中性粒细胞淋巴细胞比值预测H7N9禽流感预后的临床应用

Clinical application of neutrophil-to-lymphocyte ratio in predicting the prognosis of H7N9 avian influenza

目的探讨中性粒细胞淋巴细胞比值对H7N9禽流感预后的预测价值。方法采用回顾性分析2013年4月至2016年1月苏州大学附属第一医院救治的H7N9禽流感患者28例(治疗组),以同期健康体检者30名为健康对照组。治疗组28例患者随访半年后根据临床预后分为好转组18例和死亡组10例。收集患者入院后当天(基线)、3 d后、1周后血常规中白细胞、中性粒细胞、淋巴细胞、单核细胞、血小板计数,生物化学中肌酸激酶、乳酸脱氢酶、超敏C反应蛋白等炎性反应指标,计算中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、血小板与淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)、淋巴细胞与单核细胞比值(lymphocyte-to-monocyte ratio,LMR)、ΔNLR3(入院后3 d NLR-入院当天NLR)、ΔNLR7(入院后1周NLR-入院后3 d NLR),并以此类推计算ΔPLR3、ΔPLR7、ΔLMR3、ΔLMR7,比较好转组和死亡组上述指标的差异。正态分布的计量资料应用两独立样本t检验,非正态分布的计数资料采用Mann-Whitney U检验;二分类单因素和多因素logistic回归分析探讨影响疾病预后的因素,受试者工作特征曲线评估炎性反应指标对H7N9禽流感死亡事件的预测价值。结果治疗组基线白细胞、淋巴细胞、中性粒细胞、血小板计数,淋巴细胞、中性粒细胞、单核细胞比例,NLR、PLR、LMR与健康对照组比较,差异均有统计学意义(均P<0.01)。好转组治疗后3 d NLR、ΔNLR3分别为10.93(15.71)和0.87(-15.63),较死亡组的17.62(23.63)和7.42(22.68)明显降低,差异均有统计学意义(Z值分别为-2.16和-2.014,均P<0.05)。好转组治疗后7 d NLR、ΔNLR7分别为6.51(13.23)和-0.37(-12.38),较死亡组的27.90(25.64)和11.54(-26.22)明显降低,比较差异均有统计学意义(Z值分别为-2.444和-2.111,均P<0.05)。多因素logistic回归分析提示ΔNLR3是影响疾病预后的主要因素[比值比(OR)=1.153,95%CI:1.052~1.263,P=0.002];受试者工作特征曲线下面积为0.733(95% CI: 0.532~0.935,P=0.044);根据约登指数原则提示ΔNLR3预测死亡风险的临界值为5.453(灵敏度为0.700、特异度为0.722),ΔNLR3>5.453时H7N9流感患者病死率较高。结论动态监测NLR,特别是ΔNLR3可反映H7N9禽流感的病情和预后,是死亡事件的独立预测指标。

Objective To explore the predictive value of neutrophil-to-lymphocyte ratio on the prognosis of H7N9 avian influenza. Methods A retrospective analysis was conducted on 28 H7N9 avian influenza patients (treatment group) at the First Affiliated Hospital of Soochow University from April 2013 to January 2016. Thirty healthy physical examiners in the same period were enrolled as the healthy control group. The 28 patients were followed up for half a year and divided into the improvement group (18 cases) and the death group (10 cases) according to the clinical prognosis. Inflammatory indicators including white blood cells (WBC), neutrophil (N), lymphocyte (L), monocytes (M), platelet (PLT), creatine kinase (CK), lactate dehydrogenase (LDH), high sensitive C reactive protein were collected at day 1, day 3 and week 1 of admission. Calculation of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR),ΔNLR3 (day 3 of admission NLR-on day 1 of admission NLR),ΔNLR7 (week 1 of admission NLR -day 3 of admission NLR) and so on calculating ΔPLR3,ΔPLR7,ΔLMR3,ΔLMR7. Differences of the above indicators between the improvement group and death group were compared. The measurement data with normal distribution were tested by t-test of two independent samples, and the count data with non-normal distribution were tested by Mann-Whitney U-test. Univariate and multivariate logistic regression analysis to explore the prognostic factors and the working characteristic curve of subjects was used to evaluate the predictive value of inflammatory response indexes for H7N9 avian influenza death. Results In the treatment group, the baseline WBC, L, N, PLT, the proportion of lymphocytes, neutrophils, monocytes, and NLR, PLR, and LMR were all statistically different compared with the healthy control group (all P<0.01). After treatment, day 3 NLR,ΔNLR3 in improvement group were both significantly decreased to 10.93 (15.71) and 0.87 (-15.63), respectively when compared with death group (17.62[23.63] and 7.42[22.68], respectively)(Z=-2.16 and -2.014, respectively, both P<0.05). Day 7 NLR,ΔNLR7 in improved group were 6.51 (13.23) and -0.37 (-12.38), respectively, which were both lower than those of death group (27.90 [25.64] and 11.54 [-26.22]) with statistically significant differences (Z=-2.444 and -2.111, respectively, both P<0.05). Multivariate logistic regression analysis indicates that ΔNLR3 is the main factor that affects the prognosis of the H7N9 infection (odds ratio [OR]=1.153, 95% confidence interval [CI]: 1.052-1.263, P=0.002). Reciver operating characteristic curve analysis showed that the area under the curve was 0.733 (95% CI: 0.532-0.935, P=0.044). Based on the principle of Youden index, the cut-off value of ΔNLR3 to predict the death risk of H7N9 avian influenza was 5.453 with sensitivity of 0.700 and the specificity of 0.722. The mortality was higher when ΔNLR3 was higher than 5.453. Conclusions Dynamic monitoring NLR, especially ΔNLR3 may reflect the condition and prognosis of H7N9 infection, which is an independent predictor of death.