Chronic Obstructive Pulmonary DiseaseChronic Obstructive Pulmonary Disease

Hou-haifengHou-haifeng

LUNG STRUCTURE

NORMAL VENTILATORY FUNCTIONNORMAL VENTILATORY FUNCTION• Diaphragm contracts and descends, rib cage moves Diaphragm contracts and descends, rib cage moves

upwards and outward.upwards and outward.• Pressure in the thorax is less than in the mouth so air Pressure in the thorax is less than in the mouth so air

flow into the lungs occurs.flow into the lungs occurs.• In expiration diaphragm relaxes and moves upwards, the In expiration diaphragm relaxes and moves upwards, the

rib cage moves inward.rib cage moves inward.• Expiration is passive so no muscular contraction is Expiration is passive so no muscular contraction is

needed.needed.• Lung tissue is intrinsically elastic and has a natural ability Lung tissue is intrinsically elastic and has a natural ability

to recoil.to recoil.• During exercise expiration is aided by the contraction of During exercise expiration is aided by the contraction of

abdominal and thoracic expiratory muscles.abdominal and thoracic expiratory muscles.• Contractions generate positive pressure in the thorax Contractions generate positive pressure in the thorax

pushing air out.pushing air out.

COPD DISORDERSCOPD DISORDERS

– Chronic BronchitisChronic Bronchitis– EmphysemaEmphysema– Asthma (?)Asthma (?)

Although not strictly a COPD disorder ASTHMA is often Although not strictly a COPD disorder ASTHMA is often linked with being a COPD disorder.linked with being a COPD disorder.

DEFINITIONDEFINITION Progressive, non-reversible, obstructive airway Progressive, non-reversible, obstructive airway

disease leading to damaged alveolar walls and disease leading to damaged alveolar walls and inflammation of the conducting airwaysinflammation of the conducting airways

• Some part of the airway becomes obstructed or no longer functions efficiently

CHRONIC OBSTRUCTIVE CHRONIC OBSTRUCTIVE PULMONARY DISEASE:PULMONARY DISEASE:

Pathogenesis of COPDNOXIOUS AGENT

(tobacco smoke, pollutants, occupational agent)

COPD

Genetic factorsRespiratory infectionOther

Noxious particles and gases

Lung inflammationHost factors

COPD pathology

ProteinasesOxidative stress

Anti-proteinasesAnti-oxidants

Repair mechanisms

MECHANISMSMECHANISMS

Bronchial glands / cells inflame Bronchial glands / cells inflame Increased secretionsIncreased secretions

Inflammation spreads to smooth muscle (bronchiole)Inflammation spreads to smooth muscle (bronchiole)Airway obstruction, decreased ciliary actionAirway obstruction, decreased ciliary action

Air trapping / Collapse of small airwaysAir trapping / Collapse of small airwaysFurther air trappingFurther air trapping

HyperventilationHyperventilationIncreased pressure in airwaysIncreased pressure in airways

Weakened airway walls / wall destructionWeakened airway walls / wall destructionAlveolar destructionAlveolar destruction

Overstressed right ventricleOverstressed right ventricle

MECHANISMS IIMECHANISMS IIIncreases in RBC, Blood viscosity, BPIncreases in RBC, Blood viscosity, BP

Ventilation / Perfusion imbalancesVentilation / Perfusion imbalancesHypoxemiaHypoxemia

Carbon dioxide retentionCarbon dioxide retentionBronchial hyperreactivityBronchial hyperreactivity

HyperinflationHyperinflation

CHRONIC BRONCHITISCHRONIC BRONCHITIS• Chronic bronchitis is defined as "persistent cough with sputum Chronic bronchitis is defined as "persistent cough with sputum

production for at least 3 months in at least two consecutive production for at least 3 months in at least two consecutive years". years".

• The most important cause of chronic bronchitis is recurrent The most important cause of chronic bronchitis is recurrent irritation of the bronchial mucosa by inhaled substances, as irritation of the bronchial mucosa by inhaled substances, as occurs in cigarette smokers.occurs in cigarette smokers.

• The pathological hallmarks of chronic bronchitis are congestion The pathological hallmarks of chronic bronchitis are congestion of the bronchial mucosa and a prominent increase in the number of the bronchial mucosa and a prominent increase in the number and size of the bronchial mucus glands. Copious mucus may be and size of the bronchial mucus glands. Copious mucus may be seen within airway lumens. The terminal airways are most seen within airway lumens. The terminal airways are most susceptible to obstruction by mucus.susceptible to obstruction by mucus.

CHRONIC BRONCHITISCHRONIC BRONCHITISAetiologyAetiology

– Characterised by a chronic cough and excessive sputum Characterised by a chronic cough and excessive sputum production.production.

– There is an enlargement and an increased density of mucous There is an enlargement and an increased density of mucous glands.glands.

– The airway becomes thickened and the surface irregularThe airway becomes thickened and the surface irregular– Bronchial inflammation. (ACSM, 1998)Bronchial inflammation. (ACSM, 1998)– Reduced number of ciliated cellsReduced number of ciliated cells– Causes an increase in air flow resistanceCauses an increase in air flow resistance– In chronic severe cases right heart failure occursIn chronic severe cases right heart failure occurs– Plugged airways and decreased ciliary action encourages Plugged airways and decreased ciliary action encourages

stagnant bronchial secretions and an increased risk of stagnant bronchial secretions and an increased risk of infection.infection.

