Pathological & Clinical Aspects of COPD

Question 1

Define COPD [4]

Answer 1

• disease characterised by airflow obstruction that is:
  
  • usually progressive,
  • not fully reversible
  • does not change markedly over several months

Question 2

What are the risk factors/causes of COPD? [5]

Answer 2

1. Smoking (major)
2. Environmental pollution
3. Burning of biomass fuels
4. Occupational dusts
5. Alpha I anti-trypsin deficiency

Question 3

Describe the effects of cigarette smoke on the lung [6]

Answer 3

1. Cilial motility is reduced
   
   • Cilia are damaged/destroyed by smoking which results in:
     
     • increased infections (due to not being able to clear secretions easily)
     • damaged lung
2. Airway inflammation
   
   • Proteases are released from inflammatory cells
3. Mucus hypertrophy and hypertrophy of Goblet cells
4. Increased protease activity, anti-proteases inhibited
5. Oxidative stress → production of free radicals
6. Squamous metaplasia → higher risk of lung cancer

Question 4

What are the 2 clinical syndromes of COPD? [2]

Answer 4

1. chronic bronchitis
2. emphysema

Question 5

Define chronic bronchitis [1]

Answer 5

the production of sputum on most days for at least 3 months in at least 2 years

Question 6

Define emphysema [1]

Answer 6

abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles

Question 7

Describe the main macroscopic features in both early and late chronic bronchitis [5]

Answer 7

1. Chronic bronchitis main macroscopic features:
   
   • larger airways > 4mm in diameter
   • Inflammation leading to scarring and thickening of airways
2. Small airway disease (earlier on)
   
   • “Bronchiolitis” in airways of 2-3 mm
   • May be an early feature of COPD
   • Narrowing of the bronchioles due to:
     
     • mucus plugging,
     • inflammation
     • fibrosis

Question 8

What are the 3 main cell types involved in COPD inflammation? [3]

Answer 8

1. Macrophages,
2. CD8 (predominately) and CD4 T lymphocytes,
3. Neutrophils

Question 9

What are the inflammatory mediators involved in COPD inflammation? [9]

Answer 9

1. TNF, IL-8 and other chemokines
2. Neutrophil elastase, proteinase 3, cathepsin G
   
   • (from activated neutrophils)
3. Elastase and MMPs
   
   • (from macrophages)
4. Reactive oxygen species

Question 10

Name the 3 types of emphysema [3]

Answer 10

1. centri-acinar
2. pan-acinar
3. para-septal

Question 11

Describe the features of centri-acinar emphysema [2]

Answer 11

1. Dilatation/damage around respiratory bronchioles, the central portion of the acinus
2. Present more in upper lobes

Question 12

Describe the features of pan-acinar emphysema and what is it associated with? [3]

Answer 12

1. Uniformly enlarged/damaged of all parts of the acinus from the level of terminal bronchiole distally to the terminal blind alveoli
2. Can get large bullae
3. Associated with α1 anti-trypsin deficiency

Question 13

What are bullae? [1]

Answer 13

thin-walled air-filled space within the lung, typical of pan-acinar emphysema

Question 14

What is para-septal emphysema and what does it increase your risk of? [2]

Answer 14

1. Damage round the edges of the lungs
2. Increases risk of pneumothorax

Question 15

What are the 2 types of emphysema that cause airflow obstruction and what is the eventual complication of these types of emphysema? [3]

Answer 15

1. centri-acinar
2. pan-acinar
3. results in consequent loss of surface area for gas exchange → eventually leading to hypoxaemia

Question 16

Describe the mechanisms of airflow obstruction in COPD [10]

Answer 16

1. Loss of elasticity and alveolar attachments due to emphysema resulting in airway collapse on expiration
   
   • causes air trapping and hyperinflation → increased work of breathing → breathlessness
2. Goblet cell metaplasia with mucus plugging of lumen
3. Inflammation of the airway wall
4. Thickening of the bronchiolar wall due to:
   
   • smooth muscle hypertrophy
   • peribronchial fibrosis

Question 17

What features of COPD can be seen on a chest x-ray? [5]

