Interstitial Lung Disease (Pulmonary Fibrosis) Flashcards
What is the definition of ILD / pulmonary fibrosis / diffuse parenchymal lung disease?
Diffuse fibrosis of alveoli and perialveoli tissues
Leading to impairment of gas excahnge
Restrictive lung pathology
Diffuse infiltrates on radiography
What are the clinical signs of pulmonary fibrosis?
General
1. Comment on functional status: breathless/comfortable, oxygen therapy
2. Ask patient to cough - non-productive cough (ILD), productive cough (not ILD, unless infection)
3. Signs of associated autoimmune disease - determines etiolgoy of ILD
4. Signs of ILD treatment - steroid purpura, ciclosporin gingival hyperplasia
4A. Slate grey skin discolouration secondary to amiodarone
Peripheral
5. Clubbing
6. Peripheral and central cyanosis
7. Usually no palpable lymph nodes (unless sarcoidosis, malignancy)
Chest
8. Chest expansion equal but reduced bilaterally
9. Dull percussion, reduced focal fremitus over affected region (upper or lower)
10. Fine end inspiratory crepitations that do not change on coughing
11. Signs of pulmonary hypertension
(wheeze - indicates obstructive airways, or sarcoidosis, NOT cryptogenic ILD)
What are the causes of an upper zone/apical fibrosis?
(M: HCP BREAASTS)
- Histiocytosis X
- Coal workers pneumoconiosis
- Psoriasis
- Berylliosis
- Radiation
- Extrinsic allergic alveolitis (hypersensitivity pneumonitis)
- Ankylosing spondylitis
- Aspergillus ABPA
- Silicosis
- Tuberculosis
- Sarcoidosis
What are the causes of lower zone/basal fibrosis?
(M: RAIDS)
- Most Rheumatology/CTD except AS, psoriasis
- Rheumatoid arthritis
- Asbestosis
- Idiopathic/cryptogenic pulmonary fibrosis
- Drugs (M: Go BAN Me)
- MTX, azathioprine, bleomycin, busulphan, cyclo, chlorambucil
- Amitryptyline, phenytoin, carbamazepine
- Amiodarone, hydralazine, procainamide
- Nitrofurantoin, isoniazid
- Gold, sulphasalazine - Scleroderma, systemic sclerosis, SLE, Sjogren’s syndrome
(Asbestos is massive crystal thus affect lower zone)
What are the causes of generalised fibrosis?
(M: PLANT)
- Pulmonary haemorrhage and vasculitis syndromes - PAN, WG, CS, Goodpasture
- Lymphangiomyomatosis, carcinomatous lymphangitis
- Alveolar proteinosis (silica, aluminum dust, chronic infection, malignancy)
- Neurofibromatosis
- Tuberous sclerosis
How would you investigate a patient with suspected pulmonary fibrosis?
- Bloods
- FBC: anaemia (vasculitis), polycythaemia (chronic hypoxia), leukocytosis (hypersensitivity), eosinophilia
- Inflammatory markers (ESR, CRP)
- ABG: type 1 respiratory failure
- Immunoglobulin
- Autoimmune (ANA, RF, ENA, ANCA, anti-GBM, SLE)
- CK in polymyositis and dermatomyositis
- Precipitins - hypersensitivity pneumonitis
- Serum ACE - sarcoidosis - CXR
- Bilateral reticulonodular changes (upper/lower)
- Honeycombing appearance (advanced disease)
- Loss of heart border definition
- Small lungs
- Bilateral hilar lymphadenopathy (sarcoidosis)
- Calcified pleural plaques (asbestosis) - Lung function test
- Restrictive pattern: FEV1/FVC > 0.7
- Low TLC, FRC
- Reduced transfer factors/coefficient - HRCT or MRI Thorax
- Early: ground glass, interstitial thickening in subpleural distribution
- Late: honeycombing, areas of fibrosis, traction bronchiectasis - Bronchoalveolar lavage
- Lymphocytosis - indicates steroid responsiveness, better prognosis
- Look for malignant cells, asbestos bodies, eosinophils
- To exclude infection prior to starting treatment - Lung biopsy - identify etiology of ILD
What are the complications of ILD?
- Respiratory failure
- Recurrent chest infection
- Pulmonary hypertension and cor pulmonale
- Lung carcinoma
How would you manage patients with ILD?
