Interstitial Lung Disease (incl. CBL)

Question 1

Define interstitial lung disease [1]

Answer 1

an umbrella term for a large group of disorders that cause scarring (fibrosis) of the lungs

Question 2

Define pulmonary fibrosis [1]

Answer 2

lung disease that occurs when the lung tissue becomes damaged and scarred

Question 3

Describe the pathophysiology of pulmonary fibrosis [16]

Answer 3

1. Several precipitating factors can lead to repetitive alveolar epithelial injury. These factors include:
   
   • Age
   • Genetic factors
   • Environmental factors
   • Nature of injury
2. Repetitive alveolar epithelial injury will lead to altered alveolar microenvironment:
   
   • Oxidative stress
   • Release of chemokines and profibrotic cytokines
   • Impaired fibrinolysis
   • Eicosanoid imbalance
   • Tissue inhibitor of metalloproteinases (TIMPs) - metalloproteinases (MMPs) [TIMPs-MMPs] imbalance
3. This altered alveolar microenvironment leads to:
   
   • Dysregulated repair
   • Loss of epithelial cells
   • Accumulation of mesenchymal cells
4. This all eventually leads to fibrosis

Question 4

List the known causes of pulmonary fibrosis [4]

Answer 4

1. connective tissue disorders
   
   • rheumatoid arthritis
   • scleroderma
2. occupational
   
   • asbestos
3. medication
   
   • nitrofurantoin (antibiotic)
   • methotrexate (RA)
   • amiodarone (cardio)
4. environmental
   
   • hypersensitivity pneumonitis​

Question 5

What are the unknown causes of ILD? [3]

Answer 5

1. idiopathic pulmonary fibrosis
2. granulomatous disease: sarcoidosis
3. other (vasculitis, eosinophilic)

Question 6

Define sarcoidosis [1]

Answer 6

a multisystem inflammatory disease of unknown etiology that predominantly affects the lungs and intrathoracic lymph nodes, which is characterised by “non-necrotising granulomatous inflammation”

Question 7

Describe the typical presentation of sarcoidosis [11]

Answer 7

1. presentation depends on the extent and severity of the organ involved
2. 50% of cases:
   
   • pulmonary dyspnoea on exertion
   • cough
   • chest pain
   • haemoptysis (rare)
3. systemic symptoms occur in 45% of cases such as:
   
   • fever
   • anorexia
   • fatigue
   • night sweats
   • weight loss
4. approx. 5% of cases are asymptomatic and incidentally detected by CXR

Question 8

Describe the 4 stages of sarcoidosis based on CXR [4]

Answer 8

• Stage 1: bilateral hilar lymphadenopathy without infiltration
• Stage 2: bilateral hilar lymphadenopathy with infiltration
• Stage 3 infiltration alone
• Stage 4: fibrotic bands, bullae, hilar retraction, bronchiectasis, and diaphragmatic tenting

Question 9

Who commonly gets idiopathic pulmonary fibrosis (IPF)? [2]

Answer 9

1. Age > 50
2. More common in males (M:F = 2:1)

Question 10

List the signs [4] and symptoms [4] of IPF

Answer 10

• Symptoms:
  
  1. Progressive breathlessness (worse with exercise)
  2. Hacking dry cough
  3. Fatigue and weakness
  4. Appetite and weight loss
• Signs:
  
  1. Bibasilar crackles,
  2. Clubbing
  3. PERIPHERAL Interstitial pattern
  4. Subpleural honeycombing

Question 11

What investigations are used to diagnose IPF? [7]

Answer 11

1. Blood Tests
2. Lung Function Tests – Spirometry
   
   • showing restrictive defect
3. ABGs
4. 6 min walk test/ambulatory oxygen assessment
   
   • To assess if desaturation on exertion
5. Echocardiogram
   
   • To look for the development of pulmonary hypertension
6. High resolution CT scan (HRCT)
7. Video-assisted thoracoscopic surgery (VATS)
   
   • for biopsy

Question 12

Describe the radiological changes associated with IPF [4]

