copd review. progressive syndrome expiratory airflow obstruction chronic airway and lung parenchyma...
TRANSCRIPT
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 ages
Smoking Hx >10 pack years None, minimal
Sputum CB frequent Frequent, clear
Allergies Infrequent Frequent
Course 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 Stages
COPD 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