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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


Mathers CD, et al. PLoS Med. 2006;3:2011-2030.
Road traffic accidents 10 8
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

Monocyte Macrophage/De Neutrophil


ndritic cell
Proteases
Fibroblast
Fibrosis CD8+
Tc cell
Obstructive Mucus
bronchiolitis Emphysema hypersecretion
Chronic Inflammation plays a central role
in COPD

Smoke Pollutants Key inflammatory cells


Neutrophils
CD8+ T-lymphocytes
Inflammation
Macrophages

Chronic inflammation
Structural changes
Systemic Bronchoconstriction, Acute
inflammation oedema, mucus, 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

Neutrophils Inflammatory cells Eosinophils


CD8+ T- CD4+ T-
lymphocytes 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)
GOALS OF COPD MANAGEMENT

Relieve symptoms
Improve exercise tolerance Improve current
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
FEV1 (% of value at age 25)

regularly and or not


75 susceptible to susceptible to
its effects smoke
Disability
50
Stopped at 45
Disability
25

Death Stopped at 65
0
25 50 75
Adapted from Fletcher C and Peto R , 1977.
Age (years)
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 medication1
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
frequent exacerbations drive disease progression

Patients with frequent exacerbations


Increased mortality
Lower quality of life
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
1
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
TRIGGE
RS
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,
Copyright 2007, with permission from Elsevier. 28
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 FEV1 <50%
50% FEV1 <80% 30% FEV1
FEV1 80% <50% predicted plus
predicted
predicted predicted chronic respiratory
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
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Consider surgical
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
NYC/DAXAS/10/012
procedures
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
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
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
Mucous inflammation
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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