The pulmonary interstitium is the microscopic space between the alveolar epithelium and capillary endothelium and is crucial for gas exchange. ^[1]

Think of it as the scaffolding of the lung. It is normally extremely thin — just a wisp of elastin-rich connective tissue containing capillary blood vessels. Gas molecules (O₂ and CO₂) must diffuse across this layer. When this layer becomes thickened by inflammation or fibrosis, the diffusion distance increases, and gas exchange fails — hence why DLCO is always reduced in ILD.

Increase in interstitial tissue causes loss of lung compliance → physiological restrictive deficit. ^[1]

Normal lungs are elastic and stretch easily on inspiration. Fibrotic lungs are stiff. This means:

• The patient cannot inflate the lungs fully → reduced TLC, FVC
• FEV₁ is also reduced (smaller lungs = less air to blow out), but FEV₁/FVC ratio is preserved or increased (≥ 70%) because the airways themselves are not obstructed
• This contrasts with COPD/asthma where FEV₁/FVC < 70% (obstructive pattern)

Early stage acute pathology is an alveolitis (injury with inflammatory cell infiltration). Late stages characterised by fibrosis. ^[1]

Clinical effects due to hypoxia (respiratory failure), pulmonary hypertension, cor pulmonale and cardiac failure. ^[1]

The logic chain: thickened interstitium → impaired gas exchange → hypoxia → hypoxic pulmonary vasoconstriction → pulmonary hypertension → right ventricular strain (cor pulmonale) → right heart failure → death.

IPF is a chronic and ultimately fatal disease characterised by a progressive decline in lung function. The term 'idiopathic' is used because the cause of pulmonary fibrosis is still unknown. ^[1]

Progressive interstitial fibrosis of unknown cause. Variable association with inflammation. Associated with clubbing. Pathological process centred on fibrosis at the subpleural and basal segments. Terminal lung structures replaced by dilated spaces surrounded by fibrous walls. Reduced compliance and DLCO. ^[1]

Although the cause of IPF is unknown, several risk factors have been suggested: ^[1]

1. Age usually over 50 years 2. Dry, non-productive cough on exertion 3. Progressive exertional dyspnoea 4. Dry, inspiratory bibasilar "velcro-like" crackles on auscultation 5. Clubbing of fingers 6. Abnormal PFT with evidence of restriction and impaired gas exchange ^[1]

Why "Velcro-like" crackles? These fine, late-inspiratory crackles are generated by the sudden opening of small airways and alveoli that are stiff and tend to collapse. They sound like pulling apart Velcro. They are heard best at the lung bases (where fibrosis is worst in IPF/UIP) and do NOT clear with coughing (unlike crackles from secretions in bronchiectasis).

This is a classic exam discriminator (see 2024 EMQ Q3): bilateral fine basal crackles with JVP not raised = IPF, not heart failure (in HF, JVP would be raised). ^[6]

HRCT thorax is the best mode of investigation to diagnose interstitial lung disease. ^[1]

IPF only if known causes of ILD (e.g. environmental exposure, connective tissue disease, and drug toxicity) are excluded. ^[1]

UIP pattern on HRCT (diagnostic criteria): ^[1]

1. Subpleural, basal predominance
2. Reticular abnormality
3. Honeycombing with or without traction bronchiectasis
4. Absence of features inconsistent with UIP pattern

NSIP pattern on HRCT (for comparison): ^[1]

1. More ground glass opacity
2. Reticulation with peribronchovascular distribution
3. Less honeycomb changes and traction bronchiectasis

Why this matters: NSIP is often associated with CTD and may respond to immunosuppression. UIP/IPF does NOT respond to steroids and requires anti-fibrotic therapy. Getting the pattern wrong changes management entirely.

Diagnosis based on lung biopsy is only required if clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out. ^[1]

Potential pitfalls: Exclusion of known/environmental causes, exclusion of collagen vascular diseases, HRCT scan techniques, local expertise in ILD, multidisciplinary discussions. ^[1]

ILD is not a single disease, but encompasses many different pathological processes. Hence treatment is different for each disease. ^[1]

VEGF and multiple angiokinase inhibitor. VEGFR, FGFR, and PDGFR inhibitor. Developed as anti-vascular anti-cancer therapy. In clinical trials, showed reduction in rate of decline in lung function. One study demonstrated longer time to first exacerbation. ^[1]

Nintedanib does NOT reverse fibrosis — it slows progression. The mechanism targets the pro-fibrotic pathways involving vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors.

Pirfenidone is the other major anti-fibrotic (not heavily detailed in this lecture but may appear in exams). Both are small molecules, both reduce FVC decline.

10mg QDS. Did not achieve primary endpoint. Improved QoL/breathlessness scores (SGRQ). Early treatment of pulmonary hypertension. ^[1]

Sildenafil is a PDE-5 inhibitor that promotes pulmonary vasodilation. In IPF patients who develop secondary pulmonary hypertension, it may improve symptoms but has not been shown to improve mortality.

Supplemental Oxygen, Patient Education, Pulmonary rehabilitation, Vaccination (influenza and pneumococcal polysaccharide vaccines), Palliative Care. ^[1]

Stone mining and cutting, pneumatic drill worker, caisson worker, jade polisher and gemstone cutter, ceramic workers, other manual labourer in construction sites. ^[1]

1. Dyspnoea exacerbated by exertion 2. Cough, often persistent and sometimes severe 3. Fatigue 4. Tachypnoea 5. Loss of appetite and weight loss 6. Chest pain ^[1]

Progressive massive fibrosis: upper lobe fibrocalcification, mediastinal lymph node enlargement with 'eggshell' calcification. ^[1]

"Eggshell calcification" = calcification of the rim of hilar/mediastinal lymph nodes, with a lucent centre. This is a classic CXR finding that screams silicosis.

