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一项用于开发基于生物标志物的急性呼吸窘迫综合征诊断模型的回顾性巢式病例对照研究。

A Retrospective, Nested Case-Control Study to Develop a Biomarker-Based Model for ARDS Diagnostics.

作者信息

Fu Xuan, Lin Jinle, Seery Samuel, Ye Jianbing, Zeng Shiyong, Luo Yi, Shang You, Zhang Wenwu, Yu Xuezhong, Wu Jian, Xu Jun, Dou Qingli, Zeng Xiaobin

出版信息

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.220210.

DOI:10.7754/Clin.Lab.2022.220210
PMID:36649504
Abstract

BACKGROUND

Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics.

METHODS

There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes.

RESULTS

C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered.

CONCLUSIONS

A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.

摘要

背景

几种生物标志物可与传统指标相结合以改善急性呼吸窘迫综合征(ARDS)的诊断。

方法

在这项回顾性巢式病例对照研究中纳入了211例重症监护病房(ICU)患者。根据柏林标准,将参与者分为ARDS组(n = 79)和非ARDS组(n = 132)。在入院后三小时内收集患者特征、生命体征和实验室检查结果。在入住ICU后三小时内以及24小时时测量 Clara细胞蛋白16(CC16)、血管生成素2(Ang-2)、可溶性晚期糖基化终末产物受体(sRAGE)、高迁移率族蛋白B1(HMGB1)和分泌型血小板因子4(SPD)。应用受试者工作特征曲线和多因素逻辑回归分析进行预测。

结果

将C反应蛋白(CRP)、N末端脑钠肽前体(NT-proBNP)和pH值与五个既定的ARDS指标以及动脉血氧分压/吸入氧分数值(PaO2/FiO2)相结合。仅分析了四个潜在指标,其中CRP具有较高的诊断价值。曲线下面积(AUC)如下:CC16(AUC:0.752;95%可信区间0.680 - 0.824),Ang-2(AUC:0.695;95%可信区间0.620 - 0.770),HMGB1(AUC:0.668;95%可信区间0.592 - 0.744),sRAGE(AUC:0.665;95%可信区间0.588 - 0.743),CRP(AUC:0.701;95%可信区间0.627 - 0.776)。没有单一指标优于PaO2/FiO2比值,其AUC为0.844(95%可信区间0.789 - 0.898)。然而,当对二元逻辑模型进行转换并构建模型时,AUC从0.647(95%可信区间0.568 - 0.726)增加到0.911(95%可信区间0.864 - 0.946)。在所测试的组合中,PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1的AUC最高,为0.910(95%可信区间0.863 - 0.945),尽管还有其他因素必须考虑。

结论

生物标志物的组合可增强ARDS的诊断,这对患者护理和预后有明显影响。有可能开发出一种预测ARDS的列线图;然而,在此处测试的组合中,我们初步推荐PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1。这是因为与使用更复杂模型所涉及的益处相比,存在成本影响。需要进一步的卫生经济学研究来考虑急诊护理政策的机会成本。

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