Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK.
BMJ Open Respir Res. 2019 Sep 24;6(1):e000440. doi: 10.1136/bmjresp-2019-000440. eCollection 2019.
Pleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.
Data and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey's post hoc tests were used to estimate statistical significance. Pearson's correlation coefficient was used to assess linear correlation.
Intrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1-3). No significant difference was detected between any groups during the post-treatment period (days 5-7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF.
We conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway.
胸腔感染（PI）是一种发病率不断上升的全球性疾病，胸腔积液（PF）引流对于成功治疗至关重要。MIST2 研究表明，胸腔内给予组织纤溶酶原激活物（t-PA）和 DNA 酶或 t-PA 单独给药均可增加引流 PF 的量。小鼠模型研究表明，体积增加是由于纤溶酶原通过单核细胞趋化蛋白 1（MCP-1）途径与胸膜相互作用所致。我们设计了一项研究，以确定在人类中给予 t-PA±DNase 时胸腔内给药后 PF 引流量诱导的时间框架，并检验诱导是通过 MCP-1 途径介导的假设。
使用 MIST2 研究的数据和样本（210 名 PI 患者随机接受 3 天治疗：t-PA 和 DNase、t-PA 和安慰剂、DNase 和安慰剂或双安慰剂）。通过 ELISA 测量 PF MCP-1 水平。使用单因素和双因素方差分析（ANOVA）和 Tukey 事后检验估计统计学意义。使用 Pearson 相关系数评估线性相关性。
t-PA±DNase 胸腔内给药在治疗期间（第 1-3 天）刺激引流 PF 量呈统计学显著增加。在治疗后期间（第 5-7 天），任何组之间均未检测到显著差异。t-PA 胸腔内给药增加了治疗期间 PF MCP-1 水平；然而，接受 t-PA 和未接受 t-PA 的患者之间未检测到统计学差异。PF MCP-1 表达与给药药物或引流 PF 量均无相关性。
我们得出结论，给予 t-PA 后观察到的 PF 引流量增加似乎并非仅通过激活 MCP-1 途径起作用。
