaan dilakukan 2- 3 kali, diambil nilai yang tertinggi
d. Alat yang dipakai
 Typical spirometric tracings
Volume
Normal

FEV1
Asthma
(after BD)
Normal
Asthma
(before BD) Asthma
(after BD)

Asthma
(before BD)

1 2 3 4 5 Volume
Time (seconds)
Note: Each FEV1 represents the highest of
three reproducible measurements

GINA 2015 © Global Initiative for Asthma

 Interpretasi hasil pemeriksaan FAAL PARU

Untuk menentukan derajat obstruktif dan restriktif yaitu :

Derajat Tipe Obstruksi Tipe Restriksi

( FEV 1 / predicted ) ( FVC / predicted )

Normal > 80 % > 80%

Ringan 60 % - 75 % 60 % - 80%

Sedang 40 % – 59 % 40 % - 60 %

Berat < 40% < 40%

Standar Prediksi Normal Orang Indonesia dari Pneumobile Project Indonesia.

Pemeriksaan Faal Paru A P E
( Arus Puncak Ekspirasi )
Monitoring APE
 DIAGNOSING ASTHMA ( cont’ )
Consider asthma if any of the following signs or symptoms are present.

 Reversible and variable airflow limitation–as

measured by using a spirometer
- PEF increases > 15 % - 15 to 20 minutes
after inhalation of a rapid-acting 2-agonist, or
- PEF varies > 20 % from morning measurement
upon arising to measurement 12 hours later in patients
taking a bronchodilator.
Variabilitas pada Asma
Normal Asthma
 3. Uji Faal paru

1 Penunjang diagnosis

2 Menentukan derajat penyakit ASMA

3 Evaluasi hasil pengobatan

4 Menentukan prognosis penyakit

 4. Pemeriksaan Laboratorium

Pemeriksaan laboratorium :
a. Darah :Eosinoflia ( Jumlah eosinofil meningkat )
b. Sputum : ditemukan eosinofil , kristal-2
c. Pemeriksaan Ig E spesifik
d. Tes Kulit dengan allergen ( Tes Allergi )

5. Pemeriksaan Radiologi

Pemeriksaan Foto Toraks ( Paru ) : tidak benyak bermanfaat untuk

diagnosa ASTHMA.
Foto Toraks bermanfaat untuk menyingkirkan adanya penyakit lain.
Cara mendiagnosa penyakit Alergi
Skin Prick Test
Cara pemeriksaan Tes Alergi
SKIN PRICK TEST– procedure

2
 SPT - methodology

“… gently lifting up of the skin”.

Pemeriksaan TES ALLERGI KULIT ( Skin Prick Test )

 Lengan didesinfeksi dg alkohol 70 %

 Ekstrak alergen diteteskan pada lengan
dg jarak 2 cm
 Dengan jarum no 26 ditusukan pada
tetesan alergen dan mengangkat sedikit
epidermis.
 Ditunggu selama 20 menit

 Dibaca hasilnya:

1. Negatif (-) : tidak ada indurasi

2. Positif ( + ) : Urticaria < 2 mm
3. Positif ( ++ ) : Urticaria 2 – 4 mm
4. Positif ( +++) : urticaria 4 – 6 mm
5. Positif (++++) : Urticaria > 6 mm
Pemeriksaan Tes alergi
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi derajat asma
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Treating asthma to control
symptoms and minimize risk

GINA Global Strategy for Asthma

Management and Prevention 2015
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.

© Global Initiative for Asthma

 Goals of asthma management

 The long-term goals of asthma management are

1. Symptom control: to achieve good control of symptoms and
maintain normal activity levels
2. Risk reduction: to minimize future risk of exacerbations, fixed
airflow limitation and medication side-effects
 Achieving these goals requires a partnership between patient
and their health care providers
 Ask the patient about their own goals regarding their asthma
 Good communication strategies are essential
 Consider the health care system, medication availability, cultural
and personal preferences and health literacy

GINA 2015 © Global Initiative for Asthma

 Treating to control symptoms and minimize risk

 Establish a patient-doctor partnership

 Manage asthma in a continuous cycle:
 Assess
 Adjust treatment (pharmacological and
non-pharmacological)
 Review the response
 Teach and reinforce essential skills
 Inhaler skills
 Adherence
 Guided self-management education
• Written asthma action plan
• Self-monitoring
• Regular medical review

GINA 2015 © Global Initiative for Asthma

 Assessment of asthma

GINA Global Strategy for Asthma

Management and Prevention 2015
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.

