Division of Infectious Diseases, Department of Medicine, University of California, San Diego, San Diego, CA, United States.
Division of Pulmonology, Medical University of Graz, Graz, Austria.
Front Immunol. 2019 Aug 2;10:1798. doi: 10.3389/fimmu.2019.01798. eCollection 2019.
Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; < 0.001) for predicting 90-day mortality. Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.
霉菌和其他病原体可诱导几种细胞因子水平升高,包括白细胞介素(IL)-6 和 IL-8。本研究旨在探讨血液和支气管肺泡灌洗液(BAL)中 IL-6 和 IL-8 以及真菌生物标志物对基础血液恶性肿瘤和疑似霉菌感染患者总生存率的预后价值。这项前瞻性队列研究纳入了 106 例接受支气管镜检查的成年患者。血液样本在 BAL 采样后 24 小时内采集,在 62 例患者的亚组中,连续血液样本在支气管镜检查后 4 天内采集。在血液和 BAL 液中检测了 IL-6、IL-8 和其他细胞因子以及半乳甘露聚糖(GM)和 β-D-葡聚糖(BDG),并在研究结束时使用受试者工作特征(ROC)曲线分析评估与总死亡率的相关性。支气管镜检查时的血液 IL-8(AUC 0.731)和血液 IL-6(AUC 0.699)以及 BAL IL-6(AUC 0.763)和 BAL IL-8(AUC 0.700)水平均为 30 天全因死亡率的预测指标。支气管镜检查后 4 天内血液中 IL-6 水平升高与 90 天死亡率升高显著相关,IL-8 水平升高也存在类似的发现。在 ROC 分析中,支气管镜检查后 4 天与支气管镜检查当天的血液 IL-8 水平差异的 AUC 为 0.829(95%CI 0.71-0.95;<0.001),可预测 90 天死亡率。在这些接受支气管镜检查以疑似霉菌感染的基础血液恶性肿瘤患者中,支气管镜检查时血液或 BAL 液中 IL-6 和 IL-8 水平升高,以及支气管镜检查后 4 天血液中水平升高,均提示死亡风险增加。