细胞因子IL-9与急性呼吸窘迫综合征患者预后的临床研究

Clinical study of the predictive value of the IL-9 cytokines in the patients with acute respiratory distress syndrome

目的探讨细胞因子IL-9在急性呼吸窘迫综合征（acuterespiratorydistresssyndrome，ARDS）患者预后中的作用。方法采用前瞻性的病例对照研究，根据2012年柏林定义的ARDS的诊断标准，纳入2013年6月至2014年7月新疆医科大学第一附属医院急诊科ARDS患者28例作为研究对象（ARDS组），其中重症肺炎23例，急性汞中毒1例，急性重症胰腺炎2例，急性百草枯中毒2例。选择同期健康体检者22例为对照组，收集资料并进行跟踪随访。收集确诊ARDS患者第1天的临床资料，根据2012年柏林定义分为中度组（18例）和重度组（10例），随访28d根据预后情况分为存活组（13例）和死亡组（15例）。患者确诊ARDS第1、3天清晨空腹抽外周血静脉血3mL，对照组抽空腹外周静脉血3mL，采用双抗体夹心酶联免疫吸附法检测患者及和健康对照组血清IL-9浓度，将ARDS组与健康对照组第1天的IL-9浓度进行比较；将中度组和重度组的第1、3天血清IL-9浓度进行比较；将存活组和死亡组第1、3天血清IL-9浓度进行比较。用SPSS19．0软件进行统计分析，并通过ROC曲线评价IL-9的预后价值。结果确诊ARDS第1天，存活组和死亡组在年龄、APACHEII评分、降钙素原、超敏C反应蛋白、白细胞计数、乳酸、白蛋白方面比较差异均无统计学意义（P〉0．05），死亡组pH明显低于存活组（P〈0．05）；ARDS患者外周静脉血清IL-9水平明显高于健康对照组，差异具有统计学意义（P〈0．05）；中度组患者与重度组患者IL-9比较差异均无统计学意义（P〉0．05）；存活组与死亡组患者外周静脉血清IL-9水平比较差异无统计学意义（P〉0．05）。ARDS确诊的第3天，中度组患者外周静脉血清IL-9水平明显低于重度组患者，差异具有统计学意义（P〈0．05）；死亡组患者外周静脉血清IL-9水平明显高于存活组患者，差异具有统计学意义（P〈0．05）。应用ROC曲线预测患者病死率分析，第1天IL-9的AUC为0．579（95％C／0．361—0．798，P〉0．05），差异无统计学意义；第3天IL-9的AUC为0．769（95％C／0．592—0．947，P〈0．05），差异具有统计学意义。最佳28d死亡预测值2．88pg／mL，其灵敏度86．7％，特异度61．5％。结论ARDS患者IL-9水平显高，早期动态观察血清IL-9水平可有助于评估ARDS严重程度和预测其预后。

Objective To investigate the predictive value of IL-9 cytokines in the patients with acute respiratory distress syndrome （ARDS）. Methods According to Berlin definition of ARDS published in 2012, data of 28 patients with ARDS and another 22 healthy subjects as control were collected for prospective study from June, 2013 to July, 2014. Of them, there were 23 patients with severe pneumonia, 1 patient with acute mercury poisoning, 2 patients with severe acute pancreatitis, 2 patients with acute paraquat poisoning. The survivors of ARDS patients were followed up. The ARDS patients were divided into moderate group （n = 18） and severe group （n = 10） as per the severity of the disease diagnosed at the first day after admission. And the ARDS patients were also divided into non-survival group （n = 15 ） and survival group （n--13 ） according to the ARDS patients survived for 28 days. Three mLs of peripheral venous blood were collected in the early morning from fasted ARDS patients on the first and the third day after diagnosis of ARDS confirmed, and those of healthy subjects were collected on the first day after admission. The IL-9 cytokine level of peripheral venous blood detected by using enzyme linked immunosorbent assay （ELISA）. The comparisons of levels of IL-9 cytokine were carried out between ARDS group and control group on the first day after diagnosis of ARDS established, between moderate group and severe group on the first day and the third day, and between survival group and non-survival group. The receiver operating characteristic （ROC） curve was used to evaluate the performance of IL-9 as a prognostic indicator in the early stage of ARDS. Data were analyzed by using SPSS 19. 0 software. Results On the first day after diagnosis of ARDS, there were no statistically significant differences in age, APACHE 11 score, procalcitonin （ PCT）, C-reactive protein （CRP）, white blood cell count, lactate, and albumin between survival group and non- survival group （P 〉 0. 05 ）. PH value in non-survival group was significantly lower than that in survival group （P 〈 0. 05 ）. IL-9 cytokine level of peripheral venous serum in ARDS group was significantly higher than that in healthy control group （ P 〈 0. 05 ）. There were no statistically significant differences in IL-9 level of peripheral venous serum both between moderate group and severe group and between survival group and non-survival group （P 〉 0. 05）. On the third day, IL-9 level in severe group was significantly higher than that in moderate group （ P 〈 0. 05 ）, and that in survival group was significantly lower than that in non- survival group （ P 〈 0. 05 ）. The ROC of IL-9 at the first day for predicting mortality had all area under curve （AUC） to be 0. 579 （95% CI 0. 361-0. 798, P 〉 0. 05）. The ROC of IL-9 on the third day for predicting mortality had AUC of 0. 769 （95% CI 0. 592-0. 947, P 〈 0.05 ）. When the cut-off value of IL-9 for the death followed up for 28 day＇s was 2. 88 pg/mL, the sensitivity was 86. 7%, and the specificity was 61.5%. Conclusions IL-9 levels of in patients with ARDS were significantly higher, and IL-9 level can be helpful for the assessment of ARDS severity in the early stage, and for prognosis as well.