CHRONIC BRONCHITISCHRONIC BRONCHITIS

• Inflammatory cells produce elastase Inflammatory cells produce elastase • Destroys connective tissue of alveolar Destroys connective tissue of alveolar

walls walls • Alpha-1 anti-trypsin (or alpha-1 Alpha-1 anti-trypsin (or alpha-1

protease inhibitor) is a protein produced protease inhibitor) is a protein produced by the liver that circulates in the blood by the liver that circulates in the blood and limits the action of elastase and limits the action of elastase

MUCUS PRODUCTIONMUCUS PRODUCTION

MUCUS PRODUCTIONMUCUS PRODUCTION

CHANGES IN LUNG VOLUMESCHANGES IN LUNG VOLUMES

VENTILATION COSTVENTILATION COST

• In COPD work of breathing is greater for any given In COPD work of breathing is greater for any given level of ventilation than normal.level of ventilation than normal.

VENTILATIONVENTILATION

WORK OF WORK OF BREATHINGBREATHING

NORMAL COPDNORMAL COPD

SEVERE COPDSEVERE COPD

MODERATE COPDMODERATE COPDThe cost of work at a The cost of work at a given ventilation for given ventilation for ‘normal’ and COPD ‘normal’ and COPD patients (ACSM, patients (ACSM, 1998)1998)

EMPHYSEMAEMPHYSEMAAETIOLOGYAETIOLOGY

Can be caused by smoking, air pollution and Can be caused by smoking, air pollution and environmental and occupational hazardsenvironmental and occupational hazards

Main characteristic is loss of lung elasticity and Main characteristic is loss of lung elasticity and reduction of elastic recoil due to alveolar destruction reduction of elastic recoil due to alveolar destruction

Destruction of elastic tissue leads to loss of elastic Destruction of elastic tissue leads to loss of elastic recoil of lungs during expiration and forced expiration recoil of lungs during expiration and forced expiration necessitatednecessitated

Eventual destruction of airway / capillary membranesEventual destruction of airway / capillary membranes Destruction due to increased protease production or a Destruction due to increased protease production or a

deficiency in anti-proteasedeficiency in anti-protease

EFFECTS OF EMPHYSEMA ON EFFECTS OF EMPHYSEMA ON HEALTHHEALTH

• Reduction in expiratory flow levelReduction in expiratory flow level• Patients are thin with general muscle wastage.Patients are thin with general muscle wastage.• Lung diffusion capacity is reduced due to loss of Lung diffusion capacity is reduced due to loss of

alveolar capillary unitsalveolar capillary units• Lactic acid threshold is much lower in COPD

patients• Exercise tolerance impaired

SYMPTOMScough

sputumdyspnea

EXPOSURE TO RISKFACTORS

tobaccooccupation

indoor/outdoor pollution

SPIROMETRY

Diagnosis of COPD

Spirometry: Normal and COPDSpirometry: Normal and COPD

0

5

1

4

2

3

Lite

r

1 65432

FVC

FVC

FEV1

FEV1

Normal

COPD

3.9005.200

2.3504.150 80 %

60 %NormalCOPD

FVCFEV1 FVCFEV1/

Seconds

MEDICAL THERAPYMEDICAL THERAPY BRONCHODILATORS BRONCHODILATORS

Adrenergic agentsAdrenergic agents • Beta-agonists bind to BBeta-agonists bind to B2 2 receptors on airway and result in smooth muscle relaxation and receptors on airway and result in smooth muscle relaxation and

bronchodilation bronchodilation • Inhaled route is preferred Inhaled route is preferred • Acute relief of symptomsAcute relief of symptoms

Anti-cholinergic agents Anti-cholinergic agents Bind to acetylcholine receptors and result in bronchodilation (of mostly larger airways) Bind to acetylcholine receptors and result in bronchodilation (of mostly larger airways) • Reduces sputum production Reduces sputum production • Inhaled route is preferred Inhaled route is preferred

MethylxanthinesMethylxanthines (i.e. theophylline) (i.e. theophylline) • Weak bronchodilator Weak bronchodilator • Delays respiratory muscle fatigue Delays respiratory muscle fatigue • Reduces trapped lung gas Reduces trapped lung gas • Improves respiratory muscle mechanicsImproves respiratory muscle mechanics

MEDICAL THERAPYMEDICAL THERAPY

Corticosteroids Corticosteroids • Reduce airway inflammation Reduce airway inflammation

Mucolytics Mucolytics • Alter viscosity of sputum Alter viscosity of sputum • May reduce symptoms in some patients May reduce symptoms in some patients • Must be used carefully (i.e. avoiding hypotension) Must be used carefully (i.e. avoiding hypotension)

EXERCISEEXERCISE

• Increase exercise toleranceIncrease exercise tolerance• Increase quality of lifeIncrease quality of life• Improve co-ordination and efficiency of Improve co-ordination and efficiency of

movementmovement• Improve strength particularly respiratory Improve strength particularly respiratory

musclesmuscles• Encourage relaxationEncourage relaxation• Confidence in physical abilitiesConfidence in physical abilities• FlexibilityFlexibility

What we want to doWhat we want to do

• As we all know there is so much data on the As we all know there is so much data on the patients deposited in the patients deposited in the hospital,however,that is not well exploitedhospital,however,that is not well exploited

• So we want to use these data to make a So we want to use these data to make a disease model to help doctors to make a disease model to help doctors to make a appropriate diagnostic and therapeutic appropriate diagnostic and therapeutic scheme for the patients with COPDscheme for the patients with COPD

• We also can use this model to predict the We also can use this model to predict the progress of the disease and the prognosisprogress of the disease and the prognosis

COPDDisease Model

Disease progress prognosis

doctortherapeutic

scheme

mathematics, statistics, cybernetics, system

theory, computer science

The information from the data base in the

hospital

The information from the data base in the

hospital

The knowledge of medicine(Pathology

Physiology Pharmacology…)

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