Interstitial lung disease Flashcards
Where is the abnormality for:
1) Consolidation
2) Reticular
3) GGO
1) Air space
2) Interstitium
3) Either or both
Nb. if see GGO, see if dilated airways - if so then know fibrotic process
What is honeycombing?
Clustered cystic airways in periphery
3-10mm (but can be larger)
What is typical UIP?
Distribution: subpleural & basal (often heterogenous)
Features: reticulation + traction & honeycombing (& no features suggestive of alternative diagnosis)
Probable:
Dist: subpleural & basal (often heterogenous)
Feat: reticulation + traction & NO honeycombing (& no features suggestive of alternative diagnosis)
Indeterminate:
Dist: variable or diffuse
Feat: fibrosis but some features suggestive of non-UIP e.g. GGO, consolidatoin
Not-UIP:
Dist: upper/mid-lung/peribronchovascular predominant
Feat: Prominent consolidation/GGO (w/o acute exacerbation)/mosaic attenuation with sharply defined lobular air trapping on expiration/diffuse nodules or cysts
What is definition of probable UIP?
Dist: subpleural & basal (often heterogenous)
Feat: reticulation + traction & NO honeycombing (& no features suggestive of alternative diagnosis)
Definite:
Distribution: subpleural & basal (often heterogenous)
Features: reticulation + traction & honeycombing (& no features suggestive of alternative diagnosis)
Indeterminate:
Dist: variable or diffuse
Feat: fibrosis but some features suggestive of non-UIP e.g. GGO, consolidatoin
Not-UIP:
Dist: upper/mid-lung/peribronchovascular predominant
Feat: Prominent consolidation/GGO (w/o acute exacerbation)/mosaic attenuation with sharply defined lobular air trapping on expiration/diffuse nodules or cysts
What is the definition of indeteminate UIP?
Dist: variable or diffuse
Feat: fibrosis but some features suggestive of non-UIP e.g. GGO, consolidatoin
Definite:
Distribution: subpleural & basal (often heterogenous)
Features: reticulation + traction & honeycombing (& no features suggestive of alternative diagnosis)
Probable:
Dist: subpleural & basal (often heterogenous)
Feat: reticulation + traction & NO honeycombing (& no features suggestive of alternative diagnosis)
Not-UIP:
Dist: upper/mid-lung/peribronchovascular predominant
Feat: Prominent consolidation/GGO (w/o acute exacerbation)/mosaic attenuation with sharply defined lobular air trapping on expiration/diffuse nodules or cysts
What is the defintion of not-UIP?
Not-UIP:
Dist: upper/mid-lung/peribronchovascular predominant
Feat: Prominent consolidation/GGO (w/o acute exacerbation)/mosaic attenuation with sharply defined lobular air trapping on expiration/diffuse nodules or cysts
Definite:
Distribution: subpleural & basal (often heterogenous)
Features: reticulation + traction & honeycombing (& no features suggestive of alternative diagnosis)
Probable:
Dist: subpleural & basal (often heterogenous)
Feat: reticulation + traction & NO honeycombing (& no features suggestive of alternative diagnosis)
Indeterminate:
Dist: variable or diffuse
Feat: fibrosis but some features suggestive of non-UIP e.g. GGO, consolidatoin
CT shows mosaic attenuation. How can you tell if black or white lung abnormal?
Are there fewer/smaller vessels in black lung?
Y (black abnormal)
–> occlusive vascular disease e.g. CTEPH (look for dilation of central PA, RV/LV ratio, subpleural opacities/linear bands, effusions)
–> small airways disease e.g. obliterative bronchiolitis (look for large airway dilatation e.g. bronchiectasis - could ask for expiratory scan if unsure)
N (white abnormal)
–> infiltrative lung disease e.g. GGO
Nb. can have both abnormal - if fewer vessels in black & GGO/fibrosis in white
–> Hypersensitivity pneumonitis OR sarcoid
Nb2. if look similar then probably white lung abnormal
What are CT findings of NSIP?
