Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.
Weir, Christopher J
Felton, Jennifer M
Brown, Alun K
Lewis, Sion M
Roy, Alistair I
Rossi, Adriano G
Walsh, Timothy S
Intensive care medicine
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Shankar-Hari, M., Datta, D., Wilson, J., Assi, V., Stephen, J., Weir, C. J., Rennie, J., et al. (2018). Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.. Intensive care medicine, 44 (11), 1836-1848. https://doi.org/10.1007/s00134-018-5389-0
Purpose: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥2 at 24 hours and/or 72 hours following ED presentation). Methods: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement, and compared patients with suspected acute infection (cohort-1), with two comparator cohorts: ICU patients with established sepsis (cohort-2); and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3). Results: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3 respectively. Of 47 T-leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15;CD24;CD35;CD64;CD312;CD11b;CD274; CD279), seven monocyte (CD35;CD64;CD312;CD11b;HLA-DR;CD274;CD279) and a CD8 -lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 (OR 1.78 (95%CI:1.23-2.57);P=0.002), higher monocyte CD279 (1.32 (1.03-1.70);P=0.03), and lower monocyte HLA-DR (0.73 (0.55-0.97);P=0.03) expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity. Conclusions: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.
Leukocytes, Humans, Sepsis, Antigens, CD, HLA-DR Antigens, Logistic Models, Cohort Studies, Reproducibility of Results, Predictive Value of Tests, Adult, Aged, Aged, 80 and over, Middle Aged, Emergency Service, Hospital, Intensive Care Units, Female, Male, Biomarkers
The study was funded by Innovate UK (Sepsis 2: 101193). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16-011). Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z).
Wellcome Trust (205214/Z/16/Z)
External DOI: https://doi.org/10.1007/s00134-018-5389-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285578