脓毒症合并急性呼吸窘迫综合征患者外周血脂质运载蛋白-2及其受体的表达及其临床意义

Expression and clinical significance of lipocalin-2 and its receptor in peripheral blood of patients with sepsis complicating ARDS

摘要:

目的 探讨脓毒症合并急性呼吸窘迫综合征（ARDS）患者外周血脂质运载蛋白-2（LCN-2）及其受体（NGALR）的表达及其临床意义。方法 选取2020年1月—2022年1月南通市第一人民医院收治的脓毒症合并ARDS患者98例作为脓毒症合并ARDS组。根据病情严重程度分为轻度组（30例）、中度组（42例）和重度组（26例），另选取同期该院收治的82例单纯脓毒症患者和74例健康体检者作为单纯脓毒症组和对照组。采用酶联免疫吸附试验测定外周血LCN-2及NGALR水平，采用Pearson分析脓毒症合并ARDS患者外周血LCN-2及NGALR水平与氧合指数（OI）的相关性。随访21 d，统计脓毒症合并ARDS患者生存情况；采用单因素分析影响脓毒症合并ARDS患者死亡的因素；并对其影响因素进行多因素Logistic回归分析；采用受试者工作特征（ROC）曲线分析外周血LCN-2及NGALR水平，预测脓毒症合并ARDS患者死亡的价值。结果 脓毒症合并ARDS组、单纯脓毒症组外周血LCN-2、NGALR水平高于对照组，脓毒症合并ARDS组高于单纯脓毒症组（P <0.05）。重度组和中度组外周血LCN-2、NGALR水平高于轻度组，重度组高于中度组（P <0.05）。Pearson相关性分析显示，脓毒症合并ARDS患者外周血LCN-2、NGALR水平与OI均呈负相关（r =-0.390和-0.487，均P <0.05）。死亡组与存活组性别、年龄、基础疾病、机械通气、WBC、PCT、FBG、TG、TNF-α、Cr、UA、TC比较，差异均无统计学意义（P >0.05），死亡组多器官衰竭患者多于存活组，CRP、LCN-2、NGALR高于存活组，OI低于存活组（P <0.05）。多因素Logistic回归分析显示：多器官衰竭［O^R=4.112（95% CI：1.246，13.569）］、OI ≤ 300 mmHg［O^R=-3.473（95% CI：1.053，11.459）］、LCN-2［O^R=3.904（95% CI：1.183，12.882）］、NGALR［O^R=4.031（95% CI：1.222，13.301）］是脓毒症合并ARDS患者死亡的危险因素（P <0.05）。ROC曲线分析显示，外周血LCN-2及NGALR水平预测脓毒症合并ARDS患者死亡的最佳截断点分别为66.92 ng/mL、63.38 ng/mL，敏感性分别为84.37%（95% CI：0.672，0947）、81.25%（95% CI：0.636，0.928），特异性分别为78.79%（95% CI：0.670，0.879）、77.27%（95% CI：0.653，0.867），曲线下面积（AUC）分别为0.851（95% CI：0.765，0.915）、0.818（95% CI：0.727，0.888），两者联合敏感性、特异性和AUC分别为78.12%（95% CI：0.600，0.907）、96.97%（95% CI：0.895，0.996）和0.925（95% CI：0.853，0.968）。结论 脓毒症合并ARDS患者外周血LCN-2、NGALR水平均异常升高，临床检测外周血LCN-2、NGALR水平可作为预测脓毒症合并ARDS患者死亡的敏感指标。

Abstract:

Objective To explore the expression and clinical significance of lipocalin-2 (LCN-2) and its receptor, neutrophil gelatinase-associated lipocalin receptor (NGALR), in peripheral blood of patients with sepsis complicating acute respiratory distress syndrome (ARDS).Methods Nighty-eight patients with sepsis complicating ARDS who were admitted to the hospital from January 2020 to January 2022 were selected and divided into mild group (30 cases), moderate group (42 cases) and severe group (26 cases) according to the severity of the disease. In addition, 82 patients with sepsis alone admitted to the hospital and 74 healthy individuals undergoing health examinations during the same period were selected as the sepsis alone group and the control group, respectively. The levels of LCN-2 and NGALR in peripheral blood were determined by enzyme-linked immunosorbent assay. The correlation between levels of LCN-2 and NGALR in peripheral blood and oxygenation index (OI) was analyzed in patients with sepsis complicating ARDS via Pearson method. During the 21-day follow-up, the survival of patients with sepsis complicating ARDS was observed. The univariate analysis was used to determine the factors affecting the death of patients with sepsis complicating ARDS, and these potential predicting factors were further verified via multivariable Logistic regression analysis. In addition, the receiver operating curve was performed to analyze the value of peripheral blood LCN-2 and NGALR levels in predicting death of patients with sepsis complicating ARDS.Results The levels of LCN-2 and NGALR in peripheral blood of patients with sepsis complicating ARDS and patients with sepsis alone were higher than those of healthy individuals (P < 0.05), and they were even higher in patients with sepsis complicating ARDS than those in patients with sepsis alone (P < 0.05). The levels of LCN-2 and NGALR in peripheral blood of patients in the moderate group and severe group were higher than those of patients in the mild group (P < 0.05), and they were even higher in patients in the severe group than those in patients in the moderate group (P < 0.05). Pearson correlation analysis showed that the levels of LCN-2 (r = -0.390, P < 0.05) and NGALR (r = -0.487, P < 0.05) in peripheral blood of patients with sepsis complicating ARDS were negatively correlated with OI. There was no significant difference in gender composition, age, underlying diseases, mechanical ventilation, white blood cell count (WBC), or procalcitonin (PCT), fasting blood glucose (FBG), triglyceride (TG), tumor necrosis factor alpha (TNF-α), creatinine (Cr), uric acid (UA), and total cholesterol (TC) levels between the death cases and the surviving patients (P > 0.05). The proportion of multiple organ failure and the levels of C-reactive protein (CRP), LCN-2 and NGALR in the death cases were higher than those in the surviving patients (P < 0.05), whereas the OI of the death cases was lower than that of the surviving patients (P < 0.05). The multivariable Logistic regression analysis showed that multiple organ failure [O^R = 4.112 (95% CI: 1.246, 13.569) ], OI ≤ 300 mmHg [O^R = -3.473 (95% CI: 1.053, 11.459) ], and high levels of LCN-2 [O^R = 8.362 (95% CI: 1.183, 12.882) ] and NGALR [O^R = 4.031 (95% CI: 1.222, 13.301) ] were risk factors for death in patients with sepsis complicating ARDS (P < 0.05). ROC analysis exhibited that the optimal cut-off points of peripheral blood LCN-2 and NGALR levels for predicting the death of patients with sepsis complicating ARDS were 66.92 ng/mL and 63.38 ng/mL, with the sensitivities being 84.37% (95% CI: 0.672, 0947) and 81.25% (95% CI: 0.636, 0.928), the specificities being 78.79% (95% CI: 0.670, 0.879) and 77.27% (95% CI: 0.653, 0.867), and the areas under the ROC curves (AUCs) being 0.851 (95% CI: 0.765, 0.915) and 0.818 (95% CI: 0.727, 0.888). The specificity and AUC of the combination of the two indicators for predicting the death of patients with sepsis complicating ARDS were 96.97% (95% CI: 0.895, 0.996) and 0.925 (95% CI: 0.853, 0.968), respectively.Conclusions The levels of LCN-2 and NGALR are abnormally elevated in peripheral blood of patients with sepsis complicating ARDS. Thus, they can be established as sensitive indicators for predicting the death of patients with sepsis complicating ARDS.