COPD

Review

• Progressive• Syndrome• Expiratory airflow obstruction• Chronic airway and lung parenchyma

inflammation

• Preventable, treatable• 24 million adults in US• 4th leading cause of death in US:

– Heart disease– Cancer– Stroke – COPD– Accidents– Diabetes

• GOLD: global initiative for chronic obstructive lung diseasae– Expiratory airflow not fully reversible– Progressive, association with an “abnormal”

lung response to noxious gases and particles

• Two major clinical types– Chronic bronchitis: inflammation of small and

medium sized airways– Leads to expiratory defect, chronic cough,

sputum production and dyspnea

• Emphysema– Inflammation of lung parenchyma– Loss of elastic recoil of lungs– Airflow limitation– Hypoxemia– dyspnea

COPD

• Irreversible airflow (as measured by FEV1 or FEV1/FVC) caused by:– Increased airway resistance in the conducting

airways, or,– Increased lung compliance due to destruction

of lung parenchyma/elasticity• Or a combination of both the above

Chronic Bronchitis

• Inflammation of the central airways (airways >4mm diameter and peripheral airways < 2 mm)

• Extends to gland ducts and into the mucus producing glands– This produces increase mucus– Defective mucociliary clearance– Disruption (destruction) of epithelial barrier

• Airflow obstruction occurs primarily in the small airways which are <2mm diameter

Emphysema

• Decrease in elastic recoil force needed to drive air out of lung (“paper sack”)

• Centrilobular or centriacinar form is associated with cigarette smoking– Major destruction of the acinus at the

respiratory bronchiole level

• Panlobular or panacinar form is associated with alpha-1 antitrypsin disease– Destruction of the entire acinus– Occurs as a result of an imbalance of

proteolytic enzymes in lung tissue

• In both forms of the disease, the cause of COPD is inflammation, both in the airways and in lung tissue

Inflammation

• Smoking, in• Chronic Bronchitis

– Neutrophils and macrophages, lymphocytes• Emphysema

– Cellular changes in terminal bronchioles– Destruction (protease enzymes) extracellular

matrix of aleveoli– Ineffective repair mechanism

COPD vs Asthma

• Asthma– Anatomical location of inflammation– With bronchodilators and steroids, lung

function returns to normal or near-normal with occasional transient inflammation

• COPD– Anatomical (airways and lung parenchyma)– Some degree of irreversible deterioration

• Cellular differences• Asthma

– Eosinophils– Mast cells– Lymphocytes– CD4 T cells

Same cells: CB & Emphysema

• COPD– Neturophils– Macrophages– No mast cells– CD8 T cells

COPD Asthma

Age 5th decade All agesSmoking Hx >10 pack years None, minimalSputum CB frequent Frequent, clearAllergies Infrequent FrequentCourse of disease

Progressive worsening

Nonprogressive

Symptoms Persistent Intermittent

A 20 pack year smoking history indicates that the subject’s lungs have received 20 of these short cyclic exposures per day for a cumulative total of 7300 exposures per year and 146,000 exposures over the lifetime of their smoking habit.

GOLD StagesCOPD Stage Airflow Limitation

1 Mild FEV1/FVC <70% FEV1 >80% predicted

2 Moderate FEV1/FVC <70% FEV1 <50%- <80%

3 Severe FEV1/FVC <70% FEV1 <30% - <50%

4 Very severe FEV1/FVC <70% FEV1 <30% or FEV1 <50% with chronic respiratory failure

In Sum

Toxic gases and particles generated in tobacco smoke come into contact with lung tissues each time a puff of smoke is inhaled

Tissue injury recurs in a cyclic fashion as each cigarette is smoked

Chronic Bronchitis

Inflammation:mucociliary clearance disruptedepithelial barrier/defense lostincreased sputum production (goblet cells)irreversible airway remodelingairflow obstruction

Emphysema

In lung tissue, the chronic inhalation also causes inflammation, destroys elastic recoil, disrupts balance of protective, anti-protease enzymes

proteinase-antiproteniase theoryelastase-antielastase

“extracellular matrix”

Toxins/free radicals Cigarette smoke Toxins/free radicals

Stimulation of alveolar macrophages &other inflammatory cells

chemotactic factors

Airway inflammation Lung (pulmonary) inflammation&

Injury to parenchymal cells

Airflow obstruction Proteinase inhibitors (alpha1-antitrypsin)

Injury to extracellular matrix

Repair of extracellular matrix

Chronic Bronchitis Emphysema

Cough excessive sputum production dyspnea at rest

Alpha1-antitrypsin

• Neutrophil elastase linked to alpha-1 antitrypsin deficiency

• Other cells producing proteinase enzymes: macrophages, lymphocytes—still not determined

• Decreased airflow resistance (airways) and decreased elastic recoil lead to:

• Hyperinflation• V/Q mismatching, which further leads to

decreases in Pa02, increases in PaC02 with decreased ventilation

• In end-stage COPD– Cor pulmonale– Pulmonary vasoconstriction (in presence of

chronic low Pa02)– Increased pulmonary vascular resistance– Increased pressure, leading eventually to right

heart enlargement

CXR

COR Pulmonale

Emphysema