Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract

Clin Vaccine Immunol. 2017 Jul 5;24(7):e00064-17. doi: 10.1128/CVI.00064-17. Print 2017 Jul.


The distinction between bacterial and viral causes of infections of the respiratory tract is a major but important clinical challenge. We investigated the diagnostic performance of human neutrophil lipocalin (HNL) in respiratory tract infections compared to those of C-reactive protein (CRP) and procalcitonin (PCT). Patients were recruited from the emergency department and from a primary care unit (n = 162). The clinical diagnosis with regard to bacterial or viral cause of infection was complemented with objective microbiological/serological testing. HNL was measured in whole blood after preactivation with the neutrophil activator formyl-methionine-leucine-phenylalanine (fMLP) (B-HNL), and CRP and PCT were measured in plasma. Head-to-head comparisons of the three biomarkers showed that B-HNL was a superior diagnostic means to distinguish between causes of infections, with areas under the concentration-time curve (AUCs) of receiver operating characteristic (ROC) analysis for HNL of 0.91 (95% confidence interval [CI], 0.83 to 0.96) and 0.92 (95% CI, 0.82 to 0.97) for all respiratory infections and for upper respiratory infections, respectively, compared to 0.72 (95% CI, 0.63 to 0.80) and 0.68 (95% CI, 0.56 to 0.79) for CRP, respectively (P = 0.001). In relation to major clinical symptoms of respiratory tract infections (cough, sore throat, stuffy nose, and signs of sinusitis), AUCs varied between 0.88 and 0.93 in those patients with likely etiology (i.e., etiology is likely determined) of infection, compared to 0.63 and 0.71 for CRP, respectively, and nonsignificant AUCs for PCT. The diagnostic performance of B-HNL is superior to that of plasma CRP (P-CRP) and plasma PCT (P-PCT) in respiratory tract infections, and the activity specifically reflects bacterial challenge in the body. The rapid and accurate analysis of HNL by point-of-care technologies should be a major advancement in the diagnosis and management of respiratory infections with respect to antibiotic treatment.

Keywords: antibiotic resistance; biomarker; lipocalin; point of care; respiratory infection.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Infections / diagnosis*
  • Bacterial Infections / pathology
  • Biomarkers / blood*
  • C-Reactive Protein / analysis
  • Calcitonin / blood
  • Female
  • Humans
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Neutrophils / immunology*
  • ROC Curve
  • Respiratory Tract Infections / diagnosis*
  • Respiratory Tract Infections / pathology
  • Sensitivity and Specificity
  • Young Adult


  • Biomarkers
  • Lipocalins
  • Calcitonin
  • C-Reactive Protein