Chronic Obstructive Pulmonary Disease

Mulyadi
Pulmonology & Respiratory Medicine Dept.
Faculty of MedicineSyiah Kuala University
Dr. Zainoel Abidin General Hospital
Banda Aceh
 Penyakit yg ditandai :
 Hambatan aliran udara
 Tidak reversibel/reversibel parsial
 Progresif
 Respons inflamasi abnormal paru
 Partikel noxiuos atau gas

 A leading cause of morbidity & mortality worldwide

 Penyebab kematian ke 4 di USA dan Eropa
 Biaya pengobatan PPOK > asma
 Updated COPD definition includes persistent respiratory symptoms

GOLD 20161 GOLD 20172

Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease
(COPD), a common preventable and (COPD) is a common, preventable and
treatable disease, is characterized by treatable disease that is characterized
persistent airflow limitation that is usually by persistent respiratory symptoms
progressive and associated with an and airflow limitation that is due to
enhanced chronic inflammatory airway and/or alveolar abnormalities
response in the airways and the lung to usually caused by significant exposure
noxious particles or gases to noxious particles or gases

1. GOLD 2016
COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease 2. GOLD 2017
 Penyebab
Faktor risiko
Host Lingkungan

-Genetik: - Rokok sigaret

defisiensi α 1 antitripsin - Occupational dust
-Airway hyperreactivity dan chemical
- Polusi indoor,outdoor
- Infeksi sal napas
 PATHOGENESIS OF COPD
PARTICLE
NOXIOUS GASES

HOST FACTORS
ANTI OXIDANTS
[ environmental ]

LUNG INFLAMMATION

ANTI OXIDANTS ANTI PROTEINASES

[ genetic ]

OXIDATIVE STRESS PROTEINASE IMBALANCE

REPAIR REPAIR
MECHANISM MECHANISM

ANTI PROTEASE ENZYME

1-Antitrypsin
Bronchus

Bronchiole

Alveoli
Diagnosis of COPD is based
on a history of exposure to risk factors
and the presence of airflow limitation
that is not fully reversible,
with or without the presence of symptoms.
 DIAGNOSIS
OF COPD

1 2

SYMPTOMS : EXPOSURE TO RISK FACTORS :

• Cough • Tobacco Smoke
• Sputum • Occupation
• Dyspnea • Indoor / outdoor pollution

SPIROMETRY
A CXRs are seldom diagnostic, it can be useful for excluding other diseases
 Spirometry in COPD Diagnosis
0
FEV1 FVC FEV1/ FVC
Normal 4.150 5.200 80 %
1 COPD 2.350 3.900 60 %

2
FEV1
Liter

3
COPD
4 FVC
FEV1

5 Normal
FVC
1 2 3 4 5 6 Seconds
GOLD Workshop Report
Four components of COPD management

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

 Education
 Pharmacologic
 Non-pharmacologic

4. Manage exacerbations
GOLD major revisions in key areas
Key areas of major revision:
 Definition of COPD
 ABCD assessment tool
 Pharmacological management
 Focus on inhaler technique
 Management of comorbidities

COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease GOLD 2017
 GOLD 2017: Updated COPD definition includes persistent
respiratory symptoms
GOLD 20161 GOLD 20172
Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease
(COPD), a common preventable and (COPD) is a common, preventable and
treatable disease, is characterized by treatable disease that is characterized
persistent airflow limitation that is usually by persistent respiratory symptoms and
progressive and associated with an airflow limitation that is due to airway
enhanced chronic inflammatory and/or alveolar abnormalities usually
response in the airways and the lung to caused by significant exposure to
noxious particles or gases noxious particles or gases

1. GOLD 2016
COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease 2. GOLD 2017
 Pendapat tradisional - FEV1 menurun progresifsepanjang waktu

100 Tak pernah merokok atau

tidak peka terhadap rokok

FEV1 (% value of age 25)

