How do you identify mimics of Acute Respiratory Distress Syndrome (ARDS)?

Identifying ARDS Mimics

Establish a systematic diagnostic protocol to identify treatable diseases masquerading as ARDS, focusing on three key categories: diffuse interstitial acute lung diseases, diffuse pulmonary infections, and drug/chemical-induced diffuse lung disease. 1

Why Recognition Matters

ARDS-mimics present with bilateral infiltrates and hypoxemia that meet Berlin criteria but have distinct pathophysiology requiring specific treatments—immunosuppressants, antimicrobials, or drug withdrawal—rather than standard ARDS supportive care. 1 These conditions can be effectively treated when correctly identified, whereas misdiagnosis leads to inappropriate management and worse outcomes. 1

Key Diagnostic Categories

Diffuse Interstitial Acute Lung Diseases

• Acute interstitial pneumonia: Bilateral infiltrates with hypoxemia that may respond to corticosteroids 2
• Organizing pneumonia: Radiographically mimics ARDS but requires immunosuppressive therapy 2
• Acute eosinophilic pneumonia: Responds dramatically to corticosteroids, unlike typical ARDS 2
• Hypersensitivity pneumonitis: Requires identification and removal of the inciting antigen 2

Diffuse Pulmonary Infections

• Pneumocystis jirovecii pneumonia: Requires trimethoprim-sulfamethoxazole and adjunctive corticosteroids 2
• Viral pneumonitis (COVID-19, influenza): May benefit from antiviral therapy and targeted corticosteroid use 2
• Disseminated fungal infections: Require antifungal therapy 2
• Miliary tuberculosis: Demands anti-tuberculous therapy 2

Drug/Chemical-Induced Diffuse Lung Disease

• Vaping-induced lung injury: Exemplifies rapidly emerging ARDS-mimics requiring specific recognition 1, 2
• Chemotherapy-induced pneumonitis: May require corticosteroids and drug discontinuation 2
• Amiodarone toxicity: Requires drug withdrawal and possible corticosteroid therapy 2
• Drug-induced acute interstitial pneumonitis: Resolves with drug cessation 2

Systematic Diagnostic Approach

Obtain Detailed Exposure History

• Occupational and environmental exposures: Identify potential inhaled antigens, chemicals, or toxins 2
• Medication review: Document all prescription drugs, over-the-counter medications, and supplements with temporal relationship to symptom onset 2
• Substance use: Specifically ask about vaping, injection drug use, and recreational drugs 1
• Travel history: Southeast Asia (Burkholderia pseudomallei), endemic fungal regions, tuberculosis exposure 1
• Animal exposures: Birds (psittacosis), rats (leptospirosis, plague) 1

Assess Immune Status

• HIV status and CD4 count: Critical for identifying Pneumocystis and other opportunistic infections 2
• Immunosuppressive medications: Chemotherapy, chronic corticosteroids, biologics 2
• Underlying autoimmune conditions: May suggest organizing pneumonia or other inflammatory mimics 2

Consider Bronchoscopy with Bronchoalveolar Lavage

• Timing matters: Bronchoscopy has high false-negative rates when performed during antibiotic therapy, but recovered organisms are often resistant to current therapy 1
• Diagnostic yield: Provides useful information in 41% of treatment failures, identifying Legionella, anaerobes, resistant pathogens, tuberculosis, fungi, and Pneumocystis 1
• Cell count and differential: Eosinophilia suggests acute eosinophilic pneumonia; lymphocytosis suggests hypersensitivity pneumonitis or organizing pneumonia 2

Evaluate for Systemic Disease

• Connective tissue disease markers: ANA, RF, anti-CCP, myositis panel 2
• Vasculitis markers: ANCA, anti-GBM antibodies 1
• Tuberculin skin test or interferon-gamma release assay: In epidemiologically at-risk patients 1

Review Temporal Relationship

• Symptom onset timing: Drug-induced disease typically occurs days to weeks after medication initiation 2
• Response to initial therapy: Lack of improvement within 72 hours suggests wrong diagnosis or resistant pathogen 1
• COVID-19 considerations: Dexamethasone benefits COVID-19 ARDS specifically, unlike typical ARDS where routine corticosteroids are not recommended 2

Advanced Imaging Considerations

• CT chest: Separates pleural fluid from parenchymal disease, demonstrates abscesses, and helps distinguish focal pneumonia from diffuse ARDS 2
• Ultrasound: Added as imaging modality in the 2024 global ARDS definition, especially useful in resource-limited settings 3
• Pattern recognition: Ground-glass with minimal reticulation suggests DIP, RBILD, or NSIP rather than typical ARDS 4

Role of 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 However, available evidence does not suggest clear outcome benefit for open lung biopsy in nonimmunosupressed patients, so reserve this for cases where diagnosis remains elusive despite comprehensive evaluation. 2, 5

Common Pitfalls to Avoid

• Assuming all bilateral infiltrates with hypoxemia are ARDS: Only a minority of patients meeting Berlin criteria actually have diffuse alveolar damage at autopsy 1
• Failing to recognize iatrogenic "second hits": Excess fluid administration, transfusions, or injurious mechanical ventilation can aggravate pulmonary edema in patients with ARDS risk factors 1, 2
• Missing congestive heart failure: Typically has signs of fluid overload that distinguish it from ARDS 6
• Overlooking noninfectious mimics: Pulmonary embolus, obstructing bronchogenic carcinoma, lymphoma, intrapulmonary hemorrhage, Wegener's granulomatosis, sarcoidosis 1

Management Implications Once Mimic Identified

• Withdraw offending agents immediately in drug/chemical-induced disease 2
• Initiate pathogen-specific antimicrobial therapy for infectious mimics 2
• Consider immunosuppression, particularly corticosteroids, for inflammatory/autoimmune mimics 2
• Continue lung-protective ventilation as supportive care while treating the underlying condition 2