慢性阻塞性肺疾病急性加重期患者血清生长分化因子15和白细胞介素6的表达水平及临床意义
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摘要
目的探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者血清生长分化因子15(GDF-15)和白细胞介素6(IL-6)的表达水平及临床意义。方法选择慢性阻塞性肺疾病(COPD)稳定期患者40例(稳定组),急性加重期患者80例(加重组),其中急性加重期1级或2级40例(加重1组),急性加重期3级或4级40例(加重2组);另选40例健康体检者为对照组。采用酶联免疫吸附试验检测各组受试者血清GDF-15、IL-6水平;分析血清GDF-15、IL-6水平与第一秒用力呼气容积占预计值百分比(FEV1%pred)的相关性;采用受试者工作特征(ROC)曲线评估GDF-15、IL-6诊断AECOPD的价值。结果加重1组、加重2组血清GDF-15、IL-6水平均高于稳定组和对照组,且加重2组高于加重1组(P <0.05)。加重1组、加重2组血清GDF-15水平均与IL-6水平呈正相关,AECOPD患者GDF-15水平和IL-6水平均与FEV_1%pred呈负相关(均P <0.05)。GDF-15诊断AECOPD的ROC曲线下面积为0.833,灵敏度、特异度和准确率分别为0.838、0.700和0.792; IL-6诊断AECOPD的曲线下面积为0.682,灵敏度、特异度和准确率分别为0.713、0.575和0.716。结论血清GDF-15、IL-6水平与AECOPD的病情严重程度相关,GDF-15对AECOPD具有较高的诊断价值。
Objective To investigate the expression levels and clinical significance of serum growth differentiation factor 15( GDF-15) and interleukin 6( IL-6) in patients with acute exacerbation of chronic obstructive pulmonary disease( AECOPD).Methods Forty patients with stable chronic obstructive pulmonary disease( COPD) were enrolled as stable group,80 patients with AECOPD as exacerbation group,including 40 cases of acute exacerbation of gradeⅠorⅡ( exacerbation 1 group),and 40 cases of acute exacerbation of grade Ⅲ or Ⅳ( exacerbation 2 group); another 40 healthy check-up individuals were enrolled as control group.Enzyme-linked immunosorbent assay was used to detect serum GDF-15 and IL-6 levels among subjects of each group; the correlation of serum GDF-15 or IL-6 level with the percentage of predicted forced expiratory volume in one second( FEV_1% pred) was analyzed; receiver operating characteristic( ROC) curve was employed to assess the efficiency of GDF-15 or IL-6 for diagnosing AECOPD.Results The serum levels of GDF-15 and IL-6 in the exacerbation 1 group and exacerbation 2 group were higher than those in the stable group and control group,and the exacerbation 2 group had higher levels than the exacerbation 1 group( P < 0.05).Among the exacerbation 1 group and exacerbation 2 group,serum GDF-15 level positively correlated with IL-6 level,and GDF-15 and IL-6 levels negatively correlated with FEV1% pred among AECOPD patients( all P < 0.05).The area under ROC curve of GDF-15 for diagnosing AECOPD was 0.833,the sensitivity,specificity and accuracy were 0.838,0.700 and 0.792,respectively; the area under the curve of IL-6 for diagnosing AECOPD was 0.682,and the sensitivity,specificity and accuracy were 0.713,0.575 and 0.716,respectively.Conclusion Serum GDF-15 and IL-6 levels are associated with the severity of AECOPD,GDF-15 has a higher diagnostic efficiency for AECOPD.
