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Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin
BMJ Open Respiratory Research ( IF 3.6 ) Pub Date : 2021-07-01 , DOI: 10.1136/bmjresp-2021-000889
Toru Arai 1 , Hiroto Matsuoka 2 , Masaki Hirose 1 , Hiroshi Kida 3, 4 , Suguru Yamamoto 5 , Yoshitaka Ogata 6 , Masahide Mori 3 , Kazuyoshi Hatsuda 1 , Chikatoshi Sugimoto 1 , Kazunobu Tachibana 1 , Masanori Akira 1 , Yoshikazu Inoue 7
Affiliation  

Background Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs. Methods This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse. Results Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality. Conclusions A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome. Trial registration number UMIN000014969. No data are available. The data that support the findings of this study have not been made available because this study was approved in 2014 and data sharing was not included in the design of this study.

中文翻译:

血栓调节蛋白治疗特发性间质性肺炎急性加重期间血清细胞因子的预后意义

背景 据报道,急性加重 (AE) 预示着特发性肺纤维化的预后不良,现在认为在特发性间质性肺炎 (IIP) 中也是如此。然而,AE-IIP 的病理生理学尚未得到充分了解。在我们之前报道的 SETUP 试验中,我们发现接受皮质类固醇和血栓调节蛋白治疗的 AE-IIP 患者比单独接受皮质类固醇治疗的患者有更好的生存率。在该研究中,我们收集了血清样本来评估细胞因子水平的变化,并回顾性检查了 AE-IIP 患者血清细胞因子的预后意义和病理生理学作用。方法 本研究纳入了来自 SETUP 试验的 28 名患者,前瞻性地为其获取了系列血清样本。AE-IIP 使用日本呼吸学会标准进行诊断。2014 年至 2016 年,所有患者均接受静脉血栓调节蛋白和皮质类固醇治疗。使用 Bio-Plex 测量 27 种细胞因子的血清水平。诊断 AE 时的高分辨率 CT 模式被分类为弥漫性或非弥漫性。结果 单变量分析显示,血清白细胞介素(IL)-2、IL-7、IL-9、IL-12、IL-13、碱性成纤维细胞生长因子、粒细胞巨噬细胞集落刺激因子、干扰素-γ诱导蛋白-10水平升高。 、血小板衍生生长因子和激活调节、AE 时表达和分泌的正常 T 细胞 (RANTES) 是 90 天生存的重要预测因子。HRCT 模式也是 90 天生存的重要临床预测因子。逐步选择的多变量分析发现,AE 时较高的血清 RANTES 水平是 90 天生存率的显着预测因子,包括在调整 HRCT 模式后。逐步选择的多变量分析表明,第 8 天血清 IL-10 水平的显着升高可以预测 90 天的死亡率。结论 AE 诊断时较高的血清 RANTES 水平预示着良好的生存结果,第 8 天升高的血清 IL-10 水平预示着较差的生存结果。试用注册号 UMIN000014969。无可用数据。支持这项研究结果的数据尚未提供,因为这项研究于 2014 年获得批准,并且数据共享并未包含在这项研究的设计中。
更新日期:2021-07-29
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