脓毒症患者免疫指标与预后的关系——基于MIMIC-Ⅳ数据库的资料分析

Relationship between immune indexes and prognosis in patients with sepsis: data analysis based on MIMIC-Ⅳ database

目的探讨脓毒症患者免疫指标变化与预后的关系。方法基于美国重症监护医学信息数据库Ⅳv2.0(MIMIC-Ⅳv2.0),检索2008至2019年患者的住院信息,筛选出完成CD3计数、CD4计数、CD8计数、CD4/CD8比值、淋巴细胞计数(LYM)和免疫球蛋白(IgA、IgG、IgM)水平等免疫指标检查患者的住院资料,包括性别、年龄、体质量指数(BMI)、序贯器官衰竭评分(SOFA)及是否患有冠心病、高血压、糖尿病等基础疾病和28 d预后,对比分析影响脓毒症患者预后的免疫学指标,绘制受试者工作特征曲线(ROC曲线),分析免疫学指标对脓毒症患者28 d预后的预测价值。结果共33745例患者纳入研究,其中脓毒症1509例,非脓毒症32236例;脓毒症患者中28 d内存活1084例,死亡425例。脓毒症组BMI(kg/m^(2):33.25±28.71比28.90±15.28)及入院后3 d内和7 d内IgA水平〔入院后3 d内和7 d内IgA水平均为(275.01±216.96)mg/L比(85.99±75.76)mg/L〕均明显高于非脓毒症组(均P<0.05),入院后3 d内和7 d内CD3计数、CD8计数均明显低于非脓毒症组〔入院后3 d内:CD3计数(个/μL)为1080.74±849.23比1242.91±889.24,CD8计数(个/μL)为558.07±368.77比625.07±529.66;入院后7 d内:CD3计数(个/μL)为1079.69±850.61比1242.48±889.23,CD8计数(个/μL)为556.70±467.23比624.93±429.78;均P<0.05〕,且合并高血压、糖尿病、冠心病等基础疾病患者比例均明显高于非脓毒症组〔高血压:10.07%(152/1509)比2.47%(796/32236),糖尿病:50.10%(756/1509)比15.18%(4895/32236),冠心病:31.21%(471/1509)比19.19%(6186/32236),均P<0.05〕。脓毒症组中28 d内存活患者入院后3 d内和7 d内CD3计数、CD4计数、CD4/CD8比值均明显高于28 d内死亡患者〔入院后3 d内:CD3计数(个/μL)为1127.20±857.14比938.26±810.50,CD4计数(个/μL)为559.76±507.18比338.75±267.11,CD4/CD8比值为1.87±0.80比1.02±0.12;入院后7 d内:CD3计数(个/μL)为1124.01±810.53比943.78±808.21,CD4计数(个/μL)为559.56±507.36比341.95±266.56,CD4/CD8比值为1.88±0.79比1.03±0.13;均P<0.05〕。入院后3 d内CD4/CD8比值预测脓毒症患者28 d预后的ROC曲线下面积(AUC)为0.615〔95%可信区间(95%CI)为0.555~0.671〕,敏感度为70.83%,特异度为52.49%。结论合并高血压、冠心病、糖尿病等基础疾病的患者更容易发生脓毒症,脓毒症患者在早期会出现免疫学指标的变化,早期CD4/CD8比值可在一定程度上预测脓毒症患者的预后情况。

Objective To investigate the relationship between the changes of immune indexes and prognosis in patients with sepsis.Methods Based on the hospitalization information from 2008 to 2019 in the American Medical Information Mart for Intensive Care-Ⅳv2.0(MIMIC-Ⅳv2.0),the hospitalized data including CD3 count,CD4 count,CD8 count,CD4/CD8 ratio,immunoglobulins(IgA,IgG,IgM)levels and lymphocyte counts,gender,age,body mass index(BMI),sequential organ failure assessment(SOFA),and prognosis of patients with coronary heart disease,hypertension,diabetes mellitus,underlying diseases,and 28-day prognosis were collected.The immunological indexes affecting the prognosis of patients with sepsis were compared and analyzed.The receiver operator characteristic curve(ROC curve)was drawn to analyze the value of immunological indexes in predicting the 28-day prognosis of patients with sepsis.Results A total of 33745 patients were enrolled in the study,including 1509 cases of sepsis and 32236 cases without sepsis.Among the patients with sepsis,there were 1084 cases alive and 425 cases died within 28 days.BMI(kg/m^(2):33.25±28.71 vs.28.90±15.28)and IgA levels within 3 days and 7 days after admission in sepsis group were significantly higher than those in the non-sepsis group[within 3 days after admission:(275.01±216.96)mg/L vs.(85.99±75.76)mg/L;within 7 days after admission:(275.01±216.96)mg/L vs.(85.99±75.76)mg/L,all P<0.05].CD3 count,CD8 count within 3 days and 7 days after admission in sepsis group were significantly lower than that in the non-sepsis group[within 3 days after admission:CD3 counts were(1080.74±849.23)/μL vs.(1242.91±889.24)/μL,CD8 counts were(558.07±368.77)/μL vs.(625.07±529.66)/μL;within 7 days after admission:CD3 counts were(1079.69±850.61)/μL vs.(1242.48±889.23)/μL,CD8 counts were(556.70±467.23)/μL vs.(624.93±429.78)/μL,all P<0.05].The proportion of patients with hypertension,diabetes and coronary heart disease were significantly higher than those in the non-sepsis group[hypertension:10.07%(152/1509)vs.2.47%(796/32236),diabetes:50.10%(756/1509)vs.15.18%(4895/32236),coronary heart disease:31.21%(471/1509)vs.19.19%(6186/32236),all P<0.05].In the sepsis group,the CD3 count,CD4 count and CD4/CD8 ratio in the survival group were significantly higher than those in the death group within 3 days and 7 days after admission[within 3 days after admission:CD3 counts were(1127.20±857.14)/μL vs.(938.26±810.50)/μL,CD4 counts were(559.76±507.18)/μL vs.(338.75±267.11)/μL,CD4/CD8 ratios were 1.87±0.80 vs.1.02±0.12;within 7 days after admission:CD3 count were(1124.01±810.53)/μL vs.(943.78±808.21)/μL,CD4 count were(559.56±507.36)/μL vs.(341.95±266.56)/μL,CD4/CD8 ratios were 1.88±0.79 vs.1.03±0.13,all P<0.05].The area under the ROC curve(AUC)of CD4/CD8 ratio within 3 days after admission in predicting the prognosis of septic patients at 28 days was 0.615[95%confidence interval(95%CI)was 0.555-0.671],the sensitivity was 70.83%,and the specificity was 52.49%.Conclusions Hypertension,coronary heart disease and diabetes are more likely to induce sepsis.The changes of immune indexes in patients with sepsis will occur in the early stage.Early CD4/CD8 index can predict the prognosis of patients with sepsis to a certain extent.