3.3 Interstitial Lung Disease & Pleural Disorders

Interstitial Lung Diseases (ILD) & Idiopathic Pulmonary Fibrosis (IPF)

Interstitial Lung Diseases (ILDs) comprise a heterogeneous group of diffuse parenchymal lung disorders characterized by inflammation and/or fibrosis of the alveolar interstitium.

Classification Scheme

1. Idiopathic Interstitial Pneumonias: Idiopathic Pulmonary Fibrosis (IPF), Nonspecific Interstitial Pneumonia (NSIP), Cryptogenic Organizing Pneumonia (COP).
2. Granulomatous ILD: Sarcoidosis, Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis).
3. Connective Tissue Disease (CTD)-Associated ILD: Systemic sclerosis (scleroderma), Rheumatoid arthritis, Polymyositis/Dermatomyositis, Systemic lupus erythematosus.
4. Drug-Induced & Exposure-Related ILD: Amiodarone, Methotrexate, Nitrofurantoin, Bleomycin, asbestos, silica.

Idiopathic Pulmonary Fibrosis (IPF)

IPF is a progressive, fatal fibrotic lung disease occurring primarily in individuals >60 years of age.

• Clinical Presentation: Progressive exertional dyspnoea, chronic dry cough, bilateral digital clubbing (50%), and fine end-inspiratory "velcro-like" crackles at lung bases.
• Pulmonary Function Tests (PFTs): Classic restrictive defect showing reduced Forced Vital Capacity (FVC <80% predicted), normal or elevated FEV1/FVC ratio (>0.70/0.80), and markedly reduced Transfer Factor for Carbon Monoxide (TLCO/DLCO <40–60% predicted).
• High-Resolution CT (HRCT) Gold Standard: Shows the Usual Interstitial Pneumonia (UIP) pattern:
  • Bilateral subpleural and basal-predominant reticular opacities,
  • Traction bronchiectasis and bronchiolectasis,
  • Honeycombing (stacked subpleural cystic air spaces with thick walls),
  • Absence of upper-lobe dominance, prominent ground-glass opacities, or mosaic attenuation.
• Disease-Modifying Pharmacotherapy:
  • Pirfenidone: Orally administered antifibrotic agent that inhibits TGF-β production and collagen synthesis.
  • Nintedanib: Intracellular triple tyrosine kinase inhibitor targeting PDGF, FGF, and VEGF receptors. Clinical Evidence: Both agents slow the rate of FVC decline in mild-to-moderate IPF (FVC 50–80%).

Contrarian Exam Warning: Long-term systemic corticosteroids are CONTRAINDICATED in IPF! The randomized controlled PANTHER-IPF trial demonstrated that triple therapy with prednisolone, azathioprine, and N-acetylcysteine caused increased mortality and hospitalisations compared to placebo. Corticosteroids are reserved strictly for acute IPF exacerbations.

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Sarcoidosis & Granulomatous Diseases

Sarcoidosis is a multisystem granulomatous disorder characterized by non-caseating epithelioid granulomas.

Classic Clinical Syndromes

• Löfgren Syndrome: Acute, self-limiting presentation characterized by the triad of:
  1. Erythema Nodosum (painful, erythematous subcutaneous nodules on anterior shins),
  2. Bilateral Hilar Lymphadenopathy (BHL) on chest radiograph, and
  3. Migratory Polyarthritis (predominantly involving ankle joints). Prognosis: Excellent spontaneous remission rate (>85%); managed symptomatically with NSAIDs.
• Heerfordt Syndrome (Uveoparotid Fever): Rare acute manifestation featuring uveitis (anterior or posterior), parotid gland enlargement, facial nerve palsy (CN VII), and low-grade fever.

Diagnostic & Laboratory Findings

• Serum Angiotensin-Converting Enzyme (ACE): Elevated in ~60% of active cases (produced by epithelioid cells within granulomas).
• Calcium Metabolism Anomalies: Hypercalcaemia and hypercalciuria occur in 10–20% of patients due to extra-renal 1-alpha-hydroxylase expression by activated granuloma macrophages, converting 25-hydroxyvitamin D into active 1,25-dihydroxyvitamin D3.
• Bronchoalveolar Lavage (BAL): Lymphocytic alveolitis with an elevated CD4/CD8 ratio (>3.5).
• Radiographic Staging:
  • Stage 0: Normal chest radiograph.
  • Stage 1: Bilateral Hilar Lymphadenopathy (BHL) alone.
  • Stage 2: BHL plus parenchymal lung infiltrates.
  • Stage 3: Parenchymal infiltrates without BHL.
  • Stage 4: End-stage pulmonary fibrosis (honeycombing, volume loss).