© Global Initiative for Asthma

 Assessment of asthma

1. Asthma control - two domains

 Assess symptom control over the last 4 weeks
 Assess risk factors for poor outcomes, including low lung function
2. Treatment issues
 Check inhaler technique and adherence
 Ask about side-effects
 Does the patient have a written asthma action plan?
 What are the patient’s attitudes and goals for their asthma?
3. Comorbidities
 Think of rhinosinusitis, GERD, obesity, obstructive sleep apnea,
depression, anxiety
 These may contribute to symptoms and poor quality of life

GINA 2015, Box 2-1 © Global Initiative for Asthma

 GINA assessment of symptom control

A. Symptom control
Level of asthma
Well-controlled
symptomUncontrolled
Partly controlled
control
In the past 4 weeks, has the patient had:

• Daytime asthma symptoms more

than twice a week?

Yes No
• Any night waking due to asthma?

Yes No 1-2 of 3-4 of

None of these
• Reliever needed for symptoms* these these
more than twice a week?

Yes No
• Any activity limitation due to asthma?

Yes No

*Excludes reliever taken before exercise, because many people take this routinely

This classification is the same as the GINA 2010-12

assessment of ‘current control’, except that lung function
now appears only in the assessment of risk factors

GINA 2015, Box 2-2A © Global Initiative for Asthma

 Assessment of risk factors for poor asthma
outcomes
Risk factors for exacerbations include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor adherence
• Smoking
• Obesity, pregnancy, blood eosinophilia
Risk factors for fixed airflow limitation include:
• No ICS treatment, smoking, occupational exposure, mucus
hypersecretion, blood eosinophilia
Risk factors for medication side-effects include:
• Frequent oral steroids, high dose/potent ICS, P450 inhibitors

GINA 2015, Box 2-2B (4/4) © Global Initiative for Asthma

 The control-based asthma management cycle

Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference

Symptoms
Exacerbations
Side-effects
Patient satisfaction
Lung function

Asthma medications
Non-pharmacological strategies
Treat modifiable risk factors

GINA 2015, Box 3-2 © Global Initiative for Asthma

 Choosing between controller options –
population-level decisions

based on group mean data for symptoms, exacerbations

and lung function (from RCTs, pragmatic studies and
observational data)

GINA 2015, Box 3-3 (1/2) Provided by H Reddel © Global Initiative for Asthma
 Stepwise approach to control asthma symptoms
and reduce risk
Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference

Symptoms
Exacerbations
Asthma medications
Side-effects
Non-pharmacological strategies
Patient satisfaction
Treat modifiable risk factors
Lung function

STEP 5

STEP 4

PREFERRED STEP 3 Refer for

STEP 1 STEP 2 add-on
CONTROLLER treatment
CHOICE Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Add tiotropium# Add tiotropium#

Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS
controller dose ICS Low dose theophylline* Low dose
High dose ICS Add low dose
+ LTRA OCS
options ICS+LTRA (or + theoph*)
(or + theoph*)
RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or
low dose ICS/formoterol**

• Provide guided self-management education (self-monitoring + written action plan + regular review)
REMEMBER
• Treat modifiable risk factors and comorbidities, e.g. smoking, obesity, anxiety
TO...
• Advise about non-pharmacological therapies and strategies e.g. physical activity, weight loss, avoidance of
sensitizers where appropriate
• Consider stepping up if … uncontrolled symptoms, exacerbations or risks, but check diagnosis, inhaler
technique and adherence first
• Consider stepping down if … symptoms controlled for 3 months + low risk for exacerbations.
Ceasing ICS is not advised.

GINA 2015, Box 3-5 (1/8) © Global Initiative for Asthma

 Stepwise management - pharmacotherapy

Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference

Symptoms
Exacerbations
Side-effects Asthma medications
Patient satisfaction Non-pharmacological strategies
Lung function Treat modifiable risk factors

STEP 5

STEP 4
*For children 6-11 years,
STEP 3 Refer for
PREFERRED STEP 1 STEP 2 theophylline is not
CONTROLLER add-on recommended, and preferred
CHOICE treatment Step 3 is medium dose ICS
Med/high
e.g.
ICS/LABA **For patients prescribed
Low dose anti-IgE BDP/formoterol or BUD/
Low dose ICS ICS/LABA* formoterol maintenance and
reliever therapy
Other Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium# Add
# Tiotropium by soft-mist
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS tiotropium#
+ LTRA Add low inhaler is indicated as add-on
options (or + theoph*)
(or + theoph*) dose OCS treatment for adults
(≥18 yrs) with a history of
As-needed short-acting beta2-agonist (SABA) As-needed SABA or
RELIEVER exacerbations
low dose ICS/formoterol**

