In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 320, No. 5 ( 2021-05-01), p. L892-L902
Abstract:
Sepsis is a heterogeneous syndrome clinically and biologically, but biomarkers of distinct host response pathways for early prognostic information and testing targeted treatments are lacking. Olfactomedin 4 ( OLFM4), a matrix glycoprotein of neutrophil-specific granules, defines a distinct neutrophil subset that may be an independent risk factor for poor outcomes in sepsis. We hypothesized that increased percentage of OLFM4 + neutrophils on sepsis presentation would be associated with mortality. In a single-center, prospective cohort study, we enrolled adults admitted to an academic medical center from the emergency department (ED) with suspected sepsis [identified by 2 or greater systemic inflammatory response syndrome (SIRS) criteria and antibiotic receipt] from March 2016 through December 2017, followed by sepsis adjudication according to Sepsis-3. We collected 200 µL of whole blood within 24 h of admission and stained for the neutrophil surface marker CD66b followed by intracellular staining for OLFM4 quantitated by flow cytometry. The predictors for 60-day mortality were 1) percentage of OLFM4 + neutrophils and 2) OLFM4 + neutrophils at a cut point of ≥37.6% determined by the Youden Index. Of 120 enrolled patients with suspected sepsis, 97 had sepsis and 23 had nonsepsis SIRS. The mean percentage of OLFM4 + neutrophils was significantly increased in both sepsis and nonsepsis SIRS patients who died ( P ≤ 0.01). Among sepsis patients with elevated OLFM4 + (≥37.6%), 56% died, compared with 18% with OLFM4 + 〈 37.6% ( P = 0.001). The association between OLFM4 + and mortality withstood adjustment for age, sex, absolute neutrophil count, comorbidities, and standard measures of severity of illness (SOFA score, APACHE III) ( P 〈 0.03). In summary, OLFM4 + neutrophil percentage is independently associated with 60-day mortality in sepsis and may represent a novel measure of the heterogeneity of host response to sepsis.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00090.2020
Language:
English
Publisher:
American Physiological Society
Publication Date:
2021
detail.hit.zdb_id:
1477300-4
SSG:
12
Bookmarklink