Restrictive Lung Diseases & ARDS
Pathology · Respiratory · lean revision notes
Restrictive Lung Diseases & ARDS
Restrictive lung diseases reduce lung compliance and total lung capacity while preserving (or even increasing) expiratory flow rates. This note groups the high-yield restrictive interstitial diseases — idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis — alongside acute respiratory distress syndrome (ARDS), the prototype of acute diffuse alveolar damage, with a focus on pathology buzzwords and the classic ARDS-vs-NRDS comparison.
Defining "restrictive" physiology
A restrictive pattern means the lung cannot expand normally. The hallmark spirometric signature is a reduced FVC and TLC with a normal or raised FEV1/FVC ratio (because both numerator and denominator fall, and elastic recoil is high). Contrast this with obstructive disease where FEV1 falls disproportionately, dropping the ratio below 0.70.
| Parameter | Restrictive | Obstructive |
|---|---|---|
| FVC | ↓ | Normal / ↓ |
| FEV1 | ↓ | ↓↓ |
| FEV1/FVC | Normal or ↑ (>0.80) | ↓ (<0.70) |
| TLC | ↓ | Normal / ↑ (air trapping) |
| RV | ↓ (parenchymal) | ↑ |
| DLCO | ↓ in interstitial disease | ↓ in emphysema |
High-yield: A normal-to-high FEV1/FVC with a low TLC = restriction. A reduced FEV1/FVC = obstruction. This single discriminator answers most spirometry MCQs.
Classification of restrictive disease
- Parenchymal / intrinsic (interstitial lung disease, ILD) → IPF, sarcoidosis, hypersensitivity pneumonitis, pneumoconioses, connective-tissue-disease ILD, drug-induced fibrosis.
- Extrinsic / extra-pulmonary (chest-wall & neuromuscular) → kyphoscoliosis, obesity, ankylosing spondylitis, Guillain-Barré, myasthenia gravis, diaphragmatic palsy. Here the lung parenchyma is normal and DLCO is preserved/normal, which separates them from parenchymal causes (DLCO low).
The interstitial diseases share a final common pathway: chronic alveolar injury → fibroblast/myofibroblast activation → collagen deposition in the alveolar wall → thickened diffusion barrier, stiff lung, and ventilation–perfusion mismatch.
Idiopathic Pulmonary Fibrosis (IPF)
IPF is the commonest idiopathic interstitial pneumonia and the prototype of progressive parenchymal fibrosis. It is a diagnosis of exclusion — no inhaled antigen, drug, or collagen-vascular disease identified.
Epidemiology & pathogenesis
Typically affects men >50–60 years, often smokers. Current concept: repetitive micro-injury to ageing alveolar epithelium (genetic predisposition — MUC5B promoter polymorphism, telomerase mutations TERT/TERC) → aberrant epithelial–mesenchymal crosstalk with TGF-β driving fibroblastic foci. It is now considered an epithelial-driven, fibrotic (not primarily inflammatory) process — which is why anti-inflammatory steroids fail and anti-fibrotics are used.
Pathology — the UIP pattern
IPF corresponds to the histological pattern called Usual Interstitial Pneumonia (UIP):
- Patchy, heterogeneous fibrosis — areas of dense scarring next to normal lung ("temporal & spatial heterogeneity").
- Fibroblastic foci — the active leading edge of fibrosis (key diagnostic feature).
- Subpleural and basal (lower-lobe) predominance.
- Honeycombing — cystic fibrotic airspaces lined by bronchiolar epithelium = end-stage.
High-yield: "Honeycomb lung" + subpleural basal reticulation + traction bronchiectasis on HRCT = UIP/IPF. Fibroblastic foci are the histological signature.
Clinical features
Insidious progressive exertional dyspnoea and a dry cough over months to years; fine end-inspiratory "Velcro" crackles at lung bases; clubbing in up to half. Late: cyanosis, cor pulmonale, pulmonary hypertension.
Investigations
HRCT is the investigation of choice and, when it shows a definite UIP pattern (basal/subpleural honeycombing + traction bronchiectasis, no atypical features), biopsy is unnecessary. PFTs show a restrictive pattern with reduced DLCO. Surgical/transbronchial cryobiopsy is reserved for HRCT-indeterminate cases.
Approach: Exertional dyspnoea + dry cough + basal Velcro crackles + clubbing → PFT (restriction, ↓DLCO) → HRCT (basal/subpleural honeycombing) → exclude CTD/drugs/exposure → if UIP pattern definite, diagnose IPF; if not, biopsy.
