{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:42:50Z","timestamp":1780602170097,"version":"3.54.1"},"reference-count":24,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T00:00:00Z","timestamp":1569196800000},"content-version":"unspecified","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research (NIHR) Oxford Biomedical Research Centre"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2019,9,12]]},"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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\u00b1DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2019s post hoc tests were used to estimate statistical significance. Pearson\u2019s correlation coefficient was used to assess linear correlation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Intrapleural administration of t-PA\u00b1DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1\u20133). No significant difference was detected between any groups during the post-treatment period (days 5\u20137). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjresp-2019-000440","type":"journal-article","created":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T13:59:05Z","timestamp":1569333545000},"page":"e000440","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients"],"prefix":"10.1136","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-2282","authenticated-orcid":false,"given":"Nikolaos I","family":"Kanellakis","sequence":"first","affiliation":[{"name":"Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK"},{"name":"Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Wrightson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9467-668X","authenticated-orcid":false,"given":"Rob","family":"Hallifax","sequence":"additional","affiliation":[{"name":"Oxford Centre for 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