Corticosteroid Indications

Systemic oral corticosteroids (Prednisolone 20–40 mg daily) are indicated for organ-threatening or symptomatic disease:

1. Cardiac sarcoidosis (conduction block, ventricular arrhythmias),
2. Neurosarcoidosis (cranial neuropathies, mass lesions),
3. Ocular sarcoidosis refractory to topical drops,
4. Severe hypercalcaemia,
5. Progressive pulmonary function loss (falling FVC/TLCO).

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Pleural Effusion Pathophysiology & Light's Criteria

Pleural effusions represent excess fluid accumulation in the pleural space, classified as either transudates or exudates.

Pathophysiological Distinction

• Transudates (Protein <30 g/L): Caused by systemic factors altering hydrostatic or oncotic pressures (e.g., Left ventricular failure, Liver cirrhosis, Nephrotic syndrome, Hypoalbuminaemia).
• Exudates (Protein >30 g/L): Caused by local disease altering pleural microvascular permeability (e.g., Malignancy, Pneumonia, Pulmonary embolism, Tuberculosis, Rheumatoid arthritis).

Light's Criteria

When pleural fluid protein concentration is borderline (25–35 g/L), Light's Criteria must be evaluated. Fluid is defined as an EXUDATE if ANY ONE of the following three criteria is satisfied:

1. Pleural Fluid Protein / Serum Protein Ratio > 0.5
2. Pleural Fluid LDH / Serum LDH Ratio > 0.6
3. Pleural Fluid LDH > 2/3 of the Upper Limit of Normal Serum LDH

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Empyema & Pneumothorax BTS Guidelines

Complicated Parapneumonic Effusion & Empyema

Parapneumonic effusions develop adjacent to bacterial pneumonia. Bacterial invasion of the pleural space triggers fibrin deposition and loculation.

• BTS Criteria for Intercostal Chest Drain Insertion:
  1. Frank pus or turbid/foul-smelling fluid aspirated on thoracocentesis,
  2. Organisms identified on Gram stain or pleural fluid culture,
  3. Pleural fluid pH <7.2 in a patient with parapneumonic effusion.
• Management Protocol: Immediate small-bore intercostal chest drain placement (12–14F), targeted IV antibiotics, and consideration of intrapleural tissue plasminogen activator (tPA) plus recombinant human DNase for loculated effusions.

Pneumothorax BTS Management Algorithm

                    Primary Spontaneous Pneumothorax (PSP)
                                    │
                  Is Rim of Air >2 cm at Hilum OR Breathless?
                                 ┌──┴──┐
                                Yes    No
                                 │      │
                       Needle Aspiration (16-18G)   Discharge & Outpatient
                                 │                   Review in 2-4 Weeks
                          Successful? (<2 cm)
                               ┌─┴─┐
                              Yes   No
                               │    │
                           Discharge Intercostal Chest Drain (12-14F)

• Primary Spontaneous Pneumothorax (PSP): No underlying lung disease.
  • Rim <2 cm and asymptomatic: Discharge with safety netting; outpatient review in 2–4 weeks.
  • Rim ≥2 cm OR breathless: Needle aspiration (16–18G cannula in 2nd intercostal space mid-clavicular line). If aspiration reduces rim to <2 cm, discharge. If aspiration fails (rim remains ≥2 cm), insert a small-bore chest drain (12–14F).
• Secondary Spontaneous Pneumothorax (SSP): Occurs in patients with underlying lung disease (COPD, CF, ILD).
  • Rim >2 cm OR breathless: Insert intercostal chest drain immediately and admit.
  • Rim 1–2 cm: Perform needle aspiration; if successful (<1 cm), admit for 24 hours observation. If aspiration fails, insert chest drain.
  • Rim <1 cm: Admit for 24 hours observation and high-flow oxygen.
• Tension Pneumothorax: Emergency clinical diagnosis (hypotension, tracheal deviation away from affected side, distended neck veins, hyper-resonance, absent breath sounds). Perform immediate emergency decompression with a large-bore cannula (14G) inserted into the 2nd intercostal space mid-clavicular line, followed by formal intercostal chest drain placement.