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COPD(CHRONIC OBSTRUCTIVE PULMONARY DISEASE)
Oleh
Dr. Supiono, SpP
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COPD (CHRONIC OBSTRUCTION PULMONARY DISEASE)COLD(CHRONIC OBSTRUCTION LUNG DISEASE)
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COPD is a disease state characterized byairflow limitation that is not fullyreversible. The airflow limitation is
usually both progressive and associatedwith an abnormal inflammatory responseof the lungs to noxious particles or gases.
GOLD, 2001
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Facts About COPD
COPD is the 4th leading cause of death inthe United States (behind heart disease,
cancer, and cerebrovascular disease).
In 2000, the WHO estimated 2.74 milliondeaths worldwide from COPD.
In 1990, COPD was ranked 12th as aburden of disease; by 2020 it is projected
to rank 5th
.
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Leading Causes ofDeaths
U.S. 1998
All other causes of death 469,314
10.
Chronic liver disease 24,936
9.
Nephritis 26,295
8.
Suicide 29,264
7.Diabetes64,574
6.
Pneumonia and influenza 93,207
5.
Accidents 94,828
4.
Respiratory Diseases (COPD) 114,381
3.
Cerebrovascular disease (stroke) 158,060
2.
Cancer 538,947
1.
Cause of Death Number
Heart Disease 724,269
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Percent Change in Age-AdjustedDeath Rates, U.S., 1965-1998
0
0.5
1.0
1.5
2.0
2.5
3.0
Proportion of 1965 Rate
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
59% 64% 35% +163% 7%
CoronaryHeart
Disease
Stroke Other CVD COPD All OtherCauses
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Facts About COPD
Between 1985 and 1995, the numberof physician visits for COPD in the
United States increased from 9.3million to16 million.
The number of hospitalizations forCOPD in 1995 was estimated to be
500,000. Medical expendituresamounted to an estimated 14.7
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COPD 1990 Prevalence
Established Market Economies 6.98 3.79
Formerly Socialist Economies 7.35 3.45
India 4.38 3.44
China 26.20 23.70
Other Asia and Islands 2.89 1.79
Sub-Saharan Africa 4.41 2.49
Latin America and Caribbean 3.36 2.72
Middle Eastern Crescent 2.69 2.83
World 9.34 7.33
*From Murray & Lopez, 1996
Male/1000
Female/1000
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Chronic
bronchitis Emphysema
COPD
Airflow obstruction
Adapted from Snider, 1995
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Risk Factors for COPD
Host Factors Genes (e.g. alpha1-antitrypsin deficiency)
HyperresponsivenessLung growth
Exposure Tobacco smokeOccupational dusts and
chemicals
Infections
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Noxious particles
and gases
Lung inflammation
Host factors
COPD pathology
ProteinasesOxidative stress
Anti-proteinasesAnti-oxidants
Repair mechanisms
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Causes of Airflow Limitation
Irreversible
Fibrosis and narrowing of the
airways Loss of elastic recoil due to
alveolar destruction
Destruction of alveolar supportthat maintains patency of smallairways
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Causes of Airflow Limitation
Reversible
Accumulation of inflammatory
cells, mucus, and plasma exudatein bronchi
Smooth muscle contraction in
peripheral and central airways
Dynamic hyperinflation duringexercise
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Facts About COPD
Cigarette smoking is the primary cause ofCOPD.
In the US 47.2 million people (28% ofmen and 23% of women) smoke.
