Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease
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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.
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.
참고문헌 (25)
- Mathers CD, "Projections of global mortality and burden of disease from 2002 to 2030", PLoS Med, 3, pp.e442~ (2006)[DOI]
- Guarascio AJ, "The clinical and economic burden of chronic obstructive pulmonary disease in the USA", Clinicoecon Outcomes Res, 5, pp.235~245 (2013)
- Mannino DM, "Economic burden of COPD in the presence of comorbidities", Chest, 148, pp.138~150 (2015)[DOI]
- Kensler TW, "Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway", Annu Rev Pharmacol Toxicol, 47, pp.89~116 (2007)[DOI]
- Boutten A, "NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease", Trends Mol Med, 17, pp.363~371 (2011)[DOI]
- Rodriguez-Roisin R, "Toward a consensus definition for COPD exacerbations", Chest, 117(5 Suppl 2), pp.398S~401S (2000)[DOI]
- Celli BR, "Exacerbations of chronic obstructive pulmonary disease", Eur Respir J, 29, pp.1224~1238 (2007)[DOI]
- Vestbo J, "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary", Am J Respir Crit Care Med, 187, pp.347~365 (2013)[DOI]
- Burge PS, "Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial", BMJ, 320, pp.1297~1303 (2000)[DOI]
- Laszlo G, "Standardisation of lung function testing: helpful guidance from the ATS", ERS Task Force, 2006, pp.61, 744~746
- Antus B, "Oxidative stress in COPD: molecular background and clinical monitoring", Curr Med Chem, 22, pp.627~650 (2015)[DOI]
- Stanojkovic I, "Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation", Respir Med, 105(Suppl 1), pp.S31~S37 (2011)[DOI]
- Seemungal TA, "Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease", Am J Respir Crit Care Med, 161, pp.1608~1613 (2000)[DOI]
- Cantin AM, "Cigarette smoke-induced proteostasis imbalance in obstructive lung diseases", Curr Mol Med, 12, pp.836~849 (2012)[DOI]
- Goven D, "Altered Nrf2", Keap1-Bach1 equilibrium in pulmonary emphysema, 2008, pp.63, 916~924
- Suzuki M, "Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease", Am J Respir Cell Mol Biol, 39, pp.673~682 (2008)[DOI]
- Fratta Pasini AM, "Nrf2 expression is increased in peripheral blood mononuclear cells derived from mild-moderate ex-smoker COPD patients with persistent oxidative stress", Int J Chron Obstruct Pulmon Dis, 11, pp.1733~1743 (2016)[DOI]
- Yanbaeva DG, "Systemic inflammation in COPD: is genetic susceptibility a key factor?", COPD, 3, pp.51~61 (2006)[DOI]
- Liang R, "Levels of leptin and IL-6 in lungs and blood are associated with the severity of chronic obstructive pulmonary disease in patients and rat models", Mol Med Rep, 7, pp.1470~1476 (2013)[DOI]
- Foschino Barbaro MP, "Inflammation, oxidative stress and systemic effects in mild chronic obstructive pulmonary disease", Int J Immunopathol Pharmacol, 20, pp.753~763 (2007)[DOI]
- Sorensen GL, "Genetic and environmental influences of surfactant protein D serum levels", Am J Physiol Lung Cell Mol Physiol, 290, pp.L1010~L1017 (2006)[DOI]
- Bowler RP, "Surfactant protein D as a biomarker for chronic obstructive pulmonary disease", COPD, 9, pp.651~653 (2012)[DOI]
- Ju CR, "Serum surfactant protein D: biomarker of chronic obstructive pulmonary disease", Dis Markers, 32, pp.281~287 (2012)[DOI]
- Sin DD, "Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease", Circulation, 107, pp.1514~1519 (2003)[DOI]
- Broekhuizen R, "Raised CRP levels mark metabolic and functional impairment in advanced COPD", Thorax, 61, pp.17~22 (2006)
