title: Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is hallmarked by inflammatory processes and a progressive decline of lung function. YKL-40 is a potential biomarker of inflammation and mortality in patients suffering from inflammatory lung disease, but its prognostic value in patients with COPD remains unknown. We investigated whether high plasma YKL-40 was associated with increased mortality in patients with moderate to very severe COPD.
  
  
  METHODS
  Four hundred and ninety-three patients with moderate to very severe COPD were followed prospectively for up to 10 years. Patients were divided into two groups according to plasma YKL-40: concentration higher than the 75th percentile for age-matched healthy subjects (i.e. high levels) and normal levels. Outcome was overall survival (OS) and was evaluated in uni- and multivariate proportional hazards Cox regression analyses and adjusted for factors affecting mortality.
  
  
  RESULTS
  Median plasma YKL-40 was increased in patients with COPD (81 ng/ml, p < 0.001) compared to healthy subjects (40 ng/ml). Patients with high plasma YKL-40 had a hazard ratio (HR) of 1.42 (95% CI: 1.15-1.75, p = 0.001) for all-cause mortality. Multivariate analysis showed that YKL-40 (HR 1.38; 95% CI: 1.11-1.72, p = 0.004), age (HR 1.05; 95% CI: 1.03-1.06, p < 0.0001), Severe COPD (HR 1.35; 95 CI: 1.03-1.76, p = 0.03) very severe COPD (HR 2.19; 95% CI: 1.60 - 2.99 < 0.0001), neutrophil granulocyte count (HR 1.05; 95% CI: 1.01-1.08, p = 0.01), and a smoking history of > 40 years (HR 1.38; 95% CI: 1.11-1.71, p = 0.003) were independent prognostic markers of OS.
  
  
  CONCLUSIONS
  High plasmaYKL-40 is associated with increased mortality in patients with moderate to very severe COPD, suggesting a role for YKL-40 as a potential biomarker of mortality in this patient group.
authors.affiliation: Department of Infectious Diseases Q, Odense University Hospital, DK-5000 Odense C, Denmark. Aesklepios@gmail.com.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Holmgaard
authors.forename: Lone H
authors.initials: LH
authors.lastname: Mygind
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Titlestad
authors.forename: Hanne
authors.initials: H
authors.lastname: Madsen
authors.forename: Svend Stenvang
authors.initials: SS
authors.lastname: Pedersen
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
mesh_terms: D054392:Adipokines / Q000097:blood*; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006098:Granulocytes; D006801:Humans; D037102:Lectins / Q000097:blood*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D009504:Neutrophils; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000401:mortality*; D012720:Severity of Illness Index; D012907:Smoking / Q000401:mortality
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins