Risk Factors for Acute Respiratory Distress Syndrome (ARDS)
ARDS develops when pulmonary or extrapulmonary insults trigger inflammatory mediator release, causing alveolar and microvascular damage that leads to noncardiogenic pulmonary edema. 1
Primary Direct Lung Injury Risk Factors
The most common precipitating factors that directly injure lung tissue include:
- Pneumonia – the leading cause of ARDS, accounting for the majority of cases 1
- Aspiration of gastric contents – causes chemical pneumonitis and inflammatory lung injury 2
- Influenza A/H1N1 infection – produces an extremely severe type of ARDS with poor response to routine treatment 2
- COVID-19 pneumonia – dramatically increased severe ARDS cases worldwide during the pandemic 3
- Inhalational injury – including toxic fume exposure, surface burns, and vaping-induced lung injury 4
Extrapulmonary Systemic Risk Factors
Conditions that cause systemic inflammation and indirectly injure the lungs:
- Sepsis – the second most common cause after pneumonia, responsible for a substantial proportion of ARDS cases 1, 2
- Severe trauma – particularly polytrauma with shock 2
- Massive blood transfusion – transfusion-related acute lung injury (TRALI) 2
- Severe acute pancreatitis – triggers systemic inflammatory response 5
- Fat embolism – typically following long bone fractures 2
Iatrogenic "Second Hit" Risk Factors
Critically, ARDS often develops days after the initial insult due to inappropriate treatment strategies that constitute a "second hit." 6 These include:
- Excessive fluid administration – aggravates pulmonary edema and worsens lung injury 4
- Injurious mechanical ventilation – high tidal volumes and plateau pressures cause ventilator-induced lung injury 4
- Multiple blood transfusions – compounds inflammatory injury 4
The recognition that iatrogenic factors contribute substantially to ARDS development has shifted the strategic focus toward identifying high-risk patients early and implementing preventive treatment strategies. 6
Patient-Specific Vulnerability Factors
While the evidence focuses primarily on precipitating insults rather than host factors, certain populations warrant heightened surveillance:
- Immunocompromised patients – may have atypical presentations and require specific diagnostic approaches to distinguish ARDS from ARDS-mimics like diffuse interstitial lung diseases 4
- Patients with metabolic syndrome – may have altered inflammatory responses 7
- Regions with endemic tuberculosis – require consideration of infectious ARDS-mimics 7
Clinical Recognition and Timing
ARDS typically manifests within one week of a known insult, presenting with rapidly progressive dyspnea, tachypnea, and hypoxemia. 1 The syndrome often develops a few days after primary lung injury or after several days of treatment for severe extrapulmonary diseases, progressing rapidly to severe ARDS that is difficult to treat. 6
Heterogeneity Considerations
Not all patients meeting ARDS criteria have the same underlying pathophysiology. 4 The current Berlin definition is highly inclusive, and only a minority of patients who fulfill ARDS criteria actually demonstrate diffuse alveolar damage on pathological evaluation. 4 Some patients have ARDS-mimics including drug-induced lung injury, diffuse pulmonary infections, or diffuse interstitial acute lung diseases that require specific treatments such as corticosteroids, antimicrobials, or drug withdrawal. 4