#49 ARDS Mimics

On this week's episode of Critical Care Time, we revisit ARDS... sort of! We are joined again by Dr. Whittney Warren & for the first time by Denitza Blagev for a dynamic discussion on ARDS imitators: Things that looks like ARDS but aren't technically ARDS - or are they? It's a bit of a confusing landscape as you'll see, where the lines are blurred and things get a bit murky. We'll unpack diagnoses like EVALI, DAH, AIP and more in the context of ARDS and help you guys come up with a framework for the "ARDS" patient who doesn't seem to respond to the tried and true approaches we discussed earlier this year on our ARDS Epic-sode!. As always, give it a listen and let us know what you think!

🗺️ Overview of ARDS Mimics

• Acute Respiratory Distress Syndrome (ARDS) is a life-threatening form of acute hypoxemic respiratory failure characterized by diffuse alveolar damage, noncardiogenic pulmonary edema, and severe oxygenation impairment.  ARDS is commonly associated with sepsis, pneumonia, aspiration, and trauma.

• However, numerous other conditions can present with similar clinical and radiographic features, often leading to misdiagnosis and inappropriate management. Recognizing these ARDS mimics is crucial, as their underlying pathophysiology and optimal treatment strategies differ significantly from true ARDS.

• ARDS is common but so are ARDS mimics.

• The definition of ARDS is deliberately broad, but sometimes it is too broad. One study found that 7.5% of ICU admissions for ARDS lacked typical ARDS risk factors and were likely ARDS mimics.

• Framework for thinking about ARDS mimics using categories:

  • Cardiogenic pulmonary edema

  • Vascular (DAH, vasculitis, PVOD, etc)

  • Transfusion associated lung injury (TRALI)

  • Infection (PJP, Strongyloides, Hantavirus, Measles, Others)

  • Cryptogenic (AIP, AEP, OP)

  • Exposures (EVALI, HP, etc)

  • Medications (BILI, APT, etc)

  • Fat embolism

  • Malignancy (Carcinomatosis, Pulmonary lymphoma, acute leukemia)

• Because treatment of ARDS mimics often differs from “classic ARDS” it is essential to make the diagnosis promptly.

  • A Large International Observational Study (JAMA 2016) found that mischaracterization of ARDS was associated with increased mortality .

  • Examples of differing treatment:

    • higher dose/duration of steroids (AEP)

    • avoidance of steroids altogether (strongyloides)

    • addition of additional antimicrobials (PJP)

    • Different transfusion thresholds (DAH)

    • addition of other immune modifying therapies (pulmonary renal syndromes)

    • avoidance of exposures (birds → HP, vaping → EVALI, etc)

  • Identifying ARDS mimics requires a high index of suspicion, a careful review of risk factors/exposures, and additional investigations like bronchoscopy.

• In this episode of critical care time, we provide an overview of some of the most common ARDS mimics, and demonstrate an approach using illustrative cases & expert guests!

🚩 Spotting an ARDS Mimic

• Red flags that might suggest an ARDS Mimic

  • Cause: No clear explanation for ARDS

  • Timing: More gradual onset - weeks not days.

    • Similar episodes in the past

  • Other systemic symptoms (Hemoptysis, Rheumatic symptoms, Glomerulonephritis, Weight loss

  • Underlying medical risk factors or exposures (AIDS, smoking/vaping, occupational exposures, owning a bird, etc)

  • Consider using the CHEST ILD questionnaire as a screening tool to identify additional exposures/risk factors.

• Unique Radiographic features may be clues about the diagnosis:

  • Many ARDS mimics look like ARDS radiographically. However some exceptions include:

    • upper vs lower lobe predominant disease (infection, HP, others)

    • honeycombing (pulmonary fibrosis)

    • cavitary nodules (granulomatosis with polyangiitis; GPA)

    • DAH pattern (peripheral sparing)

    • Crazy paving (pulmonary alveolar proteinosis)

• Laboratory tests can provide diagnostic clues

  • Serological tests (ANA + panel, ANCA, anti-GBM) → r/o connective tissue disease

  • Galactomannan → detect fungal infection

• Bronchoscopy is often the key to diagnosis:

  • Cultures and PCR are very useful for infectious causes (PJP, Strongyloides, Aspergillus, viral infection, etc).

  • Cell count is crucial:

    • Eosinophils —> consider AEP

    • Lymphocytes —> viral, inflammatory

  • Increasingly blood returns —> DAH

    • Always do more than one lavage if the first is bloody!

