Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study

Introduction Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recent...

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Main Authors: Jonathan R B Bishop, Paul Harrison, Janet M Lord, Naiem S Moiemen, Amy Bamford, Yvonne Wilson, David Barnes, Jon Hazeldine, Kirsty C McGee, Khaled Al-Tarrah, Tarek Hassouna, Krupali Patel, Rizwana Imran
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Language:English
Published: BMJ Publishing Group 2021-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/10/e052035.full
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author Jonathan R B Bishop
Paul Harrison
Janet M Lord
Naiem S Moiemen
Amy Bamford
Yvonne Wilson
David Barnes
Jon Hazeldine
Kirsty C McGee
Khaled Al-Tarrah
Tarek Hassouna
Krupali Patel
Rizwana Imran
author_facet Jonathan R B Bishop
Paul Harrison
Janet M Lord
Naiem S Moiemen
Amy Bamford
Yvonne Wilson
David Barnes
Jon Hazeldine
Kirsty C McGee
Khaled Al-Tarrah
Tarek Hassouna
Krupali Patel
Rizwana Imran
author_sort Jonathan R B Bishop
collection DOAJ
description Introduction Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recently demonstrated that a combined measurement of neutrophil phagocytic capacity, immature granulocyte (IG) count and plasma cell-free DNA (cfDNA) levels on the day of injury gave good discriminatory power for the prediction of later sepsis development. However, limited by a small sample size, single-centre design and focus on adult burns patients, these biomarkers require prospective validation in a larger patient cohort. The Scientific Investigation of the Biological Pathways Following Thermal Injury-2 study aims to prospectively validate neutrophil phagocytic activity, IG count and plasma cfDNA levels as early prognostic biomarkers of sepsis in thermally injured adult and paediatric patients.Methods and analysis This multicentre, longitudinal, observational cohort study will enrol 245 paediatric and adult patients with moderate to severe burns within 24 hours of injury. Blood samples will be obtained at 19 postinjury time points (days 1–14, day 28, months 3, 6, 12 and 24) and analysed for neutrophil phagocytic activity, IG count and cfDNA levels. Patients will be screened daily for sepsis using the 2007 American Burn Association diagnostic criteria for sepsis. In addition, daily multiple organ dysfunction syndrome and Sequential Organ Failure Assessment Scores will be recorded relationships between neutrophil phagocytic activity, IG count and plasma cfDNA levels on day 1 of injury and the development of sepsis will be examined using logistic regression models.Ethics and dissemination This study received ethics approval from the West Midlands, Coventry and Warwickshire Research Ethics Committee (REC reference:16/WM/0217). Findings will be presented at national and international conferences, and submitted for publication in peer-reviewed journals.Trial registration number NCT04693442.
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spelling doaj-art-7c1f323fd5d84139935ffdd0005752ee2025-08-20T02:22:49ZengBMJ Publishing GroupBMJ Open2044-60552021-10-01111010.1136/bmjopen-2021-052035Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) studyJonathan R B Bishop0Paul Harrison1Janet M Lord2Naiem S Moiemen3Amy Bamford4Yvonne Wilson5David Barnes6Jon Hazeldine7Kirsty C McGee8Khaled Al-Tarrah9Tarek Hassouna10Krupali Patel11Rizwana Imran12National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UKInstitute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UKQueen Elizabeth Hospital, Birmingham, UKNational Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UKUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UKBirmingham Childrens Hospital NHS Foundation Trust, Birmingham, UKAdult and Paediatric Burns Centre, St Andrew`s Centre of Plastic Surgery and Burns, Broomfield Hospital, Chelmsford, Essex, UKNational Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UKInstitute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UKInstitute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UKBurn Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UKBurn Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKIntroduction Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recently demonstrated that a combined measurement of neutrophil phagocytic capacity, immature granulocyte (IG) count and plasma cell-free DNA (cfDNA) levels on the day of injury gave good discriminatory power for the prediction of later sepsis development. However, limited by a small sample size, single-centre design and focus on adult burns patients, these biomarkers require prospective validation in a larger patient cohort. The Scientific Investigation of the Biological Pathways Following Thermal Injury-2 study aims to prospectively validate neutrophil phagocytic activity, IG count and plasma cfDNA levels as early prognostic biomarkers of sepsis in thermally injured adult and paediatric patients.Methods and analysis This multicentre, longitudinal, observational cohort study will enrol 245 paediatric and adult patients with moderate to severe burns within 24 hours of injury. Blood samples will be obtained at 19 postinjury time points (days 1–14, day 28, months 3, 6, 12 and 24) and analysed for neutrophil phagocytic activity, IG count and cfDNA levels. Patients will be screened daily for sepsis using the 2007 American Burn Association diagnostic criteria for sepsis. In addition, daily multiple organ dysfunction syndrome and Sequential Organ Failure Assessment Scores will be recorded relationships between neutrophil phagocytic activity, IG count and plasma cfDNA levels on day 1 of injury and the development of sepsis will be examined using logistic regression models.Ethics and dissemination This study received ethics approval from the West Midlands, Coventry and Warwickshire Research Ethics Committee (REC reference:16/WM/0217). Findings will be presented at national and international conferences, and submitted for publication in peer-reviewed journals.Trial registration number NCT04693442.https://bmjopen.bmj.com/content/11/10/e052035.full
spellingShingle Jonathan R B Bishop
Paul Harrison
Janet M Lord
Naiem S Moiemen
Amy Bamford
Yvonne Wilson
David Barnes
Jon Hazeldine
Kirsty C McGee
Khaled Al-Tarrah
Tarek Hassouna
Krupali Patel
Rizwana Imran
Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
BMJ Open
title Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
title_full Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
title_fullStr Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
title_full_unstemmed Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
title_short Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study
title_sort multicentre longitudinal observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries a protocol for the scientific investigation of the biological pathways following thermal injury 2 sifti 2 study
url https://bmjopen.bmj.com/content/11/10/e052035.full
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