血清GRO-α水平和MRpro-ADM水平预测稳定期慢性阻塞性肺疾病患者急性加重和死亡风险的意义研究

Assessment of Acute Exacerbation and Mortality Risk in Patients with Stable COPD by Serum GRO-α and MRpro-ADM

目的评估血清生长调节致癌基因-α(GRO-α)、肾上腺髓质素前体中段肽(MRpro-ADM)水平预测稳定期慢性阻塞性肺疾病(COPD)患者急性加重、死亡风险的意义,为临床早期识别、干预高危患者提供依据。方法选取2016年1—2月在金华市人民医院呼吸内科门诊就诊或出院后随访的稳定期COPD患者160例作为研究对象,检测其血清GRO-α、MRpro-ADM水平,分别以检测值的中位数73.5 ng/L、0.69 nmol/L为界将所有患者分为GRO-α、MRpro-ADM高水平组和GRO-α、MRpro-ADM低水平组,2016年3月开始对所有患者随访12个月,记录入组到第一次急性加重时间、急性加重发生率、住院时间及病死率,最终共有153例患者完成随诊,7例失访。采用受试者工作特征曲线(ROC曲线)分析血清GRO-α、MRpro-ADM水平预测COPD患者急性加重、死亡风险的最佳截断值以及相应灵敏度和特异度。结果 GRO-α、MRpro-ADM高水平组COPD患者急性加重发生率、病死率高于GRO-α、MRpro-ADM低水平组,入组到第一次急性加重时间短于GRO-α、MRpro-ADM低水平组,住院时间长于GRO-α、MRpro-ADM低水平组(P<0.05)。血清GRO-α水平预测COPD急性加重风险的ROC曲线下面积为0.866[95%可信区间(0.785,0.948)],最佳截断值为74.5 ng/L时灵敏度为93%,特异度为74%,Youden指数为0.67;血清GRO-α水平预测COPD死亡风险的ROC曲线下面积为0.833[95%可信区间(0.729,0.937)],最佳截断值为93.5 ng/L时灵敏度为94%,特异度为69%,Youden指数为0.62。血清MRpro-ADM水平预测COPD急性加重风险的ROC曲线下面积为0.846[95%可信区间(0.762,0.930)],最佳截断值为0.70 nmol/L时灵敏度为80%,特异度为78%,Youden指数为0.58;血清MRpro-ADM水平预测COPD死亡风险的ROC曲线下面积为0.871[95%可信区间(0.770,0.973)],最佳截断值为0.81 nmol/L时灵敏度为69%,特异度为89%,Youden指数为0.58。结论血清GRO-α、MRpro-ADM水平可以作为预测稳定期COPD患者急性加重、死亡风险的生物学指标。

Objective To estimate the acute exacerbation and mortality risk in patients with stable chronic obstructive pulmonary disease （COPD）by serum growth - regulated oncogene α （GRO - α）and midregional pro - adrenomedullin （MRpro- ADM）, so as to provide a basis for clinically identifying the high - risk ones among these patients as early as possible.Methods A total of 160 stable COPD patients enrolled were all from Department of Respiratory Medicine of Jinhua People′s Hospital,including outpatients who received medical care and inpatients who were discharged between January and February 2016.Measurement of serum GRO - α and MRpro - ADM was performed in all the participants.The values of median of these two biomarkers,73.5 ng/ L for GRO - α,and 0.69 nmol/ L for MRpro - ADM,were taken as the criterion for grouping them,respectively.Patients with GRO - α level≥73.5 ng/ L and those with GRO - α level 〈 73.5 ng/ L,were assigned to the high - level GRO - α group and low - level GRO - α group,respectively;patients with M pro - ADM level≥0.69 nmol/ L and those with MRpro - ADM level 〈0.69 nmol/ L were set as the high - level MRpro - ADM group,and low - level MRpro - ADM group,respectively.One hundred and fifty - three of them completed the 12 - month follow - up,the other 7 were missed.The attacking time of first acute exacerbation of COPD （AECOPD）after grouping,incidence of AECOPD,length of stay and mortality in the 153 participants during the follow - up period were recorded.ROC curve was used to study the optimal cut - off value and the corresponding sensitivity and specificity of GRO - α and MRpro - ADM in predicting the risk of AECOPD and mortality.Results Compared with the low - level GRO - α group,high - level GRO - α group had higher incidence of AECOPD and higher mortality,shorter period between the attacking time of first AECOPD and grouping time,and longer length of stay （P 〈0.05）in the follow - up period.High - level MRpro - ADM group had higher incidence of AECOPD and higher mortality, shorter period between the attacking time of first AECOPD and grouping time,and longer length of stay （P 〈0.05）than the low - level MRpro - ADM group during the follow - up period.For predicting the risk of AECOPD by serum GRO - α,the area under the ROC curve （AUC）was 0.866 〔95% CI （0.785,0.948）〕,the optimal cut - off value was 74.5 ng/ L with a sensitivity of 93% ,specificity of 74% and Youden′s index of 0.67.For predicting the risk of mortality by serum GRO - α,the AUC was 0.833 〔95% CI （0.729,0.937）〕,the optimal cut - off value was 93.5 ng/ L with a sensitivity of 94% ,specificity of 69% and Youden′s index of 0.62.For predicting the risk of AECOPD by serum MRpro - ADM,the AUC was 0.846 〔95% CI （0.762,0.930）〕,the optimal cut - off value was 0.70 nmol/ L with a sensitivity of 80% ,specificity of 78% and Youden′s index of 0.58.For predicting the risk of mortality by serum MRpro - ADM,the AUC was 0.871 〔95% CI （0.770,0.973）〕,the optimal cut - off value was 0.81 nmol/ L with a sensitivity of 69% ,specificity of 89% and Youden′s index of 0.58.Conclusion Serum GRO - α and MRpro - ADM can be used as the biological markers for predicting the risk of AECOPD and mortality in stable COPD patients.