Management
- Anti-fibrotics: pirfenidone (TGF-β/fibroblast inhibitor) and nintedanib (tyrosine-kinase inhibitor of PDGFR/FGFR/VEGFR) — both slow FVC decline but do not reverse fibrosis.
- Long-term oxygen, pulmonary rehabilitation, vaccination.
- Lung transplantation is the only definitive/curative option.
- Steroids are not recommended for stable IPF (contrast: they help inflammatory ILDs like hypersensitivity pneumonitis and sarcoidosis).
High-yield: Drug of choice to slow IPF progression = pirfenidone or nintedanib. Steroids are useless/harmful in IPF — a favourite distractor.
Sarcoidosis
A multisystem disorder of non-caseating epithelioid granulomas, classically in young adults (20–40 y), with female and African-American predominance; in India it is increasingly recognised and often confused with tuberculosis.
Pathology
- Non-caseating granuloma — tightly packed epithelioid macrophages and giant cells, scant central necrosis (vs caseating TB granuloma).
- Asteroid bodies — stellate eosinophilic inclusions in giant cells.
- Schaumann bodies — laminated calcium/protein concretions.
- A CD4-predominant Th1 response; bronchoalveolar lavage shows a raised CD4:CD8 ratio (>3.5).
High-yield: Asteroid bodies and Schaumann bodies are not specific to sarcoidosis (also seen in other granulomatous disease) — but they are classic exam associations. Non-caseating granuloma + raised CD4:CD8 BAL ratio is the combination tested.
Clinical & lab features
- Bilateral hilar lymphadenopathy (commonest radiographic finding), interstitial lung involvement.
- Skin: erythema nodosum, lupus pernio. Eyes: uveitis. Löfgren syndrome = fever + bilateral hilar lymphadenopathy + erythema nodosum + arthralgia (good prognosis, often self-resolves).
- Hypercalcaemia/hypercalciuria — activated macrophages express 1-α-hydroxylase → ↑1,25-(OH)₂ vitamin D.
- Raised serum ACE (non-specific marker of granuloma burden).
- Heerfordt syndrome (uveoparotid fever) = uveitis + parotid enlargement + facial palsy + fever.
Diagnosis & staging
Diagnosis = compatible clinico-radiology + non-caseating granuloma on biopsy + exclusion of TB and fungi. Chest-X-ray staging:
| Stage | CXR finding |
|---|---|
| 0 | Normal |
| I | Bilateral hilar lymphadenopathy (BHL) only |
| II | BHL + parenchymal infiltrates |
| III | Parenchymal infiltrates without BHL |
| IV | Fibrosis / honeycombing |
Management
Many cases (especially stage I and Löfgren) remit spontaneously. Systemic corticosteroids are the drug of choice for symptomatic pulmonary disease, hypercalcaemia, cardiac, neuro or ocular involvement; methotrexate/azathioprine are steroid-sparing agents.
Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)
An immunologically mediated reaction to inhaled organic antigens (Type III + Type IV hypersensitivity).
| Form | Classic antigen / exposure |
|---|---|
| Farmer's lung | Thermophilic actinomycetes in mouldy hay |
| Bird-fancier's lung | Avian proteins (droppings/feathers) |
| Bagassosis | Mouldy sugarcane (bagasse) |
| Humidifier/AC lung | Contaminated water aerosols |
| Mushroom worker's lung | Mushroom compost spores |
Pathology & features
Poorly formed non-caseating granulomas, lymphocytic interstitial infiltrate with a bronchiolocentric (peribronchiolar) distribution, and giant cells. BAL shows lymphocytosis with a low CD4:CD8 ratio (opposite of sarcoidosis).
- Acute form: flu-like fever, cough, dyspnoea 4–8 h after heavy exposure; resolves on removal.
- Chronic form: progressive fibrosis (may mimic IPF, but typically upper/mid-zone and centrilobular nodules with mosaic attenuation on HRCT).
High-yield: Sarcoidosis → high BAL CD4:CD8. Hypersensitivity pneumonitis → low CD4:CD8. This reciprocal pair is a classic question.
Management: antigen avoidance is the single most important step; corticosteroids for severe/chronic disease.
Acute Respiratory Distress Syndrome (ARDS)
ARDS is acute hypoxaemic respiratory failure from diffuse alveolar damage (DAD) causing non-cardiogenic pulmonary oedema. It is the acute, exudative counterpart to the chronic fibrotic diseases above.
Etiology
- Pulmonary (direct): pneumonia (commonest), aspiration of gastric contents, near-drowning, inhalational injury, lung contusion.
