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Inflammation Research

, Volume 66, Issue 10, pp 863–870 | Cite as

Delta neutrophil index (DNI) as a novel diagnostic and prognostic marker of infection: a systematic review and meta-analysis

  • Jae Hyon Park
  • Hyeong Ju Byeon
  • Keum Hwa Lee
  • Jong Wook Lee
  • Andreas Kronbichler
  • Michael Eisenhut
  • Jae Il ShinEmail author
Original Research Paper

Abstract

Objective

Delta neutrophil index (DNI) representing the number of immature granulocytes is an emerging marker used in diagnosis of infections and prediction of mortality in infected patients. The present study evaluated the diagnostic accuracy of DNI as a predictive and prognostic factor in infected patients.

Methods

We performed a PubMed search on January 1st, 2017 and identified studies that evaluated DNI as either a predictive or prognostic factor in infected patients. Studies with appropriate information to construct 2 × 2 contingency tables were extracted. We calculated pooled sensitivity and specificity. Meta-analysis of the multivariate logistic regression data set was performed to assess whether DNI functions as an independent factor.

Results

Overall, 12 articles fulfilled the inclusion criteria and a total of 499 cases and 9549 controls were examined. As a predictive factor of infection, DNI’s pooled sensitivity was 0.67 (95% CI 0.62–0.71, I 2 = 86.0%) and pooled specificity was 0.94 (95% CI 0.94–0.95, I 2 = 92.8%). Area under the receiver operating characteristics (ROC) curve was 0.89. As a prognostic factor for death in infected patients, DNI’s pooled sensitivity was 0.70 (95% CI 0.56–0.81, I 2 = 0.0%) and pooled specificity was 0.78 (95% CI 0.73–0.83, I 2 = 26.6%). Area under the ROC curve was 0.84. Meta-analysis of the multivariate logistic regression data set showed insignificant results.

Conclusions

DNI is a potentially useful diagnostic tool and predicts mortality among infected patients and should be more widely used in the clinical practice.

Keywords

Delta neutrophil index DNI Infection Diagnosis Prognosis 

Notes

Author contributors

JHP and HJB had the idea for and designed the study, searched the scientific literature, collected, statistically analyzed and interpreted data, and wrote and critically revised the report. KHL drafted and critically revised the report. JWL analyzed, interpreted data, drafted, and critically revised the report. AK and ME critically analyzed the report and revised it comprehensively. JIS had the idea for and designed the study, analyzed and interpreted the data, drafted and critically revised the report, supervised the study, and gave administrative, technical, and material support.

Compliance with ethical standards

Funding

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 30 kb)
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Supplementary material 3 (DOCX 80 kb)
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Supplementary material 4 (DOCX 840 kb)

