慢性阻塞性肺疾病患者血清IGFBP7、IGF-1水平与免疫功能及急性加重的关系

The Relationship Between Serum IGFBP7 and IGF-1 Levels and Immune Function and Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease

目的探究慢性阻塞性肺疾病(COPD)患者血清胰岛素样生长因子结合蛋白7(IGFBP7)、胰岛素样生长因子-1(IGF-1)水平与免疫功能和急性加重发生的关系。方法纳入2021年4月至2023年3月北京市朝阳区双桥医院收治的COPD患者276例,其中包括稳定期COPD患者141例(稳定期COPD组)和急性加重期COPD患者135例(急性加重期COPD组)。选取体检健康者141例(对照组)。收集受试者临床资料并检测肺功能;流式细胞仪测定血液CD3^(+)、CD4^(+)、CD8^(+)的百分比,并计算CD4^(+)/CD8^(+);酶联免疫吸附法检测血清IGFBP7、IGF-1水平。比较3组受试者临床资料、肺功能、免疫功能指标、血清IGFBP7、IGF-1水平;分析COPD患者血清IGFBP7、IGF-1水平之间及与吸烟史、肺功能、免疫功能指标的相关性分析,COPD发生急性加重的因素,血清IGFBP7、IGF-1水平对COPD发生急性加重的预测价值。结果对照组、稳定期COPD组、急性加重期COPD组吸烟史比例、CD8^(+)、血清IGFBP7水平依次升高,第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1占预计值百分比(FEV1%)、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、IGF-1水平依次降低(P<0.05)。COPD患者血清IGFBP7与IGF-1、FEV1/FVC、FEV1%、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)呈负相关,与吸烟史、CD8^(+)呈正相关(P<0.05);血清IGF-1与吸烟史、CD8^(+)呈负相关,与FEV1/FVC、FEV1%、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)呈正相关(P<0.05)。吸烟史、CD8^(+)、IGFBP7水平高,FEV1/FVC、FEV1%、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、IGF-1水平低是影响COPD发生急性加重的独立危险因素(P<0.05)。血清IGFBP7、IGF-1、二者联合预测COPD发生急性加重的曲线下面积(AUC)分别为0.853、0.834、0.914,二者联合预测的AUC较血清IGFBP7、IGF-1各自单独预测的更高(P<0.05)。结论COPD患者血清IGFBP7水平较高,IGF-1水平较低,二者在急性加重期COPD患者血清中变化更明显,与免疫功能相关,血清IGFBP7和IGF-1联合可用于预测COPD急性加重。

Objective To explore the relationship between serum levels of insulin-like growth factor binding protein 7(IGFBP7)and insulin-like growth factor-1(IGF-1)and immune function and acute exacerbation in patients with chronic obstructive pulmonary disease(COPD).Methods A total of 276 COPD patients admitted to Shuangqiao Hospital of Chaoyang District in Beijing City from April,2021 to March,2023 were enrolled into the study,including 141 patients with stable COPD(stable COPD group)and 135 patients with acute exacerbation COPD(acute exacerbation COPD group).A total of 141 healthy subjects(control group)were also selected.We collected clinical data of subjects and tested lung function;Percentages of blood CD3^(+),CD4^(+)and CD8^(+)were measured by flow cytometry,and CD4^(+)/CD8^(+)was calculated;Serum IGFBP7 and IGF-1 levels were detected by enzyme-linked immunosorbent assay.The clinical data,lung function,immune function indexes,serum IGFBP7 and IGF-1 levels of the three groups were compared;We then analyzed the correlation between serum IGFBP7 and IGF-1 levels and smoking history,lung function and immune function indexes in COPD patients.The risk factors causing acute exacerbation of COPD,and the predictive value of serum IGFBP7 and IGF-1 levels for acute exacerbation of COPD were evaluated.Results The proportion of smoking history,CD8^(+)and serum IGFBP7 levels in the control group,stable COPD group and acute exacerbation COPD group were increased successively,while forced expiratory volume for 1 second(FEV1)/forced vital capacity(FVC),FEV1 as a percentage of expected value(FEV1%),levels of CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and IGF-1 were decreased successively(P<0.05).Serum IGFBP7 in COPD patients was negatively correlated with IGF-1,FEV1/FVC,FEV1%,CD3^(+),CD4^(+),CD4^(+)/CD8^(+),while positively correlated with smoking history and CD8^(+)(P<0.05);Serum IGF-1 was negatively correlated with smoking history and CD8^(+),but positively correlated with FEV1/FVC,FEV1%,CD3^(+),CD4^(+),CD4^(+)/CD8^(+)(P<0.05).Smoking history,high levels of CD8^(+)and IGFBP7,and low levels of FEV1/FVC,FEV1%,CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and IGF-1 were independent risk factors for COPD acute exacerbation(P<0.05).The area under the curve(AUC)of serum IGFBP7,IGF-1,and their combination in predicting acute exacerbation of COPD were 0.853,0.834,and 0.914,respectively.AUC predicted by the combination of the two markers was higher than that predicted by serum IGFBP7 and IGF-1 alone(P<0.05).Conclusion Serum IGFBP7 levels are higher and IGF-1 levels are lower in COPD patients.Changes in serum IGFBP7 and IGF-1 levels are more pronounced in COPD patients during acute exacerbation,and are related to immune function.The combination of serum IGFBP7 and IGF-1 can be used to predict acute exacerbation of COPD.