鉴定原发性念珠菌肺炎兔模型中的早期生物标志物。
Identification of early biomarkers in a rabbit model of primary Candida pneumonia.
机构信息
Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, No. 128 Ruili Road, Shanghai, 200240, China.
Department of Respiratory, Taizhou Municipal Hospital, No. 381 East Zhongshan Road, Taizhou, 318000, Zhejiang Province, China.
出版信息
BMC Infect Dis. 2019 Aug 6;19(1):698. doi: 10.1186/s12879-019-4320-9.
BACKGROUND
Candida albicans is an opportunistic pathogen, but since it also belongs to the normal fungal flora, positive sputum culture as the solely basis for the diagnosis of invasive Candida albicans pneumonia can easily lead to excessive antifungal therapy. Therefore, identification of a pneumonia biomarker might improve diagnostic accuracy.
METHODS
A rabbit model was established by inoculating 5 × 10 cfu/mL C. albicans into the trachea of 20 rabbits with 20 rabbits as control group. Infection was monitored by chest thin-layer computed tomography (CT). 2 mL blood samples were collected daily during each infection and serum levels of potential biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Seven-day post-inoculation the rabbits were sacrificed by CO asphyxiation and lung tissue was histopathologically examined and blood was brought to culture. Data were statistically analyzed.
RESULTS
Infection became evident as early as day 3 post-inoculation. The levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble hemoglobin-haptoglobin scavenger receptor (sCD163), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) were elevated in the experimental group compared to the control (P < 0.01), whereas the levels of C-reactive protein (CRP), interleukin-6 (IL-6), IL-8 and IL-10 showed no significant differences (P > 0.05). The dynamic curves of the levels of CRP, IL-6, IL-8, IL-10, SCD163 and TNF-α in both groups demonstrated a similar trend during infection but differences between the groups was observed only in the sTREM-1 levels. Receiver-operating characteristics (ROC) curve analysis showed that the sensitivity and specificity were 85 and 80% for sTREM-1 (cut-off value: 45.88 pg/mL) and 80 and 75% for SCD163 (cut-off value: 16.44 U/mL), respectively. The values of the area under the ROC curve (AUC) of sTREM-1 and SCD163 were 0.882 (95% CI: 0.922-0.976) and 0.814 (95% CI: 0.678-0.950), respectively. Other markers did not exhibit significant differences.
CONCLUSION
sTREM-1 and SCD163 might be suitable biomarkers for pneumonia.
背景
白色念珠菌是一种机会性病原体，但由于它也属于正常的真菌菌群，因此仅通过痰液培养阳性作为侵袭性白色念珠菌肺炎的诊断依据，容易导致过度的抗真菌治疗。因此，鉴定肺炎的生物标志物可能会提高诊断的准确性。
方法
通过将 5×10cfu/ml 的白色念珠菌接种到 20 只兔子的气管中，建立了兔模型，20 只兔子作为对照组。通过胸部薄层 CT（CT）监测感染情况。在每次感染期间，每天采集 2ml 血液样本，通过酶联免疫吸附试验（ELISA）测量潜在生物标志物的血清水平。接种后 7 天，用 CO 窒息处死兔子，对肺组织进行组织病理学检查，并采血进行培养。对数据进行了统计学分析。
结果
感染在接种后第 3 天即可观察到。与对照组相比，实验组可溶性髓系细胞触发受体-1（sTREM-1）、可溶性血红蛋白-触珠蛋白 scavenger 受体（sCD163）、降钙素原（PCT）和肿瘤坏死因子-α（TNF-α）的水平升高（P<0.01），而 C 反应蛋白（CRP）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-10（IL-10）的水平无显著差异（P>0.05）。两组的 CRP、IL-6、IL-8、IL-10、sCD163 和 TNF-α水平的动态曲线在感染过程中显示出相似的趋势，但仅在 sTREM-1 水平上观察到组间差异。受试者工作特征（ROC）曲线分析显示，sTREM-1 的敏感性和特异性分别为 85%和 80%（截断值：45.88pg/ml），sCD163 的敏感性和特异性分别为 80%和 75%（截断值：16.44u/ml）。sTREM-1 和 sCD163 的 ROC 曲线下面积（AUC）值分别为 0.882（95%置信区间：0.922-0.976）和 0.814（95%置信区间：0.678-0.950）。其他标志物无显著差异。
结论
sTREM-1 和 sCD163 可能是肺炎的合适生物标志物。
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