PENATALAKSANAAN PPOK

UPDATE

SYM/030/Okt12-Okt13/RD
Dr. Syafrizal, Sp.P
 Global Strategy for Diagnosis, Management and Prevention of COPD

Definition of COPD
 COPD, penyakit yang dapat dicegah dan
ditangani, digambarkan dengan keterbatasan
aliran udara yang persisten yang biasanya
progresif dan berhubungan dengan
peningkatan respon inflamasi kronis di
saluran napas dan di paru-paru akibat
partikel atau gas berbahaya.
 Eksaserbasi dan komorbiditas berkontribusi
kepada derajat keparahan secara
keseluruhan pada pasien secara individual
© 2013 Global Initiative for Chronic Obstructive Lung Disease
 Mekanisme yang Mendasari
Pembatasan Aliran Udara pada
PPOK
Penyakit pada saluran napas
kecil
Kerusakan Parenkim
 Inflamasi pada saluran napas
• Kehilangan ikatan alveolar
 Fibrosis pada saluran napas,
luminal plugs • Penurunan elastisitas recoil

 Peningkatan hambatan udara

SYM/030/Okt12-Okt13/RD
Pembatasan Aliran Udara
GOLD updated 2013
Global Strategy for Diagnosis, Management and Prevention of COPD

Faktor Risiko COPD

Gen Pertumbuhan dan
Paparan dari partikel perkembangan paru
 Asap rokok Jenis kelamin
 Debu di lingkungan kerja, Usia
 Polusi udara dalam Infeksi pernapasan
ruangan yang berasal dari Status sosial ekonomi
pemanasan/pembakaran Hiperreaktifitas
tanpa ventilasi udara asma/bronkus
cukup
Bronkitis kronis
 Polusi udara di luar
lingkungan
 Diagnosis of COPD

EXPOSURE TO RISK
SYMPTOMS FACTORS

shortness of breath tobacco

chronic cough occupation
sputum indoor/outdoor pollution

SPIROMETRY: Required to establish diagnosis

Global initiative for chronic Obstructive Lung Disease updated 2013

Available from : http//www,goldcopd.org. Accessed on Jan 27,2014
 Gejala pada PPOK

Gejala khas PPOK adalah sesak napas kronis

dan progresif, batuk dan produksi sputum

1. Sesak napas: Progresif, menetap dan

karakteristiknya memburuk dengan aktivitas

2. Batuk kronis: bersifat intermittent dan

terkadang tidak produktif

SYM/030/Okt12-Okt13/RD
3. Produksi sputum kronis: pasien PPOK
umumnya batuk berdahak

GOLD updated 2013

 Global Strategy for Diagnosis, Management and Prevention of COPD

Penilaian pada PPOK NEW

GOLD 2013
Menilai gejala

Menilai tingkat keterbatasan aliran udara

menggunakan spirometri

Menilai risiko eksaserbasi

SYM/030/Okt12-Okt13/RD
Menilai komorbiditas

GOLD updated 2013

 Global Strategy for Diagnosis, Management and Prevention of COPD
Penilaian pada PPOK

Menilai gejala
Gunakan COPD Assessment Test (CAT)

atau

SYM/030/Okt12-Okt13/RD
Skala sesak napas mMRC

GOLD updated 2013

 COPD Assessment Test (CAT)

X 1

X 1

X 2

X 4

X 3

X 4

SYM/030/Okt12-Okt13/RD
X 2

X 5
Scoring range 0-40 Total score 2
2 Eur Respir J 2009
Jones et al.
GOLD Updated 2013
GOLD Updated 2013

SYM/030/Okt12-Okt13/RD
 Global Strategy for Diagnosis, Management and Prevention of COPD

Penilaian pada PPOK

GOLD 2013
Menilai tingkat keterbatasan aliran udara

Gunakan spirometri untuk penilaian

keparahan penyakit, menggunakan empat
tingkat /stadium dibagi pada 80%, 50% dan

SYM/030/Okt12-Okt13/RD
30% dari nilai prediksi

GOLD updated 2013

 Global Strategy for Diagnosis,
Management and Prevention of COPD
Klasifikasi batas keparahan aliran udara
pada * PPOK
Pada pasien dengan FEV1/FVC < 0.70:

