title: A Systematic Review of Diagnostic Biomarkers of COPD Exacerbation.
abstract: The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications. Patients of interest were those that have been diagnosed with COPD. MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers. We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality. Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance. Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts.
authors.affiliation: Centre for Heart Lung Innovation, Institute for Heart Lung Health at St. Paul's Hospital & Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yu-Wei Roy
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Centre for Heart Lung Innovation, Institute for Heart Lung Health at St. Paul's Hospital & Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Leung
authors.affiliation: Centre for Heart Lung Innovation, Institute for Heart Lung Health at St. Paul's Hospital & Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein