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 20302
The economic burden of COPD is high, with costs increasing as the
disease progresses
- Costs associated with severe COPD are up to 17 times higher than those
associated with mild COPD3
- High costs are associated with treatment of exacerbations, such as
hospitalisation3
- Indirect costs include loss of productivity in the workplace owing to
symptoms3
 Worldwide Prevalence of COPD
Other Asia and islands Male/1000
Female/1000
Middle Eastern Crescent

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 Symptoms
Diagnosed 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
noxious irritants
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 Weight changes

Bronchitis: coughing, sputum production Co-morbidities
Emphysema: hyperinflation, wheezing (e.g. diabetes, cardiovascular 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/Dendritic cell
Neutrophil
Monocyte

Fibroblast CD8+ Tc cell Proteases

Fibrosis

Obstructive bronchiolitis Emphysema Mucus 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 CD8+ T-lymphocytes

Macrophages

Chronic inflammation
Structural changes

Bronchoconstriction,
Systemic Acute
oedema, mucus,
inflammation exacerbation
emphysema

Airflow 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 agent Onset Sensitising agent

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

Not fully Airflow limitation Reversible

reversible

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

100
Airways with measurable cells (%)

GOLD Stage I

GOLD Stages II and III

80
GOLD Stage IV

60

40

20

Neutrophils Macrophages CD8+ cells

GOLD stage I GOLD stage II dan III GOLD stage 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

SYMPTOMS RISK FACTORS

Cough Tobacco
Sputum production + Occupational 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 SEVERE AND LIFE-

MILD MODERATE 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 flow . 75% 50 – 75% < 50 %

(% predicted)

Arterial Blood Gas Test not necessary If initial response is Yes

poor
 GOALS OF COPD MANAGEMENT

– Relieve symptoms
Improve current
– Improve exercise tolerance
– Improve health status
control

– Prevent and treat exacerbations

– Prevent disease progression Reduce future 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 FEV1
100

Smoked Never smoked or

regularly and not susceptible to
75 susceptible smoke
FEV1 (% of value at age 25)

to its effects

Disability
50
Stopped at 45

Disability
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 patient’s 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 inflammation3,4
– 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 quality of life Increased mortality rate

Increased Increased risk of

inflammation recurrent exacerbations

Faster disease Increased likelihood

progression of 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 3
inflammation

Chronic cough 2
and sputum
p<0.0001

Frequent 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
TRIGGERS

Viruses
Pollutants
Bacteria

Inflamed
COPD airways
EFFECTS
Greater airway
inflammation

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

•Sputum retention
•Bronchospasm
•Infection
•Pneumothorax
•Large bullae
•Uncontrolled O2 - 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

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

COR-PULMONALE
 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% predicted plus
FEV1 ≥80% predicted 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 / B2-AGONIST / IPRATROPIUM ]

…CONTD
 CONSERVATIVE MANAGEMENT ….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. INVASIVE TECHNIQUES FOR SPUTUM CLEARANCE
• OROPHARYNGEAL / NASOPHARYNGEAL SUCTION
• NASO-PHARYNGEAL AIR-WAY
• THERAPEUTIC AND DIAGNOSTIC F O B
• MINI TRACHEOSTOMY/ CRICOTHYROTOMY FOR SUCTION
• ENDOTRACHEAL INTUBATION
* FOR BETTER ACCESS
* FOR VENTILATORY SUPPORT
• TRACHEOSTOMY
* IF VERY THICK SECRETIONS
* INTUBATION > SEVEN DAYS
 Emphysema
• The fourth leading cause of death in the US
• 3‐4 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
 EffectiveCOPD 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

management
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.
THANK-YOU