JC15 (Medicine) - Interstitial Lung Disease Flashcards
Causes of interstitial lung disease **
Hypersensitive pneumonitis:
- Occupational (inorganic): Silicosis, Asbestosis, Berylliosis, Aluminosis…etc
- Occupational (organic): bird fancier’s lung, coffee worker’s lung, farmer’s lung, hot tub lung, humidifier lung…etc
Drugs: Abx (e.g. Nitrofurantoin), Chemotherapy (e.g. MTX, Bleomycin), Targeted therapy (e.g. Checkpoint inhibitors), Statins, Anti–arrhythmic, cocaine, heroin…etc
Infections: Atypical pneumonia, PCP, TB, RSV…etc
Connective tissue diseases: Systemic sclerosis, RA, Sjogren, SLE, Goodpasture …etc
Genetic: Familial pulmonary fibrosis, Neurofibromatosis, Pulmonary alveolar proteinosis…etc
**Idiopathic interstitial pneumonias: ** idiopathic pulmonary fibrosis, Acute interstitial pneumonia, Cryptogenic organizing pneumonia, Lymphocytic interstitial pneumonia…etc
Vasculitis: Granulomatosis with polyangiitis, Microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis…etc
Infiltrative: Amyloidosis, Sarcoidosis, eosinophilic pneumonia…etc
Define pulmonary fibrosis.
Abnormal scarring and thickening of pulmonary interstitium between the alveolar epithelium and capillary endothelium
Adversely affecting gas exchange (much larger diffusion distance)
List the physiological changes in interstitial lung disease?
- Increase in interstitial tissue causing lower lung compliance
- Restrictive deficit
- Poor gas exchange (thick alveolar-capillary interface)
Early and late stages of pulmonary fibrosis?
Area of lung affected by interstitial lung disease?
Early = alveolitis, injury with inflammatory cell infiltration
Late = Lung Fibrosis, increase vascular resistance in pulmonary circulation»_space; Pulmonary Hypertension and cor pulmonale
Area: Pleural thickening, tractional bronchiectasis mostly at lung periphery, apico-basal gradient visible for UIP (not NSIP), overall causing small lung volume/ small lungs on radiograph
4 major clincal classes of diffuse parenchymal lung diseases (DPLD)?
- DPLD of known etiology (e.g. drugs, vascular…etc)
- Idiopathic interstitial pneumonia (IIP)
- Granulomatous DPLPs (Sarcoidosis)
- Others (Eosinophilic pneumonia, LAM, HX …etc)
3 classes of idiopathic interstitial pneumonia (IIP)
Chronic fibrosing: IPF, NSIP
Smoking related: RBILD(Respiratory Bronchiolitis–Associated Interstitial Lung Disease) , DIP
Acute/ subacute: AIP, COP
Examples of drugs that can cause pulmonary fibrosis
Risk factors of idiopathic pulmonary fibrosis *
Cigarette smoking ** (>20 pack years)
Lung Infections
Chronic GERD and aspiration
Environmental pollutants (e.g. metal or wood dust, animal dust, birds, farms…etc)
Genetic: Familial pulmonary fibrosis
Symptoms of interstitial lung diseases
Symptoms:
- Constitutional symptoms: Fever, Fatigue, Weight loss, Anorexia, Central cyanosis (abrupt deterioration)
- Respiratory: Dyspnea on exertion, Intermittent non-productive cough, respiratory failure, chest pain
Signs of interstitial lung diseases
General: Finger clubbing, cachexia, respiratory failure signs
Respiratory:
- Dry, **inspiratory bibasilar “velcro-like” crackles **on auscultation
- Dry, non-productive cough
- Signs of Cor Pulmonale: Elevated JVP, Parasternal heave, Hepatic congestion, Ascites, Dilated veins…
+/- rashes, eye signs, joint deformities…etc of different etiologies
List 6 first line investigations for ILD
CXR (reticulonodular interstitial pattern) & HRCT
Lung function tests: Oximetry, Spirometry (reduced DLCO)
Blood tests
Urinalysis
Echocardiogram (Cor Pulmonale)
+/- Lung biopsy (clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out)
Main method of diagnosis of ILD?
HRCT thorax
- Finding UIP on HRCT scan does not mean dx of idiopathic pulmonary fibrosis. IPF dx needs complete exclusion of all known causes.
- UIP is associated with Collagen vascular/ connective tissue disorder, Asbestosis, Chronic hypersensitivity pneumonitis
2 main imaging patterns of Idiopathic pulmonary fibrosis?
Usual interstitial Pneumonia - UIP
Incl: Collagen vascular/ connective tissue disorder, Asbestosis and inorganic occupational exposures, Chronic hypersensitivity pneumonitis
Nonspecific Interstitial Pneumonia - NSIP
Differentiate UIP and NSIP pattern in Idiopathic pulmonary fibrosis *
Usual interstitial Pneumonia - UIP
- Subpleural, basal predominance with obvious apico-basal gradient
- Patchy, irregular reticular/reticulo-nodular abnormality
- Predominant Honeycomb with tractional bronchiectasis
Nonspecific Interstitial Pneumonia - NSIP
- Ground glass opacity (more temporally and spatially homogenous) with No obvious gradient
- Reticulation with peri-bronchovascular fibrosis/ micronodules
- Rare honeycomb or tractional bronchiectasis
Tests for progression of Idiopathic pulmonary fibrosis?