Objective To investigate the expression levels and clinical significance of serum growth differentiation factor 15( GDF-15) and interleukin 6( IL-6) in patients with acute exacerbation of chronic obstructive pulmonary disease( AECOPD).Methods Forty patients with stable chronic obstructive pulmonary disease( COPD) were enrolled as stable group,80 patients with AECOPD as exacerbation group,including 40 cases of acute exacerbation of gradeⅠorⅡ( exacerbation 1 group),and 40 cases of acute exacerbation of grade Ⅲ or Ⅳ( exacerbation 2 group); another 40 healthy check-up individuals were enrolled as control group.Enzyme-linked immunosorbent assay was used to detect serum GDF-15 and IL-6 levels among subjects of each group; the correlation of serum GDF-15 or IL-6 level with the percentage of predicted forced expiratory volume in one second( FEV_1% pred) was analyzed; receiver operating characteristic( ROC) curve was employed to assess the efficiency of GDF-15 or IL-6 for diagnosing AECOPD.Results The serum levels of GDF-15 and IL-6 in the exacerbation 1 group and exacerbation 2 group were higher than those in the stable group and control group,and the exacerbation 2 group had higher levels than the exacerbation 1 group( P < 0.05).Among the exacerbation 1 group and exacerbation 2 group,serum GDF-15 level positively correlated with IL-6 level,and GDF-15 and IL-6 levels negatively correlated with FEV1% pred among AECOPD patients( all P < 0.05).The area under ROC curve of GDF-15 for diagnosing AECOPD was 0.833,the sensitivity,specificity and accuracy were 0.838,0.700 and 0.792,respectively; the area under the curve of IL-6 for diagnosing AECOPD was 0.682,and the sensitivity,specificity and accuracy were 0.713,0.575 and 0.716,respectively.Conclusion Serum GDF-15 and IL-6 levels are associated with the severity of AECOPD,GDF-15 has a higher diagnostic efficiency for AECOPD.
引文
[1]Vogelmeier CF,Criner GJ,Martinez FJ,et al.Global Strategy for the Diagnosis,Management,and Prevention of Chronic Obstructive Lung Disease 2017 Report:Gold Executive Summary[J].Respirology,2017,22(3):575-601.
[2]Pantzaris ND,Spilioti DX,Psaromyalou A,et al.The use of serum procalcitonin as a diagnostic and prognostic biomarker in chronic obstructive pulmonary disease exacerbations:a literature review update[J].J Clin Med Res,2018,10(7):545-551.
[3]Kim M,Cha SI,Choi KJ,et al.Prognostic value of serum growth differentiation factor-15 in patients with chronic obstructive pulmonary disease exacerbation[J].Tuberc Respir Dis(Seoul),2014,77(6):243-250.
[4]Vogelmeier CF,Criner GJ,Martinez FJ,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive lung disease 2017 report:Gold executive summary[J].Am J Respir Crit Care Med,2017,195(5):575-582.
[5]Sangwan V,Chaudhry D,Malik R,et al.Dyspnea,Eosinopenia,Consolidation,Acidemia and Atrial Fibrillation score and BAP-65 score,tools for prediction of mortality in acute exacerbations of chronic obstructive pulmonary disease:a comparative pilot study[J].Indian J Crit Care Med,2017,21(10):671-677.
[6]汪秀伟,余国庆.PCT、IL-6和NLR诊断慢性阻塞性肺疾病急性加重期的临床价值[J].国际检验医学杂志,2019,40(1):98-101.
[7]Chen YW,Leung JM,Sin DD.A systematic review of diagnostic biomarkers of COPD exacerbation[J].PLo S One,2016,11(7):e158843.
[8]Ghobadi H,Aslani MR,Hosseinian A,et al.The correlation of serum brain natriuretic peptide and interleukin-6 with quality of life using the chronic obstructive pulmonary disease assessment test[J].Med Princ Pract,2017,26(6):509-515.
[9]Liang R,Zhang W,Song YM.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[J].Mol Med Rep,2013,7(5):1 470-1 476.
[10]Bootcov MR,Bauskin AR,Valenzuela SM,et al.MIC-1,a novel macrophage inhibitory cytokine,is a divergent member of the TGF-beta superfamily[J].Proc Natl Acad Sci U SA,1997,94(21):11 514-11 519.
[11]Nickel N,Jonigk D,Kempf T,et al.GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells[J].Respir Res,2011,12:62.
[12]Wu Q,Jiang D,Chu HW.Cigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells:implication in mucin over-expression[J].Innate Immun,2012,18(4):617-626.
