What are the causes of Acute Respiratory Distress Syndrome (ARDS)?

Causes of Acute Respiratory Distress Syndrome (ARDS)

ARDS is triggered by either direct pulmonary injury (through the airways) or indirect injury (through the bloodstream), with the most common precipitants being pneumonia, sepsis, aspiration of gastric contents, and severe trauma. 1

Direct (Pulmonary) Causes

Direct lung injury causes predominantly intra-alveolar damage and presents with prominent consolidation on imaging. 2

Infectious causes:

• Pneumonia (bacterial, viral, fungal) is one of the most frequent triggers of ARDS 1
• COVID-19 pneumonia, which has emerged as a major cause and responds specifically to dexamethasone 3, 4
• Influenza-associated ARDS, particularly when complicated by hemorrhage 4
• Pneumocystis jirovecii pneumonia in immunocompromised patients 4
• Miliary tuberculosis 4

Non-infectious direct causes:

• Aspiration of gastric contents 1
• Inhalational injury from toxic gases or chemicals 5
• Pulmonary contusion from trauma 1
• Near-drowning 6
• Vaping-induced lung injury, which has emerged as a rapidly evolving cause 3, 4

Indirect (Extrapulmonary) Causes

Indirect injury causes predominantly interstitial edema and presents with ground-glass opacification on imaging. 2

Systemic inflammatory conditions:

• Sepsis (non-pulmonary source) is a leading cause, with 28-33% of septic patients meeting ARDS criteria at sepsis onset 7
• Severe acute pancreatitis 6
• Major trauma with shock and multiple transfusions 1
• Burns 5

Blood product-related:

• Transfusion-related acute lung injury (TRALI) from blood product administration 8
• Massive transfusion in trauma patients 3

Drug and Chemical-Induced Causes

These represent critical "ARDS-mimics" that require specific recognition and treatment. 3, 4

• Chemotherapy-induced pneumonitis requiring drug discontinuation and possible corticosteroids 4
• Amiodarone toxicity requiring drug withdrawal 4
• Drug-induced acute interstitial pneumonitis 4
• Illicit drug use, including injection drug use and recreational drugs 4

Iatrogenic "Second Hit" Factors

These aggravating factors should be considered as additional insults that worsen existing lung injury:

• Injurious mechanical ventilation with excessive tidal volumes or pressures 3
• Excess fluid administration causing volume overload 3, 4
• Multiple blood product transfusions 3

Critical Diagnostic Considerations

The European Respiratory Society emphasizes that recognizing the underlying cause is essential because adequate treatment of the underlying disease is one of the fundamentals of ARDS care. 4

When evaluating potential ARDS causes, obtain:

• Detailed substance use history including vaping, injection drugs, and recreational substances 4
• Comprehensive medication review for drug-induced causes 4
• Occupational and environmental exposure history 4
• Travel history and animal exposures for infectious etiologies 4
• Assessment for systemic diseases including connective tissue disorders and vasculitis 4

Common Pitfalls

Failing to distinguish between true ARDS and ARDS-mimics can lead to inappropriate management, as conditions like acute eosinophilic pneumonia, organizing pneumonia, and hypersensitivity pneumonitis require immunosuppression rather than standard supportive care. 4

Only a minority of patients meeting ARDS criteria actually have diffuse alveolar damage on autopsy, highlighting significant heterogeneity within the syndrome. 4, 8

Overlooking noninfectious mimics such as pulmonary embolus, lymphoma, intrapulmonary hemorrhage, Wegener's granulomatosis, and sarcoidosis delays appropriate diagnosis and treatment. 4