interstitial lung disease

Question 1

what is interstitial shadowing

Answer 1

Reticular eg linear, lace like patter
Too many lug markings
May be focal or diffuse

Question 2

what is the interstitium

Answer 2

Refers to supporting structures of the lung
Includes: alveolar endothelium, capillary endothelium, basement membrane, connective tissue
In disease it can be thickened by
Fluid, cells, fibrosis

Question 3

what is the extracellular matrix

Answer 3

3D fibre mesh filled with macromolecules eg. Collagen, elastin
Several functions
Tensile strength/elasticity
Low resistance for effective gas exchange
Tissue repair/remodelling
In fibrosis, aberrant wound healing leads to excessive deposition in the interstitium

Question 4

how are ILDs classified

Answer 4

Environmental exposures
Occupational lung disease
Silicosis (silica exposure)
Coal miners lung (coal dust exposure)
Asbestosis (asbestos exposure)
Hypersensitivity pneumonitis (mould and bird proteins are common causes)
Idiopathic 
Idiopathic pulmonary fibrosis is the prototypical ILD
Systemic inflammatory diseases 
Connective tissue disease-ILD
Sarcoidosis

Question 5

how can classification be simplified

Answer 5

connective tissue disease, hypersensitivity pneumonitis, sarcoidosis, drug, occupational
no cause- idiopathic

Question 6

how does idiopathic pulmonary fibrosis present

Answer 6

Symptoms and clinical signs of IPF appear gradually and include
Slowly progressive exertional dyspnoea
Non-productive cough
Dry, inspiratory bibasal ‘velcro’ crackles
Possibly clubbing
Abnormal pulmonary function test results (restriction and impaired gas exchange)

Question 7

what is the IPF HRCT pattern

Answer 7

basal distribution, sub pleural, honeycombing, traction bronchiectasis
if present - no biopsy needed

Question 8

how can IPF be summarised

Answer 8

Progressive, irreversible fibrosis and is fatal
Limited to lungs – unlike other ILDs like sarcoidosis
Affects lower and peripheral lungs
Minimal inflammation – no role for steroids
Disease of older age (median age of 66)
2x as common in men
More common in smokers (60%)
HRCT = most diagnosis but lung biopsy may be needed

Question 9

how does IPF impact the UK

Answer 9

Approx 6000 new cases each year
Increasing by 5% each year
>32000 living with it
1/100 deaths

Question 10

what is the prognosis of IPF

Answer 10

Median survival is 3 years from diagnosis
But 20% still alive after 5
No reliable way to predict
Live with considerable uncertainty

Question 11

How is IPF managed

Answer 11

Assess suitability for anti fibrotic drugs
Pirfenidone or nintedanib
Can only be prescribed by specialist centres
Aim to slow rate of progression

Question 12

what is the criteria for IPF treatment

Answer 12

Diagnosis of IPF
FVC 50-80% predicted
drugs often poorly tolerated – weight loss, GI upset and photosensitivity
Assess suitability for lung transplant (<65, no sig comorbidities)
Offer best supportive care to all

Question 13

how can the best supportive care for IPF be provided

Answer 13

stepwise decline- intervene and treat (acute infection, PE, pneumothorax, acute exacerbation)
treat comorbidities (GORD, COPD, lung cancer)
Palliate symptoms (LTOT, Pulmonary rehab, benzos, opiates)
refer to palliative care

Question 14

what is hypersensitivity pneumonitis

Answer 14

Diffuse inflammation of parenchyma is response to inhaled antigen – teds to involve upper lobes
Bird-fanciers (bird droppings)
Farmers lung (thermophilic)
Aspergillus (ubiquitous fungus)
Antigen unknown in 50%

Question 15

how does HP present

Answer 15

Acute
SOB, cough, fever and crackles within 4-6 hours of heavy exposure
Often misdiagnosed as infection
Most develop after years of continuous or intermittent inhalation of inducing aget
Sub-acute
Gradual onset of symptoms, wight loss common
Chronic
Insidious onset, history of acute episodes may be absent
Incomplete resolution with removal of antigen
May lead to irreversible fibrosis

Question 16

how is HP diagnosed

Answer 16

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 result does not exclude HP

Question 17

how is HP managed

Answer 17

Avoid inciting antigen
Usually steroid-responsive in early disease
May progress to irreversible fibrosis

Question 18

how is drug-induced ILD diagnosed

Answer 18

Medication history important – specific questions
Many common drugs are nitrofurantoin, amiodarone, methotrexate
Always consider if medication may be implicated
Association between initiation of drug and onset of disease important but ILD may develop months-years after starting the drug

Question 19

what is connective tissue disease-related ILD

Answer 19

Rheumatoid arthritis, sjogrens, scieroderma, polymyositis
Younger patients, female predominance
Detailed history – dry eyes/mouth, raynaud’s, joint pain/swelling, rashes
Bloods – antinuclear antibodies, rheumatoid factor
Management – liaise with rheumatology, treat underlying disease (biologics, steroids, immunosuppression)

