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dc.contributor.authorPinder, Emmaen
dc.contributor.authorRostron, Anthonyen
dc.contributor.authorHellyer, Thomas Pen
dc.contributor.authorRuchaud-Sparagano, Marie-Heleneen
dc.contributor.authorScott, Johnathonen
dc.contributor.authorMacFarlane, James Gen
dc.contributor.authorWiscombe, Sarahen
dc.contributor.authorWiddrington, John Den
dc.contributor.authorRoy, Alistair Ien
dc.contributor.authorLinnett, Vanessa Cen
dc.contributor.authorBaudouin, Simon Ven
dc.contributor.authorWright, Stephen Een
dc.contributor.authorThomas, Chadwicken
dc.contributor.authorFouweather, Anthonyen
dc.contributor.authorJuss, Jatinder Ken
dc.contributor.authorChilvers, Edwinen
dc.contributor.authorBowett, Susan Aen
dc.contributor.authorParker, Jennieen
dc.contributor.authorMcAuley, Daniel Fen
dc.contributor.authorConway Morris, Andrewen
dc.contributor.authorSimpson, A Johnen
dc.date.accessioned2018-09-05T12:51:14Z
dc.date.available2018-09-05T12:51:14Z
dc.identifier.issn0040-6376
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279643
dc.description.abstractBackground. Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired Methods. This was a multi-centre, phase 2a randomised, placebo-controlled clinical trial Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 microgrammws/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression, and safety. Results. Thirty-eight patients were recruited from 5 intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis >50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was pyrexia. Conclusions. GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.
dc.description.sponsorshipThis work was funded by a grant from the Medical Research Council (G1100233), with additional support from the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre. It was sponsored by Newcastle University
dc.publisherBMJ Publishing Group
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleRandomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosisen
dc.typeArticle
prism.publicationNameThoraxen
dc.identifier.doi10.17863/CAM.27012
dcterms.dateAccepted2018-04-23en
rioxxterms.versionofrecord10.1136/thoraxjnl-2017-211323en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-04-23en
dc.contributor.orcidChilvers, Edwin [0000-0002-4230-9677]
dc.contributor.orcidConway Morris, Andrew [0000-0002-3211-3216]
dc.identifier.eissn1468-3296
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (205214/Z/16/Z)
pubs.funder-project-idMRC (MR/J00345X/1)
cam.issuedOnline2018-07-31en


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)