YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia

Respirology. 2017 Apr;22(3):542-550. doi: 10.1111/resp.12924. Epub 2016 Oct 26.

Abstract

Background and objective: The aim of this study was to investigate the prognostic value of four biomarkers, YKL-40, chemokine (C-C motif) ligand 18 (CCL18), surfactant protein-D (SP-D) and CA 15-3, in patients admitted with community-acquired pneumonia (CAP). These markers have been studied extensively in chronic pulmonary disease, but in acute pulmonary disease their prognostic value is unknown.

Methods: A total of 289 adult patients who were hospitalized with CAP and participated in a randomized controlled trial were enrolled. Biomarker levels were measured on the day of admission. Intensive care unit admission, 30-day, 1-year and long-term mortality (median follow-up of 5.4 years, interquartile range (IQR): 4.7-6.1) were recorded as outcomes.

Results: Median YKL-40 and CCL18 levels were significantly higher and levels of SP-D were significantly lower in CAP patients compared to healthy controls. Significantly higher YKL-40, CCL18 and SP-D levels were found in patients classified in pneumonia severity index classes 4-5 and with a CURB-65 score ≥2 compared to patients with less severe pneumonia. Furthermore, these three markers were significant predictors for long-term mortality in multivariate analysis and compared with C-reactive protein and procalcitonin level on admission, area under the curves were higher for 30-day, 1-year and long-term mortality. CA 15-3 levels were less predictive.

Conclusion: YKL-40, CCL18 and SP-D levels were higher in patients with more severe pneumonia, possibly reflecting the extent of pulmonary inflammation. Of these, YKL-40 most significantly predicts mortality for CAP.

Keywords: YKL-40 protein, human; biomarkers; chemokine (C-C motif) ligand 18 protein, human; mortality; pneumonia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers / blood
  • C-Reactive Protein
  • Calcitonin / blood
  • Chemokines, CC / blood*
  • Chitinase-3-Like Protein 1 / blood*
  • Community-Acquired Infections / blood*
  • Community-Acquired Infections / mortality
  • Female
  • Hospitalization
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Pneumonia / blood*
  • Pneumonia / mortality
  • Prognosis
  • Pulmonary Surfactant-Associated Protein D / blood*
  • ROC Curve
  • Severity of Illness Index

Substances

  • Biomarkers
  • CCL18 protein, human
  • Chemokines, CC
  • Chitinase-3-Like Protein 1
  • Mucin-1
  • Pulmonary Surfactant-Associated Protein D
  • Calcitonin
  • C-Reactive Protein