JC15 (Medicine) - Interstitial Lung Disease

Question 1

Causes of interstitial lung disease **

Answer 1

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

Question 2

Define pulmonary fibrosis.

Answer 2

Abnormal scarring and thickening of pulmonary interstitium between the alveolar epithelium and capillary endothelium
Adversely affecting gas exchange (much larger diffusion distance)

Question 3

List the physiological changes in interstitial lung disease?

Answer 3

• Increase in interstitial tissue causing lower lung compliance
• Restrictive deficit
• Poor gas exchange (thick alveolar-capillary interface)

Question 4

Early and late stages of pulmonary fibrosis?

Area of lung affected by interstitial lung disease?

Answer 4

Early = alveolitis, injury with inflammatory cell infiltration

Late = Lung Fibrosis, increase vascular resistance in pulmonary circulation&raquo_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

Question 5

4 major clincal classes of diffuse parenchymal lung diseases (DPLD)?

Answer 5

1. DPLD of known etiology (e.g. drugs, vascular…etc)
2. Idiopathic interstitial pneumonia (IIP)
3. Granulomatous DPLPs (Sarcoidosis)
4. Others (Eosinophilic pneumonia, LAM, HX …etc)

Question 6

3 classes of idiopathic interstitial pneumonia (IIP)

Answer 6

Chronic fibrosing: IPF, NSIP

Smoking related: RBILD(Respiratory Bronchiolitis–Associated Interstitial Lung Disease) , DIP

Acute/ subacute: AIP, COP

Question 7

Examples of drugs that can cause pulmonary fibrosis

Answer 7

Question 8

Risk factors of idiopathic pulmonary fibrosis *

Answer 8

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

Question 9

Symptoms of interstitial lung diseases

Answer 9

Symptoms:
- Constitutional symptoms: Fever, Fatigue, Weight loss, Anorexia, Central cyanosis (abrupt deterioration)
- Respiratory: Dyspnea on exertion, Intermittent non-productive cough, respiratory failure, chest pain

Question 10

Signs of interstitial lung diseases

Answer 10

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

Question 11

List 6 first line investigations for ILD

Answer 11

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)

Question 12

Main method of diagnosis of ILD?

Answer 12

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

Question 13

2 main imaging patterns of Idiopathic pulmonary fibrosis?

Answer 13

Usual interstitial Pneumonia - UIP
Incl: Collagen vascular/ connective tissue disorder, Asbestosis and inorganic occupational exposures, Chronic hypersensitivity pneumonitis

Nonspecific Interstitial Pneumonia - NSIP

Question 14

Differentiate UIP and NSIP pattern in Idiopathic pulmonary fibrosis *

Answer 14

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

Question 15

Tests for progression of Idiopathic pulmonary fibrosis?

Answer 15

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

Question 16

Treatment options for Idiopathic lung fibrosis

Answer 16

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

Question 17

Definitive treatment options for Idiopathic lung fibrosis

Answer 17

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

Question 18

Supportive care/ Long-term management for interstitial lung disease

Answer 18

Supplementary O2
Patient education
Pulmonary rehab
Vaccination - influenza and pneumococcal polysaccharide
Palliative care

Question 19

Name a group of ILD associated with organic* dust exposure.

3 examples of organic dust

Test?

Answer 19

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

Question 20

Name a group of ILD associated with mineral* dust exposure.

3 subtypes?

Answer 20

Pneumoconiosis

Asbestosis
Talcosis
Silicosis

Question 21

Area of lung commonly affected by Silicosis and other occupational lung diseases?

Features on CXR

Answer 21

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

Question 22

6 occupations associated with occupational lung diseases

Answer 22

Stone mining and cutting

Pneumatic drill worker

Caisson worker

Jade polisher and gemstone worker

Ceramic workers

Some* construction workers with exposure

Question 23

Clinical features of silicosis?

Answer 23

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

Question 24

Imaging features of silicosis?

Answer 24

Progressive massive fibrosis - PMF

Upper lobe fibro-calcification
Mediastinal LN enlargement with ‘eggshell’ calcification

Question 25

Occupations at risk of asbestosis
1 complication of asbestosis

Answer 25

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

Question 26

Pathogenesis of ILD

Answer 26

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

Question 27

Pathogenesis of silicosis

Answer 27

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

Question 28

Pathogenesis of asbestosis

Answer 28

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

Question 29

Malignancy most directly associated with asbestosis**

Answer 29

Malignant mesothelioma at pleura, pericardium or peritoneum

Question 30

Treatment approach for asbestosis and silicosis

Answer 30

Both irreversible with no cure

Alleviate symptoms and prevent complications:

• Cough suppressant
• Antibiotics for bacterial lung infection
• TB prophylaxis +/- Anti-TB drugs

Question 31

Causes of Chronic interstitial lung diseases

Answer 31

• IPF
• Sarcoidosis (interstital lung disease is leading cause of death from sarcoidosis)
• Hypersensitivity Pneumonitis > organic or inorganic cause
• Connective tissue disease