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Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: results of a 5-year follow-up cohort study

William W. Siljan, Jan C. Holter, Annika E. Michelsen, Ståle H. Nymo, Trine Lauritzen, Kjersti Oppen, Einar Husebye, Thor Ueland, Tom E. Mollnes, Pål Aukrust, Lars Heggelund
ERJ Open Research 2019 5: 00014-2019; DOI: 10.1183/23120541.00014-2019
William W. Siljan
1Dept of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • ORCID record for William W. Siljan
  • For correspondence: williasi@ulrik.uio.no
Jan C. Holter
1Dept of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Annika E. Michelsen
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Ståle H. Nymo
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Trine Lauritzen
4Dept of Medical Biochemistry, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
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Kjersti Oppen
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
4Dept of Medical Biochemistry, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
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Einar Husebye
1Dept of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Thor Ueland
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
5Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway
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Tom E. Mollnes
5Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway
6Research Laboratory, Nordland Hospital, Bodø, Norway
7Dept of Immunology, Faculty of Medicine, University of Oslo, Oslo, Norway
8K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
9Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
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Pål Aukrust
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
8K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
10Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Lars Heggelund
1Dept of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • FIGURE 1
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    FIGURE 1

    Biomarker levels at hospital admission, clinical stabilisation and 6-week follow-up in 267 hospitalised patients with community-acquired pneumonia. a) White blood cells; b) C-reactive protein; c) procalcitonin; d) calprotectin; e) pentraxin 3; f) presepsin. *: p<0.05; **: p<0.01; ***: p<0.001. Two-group comparison performed with Wilcoxon signed-rank test.

  • FIGURE 2
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    FIGURE 2

    Biomarker levels at hospital admission stratified by microbial aetiology in 267 hospitalised patients with community-acquired pneumonia. Data are presented as medians with interquartile ranges. Multiple group comparison performed with Kruskal–Wallis test and two-group comparison performed with Mann–Whitney test. Patients with unknown aetiology were excluded from statistical analysis. a) White blood cells; b) pentraxin 3; c) presepsin; d) C-reactive protein; e) procalcitonin; f) calprotectin.

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    FIGURE 3

    Receiver operating characteristic curves for biomarkers and CURB-65 severity score (confusion, urea >7 mmol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) at hospital admission for prediction of an adverse short-term outcome. a) Procalcitonin; b) pentraxin 3; c) presepsin. AUC: area under the curve.

  • FIGURE 4
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    FIGURE 4

    Kaplan–Meier plots of biomarkers at 6-week follow-up and associations with 5-year all-cause mortality, stratified by quartiles of a) calprotectin (p<0.001 by the log-rank test) and b) white blood cell count (p<0.001). Q: quartile.

Tables

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  • TABLE 1

    Microbial findings in 267 hospitalised patients with community-acquired pneumonia

    Bacterial pathogensPatients with positive findingsViral pathogensPatients with positive findings
    Streptococcus pneumoniae81 (30%)Influenza viruses§40 (15%)
    Bordetella pertussis15 (6%)Rhinovirus32 (12%)
    Haemophilus influenzae14 (5%)Parainfluenza virusesƒ8 (3%)
    Mycoplasma pneumoniae10 (4%)Respiratory syncytial virus7 (3%)
    Chlamydophila pneumoniae7 (3%)Metapneumovirus7 (3%)
    Legionella pneumophila7 (3%)Enterovirus5 (2%)
    Enterobacteriaceae#6 (2%)Adenovirus1 (0.4%)
    Moraxella catarrhalis5 (2%)
    Miscellaneous¶3 (1%)
    Haemophilus parainfluenzae2 (1%)
    Total+126 (47%)Total+92 (34%)

    #: Escherichia coli, Pseudomonas aeruginosa or Enterobacter spp.; ¶: group A Streptococcus, Prevotella spp. or Dialister pneumosintes; +: number of patients does not sum to number of pathogens because some patients had multiple pathogens detected; §: influenza A and B viruses; ƒ: parainfluenza virus types 1–3.

    • TABLE 2

      Logistic regression analysis and diagnostic accuracy of biomarker levels at hospital admission for prediction of bacterial aetiology in 267 hospitalised patients with community-acquired pneumonia

      BiomarkerUnivariate analysisArea under the curve
      OR (95% CI)p-valueAUC (95% CI)p-value
      CRP1.90 (1.16–3.12)0.0110.66 (0.56–0.75)0.003
      PCT1.44 (1.15–1.81)0.0020.67 (0.58–0.77)0.001
      Calprotectin2.15 (1.05–4.41)0.0360.63 (0.52–0.73)0.022

      CRP: C-reactive protein; PCT: procalcitonin.

      • TABLE 3

        Logistic regression analysis of biomarker levels at hospital admission and associations to adverse short-term outcome in 267 hospitalised patients with community-acquired pneumonia

        BiomarkerUnivariate analysisMultivariate analysis#
        OR (95% CI)p-valueOR (95% CI)p-value
        PCT1.40 (1.16–1.69)0.0011.29 (1.06–1.58)0.012
        PTX32.46 (1.49–4.06)<0.0011.88 (1.11–3.19)0.018
        Presepsin1.40 (1.12–1.74)0.0031.32 (1.04–1.67)0.022

        PCT: procalcitonin; PTX3: pentraxin 3. #: adjusted for the CURB-65 severity score (confusion, urea >7 mmol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years).

        • TABLE 4

          Cox regression analysis of biomarker levels at the 6-week follow-up and associations to 5-year all-cause mortality in 267 hospitalised patients with community-acquired pneumonia

          BiomarkerUnivariate analysisMultivariate analysis#
          HR (95% CI)p-valueHR (95% CI)p-value
          WBCs4.74 (1.89–11.87)0.0012.81 (1.06–7.44)0.037
          CRP1.67 (1.34–2.08)<0.0011.29 (0.99–1.67)0.055
          PCT2.82 (1.71–4.63)0.0011.73 (0.97–3.09)0.063
          Calprotectin2.56 (1.62–4.04)<0.0012.18 (1.27–3.74)0.005
          PTX32.31 (1.49–3.59)<0.0011.26 (0.83–1.92)0.282

          HR: hazard ratio; WBC: white blood cell; CRP: C-reactive protein; PCT: procalcitonin; PTX3: pentraxin 3. #: adjusted for age, heart failure, active malignant disease, chronic obstructive pulmonary disease and renal disease.

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          Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: results of a 5-year follow-up cohort study
          William W. Siljan, Jan C. Holter, Annika E. Michelsen, Ståle H. Nymo, Trine Lauritzen, Kjersti Oppen, Einar Husebye, Thor Ueland, Tom E. Mollnes, Pål Aukrust, Lars Heggelund
          ERJ Open Research Feb 2019, 5 (1) 00014-2019; DOI: 10.1183/23120541.00014-2019

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          Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: results of a 5-year follow-up cohort study
          William W. Siljan, Jan C. Holter, Annika E. Michelsen, Ståle H. Nymo, Trine Lauritzen, Kjersti Oppen, Einar Husebye, Thor Ueland, Tom E. Mollnes, Pål Aukrust, Lars Heggelund
          ERJ Open Research Feb 2019, 5 (1) 00014-2019; DOI: 10.1183/23120541.00014-2019
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