Interstitial Lung Disease Update 2023 Flashcards
1. Understanding ILD terminology 2. Basic mgt principles 3. Idiopathic pulmonary fibrosis - focus on this 4. Other important ILDs 5. Short telomeres as a cause of pulmonary fibrosis
Features of pulmonary fibrosis radiologically?
Reticulation
Traction bronchiectasis
Honeycombing
Architectural distortion
Volume loss
Example of reticulation as feature of pulmonary fibrosis
Example of traction bronchiectasis as feature of pulmonary fibrosis
Example of honeycombing as feature of pulmonary fibrosis
End stage of any form of pulmonary fibrosis
Some radiological features of ILD
Why is a good history important for differentiating different types of ILDs?
ILD classification is based on different radiological and histological features - and different ILD diseases may have overlap of similar histological/radiological features, so really important to differentiate based on good history
e.g. while IPF is characterised by UIP, UIP is NOT exclusive to this disease
3 different basic management principles of dealing with ILD
- Exposure avoidance +/- immunosuppression
- Observation +/- immunosuppression
- Anti-fibrotics i.e. Pirfenidone/Nintedanib
ILDs which tend to be treated with:
Exposure avoidance +/- immunosuppression
Pneumoconiosis
Iatrogenic (e.g. Amiodarone, Nitrofurantoin)
Hypersensitivity pneumonitis (birds, mould etc)
Histiocytosis - avoid cigarette smoke!
Smoking-related:
- RB-ILD (Respiratory bronchiolitis interstitial lung disease)
- DIP (Desquamative interstitial pneumonia)
ILDs which tend to be treated with:
Observation +/- immunosuppression
Sarcoidosis
Idiopathic LIP (lymphocytic interstitial pneumonia)
COP
NSIP (Non-specific interstitial pneumonia)
CTD-ILD
IPAF
ILDs which tend to be treated with:
Anti-fibrotics i.e. Pirfenidone/Nintedanib
IPF and…
Recently however, have data to demonstrate that Nintedanib is effective across a WHOLE RANGE of different ILDs, not just IPF!
Idiopathic pulnonary fibrosis (IPF)
- definition
Chronic inexorably progressive fibrosing lung disease of unknown cause
Requires an exclusion of other causes of pulmonary fibrosis (e.g. CTD, drugs, occupational/environmental exposures)
Characterised by UIP histologically (but we use radiological UIP as a strong surrogate for this)
NB: surgical lung biopsy is now rarely required - and does carry a mortality risk!
Importantly, diagnosis MUST be made at an ILD-MDM as this allows access to funding for anti-fibrotic agents
Risk factors for IPF?
- Older age typically 6th/7th decade
(however beware younger patients with a familial IPF) - Male gender 2:1
- Previous smoking history
- GORD
- Family history of ILD
Pre-test probability of IPF based on risk factors
The whole point is that ‘idiopathic’ pulmonary fibrosis is just that - IDIOPATHIC
The ‘sqwuaks’ or squeeks on chest auscultation suggests presence of gas trapping which suggests presence of hypersensitifity pneumonitis
Treatment of IPF - previous
Prior to 2011 standard trt as through immunosuppression, via combination of
- Azathioprine
- Prednisolone
- N- acetylcysteine
However in 2011 PANTHER study RCT showed that this treatment regimen increased mortality c.f. placebo
Treatment of IPF - current
1) AVOIDANCE of immunosuppressants (aside from corticosteroids in acute exacerbations)
2) Anti-fibrotic agent
Pirfenidone
OR
Nintedanib
NB: there has not yet been a head-to-head comparison of the two anti-fibrotic agents but data suggests both associated with slowing of fibrosis as evidenced by measures of reduction of FVC
Also some (not so robust data) that both improve survival
For Nintedanib - some data that reduces incidence of acute exacerbations
Treatment with anti-fibrotic agents makes patients with IPF feel better, T or F?
False - these treatments SLOW fibrosis but they cannot reverse it
Mechanism of action Pirfenidone
Acts through TGF-B and reduces fibroblast proliferation
Mechanism of action Nintedanib
Inhibits multiple tyrosine kinases (PDGF, VEGF, FGF)
Side effects of Pirfenidone
- Photosensitivity rash - strict sun protection!