References

  1. 1.
    Bone RC, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55.CrossRefPubMedGoogle Scholar
  2. 2.
    Martin GS, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–54.CrossRefPubMedGoogle Scholar
  3. 3.
    Investigators P. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRefGoogle Scholar
  4. 4.
    Pittet D, Rangel-Frausto S, Li N. Systemic inflamatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients. Intensive Care Med. 1995;21:302–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426–35.CrossRefPubMedGoogle Scholar
  6. 6.
    Alves-Filho JC, Spiller F, Cunha FQ. Neutrophil paralysis in sepsis. Shock. 2010;34:15–21.CrossRefPubMedGoogle Scholar
  7. 7.
    Cornbleet PJ. Clinical utility of the band count. Clin Lab Med. 2002;22:101–36.CrossRefPubMedGoogle Scholar
  8. 8.
    Ansari-Lari MA, Kickler TS, Borowitz MJ. Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis. Am J Clin Pathol. 2003;120(5):795–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Kratz A, Maloum K, O’Malley C, Zini G, Rocco V, Zelmanovic D, et al. Enumeration of nucleated red blood cells with the ADVIA 2120 Hematology System: an International Multicenter Clinical Trial. Lab Hematol. 2006;12(2):63–70.CrossRefPubMedGoogle Scholar
  10. 10.
    Fang DZ, Sran G, Gessner D, Loflus PD, Folkins A, Christopher JY 3rd, et al. Cost and turn-around time display decreases inpatient ordering of reference laboratory tests: a time series. BMJ Qual Saf. 2014;23(12):994–1000.CrossRefPubMedGoogle Scholar
  11. 11.
    Yoon NB, Son C, Um SJ. Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia. Ann Lab Med. 2013;33(2):105–10.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wyllie DH, Bowler IC, Peto TE. Relation between lymphopenia and bacteraemia in UK adults with medical emergencies. J Clin Pathol. 2004;57(9):950–5.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bermejo-Martin JF, Tamayo E, Ruiz G, Andaluz-Ojeda D, Herran-Monge R, Muriel-Bombin A, et al. Circulating neutrophil counts and mortality in septic shock. Crit Care. 2014;18(1):407.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chu H, Cole SR. Bivariate meta-analysis of sensitivity and specificity with sparse data: a generalized linear mixed model approach. J Clin Epidemiol. 2006;59:1331–2.CrossRefPubMedGoogle Scholar
  16. 16.
    Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58(10):982–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12(14):1293–316.CrossRefPubMedGoogle Scholar
  18. 18.
    Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58(9):882–93.CrossRefPubMedGoogle Scholar
  19. 19.
    Ahn JG, Choi SY, Kim DS, Kim KH. Limitation of the delta neutrophil index for assessing bacteraemia in immunocompromised children. Clin Chim Acta. 2014;436:319–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Park HJ, Ha YJ, Pyo JY, Park YB, Lee SK, Lee SW. Delta neutrophil index as an early marker for differential diagnosis of adult-onset still’s disease and sepsis. Yonsei Med J. 2014;55(3):753–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pyo JY, Park JS, Park YB, Lee SK, Ha YJ, Lee SW. Delta neutrophil index as a marker for differential diagnosis between flare and infection in febrile systemic lupus erythematosus patients. Lupus. 2013;22(11):1102–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim HW, Yoon JH, Jin SJ, Kim SB, Ku NS, Jeong SJ, et al. Delta neutrophil index as a prognostic marker of early mortality in gram negative bacteremia. Infect Chemother. 2014;46(2):94–102.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kim HW, Ku S, Jeong SJ, Jin SJ, Han SH, Choi JY, et al. Delta neutrophil index: could it predict mortality in patients with bacteraemia? Scand J Infect Dis. 2012;44(7):475–80.CrossRefPubMedGoogle Scholar
  24. 24.
    Hwang YJ, Chung SP, Park YS, Chung HS, Lee HS, Park JW, et al. Newly designed delta neutrophil index-to-serum albumin ratio prognosis of early mortality in severe sepsis. Am J Emerg Med. 2015;33(11):1577–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Lim TS, Kim BK, Lee JW, Lee YK, Chang S, Kim SU, et al. Use of the delta neutrophil index as a prognostic factor of mortality in patients with spontaneous bacterial peritonitis: implications of a simple and useful marker. PLoS One. 2014;9(1):e86884.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Seok Y, Choi JR, Kim J, Kim YK, Lee J, Song J, et al. Delta neutrophil index: a promising diagnostic and prognostic marker for sepsis. Shock. 2012;37(3):242–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Borenstein LHM, Rothstein H. Comprehensive meta-analysis. 2nd ed. Englewood: Biostat; 2005.Google Scholar
  28. 28.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMedGoogle Scholar
  29. 29.
    Cucherat M, Boissel JP, Leizorovicz A, Haugh MC. EasyMA: a program for the meta-analysis of clinical trials. Comput Methods Programs Biomed. 1997;53(3):187–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Park BH, Kang YA, Park MS, Jung WJ, Lee SH, Lee SK, et al. Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. BMC Infect Dis. 2011;11:299.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lee SM, Eun HS, Namgung R, Park MS, Park KI, Lee C. Usefulness of the delta neutrophil index for assessing neonatal sepsis. Acta Paediatr. 2013;102(1):e13–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Póvoa P. C-reactive protein: a valuable marker of sepsis. Intensive Care Med. 2002;28(3):235–43.CrossRefPubMedGoogle Scholar
  33. 33.
    Hoffmann JJ. Neutrophil CD64: a diagnostic marker for infection and sepsis. Clin Chem Lab Med. 2009;47(8):903–16.CrossRefPubMedGoogle Scholar
  34. 34.
    Ardron MJ, Westengard JC, Dutcher TF. Band neutrophil counts are unnecessary for the diagnosis of infection in patients with normal total leukocyte counts. Am J Clin Pathol. 1994;102(5):646–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Briggs C, Kunka S, Fujimoto H, Hamaguchi Y, Davis BH, Machin SJ. Evaluation of immature granulocyte counts by the XE-IG master: upgraded softward for the XE-2100 automated hematology analyzer. Lab Hematol. 2003;9:117–24.PubMedGoogle Scholar
  36. 36.
    Liu D, Su L, Han G, Yan P, Xie L. Prognostic value of procalcitonin in adult patients with sepsis: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0129450.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39(2):206–17.CrossRefPubMedGoogle Scholar
  38. 38.
    Papoff P. Use of hematologic data to evaluate infections in neonates. Hematologic Problems of the Neonate. Philadelphia: WB Saunders company; 2000. p. 389–403.Google Scholar
  39. 39.
    Greiner M, Pfeiffer D, Smith RD. Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med. 2000;45(1–2):23–41.CrossRefPubMedGoogle Scholar
  40. 40.
    Jaeschke R, Guyatt GH, Sackett DL. Users’ guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA. 1994;271(9):703–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Yonsei University College of MedicineSeoulKorea
  2. 2.Institute of Kidney Disease Research, Department of Pediatrics, Severance Children’s HospitalYonsei University College of MedicineSeoulKorea
  3. 3.Jincheon Sungmo HospitalJincheonKorea
  4. 4.Research Institute of Bacterial ResistanceYonsei University College of MedicineSeoulKorea
  5. 5.Department of Internal Medicine IV (Nephrology and Hypertension)Medical University InnsbruckInnsbruckAustria
  6. 6.Department of PediatricsLuton & Dunstable University Hospital NHS Foundation TrustLutonUK

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