COPD

CHRONIC OBSTRUCTIVE
PULMONARY DISEASE

Dr.dr.Tahan P.H., SpP., DTCE., MARS

Penyakit Dalam FK-UWKS
15-06-12
Introduction
Chronic Obstructive Pulmonary Disease (COPD) is
one of the top five causes of global mortality

COPD affects 210 million people worldwide and

causes 3 million deaths annually (5% of all
deaths worldwide)1
It is predicted to become the third leading cause
of global mortality by 203022
The
The economic
economic burden
burden of
of COPD
COPD is
is high,
high, with
with costs
costs
increasing
increasing asas the
the disease
disease progresses
progresses
-- Costs
Costs associated
associated with
with severe
severe COPD
COPD are
are up
up to
to 17
17 times
times
higher
higher than
than those
those associated
associated with
with mild
mild COPD
COPD 33
-- High
High costs
costs are
are associated
associated with
with treatment
treatment ofof
exacerbations,
exacerbations, such
such as
as hospitalisation
hospitalisation33

-- Indirect
Indirect costs
costs include
include loss
loss of
of productivity
productivity in
in the
the workplace
workplace
owing
owing to
to symptoms
symptoms33
WORLDWIDE PREVALENCE OF COPD

Other Asia and islands Male/1000

Female/100
Middle Eastern Crescent
0

Latin America and Caribbean

Sub-Saharan Africa

India

Established market economies

Former Socialist economies

0 2 4 6 8 10 12

Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary
Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2005.
COPD MISDIAGNOSIS IS COMMON IN WOMEN

Hypothetical Male Patient

With
COPD Symptoms
Diagnosed as COPD by
65% of physicians
65%

49%
Hypothetical Female
Patient With COPD
Diagnosed Symptoms
as COPD by
49% of physicians

COPD symptoms in women were

most commonly misdiagnosed as
asthma
Chapman KR, et al. Chest. 2001;119:1691-1695.
COPD IS AN INCREASINGLY COMMON CAUSE
OF DEATH WORLDWIDE

Cause of Death Rank in 2002 Rank in 2030

Ischaemic heart disease 1 1
Cerebrovascular disease 2 2
Lower respiratory infections 3 5
HIV/AIDS 4 3
COPD 5 4
Perinatal conditions 6 9
Diarrhoeal diseases 7 16
Tuberculosis 8 23
Trachea, bronchus, lung cancers 9 6
Road traffic accidents 10 8

Mathers CD, et al. PLoS Med. 2006;3:2011-2030.

 What is COPD?
Global Initiative for Chronic Obstructive Lung
Disease (GOLD) defines COPD as (2009):
a preventable and treatable disease with some
significant extrapulmonary effects that may
contribute to the severity in individual patients. Its
pulmonary component is characterised by airflow
limitation that is not fully reversible. The airflow
limitation is usually progressive and associated with
abnormal inflammatory response of the lung to
noxious particles or gases
Key points:
- COPD is preventable and treatable
- Airway limitation is not fully reversible and is usually
progressive
- Extrapulmonary (systemic) effects play a significant
role
- Associated with chronic inflammation in response to
inhaled
COPD IS CAUSED BY INHALATION OF NOXIOUS
SUBSTANCES
MUCOCILIARY APPARATUS
 COPD HAS PULMONARY AND SYSTEMIC
COMPONENTS

Inhaled substances
+
Genetic
susceptibility

Airway Mucociliary Structural Systemic

inflammation dysfunction changes
inflammation
Airway limitation

Breathlessness
Breathlessness Weight
Weight changes
changes
Bronchitis:
Bronchitis: coughing, sputum
coughing, sputum production
production Co-morbidities
Co-morbidities
Emphysema:
Emphysema: hyperinflation,
hyperinflation, wheezing
wheezing (e.g.
(e.g. diabetes,
diabetes, cardiovascular
cardiovascular disease)
disease)
NYC/DAXAS/10/012
WHAT IS THE ROLE OF INFLAMMATION IN
COPD?
 COPD IS A DISEASE CHARACTERISED
BY INFLAMMATION

Cigarette smoke

Epithelial
cells

Macrophage/Dendriti
c cell Neutrophil
Monocyte

Fibroblast CD8+ Tc Proteases

Fibrosis
cell

Obstructive Emphysema Mucus

bronchiolitis hypersecretion
Reproduced from The Lancet, Vol 364, Barnes PJ & Hansel TT, "Prospects for new drugs for chronic obstructive pulmonary
disease", pp985-96. Copyright 2004, with permission from Elsevier.
 CHRONIC INFLAMMATION PLAYS A CENTRAL ROLE
IN COPD

