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

Published version
Peer-reviewed

Type

Article

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Authors

Pinder, Emma 
Rostron, Anthony 
Hellyer, Thomas P 
Ruchaud-Sparagano, Marie-Helene 
Scott, Johnathon 

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 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.

Description

Keywords

bacterial infection, gm-csf, neutrophil biology, Adult, Aged, Aged, 80 and over, Critical Illness, Female, Granulocyte-Macrophage Colony-Stimulating Factor, HLA-DR Antigens, Humans, Male, Middle Aged, Monocytes, Neutrophils, Phagocytosis, Treatment Outcome

Journal Title

Thorax

Conference Name

Journal ISSN

0040-6376
1468-3296

Volume Title

Publisher

BMJ Publishing Group
Sponsorship
Medical Research Council (MR/J00345X/1)
Wellcome Trust (205214/Z/16/Z)
MRC (MC_PC_17208)
Medical Research Council (G1100233)
This 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