Interstitial lung disease Flashcards
What are the known causes under the category of Diffuse Parenchymal Lung Disease of known cause?
Drug
1) Cytotoxics (chemotherapeutics): MTX, AZA, bleomycin, bulsulphan, cyclo, chlorambucil
2) CNS: amitryptiline, phenytoin, carbamazepine
3) CVS: amiodarone, hydralazine, procainamide
4) ABX: nitrofurantoin, isoniazid
5) Antirheumatics (DMARTS): gold, sulphasalazine
6) Radiation, aspirin, oxygen
* *= important
Connective tissue disease
- RA: There is bilateral involvement of the small joints of the hands, causing ulnar deviation of the MCPJ, swan neck deformity of the fingers, and Z thumb – indicating a RA picture
- SLE
- Dermatomyositis
- Sjogren’s
- Systemic sclerosis
Miscellaneous: don’t need to know - Langerhan cell histocytosis Lymphangioleiomyomatosis (LAM) - Alveolar proteinosis - Post-infectious
What are the known causes under the category of Granulomatous Diffuse Parenchymal Lung Disease?
Sarcoidosis
Hypersensitivity pneumonitis 🡪 due to violent IR against any insult to the lungs. Important if patient keeps exotic pets at home / go overseas to amazon jungle etc
How is idiopathic interstitial pneumonia (IIPs) categorized?
Chronic fibrosing
- idiopathic pulmonary fibrosis: most common & most important to know
- idiopathic nonspecific interstitial pneumonia
Acute/ subacute fibrosing
- Cryptogenic organising pneumonia: responds well to steroids, Cryptogenic = obscure / uncertain origin
- Acute interstitial pneumonia 🡪 rapid onset, diagnosis usually post-mortem
Smoking related 🡪 because smoking cessation can lead to improvement
- Respiratory bronchiolitis interstitial lung disease
- desquamative interstitial pneumonia
What are the causes of interstitial lung disease that manifests in the upper lobe?
Rule: tend to be caused by INHALED substances as upper lobe V>Q
Coal worker pneumoconiosis
- Pneumoconiosis = inflamm of lungs due to inhalation of dust 🡪 causing cough , inflamm and fibrosis
Histiocytosis – a group of immune conditions that causes an increase in histiocytes (aka tissue macrophages such as Langerhans cells) – wrt ILD, refers to increased histiocytes in the lung (Pulmonary Langerhans cell histiocytosis)
Ankylosing spondylitis, ABPA (will have eosinophilic picture)
- ABPA: allergic Bronchopulmonary Aspergillosis
- AS: the exception to the rule
Radiation – possibly from Breast CA radiation
TB
Silicosis, sarcoidosis
- Silicosis = a type of occupational lung disease caused by inhalation of silica dust
What are the causes of interstitial lung disease that manifests in the lower lobe?
Lower Lobe (RASIO) RA - Asbestosis - Scleroderma - Idiopathic pulmonary fibrosis - Others (drugs)
What are the causes of interstitial lung disease that manifests in the upper+ lower lobe?
Upper + Lower - “NEPAL”
- Neurofibromatosis, tuberculous sclerosis
- Extrinsic allergic alveolitis
- Pulmonary haemorrhagic syndromes
- Alveolar proteinosis
- Lymphangiomyomatosis
What are the more likely etiologies of ILD in patients 20- 40 years old?
Sarcoidosis, connective tissue disease, Lymphangioleiomyomatosis, Langerhans cell histiocytosis, other inherited forms
What are the more likely etiologies of ILD in patients >50 years old?
Idiopathic pulmonary fibrosis
What are the symptoms experienced by someone with interstitial lung disease?
Generally nonspecific Symptoms
- Cough (usually dry 🡪 differentiates from bronchiectasis)
- Exertional dyspnoea
- Rare: Wheezing and haemoptysis
Systemic Review (for connective tissue diseases):
- Instead of findings specific for ILD, we may get findings indicating underlying aetiology (eg: connective tissue disorder)
1) Any Hx of Rheum / AI dz; joint pain, rash, eye redness
2) Drug Hx and Social Hx – workplace exposure
3) Hx of TB exposure – night sweats, LOW, LOA
What are the signs seen in someone with ILD?
