What are the key mimics of Acute Respiratory Distress Syndrome (ARDS) and how are they managed?

Mimics of ARDS

ARDS-mimics are conditions presenting with similar clinical features to ARDS but requiring distinct, often specific treatments such as immunosuppressants, antimicrobials, or drug withdrawal—making their recognition essential to prevent inappropriate management and improve outcomes. 1

Key Categories of ARDS Mimics

Diffuse Interstitial Acute Lung Diseases

These conditions fall under the ARDS umbrella definition but have distinct pathophysiology requiring targeted therapy 1:

• Acute interstitial pneumonia - presents with bilateral infiltrates and hypoxemia but may respond to corticosteroids 1
• Organizing pneumonia - can mimic ARDS radiographically but typically requires immunosuppressive therapy 1
• Acute eosinophilic pneumonia - responds dramatically to corticosteroids, unlike typical ARDS 1
• Hypersensitivity pneumonitis - requires identification and removal of the inciting antigen 1

Diffuse Pulmonary Infections

These require specific antimicrobial therapy rather than supportive ARDS management alone 1:

• Pneumocystis jirovecii pneumonia - requires trimethoprim-sulfamethoxazole and adjunctive corticosteroids 1
• Viral pneumonitis (including COVID-19, influenza) - may benefit from antiviral therapy and targeted corticosteroid use 1
• Disseminated fungal infections - require antifungal therapy 1
• Miliary tuberculosis - demands anti-tuberculous therapy 1

Drug/Chemical-Induced Diffuse Lung Disease

Recognition allows for immediate intervention by withdrawing the offending agent 1:

• Vaping-induced lung injury (EVALI) - exemplifies how ARDS-mimics can emerge rapidly and require specific recognition 1
• Chemotherapy-induced pneumonitis - 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 1

Critical Diagnostic Approach

Why Recognition Matters

Only a minority of patients meeting current ARDS criteria actually have diffuse alveolar damage on pathological evaluation, highlighting the heterogeneity within the syndrome definition. 1

• ARDS-mimics can be effectively treated with immunosuppressants, antimicrobials, or drug withdrawal—interventions that differ fundamentally from standard ARDS management 1
• These patients may be inadvertently included in clinical trials if additional diagnostic testing is not performed 1
• The specific causes vary between institutions and change over time, requiring ongoing vigilance 1

Establishing the Diagnosis

There is currently no consistent diagnostic approach that accounts for the probability of ARDS-mimics, representing a critical gap in clinical practice. 1

The European Respiratory Society recommends establishing and applying a diagnostic protocol to identify treatable diseases within the syndrome diagnosis of ARDS 1:

• Obtain detailed exposure history - occupational exposures, medications (including over-the-counter and supplements), vaping, environmental exposures 1
• Assess immune status - HIV status, immunosuppressive medications, underlying immunodeficiency 1
• Consider bronchoscopy with bronchoalveolar lavage - can identify infectious etiologies, eosinophilia, hemorrhage, or malignancy 1
• Evaluate for systemic disease - autoimmune markers, vasculitis screening when clinical suspicion exists 1
• Review temporal relationship - onset within one week of known insult supports ARDS, but longer prodrome suggests alternative diagnosis 2

Management Implications

When ARDS-Mimic is Identified

Recognition of the underlying cause is essential because adequate treatment of the underlying disease, when possible, is one of the fundamentals of ARDS care. 1

• Withdraw offending agents immediately in drug/chemical-induced disease 1
• Initiate pathogen-specific antimicrobial therapy for infectious mimics 1
• Consider immunosuppression (particularly corticosteroids) for inflammatory/autoimmune mimics 1
• Continue lung-protective ventilation as supportive care while treating the underlying condition 3, 4

Common Pitfalls to Avoid

• Assuming all bilateral infiltrates with hypoxemia represent typical ARDS - this leads to missed opportunities for specific, potentially curative therapy 1
• Failing to obtain adequate diagnostic workup before labeling as ARDS - the broad ARDS definition captures increasingly heterogeneous conditions 1
• Not reassessing the diagnosis when patients fail to improve with standard ARDS management 1
• Overlooking recent medication changes or exposures in the weeks preceding presentation 1

Special Consideration: COVID-19 and Influenza

The rapid discovery of dexamethasone as effective treatment for severe COVID-19 pneumonia demonstrates the importance of recognizing underlying etiology and the potential for phenotype-aware treatment 1:

• Influenza-associated ARDS with hemorrhage requires immediate oseltamivir regardless of symptom duration in severe disease 4
• COVID-19 ARDS benefits from dexamethasone, unlike typical ARDS where routine corticosteroids are not recommended 1, 4

Research Priorities

The European Respiratory Society emphasizes that when performing randomized controlled trials, particular care must be taken to identify and possibly exclude patients with ARDS-mimic diagnoses depending on the intervention being studied 1.