GOLD 1: Mild FEV1 > 80% prediksi

GOLD 2: Moderate 50% < FEV1 < 80% prediksi

GOLD 3: Severe 30% < FEV1 < 50% prediksi

SYM/030/Okt12-Okt13/RD
GOLD 4: Very Severe FEV1 < 30% prediksi
*Based on Post-Bronchodilator FEV1

GOLD Updated 2011

GOLD updated
 Global Strategy for Diagnosis, Management and Prevention of COPD

Penilaian pada PPOK GOLD 2013

Menilai risiko eksaserbasi berdasarkan

1. Riwayat eksaserbasi dan

2. Nilai spirometri

Merupakan indikator risiko tinggi apabila :

SYM/030/Okt12-Okt13/RD
Dua eksaserbasi atau lebih selama setahun
terakhir dan nilai FEV1 < 50% dari nilai
prediksi

GOLD updated 2011

 Peningkatan frekuensi eksaserbasi akan
meningkatkan risiko kematian pada PPOK
1.0 0 exacerbations
1–2 exacerbations
≥ 3 exacerbations
0.8
Survival probability

P < 0.0002
0.6

P < 0.0001
P = 0.069
0.4

SYM/030/Okt12-Okt13/RD
0.2

0
0 10 20 30 40 50 60
Time (months)

Soler-Cataluna JJ, et al. Thorax 2005;60:925–931.

Eksaserbasi merupakan faktor penyebab
meningkatnya angka kesakitan dan angka
kematian
Eksaserbasi pada PPOK mengakibatkan :
Penurunan fungsi paru1
Peningkatan Gejala
(sesak nafas) 2

Memburuknya status kesehatan 3

Meningkat kan risiko

SYM/030/Okt12-Okt13/RD
hospitalisasi4

4,5
Meningkatkan risiko kematian
1. Donaldson GC, et al. Thorax 2002;57:847–852; 2. Donaldson GC, et al. Eur Respir J 2003;22:931–
936;
3. Seemungal TA, et al. Am J Respir Crit Care Med 1998;157:1418–1422; 4. Groenewegen KH, et al.
Chest 2003;124:459–467; 5. Soler-Cataluna JJ, et al. Thorax 2005;60:925–931.
Classification of COPD Patients
(GOLD Classification of Airflow Limitation)

4
FEV1 < 30%
>2
predicted
(C) (D)

(Exacerbation
3

history)
Risk
30% < FEV1 <
Risk

50% predicted

2
1
50% < FEV1 <
80% predicted
(A) (B)
1 0
FEV1 > 80%
predicted

mMRC 0-1 mMRC > 2

CAT < 10 CAT > 10
Symptoms
(mMRC or CAT score))
Global initiative for chronic Obstructive Lung Disease updated 2013
Available from : http//www,goldcopd.org. Accessed on Jan 27,2014
 Global Strategy for Diagnosis, Management and Prevention of COPD
Pengelolaan Rutin PPOK: Terapi Farmakologis
(Obat-obatan di setiap kotak disebutkan dalam urutan abjad, dan karena itu tidak harus dalam urutan
pilihan.)

Patient 1st choice 2nd choice Alternative Choices

LAMA
SAMA prn or
A or LABA Theophylline
SABA prn or
SABA and SAMA

LAMA
SABA and/or SAMA
B or LAMA and LABA
Theophylline
LABA

ICS + LABA
PDE4-inh.
or
C LAMA and LABA SABA and/or SAMA

SYM/030/Okt12-Okt13/RD
LAMA
Theophylline

ICS and LAMA or

ICS + LABA
ICS + LABA and LAMA or Carbocysteine
or
D ICS+LABA and PDE4-inh. or SABA and/or SAMA
LAMA
LAMA and LABA or Theophylline
LAMA and PDE4-inh.

GOLD updated 2013

Mengapa harus

L A M A ????
 Apakah semua L A M A
sebanding manfaat dan
efek sampingnya???