Symmetrical, bilateral GGO
If fibrotic, fine reticulation and volume loss + traction
Bronchovascular, subpleural sparing nb. still often peripheral though
Can have cysts but not honeycombing
Nb. nodules, mosaic attenuation or cysts should make you think of other things
What kinds of NSIP are there?
Fibrotic - worse outcome
Cellular
Causes: CTD, autoimmune, drug esp chemo, relapsing OP
What are causes of NSIP?
CTD e.g. SLE/scleroderma/myositis
Autoimmune e.g. RA, PBC, antisynthetase
Drugs e.g. chemo
Relapsing OP
What are causes of UIP?
IPF
CTD-ILD - RA common, systemic sclerosis (NSIP more common), poly/dermato (UIP/NISP/COP), mixed CTD (UIP/NSIP)
Chronic HP
Asbestosis
Radiation
ANCA vasculitis
Drugs - amidorone
What is histology of UIP?
- Dense fibrosis + architectural distortion (e.g. honeycombing)
- Predominant subpleural/paraseptal fibrosis with areas of less involved parenchyma
- Max mild inflammation only (and not lymphocytes >40% = HP)
- Fibrobastic foci
HP
- Bronchocentric/diffuse interstitial inflammation with thickened alveolar septa
- Lymphocytes >40%, plasma cells +/- occasional multinucleate giant cells
- Poorly formed granuloma
- Tiny foci of OP (scattered plugs of fibroblasts)
Sarcoid
- Lymphatic distribution
- Non-necrotising granulomas
- Central areas of macrophages, epitheliod, multinucleate giant cells, CD4 T-cells
- Surrounded by CD4+8 Tcells, B cells, monocytes, mast cells & fibroblasts
What is the histology of HP?
- Bronchocentric/diffuse interstitial inflammation with thickened alveolar septa
- Lymphocytes >40%, plasma cells +/- occasional multinucleate giant cells
- Poorly formed granuloma
- Tiny foci of OP (scattered plugs of fibroblasts)
Nb.
UIP
- Dense fibrosis + architectural distortion (e.g. honeycombing)
- Predominant subpleural/paraseptal fibrosis with areas of less involved parenchyma
- Max mild inflammation only (and not lymphocytes >40% = HP)
- Fibrobastic foci
Sarcoid
- Lymphatic distribution
- Non-necrotising granulomas
- Central areas of macrophages, epitheliod, multinucleate giant cells, CD4 T-cells
- Surrounded by CD4+8 Tcells, B cells, monocytes, mast cells & fibroblasts
What is the histology of sarcoid?
- Lymphatic distribution
- Non-necrotising granulomas
- Central areas of macrophages, epitheliod, multinucleate giant cells, CD4 T-cells
- Surrounded by CD4+8 Tcells, B cells, monocytes, mast cells & fibroblasts
Nb.
UIP
- Dense fibrosis + architectural distortion (e.g. honeycombing)
- Predominant subpleural/paraseptal fibrosis with areas of less involved parenchyma
- Max mild inflammation only (and not lymphocytes >40% = HP)
- Fibrobastic foci
HP
- Bronchocentric/diffuse interstitial inflammation with thickened alveolar septa
- Lymphocytes >40%, plasma cells +/- occasional multinucleate giant cells
- Poorly formed granuloma
- Tiny foci of OP (scattered plugs of fibroblasts)
What are RFs for IPF?
Smoking, GORD, EBV, hep C, fhx of ILD
M>F
<50 years RARE
How is IPF diagnosed?
Radiology MDT
- if not definite UIP, then can do lung biopsy (BAL not routinely recommended - main reason would be to r/o HP - lymphocytes >40%)
Histology:
- Dense fibrosis + architectural distortion (e.g. honeycombing)
- Predominant subpleural/paraseptal fibrosis with areas of less involved parenchyma
- Max mild inflammation only (and not lymphocytes >40% = HP)
- Fibrobastic foci
How is biopsy taken for UIP and when is it needed?
Only needed if diagnostic uncertainty
Often risk > benefit
Recommend surgical biopsy (or cryobiopsy - 10% PNX, 10% haemorrhage)
What are the main predictors of outcome for IPF?