Pendapat
75
tradisional oleh
Fletcher dan Peto:
Faal paru menurun 50 Perokok dan peka
lambat pada awal terhadap rokok
DISABILITAS
dan meningkat
25
pada stadium lanjut
KEMATIAN

0
25 50 75
Umur (tahun)

Cohort study with 792 working men, 8-year follow-up period, measurement of FEV1 every 6 months
Modified version of the Fletcher and Peto graph showing the decline in FEV1

Fletcher C, Peto R. BMJ 1977; 1: 1645–1648

Paradigma baru –percepatan faal paru menurun terutama pada stadium awal PPOK

100
GOLD 1
Pendapat terkini
oleh Tantucci:  40 mL/th
80

FEV1 (% predicted)
Pasien GOLD 2
paling tinggi  47–79 mL/th GOLD 2
penurunan FEV1 50
dibanding pada GOLD 3
 56–59 mL/th
stadium
30
akhirCOPD1,2 GOLD 4
 <35 mL/th

0
Tahun

Analysis based on randomized control arms of longitudinal studies with a follow-up period ≥3 years
Dashed lines indicate any stage or portion for which consistent information is lacking

1. Tantucci C, Modina D. Int J Chron Obstruct Pulmon Dis 2012; 7: 95–99;

2. Welte T, et al. Int J Clin Pract; 2015; 69:336–349
Eksaserbasi berat merupakan awal lingkaran setan (vicious circle) dengan
waktu pemulihan lebih pendek dan peningkatan risiko eksaserbasi lebih
berat

Hazard function of the time terhadap eksaserbasi selanjutnya untuk 10 eksaserbasi berat
setelah rawat inap karena PPOK pertamakali.
< 4 bulan Median waktu antara eksaserbasi berat
100 menurun dengan setiap eksaserbasiberat baru ①
Jumlah eksaserbasi berat seanjutnya

n= 73106; dari sekitar 4,5 tahun sejak pertama ke kedua

80 sampai < 4 bulan dari ke 9 ke 10.
per 10000 perhari

①
Risiko terjadi eksaserbasi meningkat ②
60 dan tidak dapat kembali ke risiko baseline ③.

40

5.4 tahun
20 ②+③

0
0 2 4 6 8 10 12
Waktu setelah eksaserbasi berat pertama (tahun)

Suissa et al. Thorax 2012; 67: 957-963.

GOLD : The changing role of spirometry
• Post-bronchodilator spirometry is required for the diagnosis and
assessment of COPD
• However, assessing the degree of reversibility of airflow limitation (e.g.
measuring FEV1 before and after bronchodilator or corticosteroids) to
inform therapeutic decisions is no longer recommended
• Spirometry remains key in the diagnosis, prognostication and
treatment with non-pharmacological therapies

COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second
GOLD = Global Initiative for Chronic Obstructive Lung Disease GOLD 2017
 GOLD : Symptoms and exacerbation risk should be assessed to
determine appropriate treatment
1. Diagnose COPD and determine the severity of airflow limitation (GOLD Grade 1–4) using spirometry
2. Determine GOLD Group (A–D) and subsequent appropriate pharmacological treatment by assessing
symptoms and exacerbation history (including prior hospitalizations)

Spirometrically Assessment of Assessment of symptoms/

confirmed diagnosis airflow limitation risk of exacerbations

Exacerbation
history

FEV1
Grade (% pred.) >2 or ≥1

1 ≥80
leading to C D
hospitalization
Post-bronchodilator
2 50–79
FEV1/FVC <0.7
0 or 1
3 30–49 (not leading to A B
hospital admission)
4 <30

mMRC 0–1 mMRC 2+

CAT <10 CAT 10+
CCQ <1 CCQ 1+
CAT = COPD Assessment Test; CCQ = Clinical COPD Questionnaire; COPD = chronic obstructive pulmonary disease
FEV1 = forced expiratory volume in 1 second; GOLD = Global Initiative for Chronic Obstructive Lung Disease
mMRC = modified Medical Research Council GOLD 2017
The goals of COPD treatment

• Relieve symptoms
Reduce
• Improve exercise tolerance
symptoms
• Improve health status