Smoke Pollutants Key inflammatory cells

Neutrophils

Inflammation
Inflammation CD8+ T-lymphocytes

Macrophages

Chronic
Chronic inflammation
inflammation
Structural
Structural changes
changes

Bronchoconstricti
Bronchoconstricti
Systemic
Systemic on,
on, Acute
Acute
inflammation
inflammation oedema,
oedema, mucus,
mucus, exacerbation
exacerbation
emphysema
emphysema

Airflow
Airflow
limitation
limitation

Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
NYC/DAXAS/10/012
 COPD INFLAMMATION IS DIFFERENT FROM ASTHMA
INFLAMMATION

COPD Asthma
Noxious
Noxious agent
agent Onset Sensitising
Sensitising agent
agent

Inflammatory cells Eosinophils

Neutrophils Eosinophils
Neutrophils CD4+
CD8+ CD4+ T-
T-
CD8+ T-lymphocytes
T-lymphocytes
lymphocytes
lymphocytes
Macrophages
Macrophages Mast
Mast cells
cells

Not fully Reversibl

Airflow limitation
reversible e

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for
Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
NYC/DAXAS/10/012
 AIRWAY INFLAMMATION OCCURS FROM COPD ONSET
AND INCREASES WITH DISEASE SEVERITY
Airways with measurable cells (%)

Neutrophils Macrophages CD8+ cells

GOLD stage GOLD stage II GOLD stage

I dan III IV
Adapted from Hogg JC et al, 2004.
NYC/DAXAS/10/012
 HOW IS COPD DIAGNOSED
AND MANAGED?

NYC/DAXAS/10/012
 COPD IS DIAGNOSED BASED ON SYMPTOMS,
RISK FACTORS AND SPIROMETRY

RISK FACTORS
SYMPTOMS Tobacco
Cough Occupational
Sputum production + hazards
Shortness of breath Indoor/outdoor
pollution

Spirometry

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for
Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
NYC/DAXAS/10/012
 CLASSIFICATION OF
COUGH
Cough is classified into acute
and chronic
and
Clinically subdivided into
productive and dry cough.
Productive cough
is present at an expectoration
rate of
30 ml/24 hours,
 CLASSIFICATION OF
COUGH
Acute cough is defined as one
lasting less than three weeks

Chronic cough is defined as one

lasting greater than eight weeks
ACUTE COUGH ... < 3 WEEKS

Differential Diagnosis

URTI : Sinusitis viral / bacterial

URTI triggering exacerbations of Chronic
Lung Disease eg Asthma; COPD
Pneumonia
Left Ventricular Heart Failure
Foreign Body Aspiration
 INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN
ADULTS

SYMPTOMS
MILD MODERATE SEVERE AND LIFE-
THREATENING
Physical
Exhaustion No No Yes, may have
paradoxical chest wall
movement
Pulse rate < 100 / min 100 120 / min > 120 / min
Central cyanosis absent May be present Likely to be present
Wheeze intensity variable Moderate Often quiet
Peak expiratory . 75% 50 75% < 50 %
flow
(% predicted)

Arterial Blood Gas

Test not If initial response Yes
necessary is poor
 GOALS OF COPD MANAGEMENT

Relieve symptoms
Improve current
Improve exercise tolerance
Improve health status
control

Reduce future
Prevent and treat exacerbations
Prevent disease progression
risks
Prevent and treat complications
Reduce mortality

Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative
for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
NYC/DAXAS/10/012
 CONTINUED SMOKING LEADS TO RAPID DECLINE
OF FEV11

100

Smoked Never smoked or

regularly not susceptible to
FEV1 (% of value at age

75 and smoke
susceptibl
e to its
effects
Disabili
ty
25)

50
Stopped
at 45
Disabili
ty
25

Death Stopped at
65
0
25 50 75
Age (years)
Adapted from Fletcher C and Peto R , 1977.
NYC/DAXAS/10/012
 WHAT ARE EXACERBATIONS ?

NYC/DAXAS/10/012
 WHAT ARE EXACERBATIONS?

