What are the key considerations and diagnostic steps for differentiating Acute Respiratory Distress Syndrome (ARDS) from its mimics, such as cardiogenic pulmonary edema, pneumonia, and acute interstitial lung disease?

ARDS Mimics: Recognition and Differentiation

ARDS-mimics are conditions presenting with bilateral infiltrates and hypoxemia that require distinct treatments—such as immunosuppressants, antimicrobials, or drug withdrawal—making their recognition essential to prevent inappropriate management and improve outcomes. 1

Why Recognition Matters

The European Respiratory Society emphasizes that ARDS-mimics show known and distinct pathophysiology requiring specific treatment, and these patients may be inappropriately included in clinical trials if additional diagnostic tests are not performed. 2 Recognition of the underlying cause is essential because adequate treatment of the underlying disease is one of the fundamentals of ARDS care. 2 Only a minority of patients who fulfill current ARDS criteria actually have diffuse alveolar damage at autopsy, highlighting the heterogeneity within the syndrome. 2

Three Major Categories of ARDS Mimics

Diffuse Interstitial Acute Lung Diseases

Acute interstitial pneumonia presents with bilateral infiltrates and hypoxemia but may respond to corticosteroids, unlike typical ARDS. 1

• Organizing pneumonia mimics ARDS radiographically but typically requires immunosuppressive therapy rather than supportive care alone. 1
• Acute eosinophilic pneumonia responds dramatically to corticosteroids and can be identified by bronchoalveolar lavage showing >25% eosinophils. 1
• Hypersensitivity pneumonitis requires identification and removal of the inciting antigen (occupational exposures, bird antigens, mold). 1

Diffuse Pulmonary Infections

Pneumocystis jirovecii pneumonia requires trimethoprim-sulfamethoxazole and adjunctive corticosteroids, not standard ARDS management. 1

• Viral pneumonitis (COVID-19, influenza) may benefit from antiviral therapy and targeted corticosteroid use—notably, COVID-19 ARDS benefits from dexamethasone, unlike typical ARDS where routine corticosteroids are not recommended. 1
• Disseminated fungal infections require antifungal therapy (aspergillosis, mucormycosis in immunocompromised patients). 1
• Miliary tuberculosis demands anti-tuberculous therapy and can present with ARDS-like features. 1

Drug/Chemical-Induced Diffuse Lung Disease

Vaping-induced lung injury exemplifies how ARDS-mimics can emerge rapidly and require specific recognition rather than standard ARDS protocols. 2, 1

• Chemotherapy-induced pneumonitis (bleomycin, methotrexate) may require corticosteroids and drug discontinuation. 1
• Amiodarone toxicity requires drug withdrawal and possible corticosteroid therapy. 1
• Drug-induced acute interstitial pneumonitis resolves with drug cessation (nitrofurantoin, NSAIDs, antibiotics). 1

Diagnostic Protocol to Identify ARDS Mimics

The European Respiratory Society recommends establishing and applying a diagnostic protocol to identify treatable diseases within the syndrome diagnosis of ARDS. 2, 1 This protocol should include:

Detailed exposure history: Inquire about vaping, occupational exposures, new medications (within 6 months), bird or mold exposure, and recent travel. 1

Immune status assessment: HIV status, immunosuppressive medications, chemotherapy, and underlying immunodeficiency. 1

Bronchoscopy with bronchoalveolar lavage: Consider when clinical presentation is atypical, when there is no clear ARDS risk factor, or when initial therapy fails. This can identify eosinophilia, infectious organisms, or hemorrhage. 1, 3

Systemic disease evaluation: Look for connective tissue disease features, vasculitis symptoms, or systemic inflammatory conditions. 1

Temporal relationship: Assess timing between potential insult and symptom onset—drug reactions typically occur within days to weeks of exposure. 1

Critical Pitfalls in Differentiating ARDS from Cardiogenic Pulmonary Edema

Congestive heart failure typically has signs of fluid overload (elevated jugular venous pressure, peripheral edema, S3 gallop) that are absent in ARDS. 4

• Bedside ultrasound with a "triple scan" approach (lung ultrasound for B-lines, cardiac ultrasound for left ventricular function, inferior vena cava assessment) can rapidly differentiate ARDS from cardiogenic pulmonary edema. 5
• B-lines on lung ultrasound indicate alveolar-interstitial edema but cannot independently distinguish cardiogenic from noncardiogenic causes. 5
• Cardiac ultrasound showing preserved left ventricular function and normal left atrial size favors ARDS over cardiogenic edema. 5

Differentiating ARDS from Pneumonia

Pneumonia can trigger ARDS but may also present with similar radiographic findings without meeting full ARDS criteria. 4

• Autopsy studies show that among patients meeting clinical ARDS criteria, many have pneumonia without diffuse alveolar damage. 6
• The American Thoracic Society notes that computerized tomographic scanning can separate pleural fluid from parenchymal disease and demonstrate parenchymal abscesses, helping distinguish focal pneumonia from diffuse ARDS. 2
• In patients with severe community-acquired pneumonia, ARDS was not a risk factor for mortality, suggesting these may represent distinct entities. 2

Management Implications When ARDS Mimic is Identified

Withdraw offending agents immediately in drug/chemical-induced disease—this is the primary intervention and may lead to rapid improvement. 1

Initiate pathogen-specific antimicrobial therapy for infectious mimics (trimethoprim-sulfamethoxazole for PCP, oseltamivir for influenza with hemorrhage regardless of symptom duration). 1

Consider immunosuppression, particularly corticosteroids, for inflammatory/autoimmune mimics (acute eosinophilic pneumonia, organizing pneumonia, acute interstitial pneumonia). 1

Continue lung-protective ventilation as supportive care while treating the underlying condition—low tidal volume ventilation remains appropriate even when treating an ARDS mimic. 1

When to Consider Open Lung Biopsy

Open lung biopsy should be considered when bronchoscopy demonstrates no unusual or resistant organisms, aggressive search for extrapulmonary infectious foci is unrevealing, and the patient deteriorates despite appropriate empiric therapy. 2

• The decision must weigh the patient's clinical trajectory—if there is slow but progressive improvement, close observation may be more appropriate than invasive biopsy. 2
• In skilled hands, open lung biopsy may have management implications by identifying specific treatable conditions or confirming diffuse alveolar damage. 3
• The available evidence does not suggest a clear outcome benefit for open lung biopsy in nonimmunosuppressed patients, so the decision should be reserved for cases where diagnosis remains elusive despite comprehensive evaluation. 2

Special Considerations for Specific Mimics

COVID-19 ARDS represents a unique phenotype where dexamethasone improves mortality, contrasting with typical ARDS where routine corticosteroids are not recommended. 1 This highlights the importance of recognizing specific aetiologies within the ARDS syndrome.

Influenza-associated ARDS with hemorrhage requires immediate oseltamivir regardless of symptom duration in severe disease, as delayed antiviral therapy is associated with worse outcomes. 1

Iatrogenic injury from excess fluid administration, transfusions, or injurious mechanical ventilation should be considered a "second hit" that aggravates pulmonary edema in patients with ARDS risk factors. 2