Disease Findings
- Tachypnoea
- Clubbing
- Reduced chest expansion
- Bilateral, Fine, Velcro-like, end inspiratory crepitation (usually heard at bases)
S&S of Complications
- Signs of cor pulmonale/pulmonary hypertension/polycythaemia (from prolonged hypoxia): Elevated JVP, Pedal edema, Palpable P2, Parasternal heave
- Signs of respiratory distress: Tachypnoea, using accessory respi muscles, supplemental O2
S&S of Aetiology
- RA: deforming symmetrical polyarthropathy, rheumatoid nodules
- SLE: malar rash
- Scleroderma: CREST Syndrome (Calcinosis, Reynaud’s, Esophageal Dysmotility, Sclerodactyly, Telangiectasia)
- Dermatomyositis: Gottron’s papules, mechanics hands, shawl/V sign, heliotrope rash, proximal myopathy
- Sarcoidosis: Uveitis, salivary gland enlargement, lymphadenopathy, hepatosplenomegaly
What are the investigations required for diagnosis of ILD?
CXR
- Bilateral heterogenous diffuse reticulo-nodular opacities / Reticular Shadowing (hallmark)
- Reticular = Net-like; multiple fine lines crossing each other
- Caused by thickening of interstitium from inflammation or fibrosis
HRCT (may provide etiology in certain cases)
- HRCT makes thinner cuts which are wider apart
- Subpleural/ Basal-predominant reticular abnormalities (sensitive for IPF)
- Honeycombing / reticular changes 🡪
- May have bronchiectatic changes – traction bronchiectasis (pulling of the airways open from fibrosis)
Lung Function Tests
- Spirometry: restrictive picture (↑ or normal FEV1/FVC)
- Lung volume (↓ TLC ↓ VC)
- Diffusion test (reduced DLCO): Extent that O2 is able to pass from alveoli into blood
- 6-minute walk test : Look for any desaturation during and after test. Baseline measurement for monitoring
What are the investigations required for etiology of ILD?
Bloods
1) IGRA / T Spot test / Tuberculin skin test
2) Autoimmune workup:
- ANA (SLE), anti-dsDNA (more specific for SLE), C4=3, C4, anti-Ro/La (in SLE and Sjogerns), anti-RF (RA), anti-CCP (RA) first.
- If negative, check the rest Scleroderma (anti-Scl-70) & Dermatomyositis (anti-Jo1, antisynthetase, CK).
3) ESR/CRP
4) Calcium : If raised 🡪 sarcoidosis?
5) Retroviral Screen: HIV 🡪 mimicker of diseases
Bronchoalveolar Lavage
1) Lavage for sputum 🡪 to send for culture and other tests
2) Evaluation of patients with:
- Haemoptysis,
- Acute or rapidly progressive ILD
- Likely caused by one of the following diseases: sarcoidosis, hypersensitivity pneumonitis, pulmonary Langerhans histiocytosis, or infection
Lung Biopsy
- Transbronchial (only can access central lung) or surgical
- Only if uncertain of diagnosis – esp for non-cryptogenic causes of ILD, there may not be characteristic features of honeycombing and traction bronchiectasis
Others
- Sarcoidosis: check serum ACE, prominent hilar lymphadenopathy on HRCT
- Hypersensitivity pneumonitis: screen for antibody to the suspected antigen
- Vasculitis: ANCA, urinalysis
What are the investigations required for complications of ILD?
ECG/Echocardiogram – to look for heart function
- Pulmonary hypertension
- Right HF
What is the definition of idiopathic pulmonary fibrosis?
- Specific form of chronic, progressing, fibrosing interstitial pneumonia of unknown cause
- Associated with characteristic histopathologic and or radiologic pattern (see below)
- Dx of exclusion – Rule out smoking-related, cryptogenic organising pneumonias (due to adjacent infection)
What is idiopathic pulmonary fibrosis associated with?
