Week 4- Siliocosis Flashcards
T/F
Idiopathic Pulmonary disease is rare
true
5 year mortality rate of IPF?
60%-80%
How many people does IPF affect?
3 million. It is the most common type of interstitual lung diseases
What are thought to be the causes of IPF?
certain antibiotics/medicine, smoking, certain environmental exposures, certain viruses/bacteria, genetics, GERD, radiation
Pathophysiology of IPF
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
Symptoms of IPF
shortness of breath, persistent dry hacking cough, fatigue, clubbing fingers(increased growth factors and decreased O2(because of parenchymal fibrosis))
Treatments for IPF
Treating IPF progression
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
adverse side effects of pirfenidone
Nintedanib
adverse effects of nintedanib
final options for IPF
Silicosis
- also known as fibrotic pneumoconiosis
- occupational lung disease
is silicosis curable?
no, there is no effective treatment
What causes silicosis
Inhaled respirable crystalline silicon dioxide( RCS, silica, SiO2) dust particles
What stones are worse for the lungs?
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%
Acute silicosis
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
Accelerated Silicosis
from prolonged high exposures. sees a rapid increase in scarring in lung tissue/fibrosis within 10 years of first exposure
Chronic silicosis
most common form
fibrosis occurs more slowly over 10-30yrs after first being exposed
Pathogeneiss of silicosis
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.
Silica uptake by macrophages
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
Do all stones produce the same cytotoxicity and mediator profile
no they’ve been found to be different, the different pigments in the stones are also thought to contribute
Treatment of Silicosis
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.
How to fibrosis in silicosis sets in?
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
Using relaxin for silicosis?
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.
Whole lung lavage
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