[13]Mutlu LC,Altintas N,Aydin M,et al.Growth differentiation factor-15 is a novel biomarker predicting acute exacerbation of chronic obstructive pulmonary disease[J].Inflammation,2015,38(5):1 805-1 813.
[14]李磊,倪正义,汤中文,等.血浆中生长分化因子-15在慢性阻塞性肺疾病中的表达和临床应用价值[J].实用医学杂志,2017,33(15):2 443-2 447.
[15]Fairlie WD,Moore AG,Bauskin AR,et al.MIC-1 is a novel TGF-beta superfamily cytokine associated with macrophage activation[J].J Leukoc Biol,1999,65(1):2-5.
[16]王善全,刘成洲,刘同祥.血清生长分化因子-15、C反应蛋白在慢性阻塞性肺疾病中的表达水平[J].中国医药导报,2018,15(1):68-71.
[2]Pantzaris ND,Spilioti DX,Psaromyalou A,et al.The use of serum procalcitonin as a diagnostic and prognostic biomarker in chronic obstructive pulmonary disease exacerbations:a literature review update[J].J Clin Med Res,2018,10(7):545-551.
[3]Kim M,Cha SI,Choi KJ,et al.Prognostic value of serum growth differentiation factor-15 in patients with chronic obstructive pulmonary disease exacerbation[J].Tuberc Respir Dis(Seoul),2014,77(6):243-250.
[4]Vogelmeier CF,Criner GJ,Martinez FJ,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive lung disease 2017 report:Gold executive summary[J].Am J Respir Crit Care Med,2017,195(5):575-582.
[5]Sangwan V,Chaudhry D,Malik R,et al.Dyspnea,Eosinopenia,Consolidation,Acidemia and Atrial Fibrillation score and BAP-65 score,tools for prediction of mortality in acute exacerbations of chronic obstructive pulmonary disease:a comparative pilot study[J].Indian J Crit Care Med,2017,21(10):671-677.
[6]汪秀伟,余国庆.PCT、IL-6和NLR诊断慢性阻塞性肺疾病急性加重期的临床价值[J].国际检验医学杂志,2019,40(1):98-101.
[7]Chen YW,Leung JM,Sin DD.A systematic review of diagnostic biomarkers of COPD exacerbation[J].PLo S One,2016,11(7):e158843.
[8]Ghobadi H,Aslani MR,Hosseinian A,et al.The correlation of serum brain natriuretic peptide and interleukin-6 with quality of life using the chronic obstructive pulmonary disease assessment test[J].Med Princ Pract,2017,26(6):509-515.
[9]Liang R,Zhang W,Song YM.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[J].Mol Med Rep,2013,7(5):1 470-1 476.
[10]Bootcov MR,Bauskin AR,Valenzuela SM,et al.MIC-1,a novel macrophage inhibitory cytokine,is a divergent member of the TGF-beta superfamily[J].Proc Natl Acad Sci U SA,1997,94(21):11 514-11 519.
[11]Nickel N,Jonigk D,Kempf T,et al.GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells[J].Respir Res,2011,12:62.
[12]Wu Q,Jiang D,Chu HW.Cigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells:implication in mucin over-expression[J].Innate Immun,2012,18(4):617-626.
[13]Mutlu LC,Altintas N,Aydin M,et al.Growth differentiation factor-15 is a novel biomarker predicting acute exacerbation of chronic obstructive pulmonary disease[J].Inflammation,2015,38(5):1 805-1 813.
[14]李磊,倪正义,汤中文,等.血浆中生长分化因子-15在慢性阻塞性肺疾病中的表达和临床应用价值[J].实用医学杂志,2017,33(15):2 443-2 447.
[15]Fairlie WD,Moore AG,Bauskin AR,et al.MIC-1 is a novel TGF-beta superfamily cytokine associated with macrophage activation[J].J Leukoc Biol,1999,65(1):2-5.
[16]王善全,刘成洲,刘同祥.血清生长分化因子-15、C反应蛋白在慢性阻塞性肺疾病中的表达水平[J].中国医药导报,2018,15(1):68-71.