title: Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality - a cohort study.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive decline in pulmonary function. Neutrophil-to-lymphocyte ratio (NLR), YKL-40 and calprotectin are biomarkers of inflammation and predict mortality in patients with different inflammatory diseases. We aimed to investigate the correlation between levels of these three biomarkers and neutrophil granulocyte and lymphocyte count in patients with moderate to very severe COPD stratified by use of systemic glucocorticoids. Furthermore, we studied the ability of these biomarkers to predict all-cause mortality.
  
  
  METHODS
  386 patients with moderate to very severe COPD were followed prospectively for 10 years. Patients were divided into two groups according to systemic glucocorticoid use at baseline. Correlations between biomarkers were assessed by Spearman's Rho, and mortality was evaluated in uni- and multivariate Cox regression analyses with hazard ratios (HR) and 95% confidence intervals (CI).
  
  
  RESULTS
  Plasma calprotectin was positively correlated with neutrophil granulocyte count and NLR. No significant association was found between plasma YKL-40 and the cellular biomarkers, irrespective of glucocorticoid treatment. In the group not treated with systemic glucocorticoids, plasma calprotectin [HR 1.002 (95% CI 1.000 - 1.004)], NLR [HR 1.090 (1.036 - 1.148)] and lymphocyte count [HR 0.667 (0.522 - 0.851)] were significantly associated with higher mortality. In the group treated with systemic glucocorticoids, higher plasma YKL-40 was significantly associated with mortality in univariate Cox regression analysis [HR 1.006 (1.003 - 1.008)].
  
  
  CONCLUSIONS
  Calprotectin was related to neutrophil granulocyte count and NLR in patients with moderate to very severe COPD in stable phase and not in treatment with systemic glucocorticoids. Lymphopenia, higher plasma calprotectin and higher NLR were independent predictors of increased all-cause mortality in this group. Our data also suggests that treatment with systemic glucocorticoids has a significant impact on the ability of inflammatory biomarkers to predict all-cause mortality.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00132860.
authors.affiliation: Department of Infectious Diseases Q, Odense University Hospital, Odense, Denmark.
authors.forename: Allan Klitgaard
authors.initials: AK
authors.lastname: Sørensen
authors.affiliation: Department of Clinical Microbiology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Dennis Back
authors.initials: DB
authors.lastname: Holmgaard
authors.affiliation: Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Lone Hagens
authors.initials: LH
authors.lastname: Mygind
authors.affiliation: Departments of Medicine and Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julia
authors.initials: J
authors.lastname: Johansen
authors.affiliation: Department of Infectious Diseases Q, Odense University Hospital, Odense, Denmark.
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
keywords: COPD; Calprotectin; Glucocorticoids; Lymphopenia; Mortality; Neutrophil-to-lymphocyte ratio; Prognosis; YKL-40