循环总IgG水平与慢性阻塞性肺疾病患者急性加重和死亡风险的相关性研究

The relation between plasma IgG level and acute exacerbation or death risk in patients with chronic obstructive pulmonary disease

目的探讨慢性阻塞性肺疾病(简称慢阻肺)患者血浆免疫球蛋白G(Ig G)水平与急性加重(AE)和死亡的相关性。方法选取2018年2月至2020年2月间于我院就诊的262例慢阻肺患者,根据随访1年间AE发生次数分为AE≥2组和AE≤1组,比较两组入组时一般资料以及Ig G、免疫球蛋白A(Ig A)、免疫球蛋白M(Ig M)等实验室检查结果,应用单因素分析和多因素COX回归分析患者1年间AE发生次数≥2次的影响因素,采用R软件绘制限制性立方样条评估基线Ig G水平与AE的关联。再根据患者血浆Ig G和Ig A基线水平的中位数将患者分为高Ig G组、低Ig G组、高Ig A组、低Ig A组,以Kaplan-Meier方法绘制生存曲线,分析不同水平组AE和死亡风险差异。结果随访截止至2021年2月28日,共有14例患者失访,纳入248例(AE≤1组154例,AE≥2组94例)。AE≥2组年龄和慢阻肺评估测试(CAT)评分高于AE≤1组(P<0.05)。AE≥2组白蛋白、Ig G、Ig A水平低于AE≤1组,中性粒细胞与淋巴细胞比值(NLR)高于AE≤1组(均P<0.05)。Kaplan-Meier生存分析结果示:高Ig G组和高Ig A组AE风险分别低于低Ig G组和低Ig A组(log rankχ^(2)=23.791、67.153,均P=0.000),高Ig G组死亡风险低于低Ig G组(log rankχ^(2)=6.214,P=0.013),高Ig A组死亡风险与低Ig A组相比差异无统计学意义(log rankχ^(2)=2.400,P=0.121);CAT评分(HR=1.096,P=0.001)和NLR(HR=2.061,P=0.000)为慢阻肺患者1年内AE≥2次的独立危险因素,白蛋白(HR=0.921,P=0.006)和Ig G(HR=0.572,P=0.000)为独立保护因素;限制性立方样条分析结果示:结合COX回归模型,调整Ig A、白蛋白、NLR等变量后,Ig G水平与AE呈非线性关系(P=0.000)。结论慢阻肺患者血浆Ig G水平与AE相关,有可能成为AE风险预测因子。

Objective To explore the association between plasma Ig G and acute exacerbation(AE)or death risk in patients with chronic obstructive pulmonary disease(COPD).Methods A total of 262 COPD patients treated in our hospital from February 2018 to February 2020 were recruited in our study.All patients were divided into AE≥2 group and AE≤1 group according to AE frequency during follow-up of 1 year.Basic data and laboratory data such as Ig G,Ig A and Ig M of two groups were comparatively analyzed.Univariate analysis and COX regression were performed to analyze the related factors of frequency of AE≥2 times in 1 year.Depicting restricted cubic spline was performed to analyze the relation between Ig G and AE by R software.All patients were also divided into high Ig G group,low Ig G group,high Ig A group and low Ig A group based on median of patients’baseline plasma Ig G and Ig A level,depicting survival curve by Kaplan-Meier to analyse differences between the groups with different Ig G or Ig A level in the risk of AE and death respectively.Results Finally,there were 14 patients lost to follow-up and 248 cases were included(AE≤1 group contained 154 cases,AE≥2 group contained 94 cases)until February 28,2021.Age and COPD Assessment Test(CAT)scores in the AE≥2 group were higher than those in the AE≤1 group;Albumin,Ig G and Ig A level in the AE≥2 group were lower than those in the AE≤1 group;Neutrophil to lymphocyte ratio(NLR)in the AE≥2 group was higher than that in the AE≤1 group(all P<0.05).There were 99 and 114 cases of AE in the high Ig G and low Ig G groups respectively within1 year.Kaplan Meier survival analysis showed that risk of AE in the high Ig G group and high Ig A group were lower than that in the low Ig G group and the low Ig A group(log rankχ^(2)=23.791,67.153,both P=0.000).Risk of death in the high Ig G group was lower than that in the low Ig G group(log rankχ^(2)=6.214,P=0.013),there was no statistically difference in the risk of death in the high Ig A group compared to the low Ig A group(log rankχ^(2)=2.400,P=0.121).Multivariate Cox regression analysis showed that CAT score(HR=1.096,P=0.001)and NLR(HR=2.061,P=0.000)were independent risk factors of frequency of AE≥2 times in 1 year for COPD patients,albumin(HR=0.921,P=0.006)and Ig G(HR=0.572,P=0.000)were the independent protective factors.Restricted cubic spline analysis showed that combining the COX regression model,after adjusting for Ig A,albumin,NLR and other variables,there was non-linear relationship between Ig G level and AE(P=0.000).Conclusion Plasma Ig G level is related to AE in COPD patients,and may become a reliable predictor of acute exacerbation risk in the future.