Neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio in relation to response to adjunctive dexamethasone treatment in community-acquired pneumonia

  • Esther Wittermans
    Correspondence
    Corresponding author at: Department of Internal Medicine, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands.
    Affiliations
    Department of Internal Medicine, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands

    Department of Internal Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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  • Ewoudt MW van de Garde
    Affiliations
    Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands

    Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht , the Netherlands
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  • G Paul Voorn
    Affiliations
    Department of Medical Microbiology and Immunology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein , the Netherlands
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  • Arnoud F Aldenkamp
    Affiliations
    Department of Pulmonology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands
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  • Rob Janssen
    Affiliations
    Department of Pulmonology, Canisius Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ Nijmegen, the Netherlands
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  • Jan C Grutters
    Affiliations
    Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands

    Division of Heart and Lungs, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht , the Netherlands
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  • Willem Jan W Bos
    Affiliations
    Department of Internal Medicine, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands

    Department of Internal Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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  • Santeon-CAP study group
    Author Footnotes
    1 The Santeon-CAP study group (Collaborators) are: Willem Jan W Bos (St. Antonius Hospital, Nieuwegein, the Netherlands), Ewoudt MW van de Garde (St. Antonius Hospital, Nieuwegein, the Netherlands and University of Utrecht, Utrecht, the Netherlands), Jan C Grutters (St. Antonius Hospital Nieuwegein, the Netherlands and University Medical centre Utrecht, Utrecht, the Netherlands), Ger T Rijkers (Roosevelt Academy, Middelburg, the Netherlands), Douwe H Biesma (St. Antonius Hospital, Nieuwegein, the Netherlands), G Paul Voorn (St. Antonius Hospital, Nieuwegein, the Netherlands) Simone MC Spoorenberg (University Medical centre Utrecht, Utrecht, the Netherlands), Stefan MT Vestjens (St. Antonius Hospital, Nieuwegein, the Netherlands), Esther Wittermans (St. Antonius Hospital, Nieuwegein, the Netherlands), Frank WJM Smeenk (Catharina Hospital, Eindhoven, the Netherlands) Arnoud F Aldenkamp (Catharina Hospital, Eindhoven, the Netherlands), Rob Janssen (Canisius Wilhelmina Hospital, Nijmegen, the Netherlands) Charlotte A van Ruitenbeek (Canisius Wilhelmina Hospital, Nijmegen, the Netherlands), Willem L Blok (OLVG, Amsterdam, the Netherlands) Paul Bresser (OLVG, Amsterdam, the Netherlands), Joris WT van Enschot (Maxima Medical Centre, Veldhoven, the Netherlands) Hester AA Zegers (Hospital Bernhoven, Uden, the Netherlands).
  • Author Footnotes
    1 The Santeon-CAP study group (Collaborators) are: Willem Jan W Bos (St. Antonius Hospital, Nieuwegein, the Netherlands), Ewoudt MW van de Garde (St. Antonius Hospital, Nieuwegein, the Netherlands and University of Utrecht, Utrecht, the Netherlands), Jan C Grutters (St. Antonius Hospital Nieuwegein, the Netherlands and University Medical centre Utrecht, Utrecht, the Netherlands), Ger T Rijkers (Roosevelt Academy, Middelburg, the Netherlands), Douwe H Biesma (St. Antonius Hospital, Nieuwegein, the Netherlands), G Paul Voorn (St. Antonius Hospital, Nieuwegein, the Netherlands) Simone MC Spoorenberg (University Medical centre Utrecht, Utrecht, the Netherlands), Stefan MT Vestjens (St. Antonius Hospital, Nieuwegein, the Netherlands), Esther Wittermans (St. Antonius Hospital, Nieuwegein, the Netherlands), Frank WJM Smeenk (Catharina Hospital, Eindhoven, the Netherlands) Arnoud F Aldenkamp (Catharina Hospital, Eindhoven, the Netherlands), Rob Janssen (Canisius Wilhelmina Hospital, Nijmegen, the Netherlands) Charlotte A van Ruitenbeek (Canisius Wilhelmina Hospital, Nijmegen, the Netherlands), Willem L Blok (OLVG, Amsterdam, the Netherlands) Paul Bresser (OLVG, Amsterdam, the Netherlands), Joris WT van Enschot (Maxima Medical Centre, Veldhoven, the Netherlands) Hester AA Zegers (Hospital Bernhoven, Uden, the Netherlands).
Published:November 12, 2021DOI:https://doi.org/10.1016/j.ejim.2021.10.030

      Highlights

      • Post-Hoc analysis of an RCT investigating adjunctive dexamethasone treatment in CAP.
      • We tested if WBC differential parameters modified response to dexamethasone.
      • WBC and neutrophil count and NLR modified the effect of dexamethasone on length of stay.
      • In subgroups with high values dexamethasone reduced length of stay by two days.
      • There was no reduction in length of stay in subgroups with low values.

      Abstract

      Background

      It is hypothesised that community-acquired pneumonia (CAP) patients with more severe disease or inflammation might benefit more from adjunctive corticosteroid treatment. Neutrophil count, lymphocyte count and neutrophil-lymphocyte ratio (NLR) have been associated with inflammation and disease severity in CAP. We investigated the interaction between these parameters and adjunctive dexamethasone effects on clinical outcomes in CAP.

      Methods

      We conducted a post hoc analysis of the randomised placebo-controlled Santeon-CAP trial (n = 401), which showed a positive effect of adjunctive oral dexamethasone on length of stay (LOS) in CAP patients. White blood cell (WBC) count, neutrophil count, NLR (highest tertile vs. lowest two tertiles) and lymphocyte count (lowest tertile vs. highest two tertiles) were examined as potential effect modifiers of treatment with dexamethasone on LOS (primary outcome) and ICU-admission, 30-day mortality and hospital readmission.

      Results

      WBC differential counts were available for 354 patients. The effect of dexamethasone on LOS was more pronounced in high WBC count, high neutrophil count or high NLR subgroups (difference in median LOS of 2 days versus zero days in the reference subgroups, p for interaction < 0.05). There was no effect modification for the other outcomes. Patients with low WBC and low neutrophil counts did not benefit from dexamethasone, while hospital readmission rate was higher in those treated with dexamethasone (6% vs. 11%).

      Conclusions

      WBC count and/or neutrophil might be easily available biomarkers to guide selection of CAP patients who are more likely to benefit from adjunctive dexamethasone treatment. Future prospective trials are needed to confirm this predictive potential.

      Keywords

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