Interstitial Lung Diseases

Question 1

Outline the four stages of repair in which fibroblasts are involved in

Answer 1

1. Epithelial Injury
2. Myofibroblast Activaiton
3. Myofibroblast Effects
4. Resolution and Repari

Question 2

What are the 3 ‘main’ classifications of most frequent ILD

Answer 2

1. Idiopathic​ Interstitial pneumonias
2. Associated with systemic involvement
   
   1. ​Autoimmune
3. Associated with a cause/exposure​

Question 3

Give an example of an idiopathic interstitial pneumonia

Answer 3

Idiopathic Pulmonary Fibrosis

Question 4

Give examples of ILD associated with systemic involvement

Answer 4

Connective tissue disease-ILD

Sarcoidosis

Rheumatoid arthritis

Systemic Sclerosis

SLE

Question 5

Give 3 examples of ILD associated with a cause/exposure

Answer 5

Hypersensitivity Pneumonitis

Occupational ILD

Drugs (methotrexate, nitrofurantoin, amiodarone, bleomycin)

Question 6

What risk factors/exposures are you looking for when taking a history with suspected ILD

Answer 6

• Systemic Symptoms
• Drugs
  
  • Nitrofurantoin
  • Methotrexate
  • Amiodarone
• Smoking
• Exposures
  
  • Home
  • Work
  • Hobbies
• Family History

Question 7

What are some investigations for ILD

Answer 7

• Physical Examination
• Full autoimmune screen
  
  • ANA, anti-CCP, anti- ds DNA, CK, precipitins, ENA
• HRCT chest
• Bronchoscopy with BAL

If still unclear, histology

Question 8

IPF hsd a UIP pattern. Describe this pattern found on CT

UIP = Usual Intestitial Pneumonia

Answer 8

• Heterogeneous lung
  
  • Normal alveolar walls AND
  • Dense fibrous walls
• Fibrous Walls
  
  • Collagen I
  • Immature Collagen III (not cross-linked)
• Fibiroblast aggregation
  
  • Edge of dense fibrotic tissue and normal tissue
• Honeycombing

Question 9

What are some features of hypersensitivity pneumonitis that could rule out IPF?

Answer 9

• Relevant exposures
  
  • Bird Fancier’s Lung (Parrot, Pigeon)
  • Baker’s Lung
  • Farmer’s Luung
• BAL Lymphocytosis
• HRCT Features
  
  • Mosaic Attenuation

Question 10

What are two genetic variants found in familial fibrosis

Answer 10

• Surfactant Gene Mutations (1% of families)
  
  • Imparied protein folding
  • ER stress of AEC2s
    
    • More apoptosis
• Telomere defects
  
  • Telomerase complex defects
  • TERT/TERC 10-25% familial and 1-3% sporadic IPFs

Question 11

How does a short telomere lead to increased risk of ILD

Answer 11

Telomere shortens after every division

Once reached critical point, ther is senescence

Cell division arrest

Loss of regeneratitive potnetial of progenitor cells (AEC2s) to regenerate injured AECs

Question 12

What are 5 genes found to be associated with IPF

Answer 12

• TERT
• TERC
• DSP
• MUC5B
  
  • 34% familial, 38% sporadic IPF, 9% control population
• DPP9

Question 13

Interpret this data. Combination therapy was with Azothioprine, low dose prednisolone, N-acetylcysteine

Answer 13

combination therapy:

• steady increase of probability to time to death over 15 weeks.
• Plateu between 15 and 30 weeks
• Peak at 60 weeks with 0.45 probability

Placebo:

• Slow increase from week 7 to week 45 where it peaks at 0.15 probability to time to death
• Plateus from week 45 to 60 at this level

Immunosuppression is important in IPF

Question 14

Interpret the data on microbiome in IPF

Answer 14

Graph A:

• There is an increase in 16S rRNA in IPF BAL compared to healthy control and COPD
• There is decrease in 16SrRNA in COPD compared to control.

Graph B:

• Having a high level of bacteria has a HR of 4.59 p<0.05 compared to low levels of bacteria

Question 15

Which 4 bacteria are commonly found in IPD

Answer 15

• Haemophilus
• Neisseria
• Streptococcus
• Veillonella

Question 16

What is the current management for IPF

Answer 16

• Pirfenidone (anti-TGF)
• Nintedanib (kinase inhibitor)
  
  • Both show slower decline in FEV1 than placebo half rate of decline)