慢性阻塞性肺疾病患者血清S100A8/A9和sRAGE水平变化及临床意义

The alterations and clinical significance of serum S100A8/A9 and sRAGE in patients with chronic obstructive pulmonary disease

目的分析慢性阻塞性肺疾病患者血清钙结合蛋白S100A8/A9和可溶性糖基化终末产物受体(sRAGE)水平的变化及临床意义。方法病例对照研究。选取2018年4月至2019年1月湖北中医药大学附属中西医结合医院呼吸科慢性阻塞性肺疾病(COPD)患者203例,其中男166例,女37例,年龄52~92岁,平均(69.72±9.08)岁。收集体检中心吸烟老年非COPD且相对健康体检者41例为吸烟对照组,其中男35例,女6例,年龄55~89岁,平均(68.66±8.74)岁。收集不吸烟老年健康体检者167名为不吸烟对照组,其中男132名,女35名,年龄57~92岁,平均(69.13±7.21)岁。采用酶联免疫吸附测定(ELISA)方法检测不同分期COPD患者和两组对照组血清中S100A8/A9和sRAGE的水平,将其与COPD患者的各临床指标:第一秒用力呼气容积FEVl占预计值%、FEV1/FVC(用力肺活量)、中性粒细胞比率(NEU%)、吸烟量:每日吸烟包数乘吸烟年数(pack-year)做相关性分析。利用受试者工作特征(ROC)曲线分析S100A8/A9,sRAGE以及二者联合检测对于COPD的诊断价值。结果COPD患者血清S100A8/A9水平[(2.70±1.11)μg/ml]与吸烟对照组[(1.65±0.63)μg/ml]和不吸烟对照组[(0.99±0.48)μg/ml]相比均明显上升(t=5.807,P<0.0001;t=18.45,P<0.0001);COPD患者GOLDⅠ、Ⅱ、Ⅲ、Ⅳ期血清S100A8/A9水平[(2.08±1.08)μg/ml,(2.58±1.06)μg/ml,(2.69±1.12)μg/ml,(2.95±1.10)μg/ml]与不吸烟对照组[(0.99±0.48)μg/ml]相比明显上升,差异均有统计学意义(t=6.616,P<0.0001;t=14.56,P<0.0001;t=17.10,P<0.0001;t=18.09,P<0.0001)。COPD患者血清sRAGE水平[(0.29±0.25)ng/ml]与吸烟对照组[(0.60±0.24)ng/ml]和不吸烟对照组[(0.85±0.35)ng/ml]相比均明显下降(t=7.367,P<0.0001;t=18.14,P<0.0001);COPD患者GOLDⅠ、Ⅱ、Ⅲ、Ⅳ期血清sRAGE水平[(0.46±0.40)、(0.28±0.25)、(0.29±0.25)和(0.25±0.19)ng/ml]与不吸烟对照组[(0.85±0.35)ng/ml]相比明显下降,差异均有统计学意义(t=3.459,P=0.0005;t=10.23,P<0.0001;t=13.95,P<0.0001;t=11.70,P<0.0001)。血清S100A8/A9水平与患者吸烟量、NEU%均呈正相关(r=0.4585,P<0.0001;r=0.2283,P=0.0011),与FEV1/FVC、FEV1占预计值百分比、sRAGE均呈负相关(r=-0.1906,P=0.0064;r=-0.1863,P=0.0078;r=-0.2017,P=0.0039)。sRAGE与NEU%呈负相关(r=-0.1559,P=0.0264)。ROC曲线中S100A8/A9,sRAGE以及二者联合检测的曲线下面积分别为0.922[95%CI(0.897~0.947)],0.926[95%CI(0.899~0.952)],0.966[95%CI(0.950~0.983)]。结论S100A8/A9和sRAGE水平与气流受限严重程度和血清炎症介质水平相关,有望作为COPD的潜在的生物标志物。

Objective To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products(sRAGE)levels in patients with chronic obstructive pulmonary disease(COPD).Methods Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166,female 37,aged 52-92 years,average years(69.72±9.079)]and in 41 smoking elderly non-COPD patients[male 35,female 6,aged 55-89 years,average years(68.66±8.74)],and 167 non-smoking healthy subjects as the control group[male 132,female 35,aged 57-92 years,average years(69.13±7.21)]from April 2018 to January 2019.The relationship between the S100A8/A9,sRAGE and clinical biomarkers[the percentage of fored expiratory volume in one second(FEV1)in the predicted value,FEV1/fored vital capacity(FVC),neutrophile granulocyte(NEU)%,pack-year]were investigated.The diagnostic value of S100A8/A9,sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve.Results The serum S100A8/A9 level[(2.70±1.11)μg/ml]in COPD patients was significantly higher than that in the smoking control group[(1.65±0.63)μg/ml]and the non-smoking control group[(0.99±0.48)μg/ml],t=5.807,P<0.0001;t=18.45,P<0.0001.The serum S100A8/A9 levels in patients with COPD[GOLDⅠ(2.08±1.08)μg/ml,GOLDⅡ(2.58±1.06)μg/ml,GOLDⅢ(2.69±1.12)μg/ml,GOLDⅣ(2.95±1.10)μg/ml]were significantly higher than the non-smoking control group(0.99±0.48)μg/ml,t=6.616,P<0.0001;t=14.56,P<0.0001;t=17.10,P<0.0001;t=18.09,P<0.0001.The serum sRAGE level[(0.29±0.25)ng/ml]in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml]and the non-smoking control group[(0.85±0.35)ng/ml],t=7.367,P<0.0001;t=18.14,P<0.0001.The serum sRAGE levels in patients with COPD[GOLDⅠ(0.46±0.40),GOLDⅡ(0.28±0.25),GOLDⅢ(0.29±0.25),GOLDⅣ(0.25±0.19)ng/ml]were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml],t=3.459,P=0.0005;t=10.23,P<0.0001;t=13.95,P<0.0001;t=11.70,P<0.0001.Serum S100A8/A9 levels were positively correlated with smoking amount and NEU%(r=0.4585,P<0.0001;r=0.2283,P=0.0011),negatively correlated with FEV1/FVC,the percentage of FEV1 in the predicted value,and sRAGE(r=-0.1906,P=0.0064;r=-0.1863,P=0.0078;r=-0.2017,P=0.0039).sRAGE levels were negatively correlated with NEU%(r=-0.1559,P=0.0264).In the ROC curve,the area under the curve of S100A8/A9,sRAGE and combined detection were 0.922[95%CI(0.897-0.947)],0.926[95%CI(0.899-0.952)]and 0.966[95%CI(0.950-0.983)],respectively.Conclusion S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators,which are expected to be as potential biomarkers of COPD.