Interstitial lung diseases Flashcards
What does this chest x-ray show?
Interstitial shadowing
What are the features of interstitial shadowing on a chest x-ray?
- Reticular i.e. linear, lace-like pattern
- “too many lung markings”
- May be focal or diffuse
What is the interstitium?
Refers to supporting structures of the lung
Includes:
- alveolar endothelium
- capillary endothelium
- basement membrane
- connective tissue
What can thicken the interstitium?
In disease it can be thickened by:
- Fluid
- Cells
Fibrosis
Where does interstitial lung disease affect?
What does the second image show?
Thickened septa
What is the extraceullar matrix?
3D fibre mesh filled with macromolecules e.g. collagen, elastin
What are the functions of the extracellular matrix?
- Tensile strength/elasticity
- Low resistance for effective gas exchange
- Tissue repair/modelling
What does aberrant wound healing cause in fibrosis?
In fibrosis, aberrant wound healing leads to excessive deposition in the interstitium
What are the types of interstitial lung disease?
ENVIRONMENTAL EXPOSURE
◦Occupational lung disease
- Silicosis (silica exposure)
- Coal miners lung (coal dust exposure)
- Asbestosis (asbestos exposure)
◦Hypersensitivity pneumonitis - mold and bird proteins are common causes
IDIOPATHIC (unknown cause)
Idiopathic pulmonary fibrosis is the prototypical ILD
SYSTEMIC INFLAMMATORY DISEASES
Connective tissue disease-ILD
Sarcoidosis
What is the simplified classification of interstitial lung disease?
What does this chest x-ray show?
◦Small lungs
◦Increased reticular shadowing
What do these lung function tests indicate?
◦FEV1 56%
◦FVC 50%
◦FEV1/FVC 86%
◦TLCO 50%
◦FEV1 56%
◦FVC 50%
◦FEV1/FVC 86%
= restrictive
◦TLCO 50%
= impaired gas transfer
Whats the diagnosis?
◦Older man
◦Chronic history of dyspnoea
◦Radiological evidence of ILD
◦Restrictive lung function with impaired gas transfer
◦No identifiable cause
◦Dx = Idiopathic Pulmonary Fibrosis
What are the symptoms of idiopathic pulmonary fibrosis?
Symptoms and clinical signs of IPF often appear gradually and include:
◦Slowly progressive exertional dyspnoea
◦Non-productive cough
◦Dry, inspiratory bibasal “Velcro®” crackles
◦+/- Clubbing of fingers
◦Abnormal pulmonary function test results
◦restriction and impaired gas exchange
What is the HRCT pattern?
To diagnose idiopathic pulmonary fibrosis on CT -
Basal distribution
Subpleural
Traction bronchiectasis
Honeycombing
If present on CT – no biopsy needed
What disease is this?
Idiopathic pulmonary fibrosis
Who is more likley to have idiopathic pulmonary fibrosis?
◦is a disease of older age (median age 66yrs)
◦is more common in men (2:1)
◦is more common in smokers (60%)
What are the clinical features of idiopathic pulmonary fibrosis?
◦is of unknown cause
◦causes progressive, irreversible fibrosis and is fatal
◦is limited to the lungs (unlike other ILDs eg sarcoidosis)
◦Affects lower and peripheral lung
◦Minimal inflammation – no role for steroids
Is prevelance of IPF in the UK increasing or decreasing?
Increasing
What is the prognosis for IPF patients?
◦median survival is 3 years from diagnosis
◦BUT 20% still alive at 5 years
◦no reliable way to predict prognosis
◦patients therefore live with considerable uncertainty
How is IPF managaed?
oAssess suitability for anti-fibrotic drugs
- Pirfenidone or Nintedanib
- Can only be prescribed by specialist centres
- Aim is to slow rate of disease progression
- Criteria
- diagnosis of IPF
- FVC 50-80% predicted
oAssess suitability for Lung transplant
- Age <65
- No significant comorbidities
oOffer best supportive care to all
- Treat co-morbidities
- Palliate symptoms
- Refer to palliative care
Why are anti-fibrotic drugs often poorely tolerated?
Often poorly tolerated – weight loss, GI upset, photosensitivity
Whats the diagnosis?