GINA 2015, Box 3-5 (2/8) (upper part) © Global Initiative for Asthma
 Stepwise management – additional components

• Provide guided self-management education

REMEMBER
• Treat modifiable risk factors and comorbidities
TO...
• Advise about non-pharmacological therapies and strategies
• Consider stepping up if … uncontrolled symptoms, exacerbations or risks,
but check diagnosis, inhaler technique and adherence first
• Consider stepping down if … symptoms controlled for 3 months
+ low risk for exacerbations. Ceasing ICS is not advised.

GINA 2015, Box 3-5 (3/8) (lower part) © Global Initiative for Asthma
 Step 1 – as-needed inhaled short-acting
beta2-agonist (SABA)

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Consider low Med/high dose ICS Add tiotropium# Add

Leukotriene receptor antagonists (LTRA) tiotropium#
controller dose ICS Low dose ICS+LTRA High dose ICS
Low dose theophylline* Add low
options (or + theoph*) + LTRA
(or + theoph*) dose OCS

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol**

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
GINA 2015, Box 3-5, Step 1 (4/8) © Global Initiative for Asthma
 Step 1 – as-needed reliever inhaler

 Preferred option: as-needed inhaled short-acting beta2-

agonist (SABA)
 SABAs are highly effective for relief of asthma symptoms
 However …. there is insufficient evidence about the safety of
treating asthma with SABA alone
 This option should be reserved for patients with infrequent
symptoms (less than twice a month) of short duration, and with no
risk factors for exacerbations
 Other options
 Consider adding regular low dose inhaled corticosteroid (ICS) for
patients at risk of exacerbations

GINA 2015 © Global Initiative for Asthma

 Step 2 – low-dose controller + as-needed
inhaled SABA

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Consider low Med/high dose ICS Add tiotropium# Add

Leukotriene receptor antagonists (LTRA) tiotropium#
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS Add low
options (or + theoph*) + LTRA
(or + theoph*) dose OCS

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol**

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
GINA 2015, Box 3-5, Step 2 (5/8) © Global Initiative for Asthma
 Step 2 – Low dose controller + as-needed SABA

 Preferred option: regular low dose ICS with as-needed inhaled SABA
 Low dose ICS reduces symptoms and reduces risk of exacerbations
and asthma-related hospitalization and death
 Other options
 Leukotriene receptor antagonists (LTRA) with as-needed SABA
• Less effective than low dose ICS
• May be used for some patients with both asthma and allergic rhinitis, or if
patient will not use ICS
 Combination low dose ICS/long-acting beta2-agonist (LABA)
with as-needed SABA
• Reduces symptoms and increases lung function compared with ICS
• More expensive, and does not further reduce exacerbations
 Intermittent ICS with as-needed SABA for purely seasonal allergic
asthma with no interval symptoms
• Start ICS immediately symptoms commence, and continue for
4 weeks after pollen season ends

GINA 2015 © Global Initiative for Asthma

 Step 3 – one or two controllers + as-needed
inhaled reliever

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Consider low Med/high dose ICS Add tiotropium# Add

Leukotriene receptor antagonists (LTRA) tiotropium#
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS Add low
options (or + theoph*) + LTRA
(or + theoph*) dose OCS

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol**

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
GINA 2015, Box 3-5, Step 3 (6/8) © Global Initiative for Asthma
 Step 3 – one or two controllers + as-needed
inhaled reliever
 Before considering step-up
 Check inhaler technique and adherence, confirm diagnosis
 Adults/adolescents: preferred options are either combination low dose
ICS/LABA maintenance with as-needed SABA, OR combination low dose
ICS/formoterol maintenance and reliever regimen*
 Adding LABA reduces symptoms and exacerbations and increases FEV1, while
allowing lower dose of ICS
 In at-risk patients, maintenance and reliever regimen significantly reduces
exacerbations with similar level of symptom control and lower ICS doses
compared with other regimens
 Children 6-11 years: preferred option is medium dose ICS with
as-needed SABA
 Other options
 Adults/adolescents: Increase ICS dose or add LTRA or theophylline (less
effective than ICS/LABA)
 Children 6-11 years – add LABA (similar effect as increasing ICS)

*Approved only for low dose beclometasone/formoterol and low dose budesonide/formoterol
GINA 2015 © Global Initiative for Asthma
 Step 4 – two or more controllers + as-needed
inhaled reliever UPDATED!

