Restrictive lung disease

Question 1

What do type 1 pneumocytes release when damaged?

Answer 1

Transforming growth factor beta-1

TGFB1

Question 2

What is the role of TGFB-1?

Answer 2

To stimulate type 2 pneumocytes

Question 3

What occurs when type 2 pneumocytes are stimulated?

Answer 3

stimulated type 2 pneumocytes will activate fibroblast cells
fibroblast cells proliferate and differentiate into myofibroblast cells
myofibroblast cells secrete collagen fibres and elastic fibres and then undergo cell death

Question 4

What type of collagen fibres are secreted by myofibroblasts?

Answer 4

Reticular/type III

Question 5

Describe the pathophysiology of idiopathic pulmonary fibrosis (IPF).

Answer 5

• T2 pneumocytes overproliferate
• Additional stimulation of myofibroblasts
• therefore more collagen is produced
• however, the myofibroblasts do not undergo apoptosis = even more collagen
• interstitium becomes thicker = impairs gas exchange
• stiffens the lungs = restricted lung expansion

Shape of the alveoli becomes distorted and there is scarred interstitium –> this increases the distance between blood vessels and alveolus, impairing gas exchange

*cause is unknown

Question 6

What are the signs of IPF?

Answer 6

Cyanosis

Clubbing

Question 7

What are the symptoms of IPF?

Answer 7

Progressive
Dry cough 
Exertional dyspnoea
Malaise
Weight loss
Arthralgia

Question 8

What are the risk factors for IPF?

Answer 8

Smoking (most important RF)
environmental factors/occupational exposures
increased age
male
GORD

Question 9

How is IPF diagnosed?

Answer 9

CT scan: honeycomb pattern (loss of alveoli, increased fluid filled spaces -cysts- surrounded by thick interstitium)

Spirometry: reduced TLC, FVC and FEV

Question 10

How is IPF treated?

Answer 10

• Remove risk factors
• Supplemental O2
• Pulmonary rehab
• Pirfenidone: immunosuppressed with antifibrotic = reduced lung scarring and increased life expectancy
• Nintedanib: tyrosine kinase inhibitor –> targets 3 growth factor receptors involved in IPF
• Antacids (if accompanied by reflux)
• Lung transplant (rare)

Question 11

What is sarcoidosis and who does it affect most?

Answer 11

Multisystem granulomatous disease
Occurs when large amount of granulomas accumulate in areas of the body (lungs, eyes, skin, lymphatics)
Cause is unknown

More common in females, usually 20-40 y/o
More common in Afro-Caribbean

Question 12

Which class(es) of HLA is sarcoidosis associated with?

Answer 12

MHC Class II

usually HLA-DRB1 and HLA-DQB1

Question 13

How does sarcoidosis generally present?

Answer 13

General:

• fatigue
• weakness
• aching of muscles
• swollen lymph nodes
• lack of appetite
• weight loss

Question 14

How is sarcoidosis diagnosed?

Answer 14

• 20-40% incidental finding on routine CXR –> bilateral hilar lymphadenopathy
• blood test: high ACE, immunoglobulins and calcium
• biopsy of lung: most accurate diagnostic test

Question 15

What is Löfgren syndrome?

Answer 15

Type of acute sarcoidosis 
Characterised by:
- acute hilar lymphadenopathy* (on CXR)
- fever 
- erythema nodosum* 
- polyarthralgia*
- arthritis 

• = Löfgren triad

Question 16

How is sarcoidosis treated?

Answer 16

• may not always need treatment
• 60% make spontaneous recovery within 2 years
• 20% need steroid therapy –> prednisolone
• use MTX if steroids are ineffective
• Very severe cases might require lung transplant

Question 17

What are the pulmonary symptoms associated with sarcoidosis?

Answer 17

Pulmonary:

• 90% have granulomas in lungs
• SOB
• Wheeze
• Dry cough

Question 18

How does sarcoidosis affect the skin?

Answer 18

Skin:

• Erythema nodosum
• Rash
• Lupus pernio (raised purplish lesion, usually affecting face)

Question 19

How does sarcoidosis affect the eyes?

Answer 19

Eyes:

• Blurred vision
• Photophobia
• Tearing
• Blindness