Drop of SATS during 6MWT
TLCO at presentation (<40% = advanced disease)
Drop of FVC 10% or FEV1 15% in first 6-12 months
Overnight oximetry
What is most common mutation associated with IPF?
MUC5B (also ass with UIP with RA)
What is treatment for IPF?
Criteria: FVC 50-80% for pirfenidone or >50% for nintedanib+ MDT diagnosis
Stop if: FVC decline >10% in 1 year
Pirfenidone SEs. N, decrease appetite, photosensitive rash (30%)
Nintedanib SEs. D
Nb. slow decline in FVC by 50% (and nintedanib increases time to first exacerbation)
Monitor: LFTs at 1/12 for 6/12 then 3/12
- if 3-5xULN then reduce dose or stop but can return when normal (reduced dose and uptitrate)
- if >5ULN then stop (or <5 with symptoms of liver dysfunction)
Nb2. Can consider steroids if lots of GGO suggestive of exacerbation
What are SEs of Pirfenidone? When can it be used and what do you have to monitor?
Nausea, decrease appetite, photosensitive rash (30%), wt loss
Indications: FVC 50-80% + MDT diagnosis of IPF –> start low dose and uptitrate
Stop if: FVC decline >10% in 1 year
Monitor: LFTs monthly for 6/12 then three-monthly
–> if 3-5xULN then decrease dose/interrupt and restart when normal
–> >5ULN then stop (or <5 but symptoms of liver dysfunction)
Suggest take with food due to SEs.
Approx 801mg TDS
Contraindications: pregnancy/breast feeding, smoking, eGFR<30, severe hepatic impairment
Caution: mild hepatic/renal impairment
Common interactions: ciprofloxacin (reduce does of pirfenidone and give high dose cipro 750mg)
What are SEs of Nintedanib? What are indications for use? What monitoring is required?
Diarrhoea, increased bleeding risk
Indications: FVC >50% + MDT diagnosis of IPF
OR progressive-fibrosing ILD and 10% FVC decline over 24months or 5-10% + symptoms
–> start at full dose (150mg BD)
Stop if: FVC decline >10% in 1 year
Monitor: LFTs monthly for 6/12 then three-monthly
–> if 3-5xULN then decrease dose/interrupt and restart when normal
–> >5ULN then stop (or <5 but symptoms of liver dysfunction)
Nb. only 1% renally excreted therefore can use in patients with very low renal function
What is definition of progressive fibrotic ILD?
2/3 of:
- Worsening symptoms
- Radiological progression
- Physiological progression (decrease FVC ≥5% or DLCO ≥10% in 1 year)
All within 1 year in a patient with ILD that isn’t IPF and no other explanation for decline
What radiology patters do you see in CTD-ILD?
Chronic fibrosing: NSIP (SSc) or UIP (RA)
Subacute/acute: OP/NSIP/DAD (idiopathic inflammatory myositis)
Nb. if underlying disease quiescent, less likely to be this
What is the most common cause of CTD-ILD? What are the predictors of severity?
SSc - tends to present in more chronic way (NSIP)
Severity:
- Increased extent at presentation
- Scl-70, Th/To, U3RNP
- Short term progression in lung function
- ILD in first 4 years of SSc diagnosis
Nb. Anti-centromere Ab = protective (but ass with PH)
What is the typical radiological pattern for SSc-ILD?
NSIP - Symmetrical, bilateral GGO, fine reticulation and volume loss + traction, subpleural sparing nb. still often peripheral though
What is the typical radiological pattern for myositis-ILD?
OP/NSIP - particularly if subacute/chronic presentation
Can get acute presentation.
Has a good prognosis and CK levels may be normal.
What is the typical radiological pattern for RA-ILD? What are RFs?
NSIP but also UIP (NSIP more on radiology, but equal on histology)
RFs: increasing age, smoking, male, anti-CCP
What is the prognosis for RA-ILD with UIP pattern?
Very like IPF nb. also ass with Muc5b
What is treatment for CTD-ILD?
