Definition, causes and differential diagnosis of ARDS

Many past paper questions ask about the causes and differential diagnosis of " a diffuse bilateral infiltrate on CXR." There are many scenarios available.  It is important to be able to generate a lot of differentials in this sort of question.

  • Question 14 from the first paper of 2021(again, non specific "diffuse bilateral infiltrate")
  • Question 4 from the second paper of 2015 puts the infiltrate into an APML patient receiving ATRA (what you might call "differentiation syndrome")
  • Question 20 from the first  paper of 2014 talks about some non specific "diffuse bilateral infiltrate."
  • Question 17 from the second paper of 2011 puts the infiltrates into a patient recovering from a bone marrow transplant. 
  • Question 10 from the second paper of 2010 puts this radiological finding in the context of a recent cardiac arrest.

Definitions of ARDS

The most recent definition (Matthay et al, 2023) presents a comprehensive model. The contents of their Table 1 is presented below with minimal structural modification:


  • ARDS is an acute diffuse, inflammatory lung injury precipitated by a predisposing risk factor such as pneumonia, non-pulmonary infection, trauma, transfusion, burn, aspiration, or shock.
  • The resulting injury leads to increased pulmonary vascular and epithelial permeability, lung edema, and gravitydependent atelectasis, all of which contribute to loss of aerated lung tissue.
  • The clinical hallmarks are arterial hypoxemia and diffuse radiographic opacities associated with increased shunting, increased alveolar dead space, and decreased lung compliance.
  • The clinical presentation is influenced by medical management (position, sedation, paralysis, and fluid balance).
  • Histological findings vary and may include intra-alveolar edema, inflammation, hyaline membrane formation, and alveolar hemorrhage.


  • A predisposing risk factor:
    • Eg. pneumonia, non-pulmonary infection, trauma, transfusion, aspiration, or shock
    • Pulmonary edema is not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload
    • Hypoxemia/gas exchange abnormalities are not primarily attributable to atelectasis
    • However, ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS is also present.
  • Acute onset: within 1 week of exposure to the risk factor
  • Radiological criteria:
    • Bilateral opacities on chest radiograph and computed tomography, OR:
    • Bilateral B lines and/or consolidations by ultrasound
    • Not fully explained by effusions, atelectasis, or nodules/masses.
  • Oxygenation criteria:
    • If in a resource-limited setting: 
      • SpO2/FiO2 less than 315 (if SpO2 at least lower than 97%)
    • If not intubated: 
      • PaO2/FiO2 less than 300 mmHg, OR
      • SpO2/FiO2 less than 315 (if SpO2 at least lower than 97%)
      • on HFNO with a flow of at least 30 liters per minute, OR
      • on NIV/CPAP with at least 5 cm H2O expiratory pressure
    • If intubated: 
      • PaO2/FiO2 ratio less than 300 on a minium PEEP of 5
        ARDS Severity   PaO2/FiO2  SpO2/FiO2  Mortality 
        Mild 200 – 300 235 – 315 27%
        Moderate 100 – 200 148 – 235 32%
        Severe < 100 < 148 45%

This is a revision of the 2012 Berlin definition, where the specific changes were:

  • Adding the idea that the onset may be more indolent (into the acute onset criteria)
  • Adding ultrasound into the radiological criteria (because not everywhere has Xray facilities available)
  • Adding pulse oximetry criteria (because these are well validated)
  • Adding a whole set of categories for different resource settings and incorporating patients who are not intubated

The Berlin definition in turn improved on even older criteria. The changes made in 2012 were:

  • There is no longer such a thing as "acute lung injury" when you have a PaO2/FiO2 ratio of 200-300.
    We call it "mild ARDS" instead.
  • Onset must be acute: within 7 days of whatever pathology is thought to be the cause
  • There is no need to exclude heart failure - you can have as much heart failure as you like, so long as its severity is insufficient to by itself explain the bilateral pulmonary infiltrates.

Differential diagnosis of pulmonary infiltrate in ICU patients

An excellent article from Silvia Blanco and Antoni Torres ( actually contains a brilliant table of differentials, which is incorporated into the table below.

Differential Diagnosis for Diffuse Bilateral Pulmonary Infiltrates


  • Pulmonary haemorrhage
  • Cardiogenic pulonary oedema


  • Bacterial
  • Viral
  • Fungal
  • PJP


  • Lymphangitis
  • Infiltrative neoplasm


  • ARDS
  • Idiopathic pneumonia syndrome


  • Eosinophilic pneumonitis
  • COP
  • Alveolar haemorrhage
  • Methotrexate-induced


  • Goodpastures (haemorrhagic)
  • Rheumatoid pneumonitis
  • Graft vs host disease in BMT
  • Engraftment syndrome
  • ATRA syndrome


  • Bilateral atelectasis
  • Pulmonary contusions
  • Chemical pneumonitis

Idiopathic pneumonia syndrome and ATRA syndrome(nowadays referred to as "differentiation syndrome") have been added since Question 4 from the second paper of 2015 introduced them into the list of differentials.


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