8.4 Acute Respiratory Distress Syndrome & Interstitial Lung Diseases

8.4 Acute Respiratory Distress Syndrome & Interstitial Lung Diseases

Acute Respiratory Distress Syndrome (ARDS) represents severe, life-threatening non-cardiogenic pulmonary edema, while Interstitial Lung Diseases (ILD) comprise a heterogeneous group of restrictive parenchymal lung disorders. Mastering the Berlin criteria and mortality-reducing mechanical ventilation strategies for ARDS, alongside diagnostic hallmarks of sarcoidosis and occupational pneumoconioses, is high-yield for USMLE Step 2 CK.

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Acute Respiratory Distress Syndrome (ARDS)

Berlin Diagnostic Definition Criteria

1. Acute Onset: Respiratory symptoms develop within 1 week of a known clinical insult or new/worsening pulmonary symptoms.
2. Bilateral Opacities: Diffuse bilateral pulmonary opacities on CXR or CT scan not fully explained by pleural effusions, lobar collapse, or lung nodules.
3. Non-Cardiogenic Origin: Respiratory failure NOT fully explained by cardiac failure or fluid overload. Confirmed by Pulmonary Capillary Wedge Pressure PCWP ≤ 18 mmHg or absence of left atrial hypertension on echocardiography.
4. Impaired Oxygenation (PaO2 / FiO2 ratio on PEEP ≥ 5 cmH2O):
   • Mild ARDS: 200 < PaO2/FiO2 ≤ 300 mmHg
   • Moderate ARDS: 100 < PaO2/FiO2 ≤ 200 mmHg
   • Severe ARDS: PaO2/FiO2 ≤ 100 mmHg

Etiologies & Pathophysiology

• Triggers: Sepsis (most common cause overall), severe pulmonary infection, severe trauma, massive blood transfusion (Transfusion-Related Acute Lung Injury - TRALI), acute pancreatitis, aspiration of gastric contents.
• Pathophysiology: Uncontrolled inflammatory cascade → pulmonary capillary endothelial and alveolar epithelial cell damage → accumulation of neutrophils in microvasculature → release of proteases and reactive oxygen species → diffuse alveolar damage (DAD) → protein-rich fluid exudation into alveoli → formation of hyaline membranes → destruction of surfactant producing type II pneumocytes → microatelectasis and severe intrapulmonary right-to-left shunting (V/Q = 0, hypoxemia refractory to supplemental oxygen).

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ARDS Mechanical Ventilation Principles (Mortality Benefit)

Standard mechanical ventilation strategies using large tidal volumes exacerbate lung injury through volutrauma (alveolar overdistension), barotrauma (high airway pressures), and atelectotrauma (repeated alveolar collapse and reopening). The ARDSNet trial established lung-protective ventilation principles that significantly improve survival.

Key Ventilator Management Principles

1. Low Tidal Volume Ventilation: Set initial tidal volume to 4–8 mL/kg of Predicted Body Weight (PBW) (calculated based on biological sex and height, NOT actual body weight!).
2. Limit Plateau Pressure: Maintain end-inspiratory plateau pressure Pplat ≤ 30 cmH2O.
3. Permissive Hypercapnia: Tolerating moderate hypercapnia and respiratory acidosis (pH down to 7.20–7.25) as an acceptable trade-off for maintaining lung-protective low tidal volumes.
4. High PEEP Titration: Titrate Positive End-Expiratory Pressure (PEEP) alongside FiO2 using PEEP/FiO2 tables to recruit collapsed alveoli, prevent end-expiratory alveolar collapse, and maintain oxygenation (target PaO2 55–80 mmHg or SpO2 88–95%).
5. Prone Positioning: Indicated for patients with severe ARDS (PaO2/FiO2 < 150); performing prone positioning for ≥16 hours per day improves V/Q matching and significantly reduces mortality.

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Interstitial Lung Diseases (ILD) Overview

Interstitial lung diseases (also termed diffuse parenchymal lung diseases) are characterized by inflammation and fibrosis of the alveolar septum and lung interstitium.

Clinical & Spirometric Pattern

• Clinical Presentation: Progressive exertional dyspnea, dry non-productive cough, fine bilateral end-inspiratory "velcro-like" crackles on auscultation, and digital clubbing.
• Pulmonary Function Testing (Restrictive Defect):
  • FEV1/FVC Ratio: Normal or Increased (> 0.70)
  • Forced Vital Capacity (FVC): Decreased (<80% predicted)
  • Total Lung Capacity (TLC): Decreased (<80% predicted)
  • DLCO: Decreased (due to destruction and thickening of the alveolar-capillary interface)

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Major Subtypes of Interstitial Lung Disease

1. Idiopathic Pulmonary Fibrosis (IPF)

• Progressive fibrotic lung disease typically affecting patients >60 years old.
• HRCT Findings: Subpleural reticular opacities, traction bronchiectasis, and honeycombing (Usual Interstitial Pneumonia [UIP] pattern).
• Pharmacotherapy: Antifibrotic agents (Nintedanib, Pirfenidone) slow the rate of FVC decline; definitive cure requires lung transplantation.

2. Sarcoidosis

• Multisystem granulomatous disease predominantly affecting young African American women and individuals of Northern European descent.
• Histology: Non-caseating granulomas composed of epithelioid histiocytes and multinucleated giant cells.
• Clinical Features: Asymptomatic (incidental CXR finding), fatigue, low-grade fever, weight loss, anterior uveitis, erythema nodosum (tender red pretibial nodules), bell palsy, Heerfordt syndrome (uveitis, parotid gland enlargement, facial nerve palsy, fever).
• Laboratory Findings: Elevated serum ACE levels, hypercalcemia and hypercalciuria (caused by extrarenal 1-α-hydroxylase production in granuloma macrophages → increased 1,25-dihydroxyvitamin D).
• Chest Radiograph: Bilateral hilar lymphadenopathy with or without parenchymal reticular opacities.
• Treatment: Oral Systemic Corticosteroids (prednisone) indicated for symptomatic patients or end-organ impairment (ocular, cardiac, neuro, or severe pulmonary involvement).

3. Occupational Pneumoconioses

4. Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

• Immunologic reaction to inhaled organic antigens (e.g., Farmer's lung from moldy hay containing Saccharopolyspora rectivirgula; Bird fancier's lung from avian proteins).
• Presentation: Acute episodes of fever, cough, and dyspnea 4-8 hours post-exposure; chronic exposure leads to upper/middle lobe pulmonary fibrosis.
• Treatment: Complete avoidance of antigen exposure ± systemic corticosteroids.