Abstract
IntroductionDespite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.MethodsThis was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.ResultsUsing the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.ConclusionsAbnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
Highlights
Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment
Several plasma biomarkers have been studied in patients with ARDS, but no studies have tested the possible value of a panel of plasma biomarkers in patients with severe sepsis who have developed ARDS by clinical criteria and determined if a combination of abnormal biomarkers could be used for confirming the diagnosis of ARDS on biologic grounds
From among the 11 biomarkers tested in this exploratory study, a panel that included the five topperforming biomarkers (SP-D, Receptor for advanced glycation endproducts (RAGE), Interleukin 8 (IL-8), CC-16 and Interleukin 6 (IL-6)) had an area under the curve (AUC) of 0.75 for the diagnosis of ARDS
Summary
The clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis. Several recent studies in ARDS have shown the superiority of a multiple biomarker approach for diagnosis in patients with trauma [6] and for prognosis in established ARDS due to a variety of causes [7,8]. Several plasma biomarkers have been studied in patients with ARDS, but no studies have tested the possible value of a panel of plasma biomarkers in patients with severe sepsis who have developed ARDS by clinical criteria and determined if a combination of abnormal biomarkers could be used for confirming the diagnosis of ARDS on biologic grounds
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
