Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease

Korean J Intern Med. 2018 Jul;33(4):745-752. doi: 10.3904/kjim.2017.030. Epub 2018 Mar 13.

Abstract

Background/aims: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear.

Methods: Patients diagnosed with COPD were recruited from St. Paul's Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters.

Results: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = -0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = -0.342, p = 0.014). However, CRP level was not correlated with any measured parameter.

Conclusions: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.

Keywords: Biomarkers; Chronic obstructive; NF-E2-related factor 2; Lung diseases.

MeSH terms

  • Aged
  • Biomarkers* / blood
  • C-Reactive Protein / analysis
  • Disease Progression
  • Female
  • Forced Expiratory Volume
  • Humans
  • Inflammation
  • Lung / physiopathology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2* / blood
  • Pulmonary Disease, Chronic Obstructive* / immunology
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Retrospective Studies
  • Vital Capacity

Substances

  • Biomarkers
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • C-Reactive Protein