General:
Prednisolone 0.5-1mg/kg +/- iv/oral cyclophosphamide or azathioprine
–> taper to maintenance <10mg
Dermato/poly - early treatment with the above
SSc - MMF –> use low dose steroids and cyclo if needed to get ression (only use low dose steroids due to risk of renal crisis)
Nintedanib if progressive fibrosing (>10% fibrosis on CT)
What are the CT features of hypersensitivity pneumonitis?
Non-fibrotic pattern:
- GGO/mosaic attenuation (suggest parenchymal infiltration)
- Air trapping/ill-defined centirolobular nodules (suggest small airways disease)
- Diffuse distribution +/- basal sparing
Fibrotic:
- reticulation/bronchiectasis/honeycomb (ie. fibrotic features)
+/- centirolobular nodules, mosaic attenuation, 3-density pattern (ie. .small airways involvement)
- Diffuse distribution +/- basal sparing
Nb. BAL very helpful –> >30% lymphocytes (20% in non-smokers) +/- granulomas
How does HP present?
Very variable presentation and progression
Squawks very helpful but not always present
Nb. is a type 3 hypersensitivity mediated by IgG complexes
How is HP classified?
Fibrotic
Non-fibrotic
Nb. is a type 3 hypersensitivity mediated by IgG complexes
How is HP treated?
Avoid exposure (may be sufficient in mild disease)
High dose steroids (0/5mg/kg 2-4 weeks) then taper
MMF/azathioprine/Rituximab to maintain stability or if intolerant to pred
Progressive fibrosing - Nintedanib
What are some common drug causes of HP?
Amiodarone, nitro, biologics
Other causes: mould, gardening, hot tub (m.avium), farmers (fungi), bird proteins
What are histology features of HP?
Lymphocytosis on BAL (>20% or 30% in smokers)
BUT may be normal if fibrotic HP
Granulomas - ‘ill defined’ ‘loose forming’
How do you define inflammatory non-fibrotic HP on CT?
1 of GGO/mosaic attenuation
1 or air trapping/ill-defined centirolobular nodules
Dist: top>bottom
Nb. Resp bronchiolitis in ILD tends to be centirolobular nodules in diffuse distribution
Fibrotic:
1 of reticulation/bronchiectasis/honeyco
1 of centirolobular nodules/mosaic atten/3-density pattern
Dist: top > bottom
How is HP diagnosed?
Clinical + CT + BAL +/- biopsy
BAL: lympocytes >20% (30% smokers) >50% = highly suggestive
May be normal in fibrotic HP. May see granulomas ‘ill formed’ ‘loose forming’. May see giant cells with cholesterol clefts.
Biopsy (transbronchial if non-fibrotic, transbronchial cryo or surgical if fibrotic): granulomatous, bronchocentric inflammation
Nb. IgG against specific Ag marker of exposure, not disease. Helpful but not diagnostic.
What are RFs for mortality with HP?
UIP like pattern
Increasing age
Clubbing
Higher severity disease
Declining FVC
Failure to identify trigger
Intense exposure
Smoker
Short-telomeres
What causes a lymphocitic BAL? ie. >15%
Sarcoid
NSIP
HP (nb. >50% highly suggestive for this)
Drug-induced pneumonitis
Collagen vascular disorders
Lymphocytic interstitial pneumonia
Cryptogenic organising pneumonia
Lymphoproliferative disorders
Nb. >25% highly suggestive of granulomatous disease (sarcoid, HP, berylliosis)
Nb2. Elevated CD4/CD8 ratio suggestive of sarcoid
What causes a neutrophilic BAL? ie. >3%
IPF
Aspiration
Collagen vascular disease
Infection
Asbestosis
Bronchitis
ARDS
What causes an eosinophilic BAL? ie. >1%
Eosinophilic pneumonias
Drug-induced pneumonitis
BM transplant
Asthma, bronchitis
Churg-Strauss
ABPA
Infection
Hodgkins
What is the difference between a cyst and cavity on CT?
Cyst wall <2mm
CT shows bizarre-shaped cysts with thick walls. What is the diagnosis?
