Causes of Acute Respiratory Distress Syndrome (ARDS)
ARDS results from both direct pulmonary insults and indirect systemic injuries that trigger diffuse alveolar damage through inflammatory and vascular pathways.
Direct (Pulmonary) Causes
Direct lung injury occurs through the airways and alveolar space, causing predominantly intra-alveolar damage with characteristic consolidation patterns 1, 2:
- COVID-19 pneumonia is now a major cause of ARDS and represents a distinct entity that responds to dexamethasone 1
- Bacterial and viral pneumonias cause direct alveolar epithelial injury 3, 4
- Aspiration of gastric contents leads to chemical pneumonitis and subsequent ARDS 4
- Vaping-induced lung injury has emerged as a rapidly evolving cause requiring specific recognition 1
- Inhalational injuries from toxic gases or smoke cause direct airway and alveolar damage 5
- Pulmonary contusion from trauma directly injures lung parenchyma 3
- Near-drowning causes direct alveolar flooding and surfactant dysfunction 3
Indirect (Extrapulmonary) Causes
Indirect injury occurs through the bloodstream, causing predominantly interstitial edema with ground-glass opacification patterns 2, 5:
- Sepsis is the leading cause, with 28-33% of septic patients meeting ARDS criteria at sepsis onset 1, 6
- Severe acute pancreatitis releases inflammatory mediators systemically 3
- Multiple trauma without direct chest injury triggers systemic inflammatory response 3, 4
- Transfusion-related acute lung injury (TRALI) from blood product administration causes endothelial injury 1
- Non-pulmonary sepsis from abdominal or urinary sources 4
Iatrogenic "Second Hit" Factors
These aggravate existing lung injury and should be actively avoided 1, 7:
- Injurious mechanical ventilation with excessive tidal volumes or pressures worsens alveolar damage 1
- Excess fluid administration causing volume overload exacerbates pulmonary edema 1
- Multiple blood transfusions contribute to inflammatory lung injury 1
Drug and Chemical-Induced Causes
These require specific recognition because treatment involves drug withdrawal rather than standard ARDS management 7:
- Chemotherapy agents cause pneumonitis requiring drug discontinuation and possible corticosteroids 7
- Amiodarone toxicity requires immediate drug withdrawal 7
- Vaping products (particularly THC-containing products) cause acute lung injury 1, 7
- Recreational drugs including cocaine and opioids 7
Critical Diagnostic Approach
The European Respiratory Society emphasizes that recognizing the underlying cause is essential because adequate treatment of the underlying disease is fundamental to ARDS care 1, 7:
- Obtain detailed substance use history including vaping, injection drugs, and recreational substances 7
- Comprehensive medication review to identify drug-induced causes 1
- Exposure history including occupational, environmental, travel, and animal exposures 7
- Consider bronchoscopy with bronchoalveolar lavage which has 41% diagnostic yield in treatment failures, identifying Legionella, resistant pathogens, tuberculosis, fungi, and Pneumocystis 7
- Evaluate for systemic disease including connective tissue disease markers and vasculitis 7
Common Pitfalls to Avoid
- Do not assume all bilateral infiltrates are standard ARDS—only a minority of patients meeting Berlin criteria actually have diffuse alveolar damage at autopsy 7
- Actively search for ARDS mimics such as acute eosinophilic pneumonia, organizing pneumonia, or hypersensitivity pneumonitis, which require immunosuppression rather than supportive care alone 7
- Recognize that multiple organ failure or recurrent sepsis, not refractory respiratory failure, represents the most common cause of death in ARDS 6
- Distinguish between direct and indirect causes as they have different radiological patterns, mechanical properties, and responses to interventions like PEEP and prone positioning 2