PMID- 31673364
OWN - NLM
STAT- MEDLINE
DCOM- 20200429
LR  - 20210110
IS  - 2052-4439 (Print)
IS  - 2052-4439 (Electronic)
IS  - 2052-4439 (Linking)
VI  - 6
IP  - 1
DP  - 2019
TI  - Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural 
      delivery in pleural infection patients.
PG  - e000440
LID - 10.1136/bmjresp-2019-000440 [doi]
LID - e000440
AB  - 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. 
      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. 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. 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.
CI  - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Kanellakis, Nikolaos I
AU  - Kanellakis NI
AUID- ORCID: 0000-0002-0065-2282
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
AD  - Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department 
      of Medicine, University of Oxford, Oxford, Oxfordshire, UK.
AD  - National Institute for Health Research Oxford Biomedical Research Centre, 
      University of Oxford, Oxford, Oxfordshire, UK.
FAU - Wrightson, John M
AU  - Wrightson JM
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Hallifax, Rob
AU  - Hallifax R
AUID- ORCID: 0000-0002-9467-668X
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Bedawi, Eihab O
AU  - Bedawi EO
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Mercer, Rachel
AU  - Mercer R
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Hassan, Maged
AU  - Hassan M
AUID- ORCID: 0000-0002-8768-6548
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Asciak, Rachelle
AU  - Asciak R
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
FAU - Hedley, Emma
AU  - Hedley E
AD  - Oxford Respiratory Trials Unit, Nuffield Department of Medicine, University of 
      Oxford, Oxford, Oxfordshire, UK.
FAU - Dobson, Melissa
AU  - Dobson M
AD  - Oxford Respiratory Trials Unit, Nuffield Department of Medicine, University of 
      Oxford, Oxford, Oxfordshire, UK.
FAU - Dong, Tao
AU  - Dong T
AD  - Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford 
      Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
AD  - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University 
      of Oxford, Oxford, UK.
FAU - Psallidas, Ioannis
AU  - Psallidas I
AUID- ORCID: 0000-0001-7284-0111
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
AD  - Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department 
      of Medicine, University of Oxford, Oxford, Oxfordshire, UK.
FAU - Rahman, Najib M
AU  - Rahman NM
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University 
      Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK.
AD  - Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department 
      of Medicine, University of Oxford, Oxford, Oxfordshire, UK.
AD  - National Institute for Health Research Oxford Biomedical Research Centre, 
      University of Oxford, Oxford, Oxfordshire, UK.
LA  - eng
GR  - MC_UU_00008/11/MRC_/Medical Research Council/United Kingdom
GR  - MR/L018942/1/MRC_/Medical Research Council/United Kingdom
GR  - PB-PG-0416-20020/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190924
PL  - England
TA  - BMJ Open Respir Res
JT  - BMJ open respiratory research
JID - 101638061
RN  - 0 (Chemokine CCL2)
RN  - EC 3.1.- (Deoxyribonucleases)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
MH  - Chemokine CCL2/analysis
MH  - Deoxyribonucleases/*administration & dosage
MH  - *Drainage
MH  - Empyema, Pleural/*therapy
MH  - Humans
MH  - Pleura
MH  - Pleural Effusion/*therapy
MH  - Tissue Plasminogen Activator/*administration & dosage
PMC - PMC6797395
OTO - NOTNLM
OT  - DNase
OT  - empyema
OT  - fibrinolytics
OT  - pleural infection
OT  - t-PA
COIS- Competing interests: None declared.
EDAT- 2019/11/02 06:00
MHDA- 2019/11/02 06:01
PMCR- 2019/09/23
CRDT- 2019/11/02 06:00
PHST- 2019/04/09 00:00 [received]
PHST- 2019/09/07 00:00 [revised]
PHST- 2019/09/12 00:00 [accepted]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2019/11/02 06:01 [medline]
PHST- 2019/09/23 00:00 [pmc-release]
AID - bmjresp-2019-000440 [pii]
AID - 10.1136/bmjresp-2019-000440 [doi]
PST - epublish
SO  - BMJ Open Respir Res. 2019 Sep 24;6(1):e000440. doi: 10.1136/bmjresp-2019-000440. 
      eCollection 2019.