  • Specific findings:

    • Milky PAS positive fluid → PAP

    • Lipid laden macrophages in EVALI, other findings (Oil Red O stain)

    • Sarcoidosis findings (CD4/CD8 ratio of lymphocytes)

    • Macrophages containing smoking-related inclusions with no or minor increases in other cell types °˙ —> smoking-related ILDs (DIP, RBILD, or PLCH)

    • Malignant cells (cytology, flow cytometry, etc) —> lung cancer, metastasis, lymphoma, etc

🫁 Overview of Common ARDS Mimics

Etiology	Exposures/Risk Factors	Clinical Findings	Imaging Findings	Bronchoscopy Findings	Treatment
Cardiogenic Pulmonary Edema	Heart failure, myocardial infarction, valvular disease, fluid overload.	Dyspnea, orthopnea, pulmonary crackles, S3 gallop, lower extremity edema.	Cardiomegaly, Kerley B lines, pleural effusions, vascular congestion.	Frothy edema fluid, no signs of infection or hemorrhage.	Diuretics, oxygen, afterload reduction (ACE inhibitors, beta-blockers).
Diffuse Alveolar Hemorrhage (DAH)	Autoimmune diseases (ANCA vasculitis, Goodpasture's), anticoagulation, DIC.	Hemoptysis (not always present), anemia, hypoxemia, fever.	Diffuse ground-glass opacities, upper lobe sparing, perihilar involvement.	Increasingly bloody lavage aliquots, hemosiderin-laden macrophages.	High-dose corticosteroids, plasmapheresis if autoimmune, treat underlying cause.
Acute Interstitial Pneumonia (AIP)	No clear risk factor, but may follow viral infections or unknown triggers.	Rapid onset of dyspnea, ARDS-like presentation, diffuse lung involvement.	Diffuse ground-glass opacities, septal thickening, traction bronchiectasis.	Non-specific alveolar damage, inflammatory infiltrates.	Supportive care, mechanical ventilation, no proven effective therapy.
Pneumocystis jirovecii Pneumonia (PJP)	HIV/AIDS, immunosuppression (steroids, chemotherapy, transplant).	Progressive dyspnea, dry cough, severe hypoxemia, minimal fever.	Bilateral ground-glass opacities, interstitial thickening, cystic changes.	Foamy macrophages, Pneumocystis cysts on silver stain.	Trimethoprim-sulfamethoxazole (TMP-SMX), steroids
Acute Eosinophilic Pneumonia (AEP)	New smoking habit, drug exposure (NSAIDs, antibiotics, inhaled toxins).	Acute onset of dyspnea, fever, hypoxia, nonproductive cough.	Bilateral ground-glass opacities, interlobular septal thickening.	Eosinophilia > 25% in BAL, no infection.	Corticosteroids, supportive oxygen, avoid triggers.
COVID-19 Pneumonia	Close contact with infected individuals, immunosuppression, recent travel.	Fever, cough, dyspnea, anosmia, myalgias, thrombosis risk.	Peripheral ground-glass opacities, consolidations, crazy paving pattern.	Lymphocytic alveolitis, viral PCR positive.	Supportive care, antivirals (remdesivir), anticoagulation in severe cases.
Organizing Pneumonia	Post-infectious, drug-related, or idiopathic lung injury.	Subacute dyspnea, cough, mild fever, nonresolving pneumonia.	Peripheral and peribronchial consolidations, ground-glass opacities.	Mixed inflammatory infiltrates, no neutrophilia.	Corticosteroids, prolonged taper over weeks to months.
Pulmonary Veno-Occlusive Disease (PVOD)	Familial or idiopathic causes, bone marrow transplant, chemotherapy.	Progressive dyspnea, signs of right heart failure, profound hypoxemia.	Septal thickening, pleural effusions, enlarged pulmonary arteries.	Pulmonary capillary congestion, hemosiderin-laden macrophages.	Supportive care, diuretics, lung transplantation in severe cases.
Fat Embolism Syndrome	Long-bone fractures, orthopedic surgery, liposuction, pancreatitis.	Petechiae, altered mental status, dyspnea, tachycardia.	Patchy ground-glass opacities, small nodules, normal CXR possible.	Fat-laden macrophages, no infection.	Supportive care, oxygen, possible corticosteroids.
Acute Hypersensitivity Pneumonitis	Exposure to organic dusts (mold, birds, hay), occupational exposures.	Recurrent episodes of fever, dyspnea, myalgias, weight loss.	Centrilobular nodules, ground-glass opacities, mosaic attenuation.	Lymphocytic alveolitis, no eosinophilia or neutrophilia.	Antigen avoidance, corticosteroids, possible immunosuppressants.
EVALI	Vaping (especially THC-containing products, vitamin E acetate)	Subacute cough, dyspnea, chest pain, fever, GI symptoms (nausea, vomiting, diarrhea), hypoxia	Bilateral ground-glass opacities, often with subpleural sparing and areas of consolidation	Lipid-laden macrophages on oil red O stain, sterile cultures	Supportive care, corticosteroids, discontinue vaping
Amiodarone Pulmonary Toxicity (APT)	Amiodarone High cumulative dose of amiodarone (>400 mg/day), age >60, preexisting lung disease, oxygen therapy	Chronic nonproductive cough, dyspnea, weight loss, rare fever	High-attenuation (hyperdense) ground-glass opacities or consolidations, interstitial fibrosis, peripheral and basal predominance	Foamy alveolar macrophages, interstitial inflammation, negative cultures	Discontinue amiodarone, corticosteroids (variable benefit), supportive care

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