A Systematic Review of Diagnostic Biomarkers of COPD Exacerbation

PLoS One. 2016 Jul 19;11(7):e0158843. doi: 10.1371/journal.pone.0158843. eCollection 2016.

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.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Interleukin-6 / blood
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Practice Guidelines as Topic
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • ROC Curve
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein

Grant support

Funding was provided by Genome Canada (www.genomecanada.ca), grant title "Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management", recipient DDS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.