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Consider low Med/high dose ICS Add tiotropium# Add

Leukotriene receptor antagonists (LTRA) tiotropium#
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS Add low
options (or + theoph*) + LTRA
(or + theoph*) dose OCS

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol**

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
GINA 2015, Box 3-5, Step 4 (7/8) © Global Initiative for Asthma
 Step 4 – two or more controllers + as-needed
inhaled reliever UPDATED!

 Before considering step-up

 Check inhaler technique and adherence
 Adults or adolescents: preferred option is combination low dose
ICS/formoterol as maintenance and reliever regimen*, OR
combination medium dose ICS/LABA with as-needed SABA
 Children 6–11 years: preferred option is to refer for expert advice
 Other options (adults or adolescents)
 Tiotropium by soft-mist inhaler may be used as add-on therapy for
adult patients (≥18 years) with a history of exacerbations
 Trial of high dose combination ICS/LABA, but little extra benefit and
increased risk of side-effects
 Increase dosing frequency (for budesonide-containing inhalers)
 Add-on LTRA or low dose theophylline

*Approved only for low dose beclometasone/formoterol and low dose budesonide/formoterol
GINA 2015 © Global Initiative for Asthma
 Step 5 – higher level care and/or add-on
treatment UPDATED!

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA anti-IgE
Low dose
Low dose ICS ICS/LABA*

Other Consider low Med/high dose ICS Add tiotropium# Add

Leukotriene receptor antagonists (LTRA) tiotropium#
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS Add low
options (or + theoph*) + LTRA
(or + theoph*) dose OCS

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol**

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.

GINA 2015, Box 3-5, Step 5 (8/8) © Global Initiative for Asthma
 Step 5 – higher level care and/or add-on
treatment UPDATED!

 Preferred option is referral for specialist investigation and

consideration of add-on treatment
 If symptoms uncontrolled or exacerbations persist despite Step 4
treatment, check inhaler technique and adherence before referring
 Add-on omalizumab (anti-IgE) is suggested for patients with
moderate or severe allergic asthma that is uncontrolled on Step 4
treatment
 Other add-on treatment options at Step 5 include:
 Tiotropium: for adults (≥18 years) with a history of exacerbations
despite Step 4 treatment; reduces exacerbations
 Sputum-guided treatment: this is available in specialized centers;
reduces exacerbations and/or corticosteroid dose
 Add-on low dose oral corticosteroids (≤7.5mg/day prednisone
equivalent): this may benefit some patients, but has significant
systemic side-effects. Assess and monitor for osteoporosis
 See Severe Asthma Guidelines (Chung et al, ERJ 2014) for more detail

GINA 2015 © Global Initiative for Asthma

 Low, medium and high dose inhaled corticosteroids
Adults and adolescents (≥12 years)
Inhaled corticosteroid Total daily dose (mcg)
Low Medium High

Beclometasone dipropionate (CFC) 200–500 >500–1000 >1000

Beclometasone dipropionate (HFA) 100–200 >200–400 >400
Budesonide (DPI) 200–400 >400–800 >800
Ciclesonide (HFA) 80–160 >160–320 >320
Fluticasone propionate (DPI or HFA) 100–250 >250–500 >500
Mometasone furoate 110–220 >220–440 >440
Triamcinolone acetonide 400–1000 >1000–2000 >2000

 This is not a table of equivalence, but of estimated clinical comparability

 Most of the clinical benefit from ICS is seen at low doses
 High doses are arbitrary, but for most ICS are those that, with prolonged use,
are associated with increased risk of systemic side-effects

GINA 2015, Box 3-6 (1/2) © Global Initiative for Asthma

 Low, medium and high dose inhaled corticosteroids
Children 6–11 years
Inhaled corticosteroid Total daily dose (mcg)
Low Medium High
Beclometasone dipropionate (CFC) 100–200 >200–400 >400
Beclometasone dipropionate (HFA) 50–100 >100–200 >200
Budesonide (DPI) 100–200 >200–400 >400
Budesonide (nebules) 250–500 >500–1000 >1000
Ciclesonide (HFA) 80 >80–160 >160
Fluticasone propionate (DPI) 100–200 >200–400 >400
Fluticasone propionate (HFA) 100–200 >200–500 >500
Mometasone furoate 110 ≥220–<440 ≥440
Triamcinolone acetonide 400–800 >800–1200 >1200

