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Sputum trypsin-like protease activity relates to clinical outcome in cystic fibrosis.

痰胰蛋白酶样蛋白酶活性与囊性纤维化的临床结局相关。

  • 影响因子:2.88
  • DOI:10.1016/j.jcf.2019.12.014
  • 作者列表:"Rehill J","Moffitt K","Douglas L","Stuart Elborn J","Jones A","Lorraine Martin S
  • 发表时间:2020-01-10
Abstract

BACKGROUND:In cystic fibrosis (CF) airways excessive levels of serine trypsin-like proteases (TLPs) activate the epithelial sodium channel (ENaC) resulting in airways dehydration and promotion of mucus secretion. Despite this the relationship of TLP activity and clinical outcome has not been studied. METHODS:We analysed supernatant (sol) prepared from CF sputum from adult CF patients in two study cohorts (29 and 33 samples, respectively). Protease activities were determined by measuring the hydrolysis of peptide-based substrates or by ELISA. Lung function was assessed by spirometry (FEV1). Mortality data was retrospectively obtained and time in months until death or transplantation used for subsequent survival analysis. RESULTS:TLP activity inversely correlated with percent predicted FEV1 (r = -0.4, p = 0.03) and was greater in individuals who did not survive beyond 5-years from the time of sample collection. A Kaplan-Meier analysis demonstrated significantly reduced survival (p = 0.04) for individuals with high TLP activity [hazard ratio (HR) of 7.21 per log unit TLP activity (p = 0.03)]. In contrast, neutrophil elastase displayed no significant associations with lung function or patient survival. Similar findings were evident in the second study cohort. CONCLUSIONS:Sputum TLP activity may represent a novel non-invasive biomarker and/or therapeutic target for CF lung disease.

摘要

背景: 在囊性纤维化 (CF) 气道中,过量的丝氨酸胰蛋白酶样蛋白酶 (TLPs) 激活上皮钠通道 (ENaC),导致气道脱水和促进粘液分泌。尽管如此,尚未研究 TLP 活性与临床结局的关系。 方法: 我们分析了两个研究队列 (分别为 29 份和 33 份样本) 中成人 CF 患者 CF 痰制备的上清液 (sol)。通过测定肽基底物的水解或 ELISA 测定蛋白酶活性。肺功能通过肺活量测定法 (FEV1) 评估。回顾性获得死亡率数据,并在 6 个月内获得时间,直至死亡或移植用于随后的生存分析。 结果: TLP 活性与预计 FEV1 百分比呈负相关 (r =-0.4,p = 0.03),在样本采集后存活时间未超过 5 年的个体中,TLP 活性更大。Kaplan-Meier 分析显示,高 TLP 活性个体的生存率显著降低 (p = 0.04) [每个日志单位 TLP 活性的风险比 (HR) 为 7.21 (p = 0.03)]。相比之下,中性粒细胞弹性蛋白酶与肺功能或患者生存率无显著相关性。在第二个研究队列中也有类似的发现。 结论: 痰 TLP 活性可能代表 CF 肺病的一种新型非侵入性生物标志物和/或治疗靶点。

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翻译标题与摘要 下载文献
影响因子:4.40
发表时间:2020-01-01
DOI:10.1007/s00262-019-02431-8
作者列表:["Shibaki, Ryota","Murakami, Shuji","Matsumoto, Yuji","Yoshida, Tatsuya","Goto, Yasushi","Kanda, Shintaro","Horinouchi, Hidehito","Fujiwara, Yutaka","Yamamoto, Nobuyuki","Kusumoto, Masahiko","Yamamoto, Noboru","Ohe, Yuichiro"]

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翻译标题与摘要 下载文献
影响因子:4.04
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作者列表:["Sousa SA","Soares-Castro P","Seixas AMM","Feliciano JR","Balugas B","Barreto C","Pereira L","Santos PM","Leitão JH"]

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