ppok (penyakit paru obstruktif kronik).semester 3

8/3/2019 Ppok (Penyakit Paru Obstruktif Kronik).Semester 3

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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
http://d/Slide%20sets/References%20file/Pauwels%20et%20al%202001.pdfhttp://d/Slide%20sets/References%20file/Pauwels%20et%20al%202001.pdf


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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
http://d/Slide%20sets/References%20file/Snider%201995.pdfhttp://d/Slide%20sets/References%20file/Snider%201995.pdf


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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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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
http://d/Slide%20sets/References%20file/Rutgers%20et%20al%202000.pdfhttp://d/Slide%20sets/References%20file/Rutgers%20et%20al%202000.pdf


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Airwayinflammation

Increased numbers/activation:- neutrophils,- macrophages,- CD8+ lymphocytes


Mucosal oedema

01234567

0 20 40 60 80 100 120FEV1(% predicted)

Proteinleak(%)

Relationship between airway protein leakageand spirometry in COPD

Hill et al, 1999
http://d/Slide%20sets/References%20file/Hill%20et%20al%201999.pdfhttp://d/Slide%20sets/References%20file/Hill%20et%20al%201999.pdf


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Airwaystructuralchanges

Alveolar destruction

Epithelial hyperplasia Glandular hypertrophy

Goblet cell metaplasia

Airway fibrosis

Asthma

COPD


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Mucus hyper-secretion

Increased mucusviscosity

Reduced mucociliarytransport

Mucosal damage

Healthy

H. influenzae


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Airwayinflammation


Airwayobstruction

Airwaystructuralchanges

Increased numbers/activation:- neutrophils- macrophages- CD8+ lymphocytes


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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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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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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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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ppok (penyakit paru obstruktif kronik).semester 3

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