- Nausea and other GI upset
Side effects Nintedanib
- Possible small increase in bleeding risk - avoid in those on anticoagulants
- Diarrhoea
- Weight loss
- Possible CVS risk
What is the role of anti-fibrotic agents OUTSIDE of IPF?
Evidence that both have anti-fibrotic effects in other fibrotic lung diseases
- particular evidence for Nintedanib
e.g. in Systemic Sclerosis Associated Interstitial Lung Disease
Genetics of IPF?
Most common genetic pathway implicated = mutations affecting telomeres -> shortening
Tend to be autosomal dominant pattern of inheritance
Also display genetic anticipation - worsening of phenotype in subsequent generations e.g. first and second generations may have IPF but in 3rd get dyskeratosis congenita in a child (this is caused by critically short telomeres in childhood)
Telomeropathy syndrome
In high turnover tissues:
- Premature greying
- Aplastic anaemia
- Macrocytosis
- Thrombocytopenia
- Opportunistic infections B, T and NK cell immunodeficiency
In slow turnover tissues
- Pulmonary fibrosis
- Premature onset emphysema
- Cryptogenic cirrhosis
- Osteoporosis
- Avascular necrosis
- Epithelial cancers
- Haematological malignancies
Connective Tissue Disease Associated ILD
- which connective tissue diseases does this manifest in?
Can manifest in ANY connective tissue disease
However, most common in
-RA
-Systemic sclerosis
-Idiopathic inflammatory myopathies
RA-associated ILD has a predilection for which type of histological/radiological pattern?
UIP
(Usual Interstitial Pneumonia)
Systemic sclerosis- associated ILD has a predilection for which type of histological/radiological pattern?
NSIP
(Non-specific Interstitial Pneumonia)
- characterised by diffuse ground glass opacity
Idiopathic inflammatory myopathy- associated ILD has a predilection for which type of histological/radiological pattern?
OP
(Organising pneumonia)
Sjogren syndrome can be associated with which type of ILD?
Lymphoid interstitial pneumonia (LIP) - characterised by presence of ground glass opacities and cysts
What does this show?
Scleroderma-associated ILD with NSIP (non-specific interstitial pneumonia) pattern characterised by diffuse ground glass opacity - and also noted a dilated oesophagus which can be a feature of scleroderma
ILD can be a first presentation of a connective tissue disorder (CTD). What is the significance of this?
Important in any ILD patient to do a screen for CTD
- ANA
- ENA
- RF
- Anti-CCP
+/- myositis screen
- ANCA - if presentation is with haemoptysis
Management of CTD- associated ILD?
Immunosuppression
In some cases, can be difficult to distinguish CTD associated ILD from a drug toxicity effect e.g. in many RA patients taking anti-TNF therapy
NB: IMPORTANT to note that although historically blamed, Methotrexate as a cause of ILD has now been largely debunked
So very unlikely that in a patient with RA who has been on stable Methotrexate that the Methotrexate is a cause of their ILD - it is much more likely that they have developed an CTD-associated ILD
Hypersensitivity pneumonitis can be non-fibrotic or fibrotic T or F?
True
What is the histological/radiological pattern most commonly seen in fibrotic hypersensitivity pneumonitis (HP) ?
UIP
(Usual interstitial pneumonia)
- can look very like IPF
Can use HRCT to differentiate if see presence of ground - glass opacity, gas trapping as this points to HP
What are some examples of smoking-related ILD?
- RB -ILD (Respiratory bronchiolitis ILD) - characterised by accum of macrophages in bronchioles
- DIP (Desquamative interstitial pneumonia) - characterised by macrophage infiltration of alveoli
- Langerhans cell (antigen presenting cells) histiocytosis - characterised by proliferation of abnormal APCs
Key to management of smoking-related ILD?
Smoking cessation!
Sarcoidosis principles of management
1) Treat life or organ threatening disease
2) Treat quality of life altering disease - so if life not affected don’t treat!
Most common occupational ILDs (Pneumoconiosis) seen in Australia?
- Silicosis (current spike from artificial workbench manufacturing)
- Asbestosis
- Coal work’ers pneumoconiosis
Important to take a detailed occupational history in anyone with suspected ILD!
Accurate diagnosis has big impact on compensation/financial wellbeing for patients
