Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Emma M. Pinder, Anthony J. Rostron, Thomas P. Hellyer, Marie Helene Ruchaud-Sparagano, Jonathan Scott, James G. MacFarlane, Sarah Wiscombe, John D. Widdrington, Alistair I. Roy, Vanessa C. Linnett, Simon V. Baudouin, Stephen E. Wright, Thomas Chadwick, Tony Fouweather, Jatinder K. Juss, Edwin R. Chilvers, Susan A. Bowett, Jennie Parker, Daniel F. McAuley, Andrew Conway MorrisA. John Simpson*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Background: 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 multicentre, phase IIa 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 μg/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 five 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 fever. 

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.

Original languageEnglish
Pages (from-to)918-925
Number of pages8
JournalThorax
Volume73
Issue number10
Early online date31 Jul 2018
DOIs
Publication statusPublished - Oct 2018

Keywords

  • bacterial infection
  • gm-csf
  • neutrophil biology

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Pinder, E. M., Rostron, A. J., Hellyer, T. P., Ruchaud-Sparagano, M. H., Scott, J., MacFarlane, J. G., Wiscombe, S., Widdrington, J. D., Roy, A. I., Linnett, V. C., Baudouin, S. V., Wright, S. E., Chadwick, T., Fouweather, T., Juss, J. K., Chilvers, E. R., Bowett, S. A., Parker, J., McAuley, D. F., ... Simpson, A. J. (2018). Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis. Thorax, 73(10), 918-925. https://doi.org/10.1136/thoraxjnl-2017-211323