General
1. Multidisciplinary teams - respi, PT, OT, RT
2. Cessation of triggers - stop smoking, remove exposure/change workplace
3. Treat infections (antibiotics) and symptoms (NAC)
4. LTOT if indicated
5. Vaccination
Immunosuppression
5. Prednisolone 40mg OM for at least 6 weeks, continue if good response
- Taper and discontinue over 1 week if response is not good
6. Steroid non-responsive - consider azathioprine, methotrexate, cyclophosphamide
7. Pirfenidone, nintedanib for usual interstitial pneumonia when FEV1 50-80% predicted (ASCEND, INBUILD)
8. Others - colchicine, D-penicillamine for idiopathic ILD
Surgery
9. Single or double lung transplantat - advanced disease
(survival: single 74% at 1 year, 58% at 3 years, 47% at 5 years, 25% at 10 years)
What is the prognosis of pulmonary fibrosis?
Variable as depends on aetiology
Increased risk of bronchogenic carcinoma
Highly cellular with ground glass infiltrates
–> Responds to immunosuppression –> 80% 5 year survival
Honeycombing
–> Usually no response to immunosuppression –> 80% 5 year mortality
Affected zone of fibrosis and peripheral stigmata differentiating different CTD resultant ILD
A. Upper zone fibrosis
1. Ankylosing spondylitis
- Loss of lumbar lordosis
- Fixed kyphosis
- Stooped posture
2. Sarcoidosis
- Erythema nodosum
- Maculopapular skin lesions
- Lupus pernio
- Lymphadenopathy
3. Radiation therapy
- Erythema or field markings on chest wall
B. Lower lobe fibrosis
4. Rheumatoid arthritis
- Symmetrical deformed arthropathy over the hands
- Rheumatoid nodules
5. Systemic sclerosis
- Tight, shiny skin
- Telangiectasis
- Sclerodactyly
- Calcinosis
- Atrophic nails
- Raynaud’s phenomenon
6. SLE
- Petechial rash, purpura
- Livedo reticularis
- Arthropathy
- Butterfly malar rash
7. Dermatomyositis
- Gottron’s papules
- Heliotrope rash over eyelid/periorbital
- Proximal myopathy
8. Amiodarone use
- Grey slate skin pigmentation
- Irregular pulse
C. Generalised
9. Neurofibromatosis
- Neurofiromas and cafe-au-lait patches
What is the ATS/ERS classification of interstitial lung disease
4 major groups (ABCD)
A. ILD of known cause
1. CTD-ILD (RA, SS, Sjogren, etc)
2. Drug-related ILD (amiodarone, MTX, bleomycin)
3. Pneumoconioses (Silicosis, Asbestosis, Berylliosis)
4. Hypersensitivity Pneumonitis (HP) – Bird fancier’s lung, Farmer’s lung
5. Radiation-Induced ILD
B. Idiopathic interstitial pneumonias (IIPs) – no known cause
1. Chronic fibrosing IIPs
- Idiopathic pulmonary fibrosis (IPF) as UIP
- Idiopathic non-specific NSIP
2. Smoking-related IIPs
- Respiratory bronchiolitis-ILD (RB-ILD)
- Desquamative (DIP)
3. Acute / subacute
- Acute (AIP)
- Cryptogenic organising pneumonia (COP)
4. Rare
- Lymphoid (LIP)
- Pleuroparenchymal fibroelastosis (PPFE)
C. Granulomatous ILDs
1. Sarcoidosis
2. Chronic Hypersensitivity Pneumonitis (HP)
D. Rare ILDs & Other ILD-like Conditions
1. Lymphangioleiomyomatosis (LAM) – in young women, TSC mutation
2. Pulmonary Langerhans Cell Histiocytosis (PLCH) – Smoking-related
What is Hamman-Rich syndrome?