Question 20

How are ILDs diagnosed

Answer 20

Clinical assessment – identifiable cause
CTD symptoms, drugs, exposures
Bloods – ANA, RF, angiotensin-converting enzyme (ACE)
Spirometry/lung function tests
FVC, FEV1/FVC ratio (normal or high), gas transfer (may have co-existent COPD)
CXR – reticular shadowing
HRCT pattern of disease – cornerstone of diagnosis but only 60% are diagnostic
Lung biopsy – enhances diagnosis but risk often outweighs the benefit, may differentiate IPF from other potentially reversible causes

Question 21

how are ILDs treated

Answer 21

MD1 for diagnosis
Respiratory physician, respiratory radiologist, rheumatologist (+ specialist histopathologist)
Combo of history, HRCT pattern of disease, auto-immune bloods
Remove cause.
Immunosuppression (prednisolone, hydroxychloroquine, mycophenolate mofetil, methotrexate)
Anti-fibrotics for IPF

Question 22

what is sarcoidosis

Answer 22

Multisystem granulomatous disorder – non-necrotising granulomas
Cause unknown – 3x more common in afro-caribbeans, more severe disease, some familial clusters
Disease of the young – 75% 30-60 years
Unpredictable clinical course

Question 23

what is the histology of sarcodosis

Answer 23

Characterised by granulomatous inflammation
Unknown foreign antigen stimulates immune response including
CD4+ cells, alveolar macrophages, multi-nucleate giant cells
Organise into granulomas
Granulomas occur in TB and fungal infections but in sarcoidosis they are non-necrotising
A biopsy demonstrating granulomas along with clinical picture is needed to confidently diagnose

Question 24

how does sarcoidosis manifest

Answer 24

Can effect any organ – lung involvement 90%
Lung and thoracic lymph nodes – dyspnoea, cough, chest pain, pulmonary hypertension, mixed pulmonary function test, abnormalities (obstruction, restriction, diffusion, deficits)

Question 25

how does sarcoidosis commonly present

Answer 25

chest - cough, SOB, wheeze, incidental finding
skin - erythema nodosum, lupus permit, plaques, nodules
eyes- anterior uveitis
lymph node biopsy- suspect malignancy
hypercalcaemia
peripheral nerves- Bell’s palsy, mono neuropathies

Question 26

what is lofgren’s syndrome

Answer 26

Erythema nodosum
Bilateral hilar lymphadenopathy
Arthalgia
Excellent prognosis, usually self limiting

Question 27

what are the symptoms of pulmonary sarcoidosis

Answer 27

May be asymptomatic (especially with isolated lymphadenopathy)
Cough, dyspnoea, chest tightness
Systemic symptoms: fatigue, sweats, weight loss, fevers, arthalgia

Question 28

how does pulmonary sarcoidosis progress

Answer 28

2/3 remission and 1/3 chronic disease(inflammation can = fibrosis)
variable clinical course
stages
lymphadenopathy, LA + infiltrates, infiltrates and fibrosis
may be asymptomatic despite significant CXR abnormalities

Question 29

how is sarcoidosis diagnosed

Answer 29

No single diagnostic test
Combo of clinical picture, exclusion of alternative diagnosis (esp lymphoma and TB)
Baseline tests – renal, liver function, calcium, serum ACE, CXR, ECG
Serum 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)

Question 30

what are the types of sarcoidosis

Answer 30

Major organ involvement – ocular disease not responding to topical treatment, cardiac, neurological
Less clear-cut pulmonary disease – 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

Question 31

how is sarcoidosis treated

Answer 31

Corticosteroids for 6-24 months are mainstay – inhaled corticosteroids may give symptomatic benefit, additional immunosuppressants eg methotrexate, azathioprine may be necessary

Question 32

what might spirometry reveal on lung function tests

Answer 32

obstructive - problem in airways, useful Dx (reversible - asthma, fixed and smoker - COPD)
only a few other airway disease (bronchiectasis, obliterative bronchiolitis)
restrictive - problem but not useful Dx, useful for monitoring change (acute, chronic or risk of ventilatory failure), treatment criteria for IPF

Question 33

what is restrictive spirometry

Answer 33

Restriction of lung expansion or loss of lung volume
Directly measured by TLC – requires lung function lab
FVC reflects the TLC – can be done in clinic and useful for disease monitoring
Think anatomically to explain

Question 34

what can cause restrictive spirometry

Answer 34

Skin – extensive burns, scleroderma
Subcutaneous tissues – raised BMI
Thoracic cage – Kyphoscoliosis
Neuromuscular system – eg MND, guilian-barre
Pleura – thickening
Loss of lung vol – pneumonectomy, pleural effusion
Lung parenchyma – ILD

Question 35

what do lung function tests show for ILD

Answer 35

Fibrotic lungs small and stiff
Higher elastic recoil than expected for volume
FEV1/FVC ratio may be high – but also may be normal
TLCO (gas transfer) – impaired gas exchange due to disruption of alveolar-capillary interface or reduced total surface area
FVC and TLC dec
compliance dec intrinsic or normal extrinsic