- 24yo man
- Rapidly progressive SOB and cough over 3 months, struggling with ADLs
- No response to antibiotics or inhalers
- PMHx: depression, on Sertraline
- Smoker 20/day
- Unemployed
- Unable to complete sentences, bilateral crackles, sats 89%
- No rheumatological symptoms, CTD screening bloods normal
Sertraline-induced ILD
Whats the diagnosis?
◦63yo lady
◦Admitted with 10/52 history dry cough and SOB
◦Bilateral crackles all zones, sats 85%
◦
◦No PMHx or regular meds
◦Non smoker
◦No occupational exposures
◦Kept budgies for several years
Hypersensitivity Pneumonitispe
What is Hypersensitivity Pneumonitis?
- Diffuse inflammation of parenchyma in response to inhaled antigen
- Tends to involve upper lobes
What are the antigens that cause Hypersensitivity Pneumonitis?
- Bird-fanciers (bird droppings)
- Farmers lung (thermophilic fungi)
- Aspergillus (ubiquitous fungus)
- Can be anything…
- Antigen unknown in 50%
How does Hypersensitivity Pneumonitis present acutely?
- SOB, cough, fever, malaise, crackles within 4-6 hours of heavy exposure
- Often misdiagnosed as infection
How does Hypersensitivity Pneumonitis present sub-acute and chronically?
Subacute
•Gradual onset of symptoms, weight loss common
Chronic
- Insidious onset, history of acute episodes may be absent
- Incomplete resolution with removal of antigen
- May lead to irreversible fibrosis
What is the most common presentation of hypersensitivity pneumonitis?
Most cases of hypersensitivity pneumonitis develop only after many years of continuous or intermittent inhalation of the inciting agent
How is Hypersensitivity Pneumonitis diagnosed?
Serum precipitins (circulating IgG antibody-antigen complexes) to specific antigen may be helpful
- Infinite number of possible antigens
- May be positive in asymptomatic individuals
Negative results does not exclude HP
What is the management for Hypersensitivity pneumonitis?
- Avoidance of inciting antigen
- Usually steroid-responsive in early disease
- May progress to irreversible fibrosis
What 3 drugs cause drug-induced ILD?
◦Many drugs but most common:
◦Nitrofurantoin
◦Amiodarone
Methotrexate
Drug induced ILD may develop months-years after starting the drug.
True or false?
True
Which conditions cause Connective Tissue Disease-related ILD?
- Rheumatoid Arthritis
- Sjogrens
- Scleroderma
- Polymyositis
Which patients are more likely to have Connective Tissue Disease-related ILD?
◦Younger patients
◦Female preponderance
What should you ask about in a patient’s history when considering Connective Tissue Disease-related ILD?
dry eyes/mouth (sicca), Raynaud’s, joint pain/swelling, rashes
What tests are done to diagnose Connective Tissue Disease-related ILD?
Bloods: Antinuclear antibodies (ANA), rheumatoid factor (RF)
What is the management for Connective Tissue Disease-related ILD?
Liaise with rheumatology, treat underlying disease (biologics, steroids, immunosuppression)
How is ILD diagnosed?
Clinical assessment – IS THERE AN IDENTIFIABLE CAUSE? - CTD symptoms, drugs, exposures
Bloods
- Antinuclear Antibodies (ANA), Rheumatoid factor, Angiotensin-converting enzyme (ACE)
Spirometry/Lung function tests
- FVC, FEV1/FVC ratio (normal or high), gas transfer NB may have co-existent COPD
CXR
- Reticular shadowing
HRCT pattern of disease - the cornerstone of diagnosis but, only 60% are diagnostic
•Lung biopsy
- Enhances diagnosis but risk often outweighs benefit
- May differentiate IPF from other potentially reversible causes
How is ILD treated?
MDT for diagnosis:
- respiratory physician, respiratory radiologist, rheumatologist, +/- specialist histopathologist
- combination of history, HRCT pattern of disease, auto-immune bloods
Treatment
- Remove cause - budgie, medication, bagpipes(!) etc…
- Immunosupression (prednisolone, hydoxychloroquine, Mycophenolate mofetil, methotrexate)
- Anti-fibrotics for IPF
What is sarcoid?
- Multisystem granulomatous disorder
- non-necrotising granulomas
What causes sarcoid?
