COPD

(CHRONIC OBSTRUCTIVE PULMONARY DISEASE)

Oleh

Dr. Supiono, SpP

COPD (CHRONIC OBSTRUCTION PULMONARY DISEASE) COLD(CHRONIC OBSTRUCTION LUNG DISEASE)

COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

GOLD, 2001

Facts About COPD

COPD is the 4th leading cause of death in the United States (behind heart disease, cancer, and cerebrovascular disease).

In 2000, the WHO estimated 2.74 million deaths worldwide from COPD. In 1990, COPD was ranked 12th as a burden of disease; by 2020 it is projected to rank 5th.

Leading Causes of Deaths U.S. 1998

Cause of Death 1. 2. 3. 4. 5. 6. 7. 8. Number

Heart Disease

724,269

Cancer 538,947 Cerebrovascular disease (stroke) 158,060 Respiratory Diseases (COPD) 114,381 Accidents 94,828 Pneumonia and influenza 93,207

9.
10.

64,574 Suicide Nephritis Chronic liver disease

All other causes of death

Diabetes

29,264 26,295 24,936 469,314

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998

Proportion of 1965 Rate
3.0 3.0 2.5 2.5

Coronary Heart Disease

Stroke

Other CVD

COPD

All Other Causes

2.0 2.0 1.5 1.5 1.0 1.0

0.5 0.5 0.0 0

59%

64%

35%

+163%

7%

1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

Facts About COPD

Between 1985 and 1995, the number of physician visits for COPD in the United States increased from 9.3 million to 16 million. The number of hospitalizations for COPD in 1995 was estimated to be 500,000. Medical expenditures amounted to an estimated $14.7

COPD 1990 Prevalence

Male/100 Female/100 0 0 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

COPD

Chronic bronchitis

Emphysema

Airflow obstruction

Adapted from Snider, 1995

Risk Factors for COPD

Host Factors antitrypsin Genes (e.g. alpha1deficiency) Hyperresponsiveness Lung growth
Tobacco smoke Occupational dusts and Infections

Exposure chemicals

Noxious particles and gases

Host factors

Lung inflammation
Anti-oxidants

Anti-proteinases

Oxidative stress

Proteinases
Repair mechanisms

COPD pathology

Causes of Airflow Limitation

Irreversible Fibrosis and narrowing of the airways Loss of elastic recoil due to alveolar destruction Destruction of alveolar support that maintains patency of small airways

Causes of Airflow Limitation

Reversible Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi Smooth muscle contraction in peripheral and central airways Dynamic hyperinflation during exercise

Facts About COPD

Cigarette smoking is the primary cause of
COPD.

In the US 47.2 million people (28% of

men and 23% of women) smoke.

The WHO estimates 1.1 billion smokers

worldwide, increasing to 1.6 billion by 2025. In low- and middle-income countries, rates are increasing at an

Asthma and COPD are both characterised by inflammation

Asthma

COPD

Mast cell CD4+ T-cell IL-8 IL-4 IL-13

Neutrophil Eosinophil

Macrophage CD8+ T-cell IL-8 TNF LTB4

Pathogenesis of COPD
NOXIOUS AGENT
(tobacco smoke, pollutants, occupational agent)
Genetic factors Respiratory infection Other

COPD

COPD: a multi-component airway disease

Airway inflammation

Mucociliary dysfunction

Airway obstruction

Airway structural changes

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

Pathophysiological features of COPD

Airway obstruction

Normal

COPD

Smooth muscle contraction

Increased cholinergic tone Bronchial hyperreactivity
Parenchymal tethering Loss of tethering

Loss of elastic recoil

Pathophysiological features of COPD

Airway inflammation

Sputum inflammatory cell levels

p = 0.0001 100 90 80 70 60 50 40 30 20 10 0 Sputum neutrophils (%)

Increased numbers/ activation: - neutrophils, - macrophages, - CD8+ lymphocytes Elevated IL-8, TNF, LTB4 Protease/anti-protease imbalance

Mucosal oedema

COPD

Healthy

Rutgers et al, 2000

Pathophysiological features of COPD

Airway inflammation

Relationship between airway protein leakage and spirometry in COPD

7

Protein leak (%)

5 4 3 2 1 0 0 20 40 60 80 100 120 FEV1 (% predicted)

Increased numbers/ activation: - neutrophils, - macrophages, - CD8+ lymphocytes Elevated IL-8, TNF, LTB4 Protease/anti-protease imbalance Mucosal oedema

Hill et al, 1999

Pathophysiological features of COPD

Airway structural changes

Asthma

Alveolar destruction
Epithelial hyperplasia Glandular hypertrophy Goblet cell metaplasia Airway fibrosis

COPD

Pathophysiological features of COPD

Mucociliary dysfunction

Healthy

Mucus hypersecretion Increased mucus viscosity Reduced mucociliary transport Mucosal damage

H. influenzae

Pathophysiological features of COPD

Airway obstruction Airway inflammation Airway structural changes Mucociliary dysfunction

Smooth muscle contraction

Increased cholinergic tone

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

Alveolar destruction
Epithelial hyperplasia Glandular hypertrophy Goblet cell metaplasia

Mucus hypersecretion
Increased mucus viscosity Reduced mucociliary transport Mucosal damage

Bronchial hyper- Elevated IL-8, TNF, LTB Airway fibrosis 4 reactivity Protease/anti-protease Loss of elastic recoil imbalance Mucosal oedema

Pathophysiological/clinic al features of COPD

Systemic component

Weight loss Poor nutritional status/reduced BMI Impaired skeletal muscle function: - Weakness