72404/February 2015
Apa bukti glycopirronium
br lebih unggul dibanding
toipropium br maupun
Placebo???
Seebri® Breezhaler®
(glycopyrronium bromide)

A new once-daily LAMA

For maintenance bronchodilator treatment to relieve symptoms in
adult patients with COPD
 Most Patients Experience COPD Symptoms
in the Morning and throughout the Day
Time of day when symptoms are experienced
0.8
3.9 4.7
Night only
15.6 14.7 Mostly night but
sometimes day
Equally both night and

Patients (%)
day
Mostly day but
40.3 sometimes at night
45.3
Day only

79% of patients report

symptoms predominantly
in the morning and
throughout the day 34.4
40.3

Patient- Physician-
reported reported
Adapted from Higgins et al. 2012
*A real-world analysis of 3813 COPD patients Poster presented at COPD8
 Most Patients Experience COPD Symptoms
in the Morning and throughout the Day
Morning symptoms (physician-reported)
• 24.4% of patients experience ≥1 % of patients
symptom(s) in the morning, mainly cough Any morning symptom 24.4
and sputum (physician-reported)
Cough 24.0

Excess sputum production 16.8

Shortness of breath
when exercising 3.8

A tight feeling in the chest 3.8

Shortness of breath
3.1
when resting

Regular throat clearing 3.1

Wheezing 3.1
Shortness of breath
when exposed to trigger 0.8

Bronchospasm 0.8

Adapted from Higgins et al. 2012

*A real-world analysis of 3813 COPD patients Poster presented at COPD8
 Most COPD Patients Indicate Morning as the
Time when their symptoms are Most Severe1
Time when COPD symptoms are worse than usual
All COPD patients (N=803)
100 Severe COPD patients (n=289)
60

50 46†
Patients (%)

40 37*
34
27 28
30 25
21
20 16 17
11 9 9
10 7
4
0
Morning Midday Afternoon Evening Night No particular Difficult to
time of day say

Morning was defined as from the time respondents woke up until they were dressed, had breakfast and were ready to start the day;
midday as the time around lunch; afternoon as the time before they had dinner; evening as from the time they had dinner until they went
to bed; and night as from the time they went to bed until they woke up in the morning.
Multiple answers were possible.

*p<0.001 versus ‘midday’ , ‘afternoon’, ‘evening’, ‘night’ and ‘difficult to say’ groups; p=0.006
1Partridge et al. CMRO 2009
versus
†
Breathlessness Affects Simple Morning Routine
Activities
• Breathlessness was most strongly correlated with extent of problems
experienced with morning routine
10
Impact on morning activities (scale 1–10)*

All COPD patients (N=803)

9 8.6 Severe COPD patients (n=289)
8
6.8
7 6.7
6.2 6.1 6.1 6.0
6 5.4
5.0
5 4.7
4.4 4.5 4.4
4.3 4.2
3.8 3.8 3.8 3.8
4 3.5 3.5
3.3
3.0 3.0 3.0
3 2.7 2.6
2.4

0
Walking Putting on Making Showering/ Drying Getting Walking Washing Getting Washing Preparing Eating Going Cleaning
up/down socks/ the bed having body with dressed around the dishes out of yourself breakfast breakfast to the your
stairs shoes a bath a towel house in bed bathroom teeth
the morning

*Rated on a scale from 1 to 10, where 1 = it is not affected at all and 10 = it is greatly affected. Adapted from Partridge
Data are weighted for age and COPD severity et al. CMRO 2009
 Most Troublesome Time of the Day for
COPD Patients
Phlegm, cough, wheezing and breathlessness were the most problematic
symptoms upon waking in the morning

Cough

Patients (%)
100 Phlegm 100
Patients (%)

56.7 48.9
60 60
40 22.3 17.3
40 26.2 14.9 18.7
16.3 16.6 11.8 20
20
0 0
In the Later in In the In the
Later in In the At night At night
evening On the morning afternoon evening
On the morning afternoon
walking walking
Breathlessness

Patients (%)
100 100
Patients (%)

31.0
60 Wheezing 60 24.0 22.5 19.5
31.1 10.6
40 21.7 26.1 25.1 40
18.3
20 20
0 0
Later in In the In the Later in In the In the
At night At night
On the morning afternoon evening On the morning afternoon evening
walking walking

Patients who had reported experiencing symptoms in the previous 7 days were asked
during what times of the day the symptoms were most troublesome.
phlegm, n=1551; cough, n=1433; wheezing, n=1018; breathlessness, n=1769
Adapted from
Pan-European study of 2441 COPD outpatients Kessler et al. Eur Respir J. 2011
 Improvement in morning activities is a major
treatment expectation of most COPD patients
• Approximately 10% of patients require assistance with normal morning activities
and, of these patients2†
 67.5% felt worried they were a burden to other people as a result2†

