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Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients.

Authors :
Kanellakis NI
Wrightson JM
Hallifax R
Bedawi EO
Mercer R
Hassan M
Asciak R
Hedley E
Dobson M
Dong T
Psallidas I
Rahman NM
Source :
BMJ open respiratory research [BMJ Open Respir Res] 2019 Sep 24; Vol. 6 (1), pp. e000440. Date of Electronic Publication: 2019 Sep 24 (Print Publication: 2019).
Publication Year :
2019

Abstract

Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Details

Language :
English
ISSN :
2052-4439
Volume :
6
Issue :
1
Database :
MEDLINE
Journal :
BMJ open respiratory research
Publication Type :
Academic Journal
Accession number :
31673364
Full Text :
https://doi.org/10.1136/bmjresp-2019-000440