Answer 17

1. Over-inflation
2. Low and flattened diaphragms
3. Bullae
4. Pruned blood vessels with large proximal vessels
5. Relatively little blood visible in peripheral lungs

Question 18

What factors should make you consider a diagnosis of COPD? [7]

Answer 18

1. Consider the diagnosis of COPD for people who are over 35yrs, and smokers or ex-smokers, with any of:
   
   • exertional breathlessness
   • chronic cough
   • regular sputum production
   • frequent winter ‘bronchitis’
   • wheeze

Question 19

How can COPD be classified in terms of spirometry (after being given a bronchodilator)? [6]

Answer 19

• spirometry shows an obstructive pattern (FEV₁/FVC ratio <70%, both reduced)
• Stage 1 (mild) → FEV₁ %predicted = 80%
• Stage 2 (moderate) → FEV₁ %predicted = 50-79%
• Stage 3 (severe) → FEV₁ %predicted = 30-49%
• Stage 4 (very severe) → FEV₁ %predicted = <30%

Question 20

What are the treatment options for COPD? [6]

Answer 20

1. Inhaled bronchodilators
   
   • Short-acting: salbutamol
   • Long acting: salmeterol, tiotropium
2. Inhaled corticosteroids
   
   • Budesonide and fluticasone — combination inhalers
3. Oxygen therapy
4. Oral theophyllines
5. Mucolytics
   
   • carbocysteine
6. Nebulised therapy

Question 21

What are 2 non-pharmacological approaches to the management of COPD? [2]

Answer 21

1. smoking cessation
2. pulmonary rehabilitation

Question 22

What are the typical features of type 1 respiratory failure? [9]

Answer 22

1. “pink puffer”
2. high respiratory drive
3. ↓PaO2, ↓PaCO2
4. desaturates on exercise
5. pursed lip breathing
6. use accessory muscles
7. wheeze
8. indrawing of intercostals
9. tachypnoea

Question 23

What are the typical features of type 2 respiratory failure? [10]

Answer 23

1. “blue bloater”
2. low respiratory drive
3. ↓PaO2, ↑PaCO2,
4. cyanosis
5. warm peripheries
6. bounding pulse
7. flapping tremor
8. confusion, drowsiness,
9. right heart failure
10. Oedema, raised JVP

Question 24

There are key differences between asthma and COPD. What are the defining inflammatory processes in COPD? [6]

• hint:
  
  • what type of agent induces COPD? [1]
  • cells involved in COPD airway inflammation [3]
  • features of airflow limitation [2]

Answer 24

1. noxious agent
2. COPD airway inflammation:
   
   • CD8+ T lymphocytes
   • neutrophils
   • macrophages
3. airflow limitation:
   
   • irreversible
   • usually progressive if exposure to noxious agents continue

Question 25

There are key differences between asthma and COPD. What are the defining inflammatory processes in asthma? [4]

• hint:
  
  • what type of agent induces asthma? [1]
  • cells involved in asthma airway inflammation [2]
  • features of airflow limitation [1]

Answer 25

1. Sensitising agent
2. Asthmatic airway inflammation
   
   • CD4+ T lymphocytes
   • Eosinophils
3. Airflow limitation is completely reversible spontaneously or with treatment

Question 26

There are key differences between asthma and COPD. Describe the clinical features of asthma under the following headings:

1. smoker or ex-smoker? [1]
2. symptoms under 35yrs? [1]
3. chronic productive cough? [1]
4. breathlessness? [1]
5. night time waking with breathlessness and/or wheeze? [1]
6. significant diurnal or day-to-day variability of symptoms? [1]

Answer 26

1. possibly
2. often
3. uncommon
4. variable
5. common
6. common

Question 27

There are key differences between asthma and COPD. Describe the clinical features of COPD under the following headings:

1. smoker or ex-smoker? [1]
2. symptoms under 35yrs? [1]
3. chronic productive cough? [1]
4. breathlessness? [1]
5. night time waking with breathlessness and/or wheeze? [1]
6. significant diurnal or day-to-day variability of symptoms? [1]

Answer 27

1. nearly all
2. rare
3. common
4. persistent and progressive
5. uncommon
6. uncommon