title: Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization.
abstract: BACKGROUND
  Chemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization.
  
  
  METHODS
  Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit.
  
  
  RESULTS
  Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL,P<0.0001). CCL-18 level was significantly correlated with the number of exacerbations (r=0.30,P=0.026), although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL) subgroups did not achieve statistical significance (P=0.09). Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92). Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68,P<0.0001) and was found to be an independent risk factor for hospitalized exacerbations in the multivariable analysis.
  
  
  CONCLUSIONS
  CCL-18 is a promising biomarker in COPD, as it is associated with frequency of exacerbations, particularly with severe COPD exacerbations requiring hospitalization, as well as with functional parameters and symptom scores.
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Asli Gorek
authors.initials: AG
authors.lastname: Dilektasli
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Demirdogen Cetinoglu
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Esra
authors.initials: E
authors.lastname: Uzaslan
authors.affiliation: Department of Immunology.
authors.forename: Ferah
authors.initials: F
authors.lastname: Budak
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Funda
authors.initials: F
authors.lastname: Coskun
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ursavas
authors.affiliation: Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey.
authors.forename: Ilker
authors.initials: I
authors.lastname: Ercan
authors.affiliation: Department of Pulmonary Disesaes.
authors.forename: Ercument
authors.initials: E
authors.lastname: Ege
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D017079:Exercise Tolerance; D005260:Female; D006760:Hospitalization; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D013147:Spirometry; D011795:Surveys and Questionnaires; D015854:Up-Regulation; D000070857:Walk Test
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC
keywords: COPD; PARC/(CCL-18); frequent exacerbator; hospitalized exacerbation