(Acute interstitial pneumonitis)
Rapid progressive and fatal variant of interstitial lung disease
Treatment: supportive, IV methylpred and broad spectrum antibiotics
Prognosis: 50% mortality
Pirfenidone in idiopathic pulmonary fibrosis (IPF)
- Mechanism of action
- CAPACITY I and II trial
- ASCEND trial
- Side effects
MOA: Modification/regulation of TGF-β and TNF-α
- Reduce fibroblast proliferation and collagen deposition
CAPACITY I and II trials
- I: Reduced FVC decline
- II: no statistical difference
ASCEND trial
- Slows decline in FVC at Week 52
- Improved progression-free survival and death
- Less but not statistically significant slowing of 6MWT decline
Side effects of pirfenidone:
1. Commonest - GI side effect: nausea / vomiting / diarrhoea or constipation
2. Photosensitivity
3. Transaminitis
4. Giddiness and headache, insomnia or somnolence
5. SJS / TEN
6. Angioedema
Drug interaction: ciprofloxacin
Absolute contraindications:
1. Pregnancy and breastfeeding
2. Cigarette smoking (increases pirfenidone clearance)
2. Severe renal impairment eGFR <30
4. Severe hepatic impairment (Child–Pugh C)
Nintedanib in idiopathic pulmonary fibrosis (IPF)
- Mechanism of action
- INPULSIS I and II trial
- INBUILD trial
MOA: tyrosine kinase inhibitor
INPULSIS I and II, INBUILD trial
- Reduced FVC decline
- Reduced risk of adjudicated acute exacerbations
- Slight reduction but not significant significant reduction in mortality in 52-week
Side effects of nintedanib
1. Commonest - GI side effect: nausea / vomiting / diarrhoea
2. Transaminitis
3. SJS / TEN
4. Hypertension
5. Acute coronary syndromes
6. Thromboembolism
7. Bleeding - epistaxis, gingival bleeding
NICE guideline criteria on pirfenidone or nintedanib use in idiopathic pulmonary fibrosis
- FVC 50–80% predicted
- Access to discount agreed in the patient access scheme (UK only)
Discontinue treatment if there is evidence of disease progression (decline in predicted FVC of 10% or more) within any 12-month period
PANTHER trial on traditional triple therapy (prednisolone, azathioprine, NAC) in treatment of idiopathic pulmonary fibrosis
Increased risk of death and hospitalisation in patients with IPF who were treated with prednisolone, azathioprine, and NAC.
Erroneously thought to be effective due to inaccurate differentiation of UIP vs NSIP
(Only some form of NSIP is responsive to steroids)
CT radiological features of UIP
📌 Key Differentiator: Honeycombing = definitive UIP → Suggests IPF if no known cause
Seen in Idiopathic Pulmonary Fibrosis (IPF) and RA-ILD
CT Features:
✅ Honeycombing (subpleural, basal predominant)
✅ Reticular opacities (fibrotic pattern)
✅ Subpleural & lower lobe involvement
✅ Traction bronchiectasis & bronchiolectasis
❌ No ground-glass opacities (GGO) or nodules
CT radiological features of NSIP
📌 Key Differentiator: GGO + fibrosis + NO honeycombing → Think NSIP
Seen in Autoimmune ILD (Scleroderma, Sjögren’s, Myositis-ILD)
CT Features:
✅ Ground-glass opacities (GGO) (diffuse, bilateral)
✅ Reticular opacities without honeycombing
✅ Basal & subpleural distribution
✅ Traction bronchiectasis (fibrotic NSIP)
CT radiological features of hypersensitivity pneumonitis
Acute HP = inflammatory (reversible)
Chronic HP = fibrotic (progressive)
📌 Key Differentiator: Mosaic attenuation + centrilobular nodules → Think HP
Acute HP (Subacute Stage):
✅ Diffuse ground-glass opacities
✅ Centrilobular nodules (micronodules)
✅ Mosaic attenuation (air trapping on expiration)
Chronic HP:
✅ Upper & mid-zone fibrosis (not just basal like IPF)
✅ Reticulation & traction bronchiectasis
✅ Headcheese sign (mosaic attenuation + fibrosis + normal areas)
CT radiological features of Sarcoidosis (Granulomatous ILD)
📌 Key Differentiator: Perilymphatic nodules + bilateral hilar lymphadenopathy → Think Sarcoidosis
CT Features:
✅ Perilymphatic nodules (along bronchovascular bundles & fissures)
✅ Reticulonodular pattern upper & mid-zone distribution
✅ Hilar & mediastinal lymphadenopathy
✅ Fibrosis (advanced stage)
CT radiological features of Organizing Pneumonia (OP) / Cryptogenic Organizing Pneumonia (COP)
📌 Key Differentiator: Patchy consolidations + Reverse halo → Think OP
