Identification of thyroxine-binding globulin as a candidate plasma marker of chronic obstructive pulmonary disease

Int J Chron Obstruct Pulmon Dis. 2017 May 25:12:1549-1564. doi: 10.2147/COPD.S137806. eCollection 2017.


Biomarkers for the management of chronic obstructive pulmonary disease (COPD) are limited. The aim of this study was to explore new plasma biomarkers in patients with COPD. Thyroxine-binding globulin (THBG) was initially identified by proteomics in a discovery panel and subsequently verified by enzyme-linked immunosorbent assay in another verification panel with a 1-year follow-up. THBG levels were elevated in patients with COPD (9.2±2.3 μg/mL) compared to those of the controls (6.6±2.0 μg/mL). Receiver operating characteristic curves suggested that THBG was able to slightly differentiate between patients with COPD and controls (area under the curve [AUC]: 0.814) and performed better if combined with fibrinogen (AUC: 0.858). THBG was more capable of distinguishing Global Initiative for Obstructive Lung Disease stages I-III and IV (AUC: 0.851) compared with fibrinogen (AUC 0.582). THBG levels were negatively associated with predicted percentage forced expiratory volume in 1 s and positively related to predicted percentage residual volume, RV/percentage total lung capacity, and percentage low-attenuation area. COPD patients with higher baseline THBG levels had a greater risk of acute exacerbation (AE) than those with lower THBG levels (P=0.014, by Kaplan-Meier curve; hazard ratio: 4.229, by Cox proportional hazards model). In summary, THBG is a potential plasma biomarker of COPD and can assist in the management of stable stage and AEs in COPD patients.

Keywords: biomarker; chronic obstructive pulmonary disease; proteomics; thyroxine-binding globulin.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Proteomics / methods
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • ROC Curve
  • Reproducibility of Results
  • Thyroxine-Binding Globulin / metabolism*
  • Time Factors
  • Up-Regulation


  • Biomarkers
  • SERPINA7 protein, human
  • Thyroxine-Binding Globulin