• Prevent disease progression

• Prevent and treat exacerbations Reduce risk
• Reduce mortality

COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease GOLD 2017
 therapeutic recommendations by GOLD Group

Group C Group D
Consider roflumilast
if FEV1 <50% pred.
LAMA + Consider
and patient has
LABA + ICS chronic bronchitis
macrolide
LABA
Further
exacerbation(s)
Further LAMA + Persistent
exacerbation(s) LABA + ICS symptoms/further
exacerbations
Further
exacerbation(s)
LAMA
LAMA LAMA + LABA LABA + ICS

Group A Group B

Continue, stop or
try alternative class LAMA + LABA
of bronchodilator

Persistent
Evaluate symptoms
effect
A long-acting bronchodilator
A bronchodilator (LABA or LAMA)

FEV1 = forced expiratory volume in 1 second; GOLD = Global Initiative for Chronic Obstructive Lung Disease
ICS = inhaled corticosteroid; LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist GOLD 2017
 Group A patients should be offered either a short- or long-acting
bronchodilator

A bronchodilator

Evaluate effect

Continue, stop or try

alternative class of
bronchodilator

• Bronchodilator treatment should be continued if symptom benefit

is seen

GOLD = Global initiative for chronic Obstructive Lung Disease GOLD 2017
 Group B patients with persistent symptoms should be stepped up
to a LABA/LAMA

LABA or LAMA

Persistent symptoms

LABA + LAMA

• Bronchodilator selection (LABA vs LAMA) in patients with less severe symptoms

should depend on the patient’s perception of symptom relief

• Patients with persistent symptoms may be stepped up to LABA/LAMA

• Patients with severe breathlessness may be started on dual bronchodilation

More than 50% of GOLD B patients have CAT scores >20 (high symptom burden),2
and therefore should receive LABA/LAMA as initial therapy,
or be stepped up from monotherapy
CAT = COPD Assessment Test; GOLD = Global initiative for chronic Obstructive Lung Disease 1. GOLD 2017; 2. Adelphi Respiratory
LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist Disease Specific Programme 2016
 ICS is no longer the preferred choice for patients in GOLD Group C

LAMA

Preferred choice for persistent Alternative

exacerbations

LABA + LAMA LABA + ICS

• Patients with persistent exacerbations may benefit from addition of LABA or a

combination of LABA/ICS1
• LAMA/LABA is the preferred choice due to pneumonia risk associated with ICS1
- There is also no evidence to suggest superiority of LABA/ICS over LABA/LAMA2

• Triple therapy is not recommended1

GOLD = Global initiative for chronic Obstructive Lung Disease; ICS = inhaled corticosteroid 1. GOLD 2017
LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist 2.Wedzicha JA, et al. N Engl J Med 2016
 Dual bronchodilation is the preferred initial therapy for patients
in Group D
LAMA superior to LABA if Option for initial therapy in
single substance selected Recommended initial therapy patients with possible ACOS

LAMA LAMA + LABA LABA + ICS

Further
Further exacerbation(s)/
exacerbation(s) persistent symptoms

LABA + LAMA + ICS

Further
exacerbation(s)

Consider roflumilast if Consider macrolide

FEV1 <50% predicted and
patient has chronic
bronchitis

ACOS = asthma-COPD overlap syndrome; FEV1 = forced expiratory volume in 1 second

GOLD = Global initiative for chronic Obstructive Lung Disease ICS = inhaled corticosteroid
LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist GOLD 2017
 GOLD : Dual bronchodilation is the preferred initial therapy for
patients in Group D

• GOLD recommends LABA/LAMA as primary-choice treatment for Group D patients1

- LABA/LAMA has demonstrated superiority versus bronchodilator monotherapy and
LABA/ICS in exacerbation prevention2,3
• LABA/ICS may be first choice in patients with a history of and/or features suggestive of
asthma-COPD overlap1
• Treatment should be escalated to triple therapy in patients who experience further
exacerbations despite treatment with LABA/LAMA or LABA/ICS1
- There is currently no evidence to support the efficacy of triple vs LABA/LAMA
• If further exacerbations develop despite treatment with triple therapy, the addition of a
macrolide or roflumilast may be considered1
- GOLD also suggest the withdrawal of ICS if exacerbations persist on triple therapy

