生物标志物对严重恶性疟患者临床肺水肿的预测能力较低：一项前瞻性观察研究。

The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study.

机构信息

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Division of Infectious Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji Shimotsuke-shi, Tochigi, 329-0498, Japan.

出版信息

Malar J. 2024 Oct 24;23(1):320. doi: 10.1186/s12936-024-05142-3.

DOI:10.1186/s12936-024-05142-3

PMID:39448997

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11515577/

Abstract

BACKGROUND

Pulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.

METHODS

An exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.

RESULTS

Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (r = 0.39; P = 0.004, r = 0.43; P = 0.001, r = 0.54; P < 0.001, r = 0.44; P < 0.001, r = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (r = 0.37; P = 0.005, r = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.

CONCLUSIONS

IL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.

摘要

背景

肺水肿是疟疾治疗开始后出现的一种严重疟疾的可怕且难以预测的并发症。促炎介质被认为在其发病机制中起核心作用。

方法

在孟加拉国的两家医院进行了一项探索性研究，以评估生物标志物对严重恶性疟患者发生临床肺水肿的预测能力。比较了入院时血浆中白细胞介素 6 (IL-6)、白细胞介素 8 (IL-8)、肿瘤坏死因子 (TNF)、晚期糖基化终产物受体 (sRAGE)、表面活性蛋白-D (SP-D)、俱乐部细胞分泌蛋白 (CC16) 和 Krebs von den Lungen-6 (KL-6) 的浓度与健康对照组。评估了这些生物标志物与血浆乳酸和恶性疟原虫富含组氨酸蛋白 2 (PfHRP2) 水平之间的相关性。构建了接收者操作特征 (ROC) 曲线以评估感兴趣的生物标志物对临床肺水肿的预测能力。

结果

在筛选出的 106 例恶性疟患者中，有 56 例被归类为患有严重疟疾，死亡率为 29%。入院后有 9 名(16%)患者发生临床肺水肿。与健康对照组相比，患者的生物标志物水平较高。IL-6、IL-8、TNF、sRAGE 和 CC16 水平与血浆 PfHRP2 水平呈良好相关性(r=0.39；P=0.004，r=0.43；P=0.001，r=0.54；P<0.001，r=0.44；P<0.001，r=0.43；P=0.001)。此外，IL-6 和 IL-8 水平与血浆乳酸水平呈良好相关性(r=0.37；P=0.005，r=0.47；P<0.001)。这些生物标志物均不能用于预测严重疟疾患者发生临床肺水肿。