The WHO estimates 1.1 billion smokersworldwide, increasing to 1.6 billion by2025. In low- and middle-income
countries, rates are increasing at an
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Asthma COPD
Mast cellCD4+ T-cell
IL-8 IL-4 IL-13
NeutrophilEosinophil
MacrophageCD8+ T-cell
IL-8TNF LTB4
Asthma and COPD are bothcharacterised by inflammation
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Pathogenesis of COPD
NOXIOUS AGENT(tobacco smoke, pollutants, occupational
agent)
COPD
Genetic factors
Respiratoryinfection
Other
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COPD: a multi-component airway disease
Airwayinflammation
Mucociliarydysfunction
Airwayobstruction
Airway structuralchanges
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Similarities between Asthma and COPD
Both are chronic diseases
Inflammation present in both
Airflow obstruction Involvement of the small airways
Mucus
Bronchoconstriction Both are consequences of gene-environment
interaction
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Pathophysiological features of COPD
Airwayobstruction
Smooth musclecontraction
Increased cholinergictone
Bronchialhyperreactivity
Loss of elastic recoil
Normal COPD
Parenchymaltethering Loss of tethering
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Pathophysiological features of COPD
Airwayinflammation
Increased numbers/activation:- neutrophils,- macrophages,- CD8+ lymphocytes
Elevated IL-8, TNF, LTB4Protease/anti-proteaseimbalance
Mucosal oedema
Rutgers et al, 2000
Sputum inflammatory cell levels
0
10
2030
40
50
60
70
8090
100
Sputumn
eutrophils(%)
COPD Healthy
p = 0.0001
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Pathophysiological features of COPD
Airwayinflammation
Increased numbers/activation:- neutrophils,- macrophages,- CD8+ lymphocytes
Elevated IL-8, TNF, LTB4Protease/anti-proteaseimbalance
Mucosal oedema
01234567
0 20 40 60 80 100 120FEV1(% predicted)
Proteinleak(%)
Relationship between airway protein leakageand spirometry in COPD
Hill et al, 1999
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Pathophysiological features of COPD
Airwaystructuralchanges
Alveolar destruction
Epithelial hyperplasia Glandular hypertrophy
Goblet cell metaplasia
Airway fibrosis
Asthma
COPD
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Pathophysiological features of COPD
Mucociliarydysfunction
Mucus hyper-secretion
Increased mucusviscosity
Reduced mucociliarytransport
Mucosal damage
Healthy
H. influenzae
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Pathophysiological features of COPD
Airwayinflammation
Mucociliarydysfunction
Airwayobstruction
Airwaystructuralchanges
Increased numbers/activation:- neutrophils- macrophages- CD8+ lymphocytes
Elevated IL-8, TNF, LTB4Protease/anti-proteaseimbalance
Mucosal oedema
Alveolar destruction
Epithelial hyperplasia
Glandular hypertrophy
Goblet cell metaplasia
Airway fibrosis
Mucus hyper-secretion
Increased mucusviscosity
Reduced mucociliarytransport
Mucosal damage
Smooth musclecontraction
Increased
cholinergic tone
Bronchial hyper-reactivity
Loss of elastic
recoil
h h l l/ l
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Systemic
component
Weight loss
Poor nutritional
status/reduced BMIImpaired skeletal musclefunction:
- Weakness
- Wasting
Pathophysiological/clinical features of COPD
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Clinical Feature Asthma COPD
Age of onset Early childhood, at any age Mid-late adult life
Smoking history Non-, ex-, or current smoker smoker or exsmoker
Atopy History of atopic present Absent
Exacerbations Common at all levels of severity Increase with increasingof severity
Family history present Absent(atopy)
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Clinical Feature Asthma COPD
Lung function Normal/obstruction Airflow obstruction ahallmark of COPD
Reversibility Characteristic of asthma Poorly reversible
Peak flow variability Characteristic of asthma, usually Often does not vary> 20 % at all
Diffusing capacity Usually normal Abnormal whenThere is emphysema
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MINIMUM REQUIREMENTS FOR THEDIAGNOSIS OF ASTHMA AND COPD
Symptom and history
Physical examination Lung function tests
Spirometry PEF Reversibility to bronchodilator
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ADDITIONAL TESTS
Reversibility to steroids
Diffusion capasity
Airway hyperresponsiveness Allergy tests
Imaging
Assessment of airway inflammationSputumExhaled nitric oxide
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Ancillary test Asthma COPD
Reversibility to steroids Usually present Usually absentLung volumes Usually normal Usually increasedDiffusion capacity Usually normal DecreasedAirway hyperresponsiveness Usually increased Usually increasedAllergy tests Usually positive Usually negativeImaging of the chest Usually normal Usually abnormalSputum Eosinophilia NeutrophiliaExhaled NO Usually increased Usually normal
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Biochemical markers in induced sputum ofstable asthma and COPD patients
Asthma COPD
Eosinophil cationic protein + + + +Myeloperoxidase + + +Human neutrophil lipocalin + + + + + +Interleukin- + + +Tumor necrosis factor- + + + +
Leukotriene B4 + + +
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30% of patients with fixed airflow limitationshave a history of asthma
Asthma : CD 4
Eosinophil
Increase thickness of the
reticular layer
COPD : CD 8
Macrophage
Neutrophil
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CLASSIFICATION OF COPDGOLD 2001 GOLD 2003
DEGREE DEGREE CLINICAL SYMPTOM SPYROMETRY
Degree nullrisk
Degree nullrisk
Clinical;cough,sputmproduction
normal
Degree I
Mild copd
Degree I
Mild copd
With or without clinical
symptom( productionsputum)
FEV1/FVC
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Fabbry et al, 2003
Inflammatory Markers
Eosinophil >
CD4 >
CD4/CD8 >
Thicker reticular layer
Higher level of exhaled NO
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HRCT scanning in patientswith Asthma and COPD
Mild-to persistent asthma Severe asthma COPD Healthy
Bronchial wall ++ +++ + -
thickening
Emphysema + ++ +++ -
Bronchiectasis + ++ -
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GOLD Workshop Report
Four Components of COPD
Management1. Assess and monitor
disease
2. Reduce risk factors
3. Manage stable COPD
Education Pharmacologic
Non-pharmacologic
4. Manage exacerbations
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Objectives of COPDManagement
Prevent disease progression
Relieve symptoms
Improve exercise tolerance Improve health status
Prevent and treat exacerbations
Prevent and treat complications Reduce mortality
Minimize side effects from
treatment
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Assess and Monitor
Disease: Key Points
Diagnosis of COPD is based on a history
of exposure to risk factors and thepresence of airflow limitation that is notfully reversible, with or without the
presence of symptoms.
