血清 suPAR 和 syndecan-4 水平可预测社区获得性肺炎的严重程度：一项前瞻性、多中心研究。
Serum suPAR and syndecan-4 levels predict severity of community-acquired pneumonia: a prospective, multi-centre study.
机构信息
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing, People's Republic of China.
出版信息
Crit Care. 2018 Jan 24;22(1):15. doi: 10.1186/s13054-018-1943-y.
BACKGROUND
Community-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. There are few studies focused on the expression of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 in patients with CAP.
METHODS
A prospective, multi-centre study was conducted between January 2014 and December 2016. A total of 103 patients with severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent assay. The t test and Mann-Whitney U test were used to compare between two groups; one-way analysis of variance and the Kruskal-Wallis test were used to compare multiple groups. Correlations were assessed using Pearson and Spearman tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and specificity were calculated. Survival curves were constructed and compared by log-rank test. Regression analyses assessed the effect of multiple variables on 30-day survival.
RESULTS
suPAR levels increased in all patients with CAP, especially in severe cases. Syndecan-4 levels decreased in patients with CAP, especially in non-survivors. suPAR and syndecan-4 levels were positively and negatively correlated with severity scores, respectively. suPAR exhibited high accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p < 0.001). In contrast, syndecan-4 exhibited poor diagnostic value for predicting SCAP (AUC 0.550, p = 0.187). The AUC for predicting mortality in patients with SCAP was 0.772 and 0.744 for suPAR and syndecan-4, respectively; the respective prediction threshold values were 10.22 ng/mL and 6.68 ng/mL. Addition of both suPAR and syndecan-4 to the Pneumonia Severity Index significantly improved their prognostic accuracy, with an AUC of 0.885. Regression analysis showed that suPAR ≥10.22 ng/mL and syndecan-4 ≤ 6.68 ng/mL were reliable independent markers for prediction of 30-day survival.
CONCLUSION
suPAR exhibits high accuracy for both diagnosis and prognosis of SCAP. Syndecan-4 can reliably predict mortality in patients with SCAP. Addition of both suPAR and syndecan-4 to a clinical scoring method could improve prognostic accuracy.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03093220 . Registered on 28 March 2017 (retrospectively registered).
背景
社区获得性肺炎（CAP）是全球范围内主要的死亡原因，其严重程度不一。目前，针对 CAP 患者中可溶性尿激酶型纤溶酶原激活物受体（suPAR）和 syndecan-4 的表达，仅有少数研究进行了关注。
方法
这是一项于 2014 年 1 月至 2016 年 12 月进行的前瞻性、多中心研究。共纳入 103 例重症 CAP（SCAP）患者、149 例非 SCAP 患者和 30 例健康对照者。所有纳入患者均记录了临床数据。通过定量酶联免疫吸附试验测定血清 suPAR 和 syndecan-4 水平。采用 t 检验和 Mann-Whitney U 检验比较两组间差异；采用单因素方差分析和 Kruskal-Wallis 检验比较多组间差异。采用 Pearson 和 Spearman 检验评估相关性。计算曲线下面积（AUCs）、最佳截断值、敏感度和特异度。通过 log-rank 检验构建和比较生存曲线。回归分析评估多个变量对 30 天生存率的影响。
结果
所有 CAP 患者的 suPAR 水平均升高，尤其是重症患者。CAP 患者的 syndecan-4 水平降低，尤其是死亡患者。suPAR 和 syndecan-4 水平与严重程度评分呈正相关和负相关。suPAR 对 CAP 患者中 SCAP 的预测具有较高的准确性，AUC 为 0.835（p<0.001）。相比之下，syndecan-4 对预测 SCAP 的诊断价值较低（AUC 0.550，p=0.187）。suPAR 和 syndecan-4 预测 SCAP 患者死亡率的 AUC 分别为 0.772 和 0.744，相应的预测截断值分别为 10.22ng/mL 和 6.68ng/mL。suPAR 和 syndecan-4 联合肺炎严重指数（PSI）可显著提高预后准确性，AUC 为 0.885。回归分析显示，suPAR≥10.22ng/mL 和 syndecan-4≤6.68ng/mL 是预测 30 天生存率的可靠独立标志物。
结论
suPAR 对 SCAP 的诊断和预后均具有较高的准确性。syndecan-4 可可靠预测 SCAP 患者的死亡率。suPAR 和 syndecan-4 联合临床评分方法可提高预后准确性。
试验注册
ClinicalTrials.gov，NCT03093220。于 2017 年 3 月 28 日注册（回溯性注册）。
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