Acute Respiratory Distress Syndrome (ARDS) Causes and Pathophysiology

Primary Causes

The American Thoracic Society suggests that sepsis is the most common cause of ARDS, accounting for approximately 40% of cases, with pneumonia and aspiration of gastric contents being other primary causes 1
Pneumonia is one of the most common direct lung causes, with pulmonary and intra-abdominal infections being the most frequently identified infection sites in ARDS patients 1

The European Respiratory Society recommends recognizing ARDS mimics, such as acute interstitial pneumonia, organizing pneumonia, and acute eosinophilic pneumonia, which require specific treatments like immunosuppressants, antimicrobials, or medication withdrawal 2
Acute interstitial pneumonia may respond to corticosteroids 3
Organizing pneumonia typically requires immunosuppressive therapy 3
Acute eosinophilic pneumonia responds dramatically to corticosteroids 3
Hypersensitivity pneumonitis requires identification and removal of the triggering antigen 3

The Society of Critical Care Medicine states that ARDS occurs through a broad activation of the host's inflammatory response, mediated by neutrophils, cytokines, and oxidative stress 4
Neutrophils play a critical role, although neutropenic patients can develop ARDS, suggesting a central role for alveolar macrophages 4, 5
Proinflammatory cytokines (TNF-α, IL-1, IL-6, IL-8) are persistently elevated and correlate with decreased survival 4, 7

The European Respiratory Society warns that fluid administration, transfusions, or harmful mechanical ventilation can act as a "second hit" after the initial injury, worsening lung edema 2
Excessive fluid administration worsens pulmonary edema in patients with ARDS risk factors 2
Blood product transfusions can contribute to lung injury 2
Harmful mechanical ventilation can add additional complexity to the syndrome 2

The assumption that all bilateral infiltrates with hypoxemia are ARDS can lead to misdiagnoses, as only a minority of patients who meet the Berlin criteria actually have diffuse alveolar damage at autopsy 3
COVID-19-ARDS benefits from dexamethasone, in contrast to typical ARDS, for which routine corticosteroids are not recommended 2, 3