Functional tests:
- Lung function tests (suggestive but not diagnostic on its own)
- Breathlessness scoring: Dyspnea- 12 score, Dyspnea severity scale
- 6 minute walk test
Imaging and histological exam:
- Flexible bronchoscopy +/- BAL +/- Transbronchial biopsy
- Thoracoscopic VATs biopsy
Treatment options for Idiopathic lung fibrosis
Known etiology:
- Remove causative agents e.g. remove inciting drug or occupational exposure…etc
- Specific treatment for underlying cause e.g. treat CTD, vasculitis, chronic infection …etc
Support:
- Supplemental Oxygen (ambulatory O2 or LTOT therapy)
- Immunosuppressants
- Systemic steroids and anti-microbials for acute exacerbations
- Seasonal influenza vaccination
Idiopathic and connective-tissue based ILD: Targeted kinase Nintedanib
Pulmonary hypertension: Sildenafil
End-stage: Lung Transplant
Definitive treatment options for Idiopathic lung fibrosis
1) Nintedanib
VEGF and multiple angiokinase inhibitor
Reduces decline in lung function, NOT ANTI-FIBROTIC
2)Lung transplantation (esp. for young patients)
3) Sildenafil in advanced case
Early treatment of pulmonary HTN
Improves QaLY
Supportive care/ Long-term management for interstitial lung disease
Supplementary O2
Patient education
Pulmonary rehab
Vaccination - influenza and pneumococcal polysaccharide
Palliative care
Name a group of ILD associated with organic* dust exposure.
3 examples of organic dust
Test?
Hypersensitivity Pneumonitis (extrinsic allergic alveolitis): Chronic inflammatory disease affecting small airways and interstitium, Type III/ IV hypersensitivity rxn
Causes:
1) Thermophilic bacteria (farmer)
2) Avian protein (bird farmer)
3) Fungal (malt farmer)
…etc
Tests:
Precipitin and antibodies in serum
Name a group of ILD associated with mineral* dust exposure.
3 subtypes?
Pneumoconiosis
Asbestosis
Talcosis
Silicosis
Area of lung commonly affected by Silicosis and other occupational lung diseases?
Features on CXR
Features:
- multiple pathcy, ‘map-like’, well-demarcated nodules/ pleural plaques
- Pleural plaques are predominantly at upper lobe and axillary region of mid chest, commonly along the anterior portion of ribs, sometimes at diaphragm
- Pleural thickening
- Mediastinal LN lymphadenopathy
6 occupations associated with occupational lung diseases
Stone mining and cutting
Pneumatic drill worker
Caisson worker
Jade polisher and gemstone worker
Ceramic workers
Some* construction workers with exposure
Clinical features of silicosis?
Symptoms:
- Dyspnea on exertion
- Persistent dry cough
- Fatigue, Loss of appetite and weight loss
- Chest pain
Signs:
- Finger clubbing
- Dry, inspiratory, bi-basilar crackles
- Non-productive cough
Presentation May overlap with COPD
Imaging features of silicosis?
Progressive massive fibrosis - PMF
Upper lobe fibro-calcification
Mediastinal LN enlargement with ‘eggshell’ calcification
Occupations at risk of asbestosis
1 complication of asbestosis
Construction workers/ shipyard workers: Handling/ demolition of asbestos bricks used for insulation
living in buildings with asbestos material is safe if the material is intact
Complication: Malignant mesothelioma
Pathogenesis of ILD
Diffuse insult (e.g. mineral dust) cause persistent inflammation of interstitium
> Fibroblasts proliferate in interstitium and secrete long collagen fibers that contract
Fibrotic tissue form in bronchiolar epithelium
Bronchiolar epithelium grows into cystic spaces, obliterate some air spaces
Honeycomb lung spaces + subpleural cysts
Pathogenesis of silicosis
Silica in airspaces causes interstitial macrophages to invade and engulf silica
Silica indestructible, release fibrinogenic factors
Fibroblasts secrete long collagen fibers and cause fibrosis
Aggregation of lymphocytes, macrophages and fibroblasts cause silicotic nodule formation WITHIN airspace
Pathogenesis of asbestosis
Asbestos fibers cause direct trauma to airspace interstitum and bleeding, hemosiderin deposit on asbestos fibers form asbestos bodies
Macrophages recruited and releases fibrinogenic factors for diffuse fibrosis around airspaces
‘Amputation’ of airspace, lung vessel vasoconstriction from chronic hypoxia
Malignancy most directly associated with asbestosis**
Malignant mesothelioma at pleura, pericardium or peritoneum
Treatment approach for asbestosis and silicosis
Both irreversible with no cure
Alleviate symptoms and prevent complications:
- Cough suppressant
- Antibiotics for bacterial lung infection
- TB prophylaxis +/- Anti-TB drugs
Causes of Chronic interstitial lung diseases
- IPF
- Sarcoidosis (interstital lung disease is leading cause of death from sarcoidosis)
- Hypersensitivity Pneumonitis > organic or inorganic cause
- Connective tissue disease