Silica impairs macrophage function → increased susceptibility to TB. This is why:

TB prophylaxis for those with positive tuberculin skin test or IGRA blood test. Prolonged anti-tuberculosis (multi-drug regimen) for those with active TB. ^[1]

Chronic inflammation → fibroblasts proliferate in interstitium → fibrosis → bronchiolar epithelium extends to line airspaces. ^[1]

Acini "simplified", become cystic spaces. Bronchiolar epithelium grows into cystic spaces. Honeycomb lung. ^[1]

Interstitial fibrosis, obliteration of some air spaces, cystic dilatation of others, chronic inflammatory cells — not always present. ^[1]

These are ferruginous bodies — asbestos fibres coated with iron-containing protein (haemosiderin). They appear as golden-brown, dumbbell-shaped structures on microscopy. Their presence in lung tissue confirms asbestos exposure.

Pleural shadows, pleural plaques ^[1]

Pleural plaques are pathognomonic of asbestos exposure (but NOT asbestosis per se — plaques indicate exposure, while asbestosis requires interstitial fibrosis). Plaques are usually bilateral, often calcified, and seen on the diaphragmatic pleura and lower lateral chest wall.

Handling of asbestos products incorporated into construction work, commercial or household products. Construction works: demolition of fireproof coatings, bricks, pipes (including shipyard workers and some seamen). Commercial/household: demolition work, insulation wall layers with broken asbestos bricks in floorings and roofings. ^[1]

Fibrosis of the lungs to dust of free silica or dust containing free silica, whether or not accompanied by TB, or any other disease of the pulmonary/respiratory organs caused by exposure to such dust; OR fibrosis of the lungs due to dust of asbestos or dust containing asbestos, whether or not accompanied by TB or any other disease caused by exposure. ^[1]

Compensation payable to any person suffering from pneumoconiosis or mesothelioma (or both) in respect of incapacity, pain, suffering and loss of amenities. ^[1]

Must be resident in Hong Kong for 5 years or more at the date of notification, or < 5 years if contracted in Hong Kong. ^[1]

Lung function impairment stratified by FVC measurement. ^[1]

The Pneumoconiosis Compensation Fund Board (PCFB) administers compensation. Workers must apply through this board.

A 61-year-old chronic smoker/drinker, construction worker since age 30, with past TB. Progressive SOB + productive cough for 3 years. Finger clubbing noted.

Expected DDx: COPD (smoking), silicosis/asbestosis (construction), post-TB bronchiectasis/destroyed lung, lung cancer, IPF.

Spirometry showed FEV₁/FVC 60% → obstructive component. Post-bronchodilator FEV₁ barely improved → COPD. But FVC also reduced → possible mixed pattern (coexistent ILD or destroyed lung from TB).

Q3: Bilateral fine basal crackles with JVP not raised → Answer: Idiopathic pulmonary fibrosis (D)

Why not heart failure? In HF, you'd expect raised JVP, ankle oedema, and crackles that may be coarser/more diffuse. IPF gives fine, "Velcro-like" crackles at the bases with normal JVP (until very late when cor pulmonale develops).

56-year-old female, former construction site worker, SOB + dry cough → developed lung mass + pleural effusion. This tests lung cancer in the occupational exposure context.

65-year-old retired construction worker, heavy smoker, cough + haemoptysis + weight loss → lung cancer with SVCO.

Stem: A 60-year-old construction site worker presents with progressive exertional dyspnoea and dry cough for 2 years. Name 5 differential diagnoses. Markscheme: Silicosis/pneumoconiosis, asbestosis, COPD (if smoker), IPF, lung cancer, TB, hypersensitivity pneumonitis.

Stem: What physical signs would you expect in a patient with IPF? Markscheme: Fine inspiratory bibasilar "Velcro-like" crackles, finger clubbing, tachypnoea, cyanosis (late), signs of cor pulmonale (raised JVP, peripheral oedema, RV heave — late).

Stem: HRCT shows subpleural, basal reticular abnormalities with honeycombing. What pattern is this? What is the most likely diagnosis? Markscheme: UIP pattern. Most likely diagnosis is IPF (after excluding known causes such as CTD, drug exposure, and occupational exposure).

Stem: How would you manage a patient diagnosed with IPF? Markscheme: Anti-fibrotic therapy (nintedanib or pirfenidone), NOT systemic steroids as first-line, supplemental O₂ for hypoxaemia, pulmonary rehabilitation, vaccinations (influenza, pneumococcal), consider lung transplant, palliative care. Multidisciplinary approach.

Stem: Under what legislation can a Hong Kong construction worker with silicosis claim compensation? State two eligibility criteria. Markscheme: Pneumoconiosis and Mesothelioma (Compensation) Ordinance (Cap 360). Criteria: diagnosis on/after 1 Jan 1981, resident in HK ≥ 5 years (or < 5 years if contracted in HK).

Stem: Name 4 drugs that can cause ILD. Markscheme: Amiodarone, bleomycin, methotrexate, nitrofurantoin, immune checkpoint inhibitors (any 4).