 This is not a table of equivalence, but of estimated clinical comparability

 Most of the clinical benefit from ICS is seen at low doses
 High doses are arbitrary, but for most ICS are those that, with prolonged use, are
associated with increased risk of systemic side-effects

GINA 2015, Box 3-6 (2/2) © Global Initiative for Asthma

 Penatalaksanaan Asma

Pengaruh
Lingkungan
(mis. pajanan Bronkodilator

Alergen)
Kontrol lingkungan

Genetik Inflamasi Penyempitan Batuk -batuk,

Asma ( Radang )) Saluran nafas Sesak dan mengi

Anti-inflamasi Oksigen,
Ekspektorans,
STEROID STEROID + β2 AGONIST
 Asthma
Control Test

Skor :

25 : Terkontrol penuh

20-24 : Terkontrol sebagian

≤ 19 ; Tidak terkontrol
Tujuan Penatalaksanaan Asma
 Penatalaksanaan Asma

Pengaruh
Lingkungan
(mis. pajanan Bronkodilator

Alergen)
β2- agonist
( Terbutalin, salbutamol)

Genetik Inflamasi Penyempitan Batuk -batuk,

Asma ( Radang ) Saluran nafas Sesak dan mengi

Penderita asma yg sering kambuh hanya memakai B-2 aginost ,

Bisakah terkontrol ?
 Pokok bahasan Asma Bronkiale
1. Pendahuluan.
2. Definisi Asma Bronkiale.
3. Patogenesis
4. Faktor Risiko
5. Diagnosis dan Klasifikasi
6. Penatalaksanaan Asma
7. Obat Asma
8. Kondisi Khusus
9. Pencegahan
 Obat Asma

1. Controller 2. Reliever

• Anti inflamasi untuk • Bronkodilator untuk

mengontrol penyakit & pengobatan saat
mencegah serangan serangan / mengatasi
eksaserbasi
 Component 4: Asthma Management and Prevention Program

Controller Medications

 Glucocorticosteroids ( inhaled / systemic )

 Leukotriene modifiers

 Long-acting β2-agonists ( inhaled / oral )

 Theophylline SR
 Cromones
 Anti-IgE
 Component 4: Asthma Management and Prevention Program

Reliever Medications

 Rapid-acting inhaled β2-agonists

 Systemic glucocorticosteroids

 Anticholinergics

 Theophylline

 Short-acting oral β2-agonists

 SISTEM SARAF PARA-SIMPATIS
1 OBAT ANTIKOLINERGIK
Bronkodilator
CHOLINERGICRECEPTOR
CHOLINERGIC RECEPTOR

GUANILCYCLASE Cyclic GMP

BRONKOKONSTRIKSI
GTP 5’GMP

ATP BRONKODILATASI 5’AMP

ADENYLCYCLASE Cyclic AMP FOSFODIESTERASE

BETA-ADRENERGIC
BETA ADRENERGIC RECEPTOR
RECEPTOR

3 OBAT METHYLXANTIN
2 OBAT BETA 2 AGONIS
SISTEM SARAF SIMPATIS
 Target Site Effect
Airway smooth muscle Bronchoprotection-decrease response nonspecific
stimuli
Air Mucosa Increase mucociliary clearance

Airway inflammatory cell Inhibit eosninophyl and lymphocite activation

Decrease number : mast cells, eosinophyls,
lymphocytes and neutrophils
Enhance the effect of inhaled steroid

Airway vessel Decreased vascular permeability, airway wall

edema, angiogenesis
Hanania NA, and Cazzola M. Bronchodilator: Beta-2-Agonist and Anticholinergics. Clinical Asthma. P.241-250.2008
 Lebih lama Cepat Cepat
Target organ
Efek samping Perlu bantuan
Efek samping
lebih banyak tenaga medis
sedikit
 Advantages and disadvantages seen with
Aerosol delivery of drugs
1) Doses are smaller

2) Onset of drug action is rapid

3) Drug delivery is targeted to the resp. System

4) Systemic side effect are fewer and less severe

5) Inhales drug therapy is painless

6) Portal to the body for inhaled aerosol agent

(e.g. Pain control, insulin )