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

defines an exacerbation as:
an event in the natural course of the disease characterized
by a change in the patients baseline dyspnea, cough, and/or
sputum that is beyond normal day-to-day variations, is acute
in onset and may warrant a change in regular medication 1

May be mild, moderate or severe in nature. More severe

exacerbations can require hospitalisation and are associated with a
prolonged recovery period2
Commonly caused by bacterial/viral infections of the lungs and
airways1
Associated with increases in markers of inflammation 3,4
Distressing for patients and their loved ones
1. From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive
Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from:
http://www.goldcopd.org. 2. Seemungal TA et al, 2000. 3. Perera et al, 2007. 4. Papi et al, 2006.
NYC/DAXAS/10/012
 FREQUENT EXACERBATIONS DRIVE DISEASE
PROGRESSION

Patients with frequent exacerbations

Lower
Lower quality
quality of
of life
life Increased
Increased mortality
mortality rat
rat

Increased
Increased Increased
Increased risk
risk of
of
inflammation
inflammation recurrent
recurrent exacerbations
exacerbations

Faster
Faster disease
disease Increased
Increased likelihood
likelihood
progression
progression of
of hospitalisation
hospitalisation
Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.
NYC/DAXAS/10/012
 COUGH AND SPUTUM PRODUCTION INDICATE AN
INCREASED RISK OF EXACERBATIONS

Number of
exacerbations
Chronic
Chronic 3
inflammation
inflammation

Number of exacerbations per

patient per year
2
Chronic
Chronic cough
cough
and
and sputum
sputum
p<0.0001
1

Frequent
Frequent exacerbations
exacerbations
0
Patients WITH Patients WITHOUT
chronic cough and chronic cough and
sputum sputum

Adapted from Burgel PR et al, 2009.

NYC/DAXAS/10/012
 DEFINITIONS OF EXACERBATIONS

COPD exacerbations were classified in clinical studies

as follows:
Severe COPD exacerbation
Requiring hospitalisation and/or leading to
death
Moderate COPD exacerbation
Initiation of oral or parenteral
glucocorticosteroid therapy is required

Calverley PMA et al, 2009. Fabbri L,et al, 2009.

NYC/DAXAS/10/012
 PULMONARY AND SYSTEMIC INFLAMMATION IN
EXACERBATIONS

TRIGGE
RS
Viruses
Pollutants
Bacteria

Inflamed
EFFECTS COPD
airways
Greater airway
inflammation
Bronchoconstri
Systemic ction
oedema,
inflammation mucus
Expiratory flow
limitation
Cardiovascula
Cardiovascula Exacerbation Dynamic
rr
symptoms hyperinflation
comorbidity
comorbidity
Reprinted from The Lancet, 370, Wedzicha JA, Seemungal TA, COPD exacerbations: defining their cause and
28
prevention, 786-796, Copyright 2007, with permission from Elsevier.
 FACTORS PRECIPITATING ACUTE
FAILURE

Sputum retention
Bronchospasm
Infection
Pneumothorax
Large bullae
Uncontrolled O22 - administration
Pulmonary embolism
Left-ventricular failure
End-stage disease
 PATHO- PHYSIOLOGY.

FACTORS AFFECTING AIR-FLOW

Mucosal edema
Hypertrophy of mucosa
Increased secretions
Increased bronchospasm
incr. Airway tortuosity
More airway turbulance
Loss of lung recoil
 PATHO-PHYSIOLOGY.contd
PATHO-PHYSIOLOGY.contd

AIR-FLOW OBSTRUCTION

PROLONGED EXPIRATION

PULMONARY HYPERINFLATION
DUE TO AIR-TRAPPING

INCREASED WORK OF BREATHING

DYSPNOEA
 PATH-PHYSIO..CONTD

ALVEOLAR DISTORTION
AND DESTRUCTION

LOSS OF
HYPOXIA CAUSING
CAPILLARY BED
PULMONARY

VASOCONSTRICTION

PULMONARY HYPERTENSION

SECONDARY VASCULAR CHANGES

 PHARMACOLOGICAL TREATMENTS SHOULD BE
ADDED STEPWISE AS COPD PROGRESSES

Stage IV:
Stage III: Very Severe
Stage II: Severe FEV1/FVC<0.70
Stage I: Moderate
Mild FEV1 <30%
FEV1/FVC<0.70 FEV1/FVC<0.70 predicted or
FEV1/FVC<0.70 30% FEV1 <50% FEV1 <50%
50% FEV1 <80%
FEV1 80% predicted predicted plus
predicted
chronic respiratory
predicted
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
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, procedures
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
NYC/DAXAS/10/012
 MANAGEMENT NONINVASIVE