• Major treatment expectations of patients are greater symptomatic relief and

mobility, faster symptomatic relief,
and improvement in morning activities1*

*n=514; a multicentre study conducted in Turkey 1Kuychu et al., Tüberküloz ve Toraks Dergisi 2011
†Pan-European study of 2441 COPD outpatients 2Kessler et al. Eur Respir J. 2011
Introduction to Seebri® Breezhaler®

• Indicated as a maintenance bronchodilator treatment to relieve

symptoms in adult patients with COPD
• A once-daily, long-term maintenance treatment; it is not
indicated as rescue therapy for the initial treatment of acute
episodes of bronchospasm
• Each capsule contains 63 μg of glycopyrronium bromide,
equivalent to 50 μg of glycopyrronium; Each delivered dose
contains 55 μg of glycopyrronium bromide, equivalent to 44 μg
of glycopyrronium
• Recommended to be administered at the same time of the
day each day

Seebri® Breezhaler® EU SmPC, 2012. Novartis Europharm Ltd.

 GLOW2: Sustained (24-hour) improvement in
lung function (Day 1)
• Improved FEV1 with Seebri® Breezhaler® were statistically superior compared
with placebo at all time points on Day 1
• Improved FEV1 from 5 minutes to 4 hours post-dose on Day 1, with statistically
significant bronchodilator efficacy versus both placebo and open-label tiotropium
1.7
Seebri Breezhaler o.d. (n=144)
1.6 Open-label tiotropium 18 µg o.d. (n=76)
Placebo (n=79)

1.5
FEV1 (L)

1.4

1.3

1.2
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Time post dose (hours)

At all time points: p<0.01, Seebri Breezhaler vs placebo
Data are from a subset of patients who underwent serial spirometry
o.d. = once-daily; FEV1 = forced expiratory volume in one second Kerwin et al. Eur Respir J. 2012
 GLOW2: Improvement in dyspnea (TDI focal
score)
• Seebri® Breezhaler® statistically • More patients achieved a clinically important
significantly improved dyspnea (TDI improvement in dyspnea versus placebo
focal score) versus placebo and was (Week 26)
comparable with open-label tiotropium
Odds ratio: 1.58 (95% CI: 1.118, 2.245); p=0.01
versus placebo
Seebri Breezhaler o.d. (N=525) 60
55.3
55.3
2 Open-label tiotropium 18 µg o.d. (N=267) 53.4
53.4
Improvement in TDI focal score

50

Patients achieving ≥1 point

44.2

improvement in TDI (%)

44.2
1.5
40
versus placebo

**
0.94
**

IMPROVEMENT
1
0.81 30
*
* 0.66 *
0.6 0.57
0.5
0.26 20

0 10

–0.5 0
Week 12 Week 26 Week 52
Seebri Breezhaler Placebo Open-label
(key secondary o.d. (N=268) tiotropium 18 μg
endpoint) (N=525) o.d.
(N=267)

*p<0.05, **p<0.01 versus placebo; Data are LSMs ± 95% CI. TDI ≥1 point = minimum clinically Adapted from Kerwin et al.
important difference; o.d. = once-daily; TDI = Transition Dyspnea Index Eur Respir J. 2012
 GLOW3: Improved exercise tolerance

• Seebri Breezhaler increased exercise endurance time by 10% on Day 1 and by 21% on Day 21 compared
with placebo
• Least squares mean (LSM) treatment difference was 43.1 seconds on Day 1 and 88.9 seconds on Day
21 (both p<0.001)

D43.1 sec (10%)*** D88.9 sec (21%)***

550
Exercise endurance time (sec)

500
Seebri Breezhaler
o.d.
450 Placebo

400

350

490.92 447.78 505.63 416.7

300
Day 1 Day 21
Crossover trial: N=108 randomized (Seebri Breezhaler/Placebo: n=55; Placebo/Seebri Breezhaler:
n=53)
***p<0.001; Treatments were taken once-daily in the morning between 8.00 AM and 1.00 PM. Beeh et al. Int J Chron
Patients were tested within one hour of dose administration. Values are LSM±SE. o.d. = once-daily; Obstruct Pulmon Dis. 2012
 GLOW3: Significantly improved exertional
dyspnea at isotime
• Modified Borg dyspnea score was statistically significantly improved with
Seebri® Breezhaler® versus placebo on Day 1 (–0.92) and Day 21 (-1.16)
7.5
D –0.92*
D –1.16*
Borg CR 10 Dyspnea Score†

