Week 4- Siliocosis

Question 1

T/F

Idiopathic Pulmonary disease is rare

Answer 1

true

Question 2

5 year mortality rate of IPF?

Answer 2

60%-80%

Question 3

How many people does IPF affect?

Answer 3

3 million. It is the most common type of interstitual lung diseases

Question 4

What are thought to be the causes of IPF?

Answer 4

certain antibiotics/medicine, smoking, certain environmental exposures, certain viruses/bacteria, genetics, GERD, radiation

Question 5

Pathophysiology of IPF

Answer 5

Genetic susceptibility + ageing+ environmental factors all contribute.

repetitive micro injuries to the epithelial layers contributes to epithelial activation( starts producing profibrotic and proinflamm mediators) and EMT( become more like fibroblasts)–>more growth factors and cytokines which contribute to ongoing inflamm and repetitive injury

Question 6

Symptoms of IPF

Answer 6

shortness of breath, persistent dry hacking cough, fatigue, clubbing fingers(increased growth factors and decreased O2(because of parenchymal fibrosis))

Question 7

Treatments for IPF

Answer 7

Question 8

Treating IPF progression

Answer 8

We use pirfenidone as it is antifibrotic and antiinflamm

inhibits TGF-B which affects profibrotic factors like FGF, IL-18, PDGF. these factors lead to ECM deposition and thus fibrosis.

ultimately drug inhibits TGF-B production and ROS production.

We need a big dose as it is not very potent

Question 9

adverse side effects of pirfenidone

Answer 9

Question 10

Nintedanib

Answer 10

Question 11

adverse effects of nintedanib

Answer 11

Question 12

final options for IPF

Answer 12

Question 13

Silicosis

Answer 13

• also known as fibrotic pneumoconiosis
• occupational lung disease

Question 14

is silicosis curable?

Answer 14

no, there is no effective treatment

Question 15

What causes silicosis

Answer 15

Inhaled respirable crystalline silicon dioxide( RCS, silica, SiO2) dust particles

Question 16

What stones are worse for the lungs?

Answer 16

the ones that have higher silica content.

artificial stones >90%

sandstone 70-90%

concrete, mortar 25-70%

tile 30-45%

brinch <30%

limestone and marble 2%

Question 17

Acute silicosis

Answer 17

develops within weeks of very heavy exposure

involves alveolar proteinosis and severe breathlessness

alveolar proteinosis is caused by alveolar macrophages becoming enlarged with proteins and then alveoli filling with protein and fluid

Question 18

Accelerated Silicosis

Answer 18

from prolonged high exposures. sees a rapid increase in scarring in lung tissue/fibrosis within 10 years of first exposure

Question 19

Chronic silicosis

Answer 19

most common form

fibrosis occurs more slowly over 10-30yrs after first being exposed

Question 20

Pathogeneiss of silicosis

Answer 20

inhalastion of silica reaches epithelia–> increase in ROS production and inflammatory and profibrotic reposnes.

the increased inflamm and fibrosis leads to silica taken up into macrophages which increases ROS production

the macrophages produce proinflamm and profibrotic cytokines which cause epithelial diff into fibroblasts.

Question 21

Silica uptake by macrophages

Answer 21

releases TNF-aloha, Il-1B, TGF-B

cannot be broken down so lead to contact apoptosis of cells and release of ROS and cytokines. also causes fibrosis

Question 22

Do all stones produce the same cytotoxicity and mediator profile

Answer 22

no they’ve been found to be different, the different pigments in the stones are also thought to contribute

Question 23

Treatment of Silicosis

Answer 23

easyl diagnosis is the most important( can be done by biomarkers and imaging)

inflammation is a possible target, uptake is not a good one as the cycle keeps repeating as the silica cannot be cleared, fibrosis is a good target and potentially can be treated with the same IPF drugs.

Whole lung lavage is also a possible idea.

Question 24

How to fibrosis in silicosis sets in?

Answer 24

aleveolar cells contantly cycle between apoptois and phagocytpsis

leads to the release of TGF-B

leads to differentiation of local cells to lung fribobalsts

leads to the increased production of collagen and a-SMA aswell as more proliferation–> all these cause fibrosis

Question 25

Using relaxin for silicosis?

Answer 25

Relaxin is a novel anti-fibrotic and an agonist of RXFP1. potential vasodialtor, bronchodilator and has been shown to be an anti-fibrotic in asthma and IPF

Relaxin has been shown to inhibit silica induced collagen production in mouse fibroblast cell lines when previously the fibroblasts increased collagen production after silica exposure.

Question 26

Whole lung lavage

Answer 26

may be used in early stages after high exposure to reduce silica load

up to 30L of saline is added to and removed from the lungs

required anesthesia and ICU monitoring

this allows a level of exposure to be measured but potentially not all the silica to be removed( could be solved by repeated lavage)

being trialed in Queensland

found to have reduced alveoli with protein engorged laden alveolar macrpahges following WLL