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 it becomes thickened by inflammation or fibrosis, diffusion becomes less efficient. DLCO is often reduced, sometimes before resting hypoxaemia develops, but a normal DLCO does not by itself exclude early or limited ILD.

In the paired histology photographs, normal alveolar septa are delicate and leave wide airspaces; the fibrotic specimen has broad collagen-rich septa with distorted, reduced airspaces. That visual difference explains both the stiff lung (restriction) and the longer alveolar–capillary diffusion path.

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 is usually preserved or increased because the airways themselves are not primarily obstructed
• This contrasts with COPD/asthma, where FEV₁/FVC is below the age-appropriate lower limit of normal. A fixed 0.70 cut-off is useful lecture shorthand but can overdiagnose obstruction in older adults and miss it in younger adults

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

This diagram is a useful teaching model, not a universal sequence. In IPF, repeated epithelial injury, abnormal repair and fibroblast activation are central; it should not be treated as a steroid-responsive alveolitis that simply progresses to scarring. Different ILDs have different balances of inflammation and fibrosis. ^[8]

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.

The lecture classifies Diffuse Parenchymal Lung Diseases (DPLD) into four major groups, with the idiopathic interstitial pneumonias further sub-classified: ^[1]

Very rare IIPs include idiopathic lymphocytic interstitial pneumonia (LIP) and idiopathic pleuroparenchymal fibroelastosis (PPFE). ^[1]

^[7]

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]

Prognostic factors in IPF (historical survival data from the 1998 study reproduced in the lecture): its Kaplan–Meier curves associate worse survival with: ^[1]

• Older age at diagnosis (≥ 75 yr worst; < 65 yr best)
• Greater radiographic profusion (severe >> mild)
• Lower baseline FVC % predicted (< 60% worst; ≥ 80% best)
• Sex had minimal impact on survival

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 (lecture features): ^[1]

1. Subpleural, basal predominance
2. Reticular abnormality
3. Honeycombing with or without traction bronchiectasis
4. No features strongly suggesting an alternative diagnosis

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 immunomodulation. Chronic corticosteroid monotherapy is not a treatment for IPF, whereas antifibrotic therapy is central. A UIP pattern from another cause is managed according to that underlying disease, so getting the clinical diagnosis right matters more than attaching a pattern label alone.

Modern HRCT reporting uses UIP, probable UIP, indeterminate for UIP, or an alternative diagnosis. In the right clinical context, probable UIP may support an IPF diagnosis after multidisciplinary discussion without mandatory surgical biopsy. When tissue is genuinely needed, the choice between transbronchial cryobiopsy and surgical biopsy depends on local expertise, diagnostic value and procedural risk. ^[8]

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

The lecture outlines a stepwise approach: ^[1]

1. History — medical/drug history, CTD symptoms, environmental/occupational exposures, smoking, family history, reflux history
2. Examination — clubbing, crackles, fever, eye signs, rashes, arthritis, hepatosplenomegaly
3. Chest radiograph — compare with previous films
4. Initial tests — oximetry, spirometry, blood tests, urinalysis, ECG
5. Refer to chest physician (ideally an ILD clinic)
6. Further assessment — HRCT chest, bronchoscopy ± BAL ± TBBx, detailed PFTs, echocardiogram, surgical lung biopsy
7. Multidisciplinary meeting — discuss and review management plan

Regular follow-up lung function tests (FVC, TLC, DLCO, KCO) provide valuable information on disease progression. ^[1]

Breathlessness scores are valuable to help grade and assess patient symptoms. ^[1]

Spirometry is suggestive, but not diagnostic, of restrictive lung physiology. ^[1]

Reading the lecture's loop and volume diagrams: an obstructive flow–volume loop has a scooped expiratory limb; a restrictive loop is small and narrow but retains its general contour. The accompanying lung-volume diagram shows reduced TLC, FRC, RV and vital capacity in restriction. A small loop alone still does not measure TLC, so it only suggests restriction.

A past paper (2023 minicase Case 1) showed FEV₁/FVC 60% with reduced FVC in a construction worker/smoker. This proves an obstructive component, not mixed disease: low FVC may reflect air trapping or submaximal effort, and mixed obstruction/restriction requires a reduced TLC. Coexistent ILD or post-TB damage remains a clinical possibility. ^[4]

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 FVC decline. The mechanism targets pro-fibrotic signalling involving vascular endothelial growth factor, fibroblast growth factor and platelet-derived growth factor receptors. Check liver tests and counsel about diarrhoea and other important adverse effects/interactions. ^[10]

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.

The slide reports a sildenafil trial that did not achieve its primary endpoint, with a secondary quality-of-life signal. ^[1]

This slide should not be converted into “start sildenafil early.” Sildenafil is not routine treatment for IPF and the older IPF evidence did not show improvement in mortality, acute exacerbation, dyspnoea, FVC or 6-minute-walk distance. Suspected pulmonary hypertension associated with ILD requires specialist assessment; echocardiography estimates probability, while right-heart catheterisation confirms haemodynamics when the result will alter management. Any PH-directed therapy is phenotype- and guideline-specific. ^[11][12]

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]

The radiographs show upper-zone nodules coalescing into bilateral mass-like opacities of progressive massive fibrosis. CT better demonstrates upper-lobe conglomerate fibrosis and calcified hilar/mediastinal nodes. “Eggshell” calcification is a thin calcified nodal rim with a relatively lucent centre: it is a classic clue, not pathognomonic, and can occur in other diseases.

Silica impairs macrophage function and silicosis substantially increases susceptibility to TB. A positive TST/IGRA should prompt exclusion of active TB first, followed by risk-based preventive treatment through the local TB programme. Active TB requires a standard susceptibility-guided multidrug regimen; it is not automatically “prolonged” merely because silicosis is present. ^[15]

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]

The micrographs and extracted-fibre image show ferruginous (asbestos) bodies: golden-brown, beaded or dumbbell-shaped fibres coated with iron-rich protein. They support prior asbestos exposure, but their mere presence does not establish asbestosis; the diagnosis requires the appropriate exposure history plus diffuse interstitial fibrosis after excluding better explanations.

Pleural shadows, pleural plaques ^[1]

The CT image shows calcified plaques along the parietal and diaphragmatic pleura. Pleural plaques are a strong marker of prior asbestos exposure, but are not themselves asbestosis and should not be called absolutely pathognomonic. Asbestosis is a lower-zone-predominant fibrotic ILD; the other pathology images progress from peribronchiolar/distal-airspace fibrosis to cystic honeycomb remodelling.

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. The lecture's eligibility dates and five-year residence rule remain consistent with the official amendment summary: residence shorter than five years may still qualify if the disease was contracted in Hong Kong. Current applications and medical assessment should follow the Board/Labour Department process rather than relying on this revision note alone. ^[17]

The slide's bar chart is historical surveillance, not the current annual burden. It reports 743 newly diagnosed cases for 2011–2020; in 2020 the chart records 112 cases (88 silicosis, 12 asbestosis and 12 mesothelioma). Its purpose is to show that the statutory scheme covers both dust-related pneumoconiosis and mesothelioma, not to supply a present-day incidence estimate. ^[1]