7 Seebri Breezhaler
o.d.

Improvement
6.5 Placebo

5.5

6.08 6.99 5.64 6.8

5
Day 1 Day 21

Crossover trial: N=108 randomized (Seebri Breezhaler/Placebo: n=55; Placebo/Seebri Breezhaler :

n=53) Beeh et al. Int J Chron
*p<0.05; †consisting of 10 statements from no breathlessness to maximum breathlessness. Values Obstruct Pulmon Dis. 2012
 Exacerbations signal disease progression

• Exacerbations increase the rate of disease progression

as well as increase deterioration in health status and
risk of death1
• Evidence from the literature shows that each
exacerbation experience contributes to an additional
FEV1 decline of 2 to 3 ml per year2
• Prolonging time to a first exacerbation may help to
improve symptom control and decrease breathlessness3

• The most recent GOLD strategy highlights the

importance of treating exacerbations effectively and
preventing future exacerbations1

1Global strategy for diagnosis, management, and prevention of COPD. 2011

2Vestbo et al. N Eng J Med. 2011
3Kessler et al. Eur Respir J. 2011
GOLD = Global Initiative for Chronic Obstructive Lung Disease
 GLOW2: Exacerbation summary

• Seebri® Breezhaler® prolonged time to first moderate-to- severe COPD exacerbation by 34% over 52
weeks

100 Seebri Breezhaler o.d. (N=525)

Placebo (N=268)
exacerbation free (%)

90
Open-label tiotropium 18 μg o.d.
80 (N=267)
Patients

70

60

50

40
0 4 8 12 16 20 24 28 32 36 40 44 48 52
Time to first exacerbation (weeks)

Seebri Breezhaler Open-label tiotropium

o.d.
Ratios for effect of active drug vs placebo on moderate to severe exacerbations (N=525)
Time to first exacerbation, HR (95% CI) 0.66*** (0.520, 0.850)
Rate of exacerbations, RR (95% CI) 0.66** (0.496, 0.869)
Exacerbations requiring systemic corticosteroids, OR (95% CI) 0.61** (0.434, 0.870)
Exacerbations requiring antibiotics, OR (95% CI) 0.69* (0.495, 0.957)
18 µg o.d.
(N=267)
0.61** (0.456, 0.821)
0.80 (0.586, 1.105)
0.62* (0.413, 0.930)
0.65* (0.438, 0.949)

*p≤0.05; **p≤0.01; ***p=0.001

CI = confidence interval; HR = hazard ration; o.d. = once-daily; OR = odds ratio; RR = rate ratio Kerwin et al. Eur Respir J. 2012
 GLOW1: Adverse events

Seebri Breezhaler
o.d. Placebo
N=550 N=267

Patients with AEs (≥3% in any group), n (%) 317 (57.5) 174 (65.2)

COPD worsening 111 (20.2) 73 (27.3)

Nasopharyngitis 28 (5.1) 21 (7.9)

Cough 26 (4.7) 13 (4.9)

Upper respiratory tract infection 23 (4.2) 20 (7.5)

Dyspnea 18 (3.3) 10 (3.7)

Pyrexia 17 (3.1) 13 (4.9)

Upper respiratory tract infection, bacterial 17 (3.1) 12 (4.5)

Headache 14 (2.5) 10 (3.7)

AEs = adverse events; o.d. = once-daily D’Urzo et al. Respir Res. 2011
 GLOW1: Serious adverse events

Seebri Breezhaler
o.d. Placebo
N=550 N=267
Serious AE(s) or significant AE(s), n (%)
Deaths* 3 (0.5) 3 (1.1)
SAEs** 46 (8.4) 24 (9.0)
COPD worsening 9 (1.6) 11 (4.1)
Pneumonia 4 (0.7) 2 (0.7)
Upper respiratory tract infection, bacterial 3 (0.5) 2 (0.7)
Atrial fibrillation 3 (0.5) 0
Discontinuation for any AE 32 (5.8) 19 (7.1)

*Includes 1 death in the 30 day follow-up period; **Includes 1 SAE in the 30

day follow-up period after the last dose of study drug; AE = adverse event,
o.d. = once-daily; SAE = serious adverse event D’Urzo et al. Respir Res. 2011
 GLOW2: Adverse events