Langerhans cell histiocytosis
- 20-30s
- Strong ass with smoking (but not essential)
- Upper & midzone bizarre shaped cysts with thick walls +/- nodules (become cysts)
- Mixed obstructive/restrictive PFTs
- Can be ass. with cysts in many places e.g. diabetes insipidus and bone cysts
- Might see Bierbeek granules
- CD1a positive cells on biopsy diagnostic
Treat: smoking cessation/cladribine
CT shows uniform shaped but variable sized cysts throughout the lungs. What is the diagnosis?
Lymphangioleimyomatosis (LAM)
- Female, often young
- Lots of uniformly shaped (all spherical) but variable sized cysts with uniform distribution in lung. Can be large.
- Mixed obstructive/restrictive PFTs
- Ass with tuberous sclerosis (epilepsy, learning difficulties) and renal angiomyolipomas
- Can get chylous effusion
- Might see raised VEGF
Pt has basal predominant cysts on CT of irregular shapes. What is most likely diagnosis?
Burt-Hogg-Dube
- Irregular shaped cysts (round and elongated), adjacent to interlobular septa, arteries and veins
- Ass with skin folliculoma and renal cysts
- Ass with FLCN gene mutation
- Increased risk of renal and lung cancer
Autosomal dominant
What causes nodules in:
1) perilymphatic distribution
2) random
3) centirolobular
1) Sarcoid, silicosis
2) Mets, TB, fungal
3) HP, ifx, bronchoalveolar ca, bronchiolitis
Pt has ill-defined centirolobar nodultes and scattered thin-walled cysts. What is most likely diagnosis?
Lymphocytic interstitial pneumonia
- Female, >50
- Patchy GGO, cysts no zonal prediliction, varying sizes (might not be loads of cysts). Sometimes get calcified nodules associated with the cysts (amyloid deposits)
- Ass with Sjogrens, HIV
BAL lymphocytes
Poly/monoclonal IgM gammopathy
What tracheobronchial abnormality is seen with granulomatosis with polyangitis?
Subglottic stenosis from granuloma (May see variable extrathoracic obstruction on flow volume loo)
What is a flow chart for lung cyst differential?
Mimic - bulla, cavity, bronchiectasis
Single - pneumatocele, congenital foregut malformation, normal aging
+ Normal lung parenchyma
—> LAM (smaller cysts but variable size, uniform distribution, ass with TS, young female)
—> BHD (large lentiform/spherical cysts, lower zone/peripheral predominant)
+ nodules
—> LCH (cavitatory nodules, upper zone predominant, bizarre shape, young smoker)
—> LIP (middle age female, GGO, no zonal prediliction, variable size)
—> amyloid
+ GGO
—> PCP (perihilar GGO)
—> LIP
What is definition of idiopathic pneumonitis with autoimmune features?
2/3 of:
- Clinical extrathoracic feature of autoimmune disease e.g. Raynaud
- Serologic (Ab)
- Radiology or histology
+ not meeting criteria of CTD
What is treatment of LAM?
Siroliumus + transplant
Avoid OCP.
Young female, cysts all round but of varying size, uniform distribution, ass with tuberous sclerosis
What imaging should be done in pt with suspected sarcoid?
CXR
+/- CT (may not need CT if typical findings and typical clinical picture)
+/- CMR - if suspicions of cardiac sarcoid and abnormal ECG or echo
Nb. should get ECG, & bloods incl calcium and LFTs annually. Regular lung function.
CT and clinical findings not sufficient to diagnose sarcoidosis. What is next test?
EBUS if LNs, otherwise TBBx
What treatment is needed for sarcoid?
Maybe none
10mg pred for longstanding and insiduously progressive disease - trial withdrawal after 6-12months
20-40mg for acute
Can try inhaled steroid for cough
2nd line: methotrexate or azathioprine
Also, leflunomide, infliximab, rituximab
What are sarcoid stages?
0 - normal CXR
1 - enlarged LNs
2 - enlarged LNs and parenchymal changes
3 - parenchymal changes w/o LNs or fibrosis
4 - fibrosis
What is Lofgren’s syndrome?
