Plasma calprotectin in the emergency department: a potential clinical biomarker for patients with infectious diseases

Torgny Wessman,Johan Ärnlöv,Mari Rosenqvist,Olle Melander,Anders Larsson,Martin Wollmer,Toralph Ruge,Per Wändell

doi:10.1080/00365513.2021.1980223

Abstract

Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.

Highlights

Calprotectin, a heterodimer of S100A8 and S100A9, constitutes approximately 45% of the cytosolic protein in neutrophils [1]
In recent years, elevated levels of circulating calprotectin have been reported in patients with infectious diseases and/or sepsis [9,10], raising the question if calprotectin could prove a useful biomarker for these conditions
Patients 18 years of age and older who presented to the emergency department (ED) during daytime on weekdays, 8:00 am to 5:00 pm, with acute dyspnea as their main complaint between 6 March 2013 and 1 July 2018 were approached by a research nurse and were offered to take part in the study

Summary

Introduction

Calprotectin, a heterodimer of S100A8 and S100A9, constitutes approximately 45% of the cytosolic protein in neutrophils [1]. Calprotectin is released upon neutrophil activation [2], and plays an important but not fully understood role in the inflammatory responses. Fecal calprotectin is a valuable biomarker for inflammatory bowel disease [3,4,5], and previous studies have shown increased levels of calprotectin in several other inflammatory diseases [6,7,8]. In recent years, elevated levels of circulating calprotectin have been reported in patients with infectious diseases and/or sepsis [9,10], raising the question if calprotectin could prove a useful biomarker for these conditions. White blood cell and neutrophil counts are widely used as infectious markers. A neutrophil activation marker should in theory be superior to the neutrophil counts for this reason

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