FEV1 = forced expiratory volume in 1 second 1. GOLD 2017

GOLD = Global initiative for chronic Obstructive Lung Disease; ICS = inhaled corticosteroid 2. Wedzicha JA, et al. Lancet Respir Med 2013
LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist 3. Wedzicha JA, et al. N Engl J Med 2016
 • Inhaler technique should be assessed regularly
• Determinants of poor inhaler technique in asthma and COPD patients
include:
- Older age
- Use of multiple devices
- Lack of previous education on inhaler technique
• Providing patients with quality education regarding proper inhaler
technique is important

COPD = chronic obstructive pulmonary disease; GOLD = Global initiative for chronic Obstructive Lung Disease GOLD 2017
 Identifying and treating comorbidities is important in patients with
COPD
 COPD often coexists with other diseases that may have a significant
impact on health status and prognosis
 Cardiovascular disease is a major comorbidity in COPD
 Probably the most frequent and most important comorbid disease
 Other common comorbidities include skeletal muscle dysfunction,
metabolic syndrome, osteoporosis, depression, anxiety and lung cancer
 Comorbidities should be actively sought and treated appropriately

COPD = chronic obstructive pulmonary disease; GOLD = Global initiative for chronic Obstructive Lung Disease GOLD 2017
GOLD 2018 peningkatan pemakaian LAMA/LABA dan
pembatasan ICS pada PPOK

LAMA/LABA pilihan yang

disukai untuk terapi
simtomatik *
!
LABA/ICS dan triple LAMA/LABA pilihan Eskalasi ke triple
therapy TIDAK yang disukai untuk therapy dianjurkan
Regimen yang direkomendasi terapi simtomatik* hanya pada grup D
sebagai terapi lini yang masih
mengandung ICS dibatasi pertama* eksaserbasi dengan
LAMA/LABA

GRUP GRUP GRUP

A,B,C,D B,D D
*LABA/ICS may be the first choice in some patients. For example, those with a history and/or findings suggestive of asthma-
COPD overlap.
©2018 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved. Use is by express license from the owner.
This overview is based on the GOLD Report 2018 (chapter 4, management of stable COPD). The new pharmacologic treatment
recommendations provided on this page should not be considered as making a claim of a complete listing of all potential
treatments recommended by GOLD 2018. It should rather be considered as a contribution from Boehringer Ingelheim to help
healthcare professionals to familiarize themselves with the new key recommendations provided by GOLD 2018.

10
1. @2018 Global Initiative forChronic Obstructive Lung Disease, all rights reserved. Use is by
express license from the owner
 GOLD 2018

Kombinasi LABA/LAMA memberikan perbaikan lebih baik pada

kualitas hidup dibandingkan dengan plasebo atau salah satu
komponennya pada pasien dengan gejala pada baseline paling
berat (Martinez et al, 2017)

9
Summary: includes major revisions in key areas
 Definition of COPD
 Refined to place more emphasis on symptoms and comorbidities

 ABCD assessment tool

 Refined to assess both symptom level and risk of future exacerbations following
the revised role of spirometry in COPD
 Pharmacological management
 Pharmacological algorithms added
 Dual bronchodilation recommended as a first-line therapy for a majority of
symptomatic patients
 ICS therapy only recommended in a minority of patients as an alternative to
preferred LABA/LAMA treatment
 Focus on inhaler technique
 Emphasizes the importance of patient education

 Management of comorbidities
 Emphasizes the importance of identifying and treating comorbidities

COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease
LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist GOLD 2017
Why doctors are reluctant to treat COPD?

 Stop smoking is difficult

 No currently available drugs slow progression
 Corticosteroids are in effective
 Slow progressive destruction process