Restrictive Respiratory Diseases

Definition & Physiology

• ↓ TLC, ↓ FVC, ↓ FEV1 — all volumes reduced
• FEV1/FVC ratio is normal or elevated (≥0.70) — distinguishing feature from obstructive disease
• ↓ DLCO — commonly reduced in parenchymal disease

Classification

I. Intrinsic (Parenchymal) — Interstitial Lung Diseases (ILDs)

A. Idiopathic Interstitial Pneumonias (IIPs)

1. Idiopathic Pulmonary Fibrosis (IPF)

• Most common ILD of unknown cause; prevalence 50–200 per 100,000
• Diagnosed in the 5th–6th decade; more common in men; associated with smoking
• 50% 3–5 year survival — poor prognosis
• HRCT: Bilateral subpleural reticular markings with posterior/basal predominance; honeycombing and traction bronchiectasis → "UIP pattern"
• Histology: Subpleural reticulation + honeycomb changes + fibroblast foci (subepithelial myofibroblasts/collagen); temporal and spatial heterogeneity → Usual Interstitial Pneumonia (UIP)
• Treatment: Antifibrotics — pirfenidone and nintedanib (proven in 2014 trials to slow FVC decline); lung transplantation for eligible patients; O₂ therapy + pulmonary rehab

2. Nonspecific Interstitial Pneumonia (NSIP)

• More common in nonsmoking females in the 5th decade; frequently associated with CTD
• 5-year survival >80% — better prognosis than IPF
• HRCT: Bilateral, symmetric subpleural ground-glass and reticular opacities; lower lung zone predominance; subpleural sparing (unlike IPF); no or rare honeycombing
• Histology: Uniform interstitial inflammation and fibrosis (cellular > fibrotic in prognosis); absence of honeycomb change; fibroblast foci rare
• Treatment: Oral steroids (prednisone), cytotoxic agents (mycophenolate, azathioprine, cyclophosphamide), biologics (rituximab, tocilizumab); antifibrotics if progressive

3. Cryptogenic Organizing Pneumonia (COP)

• HRCT: Patchy, sometimes migratory, subpleural consolidative opacities ± ground-glass; reversed halo/atoll sign
• Histology: Patchy plugs of granulation tissue in small airways, alveolar ducts, and alveoli; mononuclear infiltration; foamy macrophages

4. Smoking-Related ILDs

• RB-ILD (Respiratory Bronchiolitis-ILD) and DIP (Desquamative Interstitial Pneumonia): strong association with tobacco smoke
• Pulmonary Langerhans Cell Histiocytosis (PLCH) also in this category

5. Acute Exacerbations of IIPs

• Can occur in any ILD with pulmonary fibrosis; most severe in IPF
• Acute onset (<30 days) of respiratory distress/hypoxemia on background of pulmonary fibrosis
• Mortality >85%; histology shows DAD pattern
• Treatment is largely supportive; nintedanib may reduce AE rate in IPF

B. ILD Associated with Connective Tissue Disease (CTD-ILD)

C. Granulomatous ILDs

Sarcoidosis

• Can be asymptomatic or present with dyspnea, cough, fatigue, eye/skin/joint findings
• HRCT: Mediastinal and hilar lymphadenopathy + circular-nodular opacities along bronchovascular bundles (classic); also miliary nodules, ground-glass, or mosaic attenuation
• Histology: Non-caseating granulomas (hallmark)
• Restrictive pattern on PFTs (can also be obstructive or mixed)

Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

• Caused by repeated inhalation of organic antigens (farmer's lung, bird fancier's lung)
• Acute, subacute, and chronic forms; chronic form leads to progressive fibrosis
• HRCT: Upper lobe predominant fibrosis, air trapping, mosaic pattern

D. Occupational/Environmental ILDs (Pneumoconioses)

• Silicosis — crystalline silica exposure; upper lobe nodules, eggshell calcification of hilar nodes
• Asbestosis — lower lobe fibrosis, pleural plaques/mesothelioma risk
• Coal Worker's Pneumoconiosis — progressive massive fibrosis
• Berylliosis — resembles sarcoidosis

II. Extrinsic Causes

Key Diagnostic Approach

PFTs

• Restriction: TLC <80% predicted; FEV1/FVC ≥0.70
• Severity graded by FVC: Mild ≥70%, Moderate 50–69%, Severe <50%
• DLCO reduction suggests parenchymal disease (ILD) vs. preserved DLCO in pure chest wall restriction

HRCT Patterns (Figure 304-2 from Harrison's)

A. IPF (UIP): posterior basal honeycombing + traction bronchiectasis. B. NSIP: symmetric ground-glass, subpleural sparing. C. COP: patchy subpleural consolidation. D. Sarcoidosis: hilar adenopathy + bronchovascular nodules.

Histopathology (Figure 304-3 from Harrison's)

A. IPF/UIP: spatial heterogeneity + fibroblast foci. B. NSIP: uniform inflammation/fibrosis. C. COP: granulation tissue plugs in airways. D. Sarcoidosis: non-caseating granulomas.

Diagnostic Workup

1. History: Exposures (occupational, birds, hay), smoking, medications, CTD symptoms
2. Serology: ANA, anti-dsDNA, Scl-70 (anti-topo I), RF, anti-CCP, anti-Jo-1, anti-synthetase panel
3. HRCT chest — often definitive; multidisciplinary discussion (MDD) approach
4. BAL — cellular differential (neutrophilia in IPF, lymphocytosis in HP/sarcoidosis)
5. Lung biopsy — VATS surgical biopsy when CT non-diagnostic; transbronchial biopsy or cryo-biopsy for specific conditions

Treatment Summary