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Assess and Monitor
Disease: Key Points
For the diagnosis and assessment of
COPD, spirometry is the goldstandard.
Health care workers involved in thediagnosis and management of COPDpatients should have access to
spirometry.
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Direct and Indirect Costs ofCOPD, 1993 (US $ Billions)
Direct Medical Cost: $14.7
Total Indirect Cost: $ 9.2
Mortality related IDC 4.5
Morbidity related IDC 4.7
Total Cost $23.9
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Assess and Monitor
Disease: Key Points
Measurement of arterial blood gas
tension should be considered inall patients with FEV1 < 40%
predicted or clinical signssuggestive of respiratory failure orright heart failure.
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Bronchodilators in Stable
COPD Bronchodilators are prescribed on an as-needed
or on a regular basis to prevent or reduce
symptoms.
Long-acting inhaled bronchodilators are moreconvenient.
Combining bronchodilators may improve efficacyand decrease the risk of side effects comparedto increasing the dose of a single bronchodilator.
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Manage Stable COPD
Key Points
Regular treatment with inhaled
glucocortico-steroids should only beprescribed for symptomatic COPD patientswith a documented spirometric response
to glucocorticosteroids or in those with anFEV1 < 50% predicted and repeatedexacerbations requiring treatment withantibiotics and/or oral glucocorticosteroidsEvi n B .
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Manage Stable COPD
Key Points
Chronic treatment with systemic
glucocortico-steroids should be avoidedbecause of an unfavorable benefit-to-riskratio (Evidence A).
All COPD-patients benefit from exercisetraining programs, improving with respectto both exercise tolerance and symptoms
of dyspnea and fatigue (Evidence A).
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Manage Stable COPD
Key Points
The long-term administration of
oxygen (> 15 hours per day) topatients with chronic respiratoryfailure has been shown to increase
survival (Evidence A).
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Management of COPD:
All stagesAvoidance of noxious agents
- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure
Influenza vaccination
M E b ti
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Manage ExacerbationsKey Points
Exacerbations of respiratory symptomsrequiring medical intervention areimportant clinical events in COPD.
The most common causes of anexacerbation are infection of the
tracheobronchial tree and air pollution, butthe cause of about one-third of severeexacerbations cannot be identified
(Evidence B).
M E b ti
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Manage ExacerbationsKey Points
Inhaled bronchodilators (Beta2-agonistsand/or anticholinergics), theophylline,and systemic, preferably oral,glucocortico-steroids are effective forthe treatment of COPD exacerbations
(Evidence A).
Manage E ace bations
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Manage ExacerbationsKey Points
Patients experiencing COPDexacerbations with clinical signs of
airway infection (e.g., increasedvolume and change of color ofsputum, and/or fever) may benefit
from antibiotic treatment (Evidence B)
Manage Exacerbations
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Manage ExacerbationsKey Points
Noninvasive intermittent positive pressureventilation (NIIPPV) in acute exacerbations
improves blood gases and pH, reduces in-hospital mortality, decreases the need forinvasive mechanical ventilation andintubation, and decreases the length ofhospital stay (Evidence A).
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Conclusion
1. Differential diagnosis between asthma andCOPD becomes more difficult in elderly andwhen the patient develops a poorly reversibleairflow limitation that responds only partially totreatment
2. The noninvasive measurement of eosinophil in
sputum and exhaled NO might be clinicallyuseful to distinguish asthma from COPD
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