Pathological and Clinical Aspects of COPD

Question 1

What is the definition of COPD?

Answer 1

• Progressive airflow obstruction that is not fully reversible and does not change markedly over several months

Question 2

What are the common causes of COPD?

Answer 2

• Smoking
• Alpha 1 antitrypsin deficiency

Question 3

What is the pathogenesis of COPD?

Answer 3

• Loss of elasticity and alveolar attachements due to emphysema (airways collapse on expiration causing air trapping, hyperinflation, increased work of breathing and SOB)
• Goblet cell metaplasia with mucus plyggung of lumen
• Inflammation of the airway wall
• Thickening of bronchiolar wall (smooth muscle hypertrophy and peribronchial fibrosis)

Question 4

What is chronic bronchitis?

Answer 4

• Production of sputum on most days for at least 2 months in at least 2 years
• Larger airways >4mm in diameter
• Develop airway inflammation (predominantly neutrophilic with CD8 cytotoxic lymphocytes and some eosinophils which leads to scarring and thickening of the airways)
• Inflammatory mediators include TNF, IL-8, neutrophil elastase, proteinase 3, cathespin G, elastase and MMPs from macrophages and ROS
• Squamous metaplasia and as tissue is destroyed you lose the interstitial support of the tissue around the bronchioles making them more collapsible

Question 5

What is emphysema?

Answer 5

• Abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles
• Four general types but centri-acinar (damage around respiratory bronchioles) and pan-acinar (uniformly enlarged from the level of terminal bronchiole distally) are most important

Question 6

What are the stages of COPD?

Answer 6

• 1) Mild - FEV1 80%
• 2) Moderate - FEV1 50-79%
• 3) Severe - FEV1 30-49%
• 4) Very severe - FEV1 <30% or <50% with respiratory failure

Question 7

What does type 1 respiratory failure look like?

Answer 7

• Pink puffer
• High respiratory drive
• ↓PaO₂, ↓PaCO₂
• Signs and symptoms include desaturation on exercise, pursed lip breathing, use of accessory muscles, wheeze, indrawing of intercostals and tachypnoea

Question 8

What does type 2 respiratory failure look like?

Answer 8

• Low respiratory drive
• Type 2 respiratory failure
• ↓PaO₂, ↑PaCO₂
• Signs and symptoms include cyanosis, warm peripheries, bounding pulse, flapping tremor, confusion, drowsiness, right heart failure, oedema and raised JVP

Question 9

What are the processes in asthmatic airway inflammation?

Answer 9

• CD4+ lymphocytes
• T lymphocytes
• Eosinophils

Question 10

What are the processes involved in COPD airway inflammation?

Answer 10

• CD8+
• T lymphocytes
• Macrophages
• Neutrophils

Question 11

Why does cigarette smoking cause COPD?

Answer 11

• Cigarette smoking leads to reduced cilial motility, neutrophilic inflammation, mucus hypertrophy and Goblet cells, increased protease activity against anti-protease inhibition leading to more damage to tissues in the lungs (i.e. α1 antitrypsin is one of the main anti-proteases) and oxidative stress. Furthermore it can lead to squamous metaplasia.

Question 12

Long term management of COPD

Answer 12

• Smoking cessation
• Pneumococcal and annual flu vaccine
• Step 1 - beta-2 agonists (i.e. salbutamol, terbutaline) or short acting antimuscarinics (i.e. ipratropium bromide)
• Step 2
  
  • If no asthmatic or steroid responsive features then LABA (i.e. salmeterol) plus LAMA (i.e. tiotropium)
  • If asthmatic or steroid responsive features then LABA (i.e. salmeterol) plus inhaled corticosteroid (i.e. (budenoside, fluticasone)
• Step 3 - Combination of LABA, LAMA and ICS
• Inhaled bronchodilators (salbutamol, salmeterol)
• In severe cases can use nebulisers, oral theophylline, oral mucolytics (i.e. carbocysteine), long-term prophylactic antibiotics (i.e. azithromycin) and LTOT

Question 13

Presentation of COPD

Answer 13

• Chronic SOB
• Sputum production
• Wheeze
• Recurrent respiratory infections

Question 14

Diagnosis of COPD

Answer 14

• FEV1/FVC ratio <0.7 (obstructive picture)
• No reversibility (as seen in asthma)
• CXR to rule out lung cancer
• FBC for polycythaemia or anaemia (raised Hb is sign of chronic hypoxia)
• Transfer factor for carbon monoxide/TLCO is decreased in COPD - can indicate severity of disease

Question 15

When LTOT is considered

Answer 15

• Chronic hypoxia
• Polycythaemia
• Cyanosis
• HF secondary to pulmonary HTN

NB - Can’t be used if patient is still smoking.

Question 16

Management of acute exacerbation of COPD

Answer 16

• Investigations include:
  
  • ABG to identify respiratory failure
  • CXR to look for pneumonia
  • ECG for arrhythmia or evidence of heart strain
  • FBC for infection (WCC)
  • U&E for electrolytes
  • Sputum culture
  • Blood cultures if septic
• Management includes:
  
  • O2 titrated to saturations as too much can depress their hypoxic respiratory drive - venturi masks
  • If can be treated at home:
    
    • Prednisolone PO
    • Regular inhalers or home nebulisers
    • Antibiotics if evidence of infection
  • In hospital:
    
    • Nebuliser bronchodilators (i.e. salbutamol)
    • Steroids PO or INH
    • Antibiotics if evidence of infection
    • PT to clear sputum
  • If not responsive to treatment:
    
    • IV aminophylline
    • NIV
    • Intubation and ventilation
    • Doxapram as a respiratory stimulant where NIV or intubation is not an option