Bilateral hilar lymphadenopathy, erythema nodosum +/- bilateral ankle arthritis
What is required to make a definitive diagnosis of sarcoid? When is it not needed?
Biopsy
Not needed if Lofgren OR, long-standing pulmonary disease with typical clinical presentation and imaging
+ no obvious alternative
What might you see on biopsy in sarcoid? + BAL?
Biopsy - non-caeseating granulomas
BAL - raised lymphocytes 15-25%, CD4:CD8 >4
How should fatigue be treated in sarcoid?
Trial prednisolone only if accompanying disease activity or all other options have been exhausted
How long should pt with sarcoid be followed up?
Can d/c with Lofgren or stage 1 CXR once resolution confirmed
What is the median survival after IPF diagnosis?
3 years
Excerbation of IPF: median survival 3 months
What is Heerfordt-Waldenstrom syndrome?
Sarcoid + fever, parotid gland enlargement, facial nerve palsy and uveitis
What is Erasmus syndrome?
Progressive scleroderma in response to silica exposure
What is desquamative interstitial pneumonia?
Smoker
Middle-age
Male
CT - diffuse, peripheral patchy GGO (i.e.non-specific)
Bippsy - Pigment laden macrophages on biopsy
What factors are associated with IPF?
Age (rare in <60)
Male
Smoking
Family history
Cardiovascular disease & VTE
Occupational - metal, wood, textiles, sand, stone, silica
nb. approx 50% patients are clubbed
What factors are associated with poorer prognosis in fibrotic lung disease?
TLCO <40% at diagnosis
Decrease FVC ≥10% over 6-12 months
Decrease TLCO ≥15% over 6-12 months
Desaturation on exercise to <88%
What is the mechanism of action of nintedanib?
Tyrosine kinase inhibitor
Radiological patterns of OP?
Multifocal peripheral OR peri-lobular OR bronchocentric consolidation
Lymphocytic BAL
nb. eosinophilic pneumonia classically has multifocal peripheral consolidation but will get high eosinophils (eosinophils of BAL >10%)
What is pulmonary haemosiderosis?
Iron deposition in lung e.g. ass with Goodpastures, idiopathic
Small, ill-defined pulmonary nodules + calcification
Lung parenchymal distortion
Vignette will have haemorrhage
What are features of RB-ILD?
Need to be current smoker (can also get in RA and scleroderma)
CT: peripheral bilateral GGO & centirolobular nodules. Can get cysts from fibrosis. Tend to also have emphysema.
Pigement-laden macrophages on biopsy
What is Goodpasture’s?
Anti-GBM disease (type 2 hypersensitivity with Ab adjacent type 4 collagen in renal glomerular basement membrane and cross-reactivity with alveolar membrane)
Pulmonary haemorrhage + glomerulonephritis
Radiology: bilateral GGO –> crazy paving
+/- hilar lymphadenopathy
What is granulomatous lymphocytic interstitial pneumonia?
ILD seen in CVID
Radiology: bilateral nodules, GGO, lymphadenopathy +/- interlobular septal thickening & bronchiectasis
–> usually mid-lower lobe predominant
Tx: rituximab
What is lymphangitis carcinomatosis?
Spread of tumour through lymphatics of lung - most commonly secondary to adenoca (breast > lung > stomach)
CT: irregular and nodular interlobular septal thickening + pleural effusion
What is classic symptoms for granulomatosis with polyangiitis and how is it treated?
Triad of:
- Upper resp tract involvement: hearing loss, gingivitis, oral ulcers, subglottic stenosis
- Lower rep: nodules, infiltrates, cavities, pulmonary haemorrhage
- Glomerulonephritis
Treat
- Life-threatening: plasma exchange, dialysis, immunosuppression
- Organ-threatening: cyclophosphamide + glucocorticoid
- Maintenance after remission: azathioprine or MMF
What are features of pulmonary alveolar proteinosis?
Crazy paving appearance
Milky BAL
anti-GM-CSF Ab diagnostic
Tx: whole lung lavage