- Extra-pulmonary (indirect): sepsis (commonest overall cause), severe trauma/multiple fractures (fat embolism), acute pancreatitis, massive transfusion (TRALI), shock, burns.
Pathophysiology
Injury to the alveolar–capillary membrane → increased permeability → protein-rich exudate floods alveoli → inactivation/loss of surfactant → alveolar collapse, stiff non-compliant lungs, refractory hypoxaemia from intrapulmonary shunting. Neutrophils and pro-inflammatory cytokines (IL-1, IL-8, TNF) amplify damage.
Sequence: Insult (sepsis/pneumonia) → endothelial + epithelial injury → leaky capillaries → proteinaceous exudate + hyaline membranes (exudative phase, days 1–7) → type II pneumocyte proliferation + fibroblast organisation (proliferative phase) → fibrosis (fibrotic phase) in survivors.
Pathology — diffuse alveolar damage
The morphological hallmark is hyaline membranes — eosinophilic, glassy membranes lining the alveolar ducts, composed of fibrin-rich oedema fluid plus necrotic epithelial cell debris. Capillary congestion, interstitial/intra-alveolar oedema, and patchy atelectasis accompany them.
High-yield: The defining histology of ARDS = diffuse alveolar damage with hyaline membranes. The hyaline membrane is made of fibrin + cell debris (protein-rich exudate), reflecting capillary leak.
Hyaline membrane: ARDS vs NRDS — the classic comparison
Both diseases show "hyaline membranes," but the cause and composition differ — a perennial NEET PG favourite.
| Feature | ARDS (adult) | NRDS / Hyaline Membrane Disease (neonate) |
|---|---|---|
| Basic defect | Capillary endothelial/epithelial injury → leak | Surfactant deficiency (immature type II pneumocytes) |
| Surfactant | Inactivated/lost secondarily | Primary deficiency |
| Hyaline membrane composition | Fibrin + necrotic epithelial cell debris (exudate) | Fibrin + necrotic cell debris from collapsed alveoli; protein from leaked plasma |
| Trigger | Sepsis, pneumonia, aspiration, trauma | Prematurity, maternal diabetes, C-section |
| Key risk modifier | — | Risk ↑ in infant of diabetic mother; ↓ by maternal steroids, chronic intrauterine stress |
| Prevention | Treat underlying cause | Antenatal betamethasone; postnatal surfactant |
| L:S ratio relevance | — | Lecithin:Sphingomyelin <2 predicts immaturity/risk |
High-yield: NRDS = primary surfactant deficiency (prematurity, diabetic mother). ARDS = alveolar–capillary injury with secondary surfactant loss. Both produce hyaline membranes but the upstream mechanism differs — memorise the cause, not just the morphology.
Diagnosis — Berlin definition (2012)
All four must be present:
- Timing — within 1 week of a known insult or new/worsening respiratory symptoms.
- Imaging — bilateral opacities on CXR/CT not fully explained by effusion/collapse/nodules.
- Origin of oedema — respiratory failure not fully explained by cardiac failure or fluid overload (objectively, PCWP ≤18 mmHg / no left atrial hypertension; echocardiography if needed).
- Oxygenation (with PEEP ≥5 cm H₂O):
| Severity | PaO₂/FiO₂ ratio |
|---|---|
| Mild | 200–300 |
| Moderate | 100–200 |
| Severe | ≤100 |
High-yield: ARDS is defined by PaO₂/FiO₂ ≤300 with PEEP ≥5, bilateral infiltrates, within 1 week, with PCWP ≤18 mmHg (distinguishes it from cardiogenic pulmonary oedema). Cardiogenic oedema has high PCWP, cardiomegaly, and responds to diuresis.
Management
The cornerstone is lung-protective mechanical ventilation:
- Low tidal volume 6 mL/kg predicted body weight with plateau pressure <30 cm H₂O (ARDSnet) — proven mortality benefit.
- PEEP to recruit alveoli; permissive hypercapnia tolerated.
- Prone positioning for moderate–severe ARDS (PaO₂/FiO₂ <150) improves oxygenation and survival.
- Conservative fluid strategy; treat the underlying cause (antibiotics for sepsis).
- Neuromuscular blockade (early, severe) and ECMO for refractory hypoxaemia.
- Steroids (e.g., dexamethasone) have a role in selected/COVID-related ARDS.
High-yield: The single intervention with the strongest mortality benefit in ARDS is low-tidal-volume (6 mL/kg) lung-protective ventilation. Prone positioning helps severe cases.
