Is ARDS a Diagnosis of Exclusion?
ARDS is not strictly a diagnosis of exclusion, but rather a syndrome diagnosis based on specific clinical criteria (acute onset, bilateral opacities, hypoxemia with PaO₂/FiO₂ ≤300 mmHg on PEEP ≥5 cmH₂O) that requires ruling out cardiac failure or fluid overload as the primary explanation for respiratory failure. 1
Understanding ARDS as a Syndrome Diagnosis
ARDS is diagnosed when all four Berlin Definition components are present simultaneously: acute onset within 1 week of a known clinical insult, bilateral opacities on chest imaging not fully explained by effusions/nodules/collapse, respiratory failure not fully explained by cardiac failure or fluid overload, and hypoxemia with PaO₂/FiO₂ ≤300 mmHg with minimum PEEP of 5 cmH₂O. 1 This represents a positive diagnosis based on meeting specific criteria, not simply excluding other conditions. 2
The syndrome is characterized by noncardiogenic pulmonary edema manifesting as rapidly progressive dyspnea, tachypnea, and hypoxemia. 2 Most cases are associated with identifiable risk factors, particularly pneumonia or sepsis, with 28-33% of septic patients meeting ARDS criteria at sepsis onset. 3
The Critical Exclusion Component
While ARDS has positive diagnostic criteria, one essential exclusion must be made: cardiac failure or fluid overload cannot fully explain the respiratory failure. 1 The European Society of Intensive Care Medicine recommends performing echocardiography if no clear ARDS risk factor exists to exclude cardiogenic pulmonary edema and to look for absence of signs suggesting fluid overload. 1
ARDS often must be differentiated from congestive heart failure, which typically has signs of fluid overload. 2 This is the primary "exclusion" aspect of ARDS diagnosis—distinguishing it from cardiogenic causes of bilateral infiltrates and hypoxemia.
The ARDS-Mimics Problem
A critical caveat is that conditions meeting Berlin criteria may actually be "ARDS-mimics" requiring entirely different treatment. 4 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. 4
Only a minority of patients meeting Berlin criteria actually have diffuse alveolar damage on autopsy, highlighting the heterogeneity captured by clinical diagnostic criteria. 1 This means that while ARDS can be diagnosed positively using clinical criteria, establishing a systematic diagnostic protocol to identify treatable diseases masquerading as ARDS is essential. 4
Three Key Categories of ARDS-Mimics to Actively Exclude:
Diffuse interstitial acute lung diseases (acute interstitial pneumonia, organizing pneumonia, acute eosinophilic pneumonia, hypersensitivity pneumonitis) that may respond to corticosteroids or require antigen removal 4
Diffuse pulmonary infections (Pneumocystis jirovecii, viral pneumonitis including COVID-19/influenza, disseminated fungal infections, miliary tuberculosis) requiring pathogen-specific antimicrobial therapy 4
Drug/chemical-induced diffuse lung disease (vaping-induced lung injury, chemotherapy-induced pneumonitis, amiodarone toxicity) requiring drug withdrawal and possible corticosteroid therapy 4
Practical Diagnostic Approach
The diagnostic workup should include:
Arterial blood gas to determine PaO₂/FiO₂ ratio with minimum PEEP of 5 cmH₂O 1
Chest radiograph or CT showing bilateral opacities 1
Echocardiography if no clear ARDS risk factor exists 1
Detailed exposure history including substance use (vaping, injection drugs), occupational/environmental exposures, medication review, travel history, and animal exposures 4
Evaluation for systemic disease including connective tissue disease markers, vasculitis markers, and tuberculin testing 4
Bronchoscopy with bronchoalveolar lavage in treatment failures, which has a 41% diagnostic yield for identifying Legionella, anaerobes, resistant pathogens, tuberculosis, fungi, and Pneumocystis 4
Common Pitfall to Avoid
Assuming all bilateral infiltrates with hypoxemia meeting Berlin criteria are "true" ARDS can lead to misdiagnosis and inappropriate management. 4 Recognition of the underlying cause is essential because adequate treatment of the underlying disease is one of the fundamentals of ARDS care. 4 Failing to recognize ARDS-mimics means missing opportunities for specific, potentially curative treatments (immunosuppressants, antimicrobials, drug withdrawal) rather than purely supportive care. 4