Smoking – particularly >20 pys
GERD (90%) – can potentially worsen IPF (microaspiration of acidic contents)
- When taking respi history 🡪 should always cover GERD. GERD causes aspiration which worsens a lot of respi syndromes hence is always important to ask!
CAD, OSA, COPD
Environmental (metal/wood dust, farming, birds, etc.)
What are the clinical features associated with UIP/ IPF?
- Exclusion of other causes of ILD
- > 50 years
- Insidious onset of dyspnoea
- For > 3months
- Non-productive cough
- Typical physical findings
What is the UIP patterns present on HRCT?
1) Subpleural/ basal predominance of reticular infiltrates and honeycombing
2) Reticular abnormality
3) Honeycombing +/- Traction bronchiectasis (traction bronchiectasis is not always necessary)
4) Absence of features inconsistent w UIP
- Upper or mid-lung predominance
- Peribronchovascular predominance
- Extensive ground glass abnormality (extent >reticular abnormality)
- Profuse micronodules (bilateral, predominantly upper lobes)
- Discrete cysts (multiple, bilateral, away from areas of honeycombing)
- Diffuse mosaic attenuation/air-trapping (bilateral in three or more lobes)
- Consolidation in bronchopulmonary segment(s)/lobe(s)
If HRCT shows all 4 features 🡪 no need to do lung biopsy as HRCT alone is sufficient for diagnosis
- If there are inconsistent patterns we always need SURGICAL LUNG biopsy to diagnose! – high risk ☹
- We cannot do trans bronchial lung biopsy because parenchyma is too far!
What are the key histological features of UIP/ IPF? What are the perminent negative findings?
Key histologic features
1) Dense fibrosis causing remodelling of lung architecture with frequent “honeycomb” fibrosis.
2) Fibroblastic foci typically scattered at the edges of dense scars.
3) Patchy lung involvement.
4) Frequent subpleural and paraseptal distribution.
Pertinent negative findings
1) Lack of active lesions of other interstitial diseases (ie, sarcoidosis or Langerhans cell histiocytosis).
2) Lack of marked interstitial chronic inflammation.
3) Granulomas: inconspicuous or absent.
4) Lack of substantial inorganic dust deposits, ie, asbestos bodies (except for carbon black pigment).
5) Lack of marked eosinophilia – eosinophilia is seen in HBPA
What is the prognosis of IPF/ UIP?
- Stable progressors
- Slow progressors: 5 years
- Rapid progression: weeks to months
If acute worsening 🡪 baseline will drop
What are the prognostic markers of IPF/ UIP?
Baseline factors
- Level of dyspnoea using mMRC score
- DLCO < 40%
- Desaturation <88% during 6 minute walk test
- Extent of honeycombing on HRCT
- Pulmonary hypertension
Longitudinal factors - Increase in level of dyspnoea - Decreased FVC y <10% absolute value - Decreased in DLCO >15% Worsening of fibrosis on - HRCT
What is the management of IPF/ UIP?
Education and counselling: Stop smoking
Symptom Relief
- Pulmonary rehabilitation
- Supplemental O2
Vaccination: Pneumococcal, Influenza
Treat underlying cause
Pharmacological therapy 🡪 is disappointing ☹
1) Steroids, warfarin, Imatinib, etc all not shown to work (despite theoretically can reduce inflammation)
2) Antioxidants *not shown to work (despite theoretically can remove free radicals).
- N acetylcysteine
3) Anti-fibrotic agents
- Slow progression of disease, decreasing decline in FEV1
- Pirfenidone
Nintedanib (FDA approved)
- TKI targeting several growth factors
4) Antacids – to treat GERD
- H2 antagonist, PPIs
- GERD in 90% of patients with idiopathic pulmonary fibrosis
- Reflux shown to worsen pulmonary fibrosis
5) Treatment of symptoms: Cough, Palliative Tx of SOB
Surgical: Lung transplant
Manage complications
- Cor pulmonale
- Polycythaemia
- Respiratory failure
- Monitor for lung CA