Complications
Multi-organ failure, ventilator-associated pneumonia, barotrauma/pneumothorax, pulmonary fibrosis in survivors, and high mortality (~40%).
Key differentials & integration
- ILD vs cardiogenic pulmonary oedema: echo + PCWP; cardiogenic = high PCWP, cardiomegaly, Kerley B lines, responds to diuretics.
- Sarcoidosis vs TB: non-caseating vs caseating granuloma; AFB/culture; both cause hilar nodes but TB nodes often unilateral/necrotic.
- IPF vs chronic hypersensitivity pneumonitis: basal subpleural honeycombing (IPF) vs upper-zone centrilobular nodules + mosaic attenuation + exposure history (HP).
- IPF vs NSIP (non-specific interstitial pneumonia): NSIP is temporally uniform ground-glass, more steroid-responsive, better prognosis; UIP is heterogeneous with fibroblastic foci and worse prognosis.
Mnemonic for upper-zone fibrosis — "CHARTS": Coal worker's pneumoconiosis/Cystic fibrosis, Hypersensitivity pneumonitis/Histiocytosis, Ankylosing spondylitis/ABPA, Radiation, Tuberculosis/Silicosis, Sarcoidosis. Lower-zone fibrosis = "RASIO": Rheumatoid/scleroderma (CTD), Asbestosis, Scleroderma, IPF, Other drugs (bleomycin, amiodarone, methotrexate, nitrofurantoin).
High-yield: Drug-induced pulmonary fibrosis — remember Bleomycin, Amiodarone, Methotrexate, Nitrofurantoin, Busulfan ("BAM-N-B"). Asbestosis is lower-zone; silicosis/coal are upper-zone with "egg-shell" hilar calcification in silicosis.
Recently asked / exam angle
- Hyaline membrane composition in ARDS = fibrin + necrotic epithelial debris; and the ARDS vs NRDS mechanism distinction (capillary injury vs surfactant deficiency) — repeatedly asked.
- Berlin criteria / PaO₂:FiO₂ cut-offs for ARDS severity, and the PCWP ≤18 mmHg point separating it from cardiogenic oedema.
- Fibroblastic foci & honeycombing as the histological/HRCT signature of UIP/IPF; pirfenidone/nintedanib as therapy.
- Asteroid & Schaumann bodies, non-caseating granuloma, raised CD4:CD8 BAL ratio, raised ACE & hypercalcaemia in sarcoidosis; Löfgren and Heerfordt syndromes.
- BAL CD4:CD8 — high in sarcoidosis, low in hypersensitivity pneumonitis (reciprocal pair).
- Spirometry pattern identification (restrictive vs obstructive) and DLCO behaviour (low in parenchymal, normal in chest-wall/neuromuscular causes).
- Low-tidal-volume ventilation (6 mL/kg) as the mortality-reducing strategy in ARDS; prone positioning for severe disease.
Rapid revision
- Restriction = ↓FVC, ↓TLC, normal/high FEV1/FVC; obstruction = low FEV1/FVC.
- DLCO is low in parenchymal ILD but normal in chest-wall/neuromuscular restriction.
- IPF = UIP pattern: subpleural basal honeycombing + fibroblastic foci + traction bronchiectasis; HRCT is the investigation of choice.
- IPF treatment = pirfenidone/nintedanib slow decline; transplant is curative; steroids don't help.
- Sarcoidosis = non-caseating granuloma, asteroid & Schaumann bodies, high CD4:CD8 BAL ratio, raised ACE, hypercalcaemia.
- Löfgren = BHL + erythema nodosum + arthralgia + fever (good prognosis); Heerfordt = uveoparotid fever + facial palsy.
- Sarcoidosis stage I = bilateral hilar lymphadenopathy; drug of choice = corticosteroids (when symptomatic).
- Hypersensitivity pneumonitis = inhaled organic antigen, low CD4:CD8 BAL ratio, bronchiolocentric granulomas; treat by antigen avoidance.
- ARDS pathology = diffuse alveolar damage with hyaline membranes (fibrin + cell debris); commonest cause = sepsis.
- ARDS = capillary/epithelial injury; NRDS = surfactant deficiency — both make hyaline membranes; NRDS risk ↑ in infant of diabetic mother, ↓ by antenatal steroids; L:S <2.
- ARDS (Berlin) = bilateral infiltrates + PaO₂/FiO₂ ≤300 (PEEP ≥5) within 1 week + PCWP ≤18 (non-cardiogenic).
- ARDS management = low tidal volume 6 mL/kg, plateau <30 cm H₂O, PEEP, prone positioning for severe, ECMO if refractory.