For the gender study cohort, Ang-2 and RAGE levels that had been previously measured using kits from the same manufacturers11 were used.
To compare the performance of the biomarker panel for diagnosis of ARDS to clinician recognition of ARDS, the electronic medical record of each patient in the derivation cohort was systematically searched for documentation of a diagnosis of ARDS during the hospitalization by a clinical provider by scanning for key words including ‘acute lung injury’, ‘acute respiratory distress syndrome’, ‘ALI’ and ‘ARDS’.
ARDS was defined on the basis of Berlin criteria and ascertained by a two-physician review of all patient data for the first 7 days of hospitalization.
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See: Acute respiratory distress syndrome (ARDS) is common in patients with severe traumatic injuries.1 Although effective therapies for ARDS are limited,2 timely recognition of ARDS and treatment with a lung protective mechanical ventilation strategy improves mortality.3 4 In subgroups of patients with more severe ARDS or those with absence or resolution of shock, therapies such as prone positioning5 or conservative fluid therapy6 may also be beneficial.
All biomarkers were measured in duplicate in plasma that was collected at enrollment on the morning of ICU day 2, using commercially available enzyme immunoassay kits or radioimmunoassay: plasminogen activator inhibitor-1, American Diagnostica (Stamford, CT); von Willebrand factor antigen (VWF), Diagnostica Stago (Parsippany, NJ); procollagen peptide-III, Cis Bioscience International (Bedford, MA); club cell-16 protein (CC16), Bio Vendor (Chandler, NC); B-type natriuretic peptide, Bachem Bioscience (King of Prussia, PA); surfactant protein-D (SP-D), Yamasa Corporation (Tokyo, Japan); and angiopoietin-2 (Ang-2), interleukin-8 (IL-8), soluble receptor for advanced glycation endproducts (RAGE), R&D Systems (Minneapolis, MN).
For the ACIT validation cohort, Ang-2 and RAGE were measured in plasma that was collected 24 hours after presentation to the emergency department using the assay kits from the same manufacturers.