# BRONCHODILATORS
ROUTINELY GIVEN
HELP RESIDUAL BRONCHODILATION
AND MUCO-CILIARY CLEARANCE

[ I.V.AMINOPHYLLINE / B22-AGONIST /
IPRATROPIUM ]
 CONSERVATIVE
CONSERVATIVE MANAGEMENT
MANAGEMENT .contd
.contd
# ANTIBIOTICS
# STEROIDS AVOID IN ARF DUE TO
INFECTION
# OTHER
* STEAM / PHYSIOTHERAPY / ENCOURAGE
COUGH
* GENERAL HYDRATION
* DIURETICS / LOW DIGOXIN IF LVF
* HEPARIN S /C FOR D V T / PULM
EMBOLISM
* NUTRITION
* RESPIRATORY STIMULANTS
 MANAGEMENT - NON CONSERVATIVE.
1.
1. INVASIVE
INVASIVE TECHNIQUES
TECHNIQUES FOR
FOR SPUTUM
SPUTUM
CLEARANCE
CLEARANCE
OROPHARYNGEAL
OROPHARYNGEAL // NASOPHARYNGEAL
NASOPHARYNGEAL
SUCTION
SUCTION
NASO-PHARYNGEAL
NASO-PHARYNGEAL AIR-WAY
AIR-WAY
THERAPEUTIC
THERAPEUTIC AND
AND DIAGNOSTIC
DIAGNOSTIC F
FOOB
B
MINI
MINI TRACHEOSTOMY/
TRACHEOSTOMY/ CRICOTHYROTOMY
CRICOTHYROTOMY FOR
FOR
SUCTION
SUCTION
ENDOTRACHEAL
ENDOTRACHEAL INTUBATION
INTUBATION
*
* FOR
FOR BETTER
BETTER ACCESS
ACCESS
*
* FOR
FOR VENTILATORY
VENTILATORY SUPPORT
SUPPORT
TRACHEOSTOMY
TRACHEOSTOMY
*
* IF
IF VERY
VERY THICK
THICK SECRETIONS
SECRETIONS
*
* INTUBATION
INTUBATION >> SEVEN
SEVEN DAYS
DAYS
 Emphysema
The fourth leading cause of death in the US
34 million people in the US suffer from
emphysema
Current treatment is limited in efficacy
 Bronchoscopic Lung Volume
Reduction for Emphysema

The Concept of lung Volume Reduction

Lung volume Reduction
1. Removal of the most destroyed hyperinflated
poorly perfused areas of the lung can enhance
the
function of the remaining normal lung and
leads to func(onal and symptoma(c
improvement
2. Applicable in heterogeneous emphysema (upper
lobe predominant)
Multiple retrospective and prospective studies
reported success with surgical lung volume
reduction
 SUMMARY

COPD is a debilitating disease that presents a huge

healthcare and economic burden around the world
The major risk factor for developing COPD is tobacco
smoking
COPD encompasses damage to the airways, and
chronic pulmonary and systemic inflammation
The symptoms of COPD include breathlessness,
chronic cough and sputum production
 Chronic inflammation in the airways and systemic
circulation contributes to the pathology of COPD
COPD-specific inflammation is characterised by
increased neutrophils, CD8+ T-lymphocytes and
macrophages, as well as cytokines and other
inflammatory mediators
Inflammatory processes activated in asthma are
different from COPD-specific inflammation
Chronic inflammation is present from the onset of

COPD and increases with disease progression. Airway
inflammation increases during exacerbations
Effective COPD management should include agents
that target the chronic inflammation underlying the
disease
Exacerbations are attacks in which symptoms
increase beyond daily variations

Patients with frequent exacerbations have a

poor prognosis and increased risk of
mortality

Inflammation is increased during

exacerbations

The symptoms of chronic cough and sputum

production are associated with an increased
risk of exacerbations

Preventing exacerbations is a major goal of

 COPD is diagnosed based on medical history,
exposure to risk factors and assessment of lung
function by spirometry

GOLD guidelines recommend seven goals for

COPD management, including reducing the
frequency of exacerbations

Non-pharmacological management of COPD

includes smoking cessation

GOLD guidelines recommend stepwise addition of

pharmacological treatments based on the
severity of COPD
 THE DOWNWARD SPIRAL IN COPD
COPD Lung
inflammation
Mucous
hypersecretion
Airway
Exacerbation obstruction

Continued Impaired
smoking mucous clearance

Exacerbation
Submucousal gland
Alveolar hypertrophy
destruction
Exacerbation

Hypoxaemia

DEATH
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease,
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008. Available from: http://www.goldcopd.org.
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