Answer 12

Ground glass changes → irregular reticulonodular shadowing → honeycombing

ground glass changes = hazy areas of increased attenuation in the lung with preserved bronchial and vascular markings, caused by alveolar wall inflammation or thickening and/or partial air-space filling

Question 13

Describe the macroscopic features of a lung biopsy taken from a patient with IPF [3]

Answer 13

1. pleural surfaces of the lung are “cobblestoned”
2. fibrotic areas of lung - firm rubbery and white
3. disease mainly basal and subpleural, with thickening of the interlobular septa

Question 14

Describe the microscopic features of a lung biopsy taken from a patient with IPF [4]

Answer 14

1. dense patchy interstitial fibrosis predominantly in the subpleural region
2. destruction of the normal lung architecture and with cystically dilated air spaces and intervening fibrous tissue
3. inflammatory infiltrate, mainly of lymphocytes, plasma cells and prominent intra-alveolar macrophages
4. fibroblastic foci in early fibrosis

Question 15

What are the cell types involved in the pathogenesis of IPF and describe the role of each? [4]

Answer 15

1. eosinophils, mast cells, macrophages and lymphocytes
   
   • release cytokines such as IL-4, IL-1, TNFα and IFN-𝛾
2. damaged epithelial cells
   
   • activated to release growth factors - TGFβ1, FGF, IGF1, PDGF
3. type 1 pneumocytes are reduced
   
   • injured cells produce TGFβ1 which promotes the transformation of fibroblasts to myofibroblasts
   • fail to develop from type 2 pneumocytes add to the development of dysfunctional alveolar epithelium
   • results in reduced levels of calveolin 1, an anti-fibrotic molecule produced by these cells
4. fibroblasts/myofibroblasts
   
   • myofibroblasts secrete excessive amounts of extracellular matrix proteins, mainly collagens

Question 16

Describe the treatment options for IPF [6]

Answer 16

1. Pirfenidone
   
   • antifibrotic and anti-inflammatory effects;
   • slows lung function decline
2. Nintedanib
   
   • intracellular inhibitor of multiple tyrosine kinases
   • slows lung function decline
3. For many patients, especially if over 80yrs, therapy for IPF is essentially aimed at symptom control
   
   • Long term oxygen therapy
   • Diuretics for fluid retention if develop cor-pulmonale
   • Antibiotics to treat infection
   • Lung transplantation in younger patients (age <65yrs)

Question 17

Define Extrinsic Allergic Alveolitis (EAA)/Hypersensitivity pneumonitis (HSP) [1]

Answer 17

Immunologically (T-cell) mediated inflammatory reaction in the alveoli and in the respiratory bronchioles

Question 18

What are the causes of Extrinsic Allergic Alveolitis (EAA)/Hypersensitivity Pneumonitis (HSP)? [5]

Answer 18

• Often heavy, repeated exposure, most often at the workplace to the following:
  
  • Organic dusts (<5μm)
  • Moulds
  • Foreign proteins (animals)
  • Some chemicals (lots of others)

Question 19

List the symptoms of EAA/HSP and when do these symptoms tend to arise? [8]

Answer 19

1. Flu-like illness
2. Cough
3. High fever, chills
4. Dyspnoea
5. Chest tightness
6. Malaise
7. Myalgia
8. Symptoms arise 4-8hrs after exposure

Question 20

What are the symptoms of chronic EAA/HSP? [5]

Answer 20

1. Dyspnoea in strain
2. Sputum production
3. Fatigue
4. Anorexia
5. Weight loss

Question 21

What are the features of acute hypersensitivity pneumonitis (HSP) on a chest x-ray? [5]

Answer 21

1. numerous poorly defined small ( <5 mm) opacities throughout both lungs
2. sometimes with sparing of the apices and bases
3. airspace disease: usually seen as ground glass opacities
4. fine reticulation may also occur
5. zonal distribution

Question 22

What are the pathological features of Chronic Hypersensitivity Pneumonitis (HSP)? [5]

Answer 22

1. Bronchiolocentric pattern
2. NNGI
3. Foamy macrophages in alveolar spaces
4. Chronic interstitial inflammation
5. Organising pneumonia