- Wasting

Clinical Feature
Age of onset

Asthma
Early childhood, at any age

COPD
Mid-late adult life

Smoking history
Atopy Exacerbations

Non-, ex-, or current smoker

History of atopic present Common at all levels of severity

smoker or exsmoker
Absent Increase with increasing of severity Absent

Family history (atopy)

present

Clinical Feature
Lung function

Asthma
Normal/obstruction

COPD
Airflow obstruction a hallmark of COPD Poorly reversible Often does not vary at all Abnormal when There is emphysema

Reversibility

Characteristic of asthma

Peak flow variability Characteristic of asthma, usually > 20 % Diffusing capacity Usually normal

MINIMUM REQUIREMENTS FOR THE DIAGNOSIS OF ASTHMA AND COPD

Symptom and history Physical examination Lung function tests Spirometry PEF Reversibility to bronchodilator

ADDITIONAL TESTS

Reversibility to steroids Diffusion capasity Airway hyperresponsiveness Allergy tests Imaging Assessment of airway inflammation Sputum Exhaled nitric oxide

Ancillary test

Asthma

COPD

Reversibility to steroids Lung volumes Diffusion capacity Airway hyperresponsiveness Allergy tests Imaging of the chest Sputum Exhaled NO

Usually present Usually normal Usually normal Usually increased Usually positive Usually normal Eosinophilia Usually increased

Usually absent Usually increased Decreased Usually increased Usually negative Usually abnormal Neutrophilia Usually normal

Biochemical markers in induced sputum of stable asthma and COPD patients

Asthma COPD

Eosinophil cationic protein Myeloperoxidase Human neutrophil lipocalin Interleukin- Tumor necrosis factor- Leukotriene B4

+++ ++ ++

+ +++ ++++ +++ ++ +++

30% of patients with fixed airflow limitations have a history of asthma

Asthma : CD 4 Eosinophil Increase thickness of the reticular layer COPD : CD 8 Macrophage Neutrophil

CLASSIFICATION OF COPD
GOLD 2001 DEGREE Degree null risk Degree I Mild copd GOLD 2003 DEGREE Degree null risk Degree I Mild copd CLINICAL SYMPTOM Clinical;cough,sputm production With or without clinical symptom( production sputum) SPYROMETRY normal

FEV1/FVC<70%, FEV180% prediksi

Degree IIA Moderate COPD

Degree II Moderate COPD

With or without clinical symptom( cough,sputum production) increase in sypmtom short of breathing
With or without clinical symptom,increase in symptom short of breth + sign of respiratory and right ventricle failure

FEV1/FVC<70%, 50%<FEV1<80% prediction

Degree IIB Moderate COPD Degree III Severe COPD

DEGREE III Severe COPD Degree IV Very severe COPD

FEV1/FVC<70% 30%<FEV1<50% prediction FEV1/FVC<70% FEV1<30% prediction

Fabbry et al, 2003

Inflammatory Markers Eosinophil > CD4 > CD4/CD8 > Thicker reticular layer Higher level of exhaled NO

HRCT scanning in patients with Asthma and COPD

Mild-to persistent asthma Severe asthma COPD Healthy

Bronchial wall thickening Emphysema Bronchiectasis

++

+++

+ +

++ ++

+++ -

GOLD Workshop Report

Four Components of COPD Management

1. Assess and monitor disease 2. Reduce risk factors 3. Manage stable COPD

Education

Pharmacologic
Non-pharmacologic

4. Manage exacerbations

Objectives of COPD Management

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

Assess and Monitor Disease: Key Points

Diagnosis of COPD is based on a history of exposure to risk factors and the presence of airflow limitation that is not fully reversible, with or without the presence of symptoms.

Assess and Monitor Disease: Key Points

For the diagnosis and assessment of COPD, spirometry is the gold standard. Health care workers involved in the diagnosis and management of COPD patients should have access to spirometry.

Direct and Indirect Costs of COPD, 1993 (US $ Billions)

Direct Medical Cost:

$14.7

Total Indirect Cost: Mortality related IDC

$ 9.2
4.5 4.7

Morbidity related IDC

Total Cost

$23.9

Assess and Monitor Disease: Key Points

Measurement

of arterial blood gas tension should be considered in all patients with FEV1 < 40% predicted or clinical signs suggestive of respiratory failure or right heart failure.

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 more convenient. Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

Manage Stable COPD Key Points

Regular treatment with inhaled glucocortico-steroids should only be prescribed for symptomatic COPD patients with a documented spirometric response to glucocorticosteroids or in those with an FEV1 < 50% predicted and repeated exacerbations requiring treatment with antibiotics and/or oral glucocorticosteroids (Evidence B).

Manage Stable COPD Key Points

Chronic treatment with systemic glucocortico-steroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).

All COPD-patients benefit from exercise

training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

Manage Stable COPD Key Points

The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).

Management of COPD: All stages

Avoidance of noxious agents

- smoking cessation - reduction of indoor pollution - reduction of occupational exposure

Influenza vaccination

Manage Exacerbations Key Points

Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD.

The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).

Manage Exacerbations Key Points

Inhaled bronchodilators (Beta2-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocortico-steroids are effective for the treatment of COPD exacerbations (Evidence A).

Manage Exacerbations Key Points

Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased volume and change of color of sputum, and/or fever) may benefit from antibiotic treatment (Evidence B)

Manage Exacerbations Key Points

Noninvasive intermittent positive pressure ventilation (NIIPPV) in acute exacerbations improves blood gases and pH, reduces inhospital mortality, decreases the need for invasive mechanical ventilation and intubation, and decreases the length of hospital stay (Evidence A).

Conclusion
1.

2.

Differential diagnosis between asthma and COPD becomes more difficult in elderly and when the patient develops a poorly reversible airflow limitation that responds only partially to treatment The noninvasive measurement of eosinophil in sputum and exhaled NO might be clinically useful to distinguish asthma from COPD