- Cause unknown
- 3 x more common in Afro-caribbeans, more severe disease
some familial clusters
What age is most likely to get sarcoid?
- Disease of the young
- 75% of cases aged 30-60 years
Sarcoid has a predictable clinical course.
True or false?
False
Unpredictable clinical course
What disease is this?
Sarcoid
What disease is this?
Sarcoid
What are the histological features of sarcoidosis?
◦Characterised by granulomatous inflammation
◦Unknown foreign antigen stimulates immune response including:
- CD4+ T cells,
- alveolar macrophages
- multi-nucleate giant cells
◦Organise into granulomas
◦Granulomas occur in TB and fungal infections, but in sarcoidosis they are non-necrotising
How is sarcoidosis diagnosed?
A biopsy demonstrating granulomas along with clinical picture is needed to confidently diagnose sarcoidosis.
Where in the body does sarcoidosis manifest?
Can affect any organ - Lung involvement in 90%
What are the common presentations for sarcoid?
What is Lofgren’s Syndrome?
- Excellent prognosis
- Usually self-limiting
What are the symptoms of Lofgren’s Syndrome?
- Erythema Nodosum
- Bilateral Hilar Lymphadenopathy
- Arthralgia
What are the symptoms of pulmonary sarcoidosis?
oMay be asymptomatic (especially with isolated lymphadenopathy)
oCough
oDyspnoea with exertion
oChest tightness
oSystemic symptoms: fatigue, sweats, weight loss, fevers, arthralgia
What are the 2 possible clinical outcomes in sarcoidosis?
What are the 4 stages of pulmonary sarcoidosis?
Patients may be asymptomatic despite significant CXR abnormalities in sarcoidosis.
True or false?
True
How is pulmonary sarcoidosis diagnosed?
◦No single diagnostic test
◦Combination of clinical picture, exclusion of alternative diagnoses ( esp. lymphoma and TB) and ideally biopsy of affected tissue
◦Baseline tests
- Renal function, liver function, calcium, serum ACE, CXR, ECG
•Serum Angiotensin-converting enzyme (ACE)
- Secreted by activated alveolar macrophages in granulomas
- Low sensitivity (60%), poor specificity
- Polymorphisms in ACE gene → variation in peripheral blood ACE levels
- No correlation with CXR stage of disease
◦Biopsy everything!
- Skin, lymph nodes, blind endobronchial biopsies (44-70% yield)
What is the treatment for pulmonary sarcoidsis?
- Less clear-cut for pulmonary disease as often less severe than extra-thoracic disease with spontaneous remission common
- short-term symptomatic benefit
- long-term effect on natural history of disease not known
- Corticosteroids for 6-24 months are mainstay
- inhaled corticosteroids may provide symptomatic benefit
- additional immunosuppressants e.g. methotrexate, azathioprine may be necessary
What does a obstructive spirometry pattern indicate?
◦Indicates the problem is in the airways
◦Useful diagnostically:
- Reversible airflow obstruction (asthma)
- Fixed airflow obstruction in a smoker (COPD)
◦Only a few other diseases of the airways (bronchiectasis, obliterative bronchiolitis)
What does a restrictive spirometry pattern indicate?
◦Indicates there is a problem
◦Not useful diagnostically
◦Useful for monitoring change
- Acutely e.g. Guillain-Barre
- Chronically e.g. MND
◦Indicates risk of ventilatory failure
◦Severity indicator for ILD
◦Treatment criteria for IPF
◦Anti-fibrotics only if FVC 50-80% predicted
How is restrictive spirometry measured?
◦Directly measured by TLC - requires lung function lab
◦FVC reflects the TLC
- can be done in clinic
- useful for disease monitoring
What causes a restrictive pattern of spirometry?
Restriction of lung expansion or loss of lung volume
What are the possible causes of restrictive spirometry?
What are the features of fibrotic lungs on lung function tests?
- Fibrotic lungs are small and stiff
- Higher elastic recoil than expected for volume
- FEV1/FVC ratio may be high…but may be normal
- ↓ TLCO (gas transfer)
•Impaired gas exchange due to disruption of alveolar-capillary interface
Complete the table
Why is there a decrease in TLCO?
↓ TLCO (gas transfer)
•Reduced total surface area for gas exchange
or
•Impaired gas exchange due to disruption of alveolar-capillary interface