Idiopathic or secondary to infection, drugs, CTD
CT Features:
✅ Patchy consolidation (peripheral, subpleural, or peribronchial)
✅ Reverse halo sign (atoll sign) – central clearing with peripheral consolidation
✅ Ground-glass opacities
CT radiological features of Smoking-Related ILDs
📌 Key Differentiator: Smoking history + cysts (PLCH) or GGO (DIP/RB-ILD)
Pulmonary Langerhans Cell Histiocytosis (PLCH)
✅ Cystic lung disease (irregular walls, bizarre shapes)
✅ Upper lobe predominant
Respiratory Bronchiolitis-ILD (RB-ILD)
✅ Centrilobular ground-glass nodules
✅ Upper lobe predominant
✅ Bronchial wall thickening
✅ Areas of low attenuation due to air trapping
Desquamative Interstitial Pneumonia (DIP)
✅ Diffuse ground-glass opacities
✅ Peripheral & lower lobe distribution
CT radiological features of Pneumoconioses (Occupational ILDs)
📌 Key Differentiator: Exposure history + fibrosis + nodules (Silicosis) or pleural plaques (Asbestosis)
Silicosis / Coal Workers’ Pneumoconiosis
✅ Upper lobe nodules
✅ Eggshell calcification (lymph nodes)
✅ Progressive massive fibrosis (PMF) – Coalescing masses
Asbestosis
✅ Lower lobe fibrosis
✅ Pleural plaques (calcified along ribs/diaphragm)
Summarise CT radiological findings of different types of interstitial lung disease
Lymphangioleiomyomatosis (LAM) due to abnormal proliferation of smooth-muscle-like cells
Clinical features:
1. Premenopausal women
2. Cystic destruction of the lung with progressive pulmonary dysfunction
3. Abdominal tumours (e.g. angiomyolipomas,
lymphangioleiomyomas)
4. Associated with tuberous sclerosis
Treatment: mTOR inhibitor (sirolimus)
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) occurs in smokers with > 30 pack years
CT features include:
1. Bronchial wall thickening
2. Centrilobular nodules
3. Patchy ground–glass opacities,
4. Areas of low attenuation due to air trapping
Lung biopsy (similar to DIP):
1. Pigment-laden macrophages within alveoli
3. Peribronchial inflammation
4. Fibrosis extending into alveolar septae
Management:
1. Smoking cessation
2. Lung biopsy if symptoms persist after smoking cessation
3. LTOT in established fibrosis with hypoxia
Induction regime for:
- Polymyositis/dermatomyositis associated ILD
- SSc associated ILD
Polymyositis/dermatomyositis associated ILD
- prednisolone (0.75–1 mg/kg) and cyclophosphamide
SSc associated ILD
- low-dose oral steroids (10 mg/day) and cyclophosphamide
- Avoid high dose steroids - precipitates renal crisis
Predictors of IPF poor prognosis
- Strongest - desaturation during 6WMT
- TLCO < 40%
- Fall in FVC > 10% or TLCO > 15% in 6-12 months
BAL cell count for diagnosis of ILD
Lymphocyte differential count >25%: granulomatous disease (sarcoidosis, berylium, hypersensitivity, drug reaction, LIP)
>50%: hypersensitivity pneumonitis or cellular NSIP.
Neutrophil differential count >50%:
acute lung injury, aspiration pneumonia, or bacterial infection.
Eosinophil differential count >25%:
acute or chronic eosinophilic pneumonia.
Organising pneumonia histopathologically shows intra-alveolar buds of granulation tissue, with intermixed myofibroblasts and connective tissue.
Cryptogenic - no underlying cause is identified
Causes of organising pneumonia:
1. Idiopathic
2. Drugs
3. Infectious (bacterial, viral, and fungal)
4. Connective tissue diseases (idiopathic inflammatory myopathies, rheumatoid arthritis, Sjögren)
5. Graft versus host disease
6. Malignancy
Treatment:
1. High dose prednisolone 1mg/kg
2. Add on cyclophosphamide if not steroid responsive
3. Long term steroid sparing agent: azathioprine
Drug-induced ILD
‘Bird fancier’s lung’, a type of hypersensitivity pneumonitis (HP) caused by exposure to avian proteins in the dry dust of bird droppings and feathers.
Previously called extrinsic allergic alveolitis (EAA) - but misleading as it is NOT an allergy and it involves distal airways and alveolar spaces (not just alveolar)
Avians: pigeons, parakeets, cockatiels, budgerigars, parrots, turkeys, geese, and chickens. (even feather pillows)
Diagnostic: serum precipitins (IgG to avian proteins), HRCT hypersensitivity pneumonitis
Treatment: withdrawal of exposure +/- steroids