 Obat asma inhaler

Steroid Anti-kolinergik Β-2 agonist

 Bagaimana menggunakan Turbuhaler®

1. Buka tutup 2. Putar bagian 3. Buang napas, 4. Tutup

turbuhaler bawah ke letakan kembali
kanan lalu kiri, mouthpiece di bibir tubuhaler
sampai bunyi dan tarik napas dengan
“klik” (hirup obat) penutupnya
 Pemberian injeksi pada asma

Injeksi subkutan Injeksi intravena

( adrenalin, terbutalin, dll ) ( Aminophyllin )
Komplikasi Asma Bronkiale

1. Status Asmatikus ( Asma berat )

2. Pneumotoraks
3. Emfisema paru ( Asma kronis )
4. Kor Pulmonale
5. Infeksi ( pneumonia )
6. Gagal Nafas
7. meninggal
Anti-IgE treatment

Omalizumab is usually
given every 2 or 4 weeks.
 Treating to Maintain Asthma Control

Stepping down treatment when asthma is controlled

 When controlled on medium- to high-

dose inhaled glucocorticosteroids: 50%
dose reduction at 3 month intervals
(Evidence B)
 When controlled on low-dose inhaled
glucocorticosteroids: switch to once-daily
dosing (Evidence A)
 Treating to Maintain Asthma Control

Stepping down treatment when asthma is controlled

 When controlled on combination inhaled
glucocorticosteroids and long-acting
inhaled β2-agonist, reduce dose of inhaled
glucocorticosteroid by 50% while
continuing the long-acting β2-agonist
(Evidence B)
 If control is maintained, reduce to low-
dose inhaled glucocorticosteroids and
stop long-acting β2-agonist (Evidence D)
 Bagaimana bila Asma telah terkontrol ?

Setelah terkontrol 3 bulan

Dosis diturunkan

Monitor
Bila tetap terkontrol 3 bulan
Dosis diturunkan lagi

Dan seterusnya

Obat pengontrol bisa dihentikan, jika asma pasien tetap terkontrol pada dosis obat terendah &
tidak ada gejala yg timbul selama 1 tahun
Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2008.
The Risk of UNCONTROLLED Asthma
Poor
quality of life

Airway Increase in ER
remodeling visits /
hospitalizations
Uncontrolled
Asthma

Increase in Increased CV
cost of complications
health care
Increase risk for
asthma related
death
 IMUNOTERAPI

= Hiposensitisasi = Desensitisasi

Caranya :
• penyuntikan sejumlah kecil antigen hirup subkutan
pada penderita yang sensitif.
• Suntikan dinaikkan jumlah dan kadarnya sampai dosis
maksimal yang masih bisa di toleransi penderita
• Biasanya dilakukan pada : Asma alergi / pilek alergi
• Penyuntikan berlangsung : 3 – 5 tahun
 IMUNOTERAPI

IMUNOTERAPI MEMBERIKAN HASIL POSITIF BILA :

1. Dosis antigen yang diberikan makin meningkat tanpa

menimbulkan gejala klinis.
2. Gejala klinis yang timbul makin berkurang
3. Pemakaian obat – obat simptomatis berkurang
 Kontraindikasi IMUNOTERAPI

1. Penyakit dengan imunodefisiensi berat

2. Penyakit jantung koroner, Infeksi kronik
3. Ada efek samping berat selama terapi
4. Keganasan
5. Penderita yang mendapat obat beta blocker
6. Pasien tidak patuh
7. Asma berat yang tak terkontrol dengan obat-obat an
8. Anak – anak usia < 5 tahun
9. Kehamilan
 Cara pemberian IMUNOTERAPI
ALERGEN DOSIS / CC WAKTU 2 KALI / SEMINGGU
I 0,1 MINGGU PERTAMA
0,2
0,3 MINGGU KEDUA
0,4
0,5 MINGGU KETIGA
0,6
0,7 MINGGU KEEMPAT
0,8
0,9 MINGGU KELIMA
1,0
II 0,1 MINGGU KE ENAM
0,2
III 0,1 MINGGU KE TUJUH
0,2
DST
Alergen I : 1/10.000 ekstrak debu rumah 0,5% mg%dalam larutan cocca
Alergen II : 1/1000 ekstrak debu rumah 0,5% mg% dalam larutan cocca
Alergen II : 1/1000 ekstrak debu rumah 5% mg% dalam larutan cocca
Suntikan dilakukan subkutan, sehabis suntik ditunggu 15 – 30 menit utk melihat kemungkinan ada reaksi
Efek samping IMUNOTERAPI