Seebri Breezhaler Open-label tiotropium

o.d. Placebo 18 µg o.d.
N=525 N=268 N=267
Any AE (≥5% in any group), n (%) 402 (76.6) 205 (76.5) 198 (74.2)
COPD worsening* 191 (36.4) 116 (43.3) 90 (33.7)
Upper respiratory tract infection 57 (10.9) 33 (12.3) 30 (11.2)
Nasopharyngitis 47 (9.0) 15 (5.6) 21 (7.9)
Sinusitis 28 (5.3) 14 (5.2) 10 (3.7)
Upper respiratory tract infection bacterial 28 (5.3) 28 (10.4) 21 (7.9)
Headache 25 (4.8) 14 (5.2) 12 (4.5)
Cough 21 (4.0) 13 (4.9) 12 (4.5)
Hypertension 21 (4.0) 12 (4.5) 14 (5.2)
Dyspnoea 14 (2.7) 13 (4.9) 6 (2.2)
Pneumonia 14 (2.7) 12 (4.5) 7 (2.6)
Urinary tract infection 14 (2.7) 8 (3.0) 16 (6.0)
COPD worsening* 191 (36.4) 116 (43.3) 90 (33.7)
Upper respiratory tract infection 57 (10.9) 33 (12.3) 30 (11.2)

*includes COPD exacerbation; AE = adverse event; o.d. = once-daily Kerwin et al. Eur Respir J. 2012
 GLOW2: SAEs (≥2% in any treatment group)

Seebri Breezhaler Open-label tiotropium

o.d. Placebo 18 µg o.d.
N=525 N=268 N=267
Patients with SAEs, n (%) 67 (12.76)** 43 (16.0) 41 (15.35)***
COPD* 19 (3.6) 16 (6.0) 13 (4.9)
Pneumonia 7 (1.3) 7 (2.6) 4 (1.5)
Atrial fibrillation 4 (0.8) 0 0
Dehydration 4 (0.8) 2 (0.7) 0
Syncope 3 (0.6) 1 (0.4) 0
Transient ischaemic attack 3 (0.6) 1 (0.4) 0
Bronchitis 3 (0.6) 1 (0.4) 0
Deaths, n (%) 3 (0.6)† 2 (0.7) 2 (0.7)
Discontinuation due to AE(s) 42 (8.0) 31 (11.6) 20 (7.5)
Electrocardiographic abnormalities
Total notable 23 (4.4) 16 (6.0) 14 (5.3)
QTc >500 msec 2 (0.4) 2 (0.7) 0
Increase from baseline of 30–60 ms 83 (15.8) 39 (14.6) 43 (16.2)
Increase from baseline of >60 ms 1 (0.2) 1 (0.4) 0

AEs: Adverse events; SAEs: Serious adverse events; *Includes COPD exacerbation;
**Includes 2 SAEs in the 30-day follow-up period; *** Includes 1 SAE in the 30-day follow-up period;
†includes 1 death in the 30-day follow-up period Kerwin et al. Eur Respir J. 2012
Administering
glycopyrronium
via the Breezhaler
device
 Breezhaler® is a low airflow resistance SDDPI
suitable for use by most COPD patients
• Low airflow resistance:
- Suitable for use by patients with a wide range of COPD severities, delivering a
consistent dose irrespective of disease severity and age1

• Designed to provide dose delivery feedback mechanisms:

- Hear (spinning capsule)
- Feel (lactose taste)
- See (empty capsule)

• Compact size

Video How to
Use Breezhaler

SSDPI = Single dose dry powder inhaler 1Pavkov et al. CMRO 2010
 Kesimpulan

• Cara kita menilai PPOK menurut GOLD 2013 adalah

dengan menggabungkan penilaian gejala, spirometri,
risiko eksaserbasi dan komorbiditas.
• Frekuensi eksaserbasi dan status kesehatan merupakan
indikator yang kuat dari perkembangan penyakit dan
angka kematian
• GOLD 2013 memperkenalkan beberapa pendekatan
farmakologis baru dalam mengobati PPOK stabil

SYM/030/Okt12-Okt13/RD
• GOLD 2013 mengatakan pasien PPOK dengan riwayat
eksaserbasi, pengobatan dengan menggunakan LAMA
sangat dianjurkan
IMG_0068_edit.JPG