Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Thomas P. Hellyer; Andrew Conway Morris; Daniel F. McAuley; Timothy S. Walsh; Niall H. Anderson; Suveer Singh; Paul Dark; Alistair I. Roy; Simon V. Baudouin; Stephen E. Wright; Gavin D. Perkins; Kallirroi Kefala; Melinda Jeffels; Ronan McMullan; Cecilia M. O'Kane; Craig Spencer; Shondipon Laha; Nicole Robin; Savita Gossain; Kate Gould; Marie-Helene Ruchaud-Sparagano; Jonathan Scott; Emma M. Browne; James G. MacFarlane; Sarah Wiscombe; John D. Widdrington; Ian Dimmick; Ian F. Laurenson; Frans Nauwelaers; A. John Simpson

doi:10.1136/thoraxjnl-2014-205766

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Thomas P. Hellyer, Andrew Conway Morris, Daniel F. McAuley, Timothy S. Walsh, Niall H. Anderson, Suveer Singh, Paul Dark, Alistair I. Roy, Simon V. Baudouin, Stephen E. Wright, Gavin D. Perkins, Kallirroi Kefala, Melinda Jeffels, Ronan McMullan, Cecilia M. O'Kane, Craig Spencer, Shondipon Laha, Nicole Robin, Savita Gossain, Kate GouldMarie-Helene Ruchaud-Sparagano, Jonathan Scott, Emma M. Browne, James G. MacFarlane, Sarah Wiscombe, John D. Widdrington, Ian Dimmick, Ian F. Laurenson, Frans Nauwelaers, A. John Simpson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.

Objectives We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.

Methods A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1 beta), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination.

Results Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p

Conclusions Low BALF IL-1 beta in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Original language	English
Pages (from-to)	41-47
Number of pages	7
Journal	Thorax
Volume	70
Issue number	1
Early online date	8 Oct 2014
DOIs	https://doi.org/10.1136/thoraxjnl-2014-205766
Publication status	Published - Jan 2015

Keywords / Materials (for Non-textual outputs)

BRONCHOALVEOLAR LAVAGE FLUID
PROGNOSTIC VALUE
BRONCHOPNEUMONIA
PROCALCITONIN
INFECTION
OUTCOMES
PROTEIN
MARKER
LUNG

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10.1136/thoraxjnl-2014-205766

PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY
Iredale, J. (Principal Investigator)
MRC
1/09/12 → 31/08/16
Project: Research

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Hellyer, T. P., Morris, A. C., McAuley, D. F., Walsh, T. S., Anderson, N. H., Singh, S., Dark, P., Roy, A. I., Baudouin, S. V., Wright, S. E., Perkins, G. D., Kefala, K., Jeffels, M., McMullan, R., O'Kane, C. M., Spencer, C., Laha, S., Robin, N., Gossain, S., ... Simpson, A. J. (2015). Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia. Thorax, 70(1), 41-47. https://doi.org/10.1136/thoraxjnl-2014-205766

@article{f4853b9c44db46d59d888908924a162d,

title = "Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia",

abstract = "Background Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.Objectives We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.Methods A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1 beta), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination.Results Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (pConclusions Low BALF IL-1 beta in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.",

keywords = "BRONCHOALVEOLAR LAVAGE FLUID, PROGNOSTIC VALUE, BRONCHOPNEUMONIA, PROCALCITONIN, INFECTION, OUTCOMES, PROTEIN, MARKER, LUNG",

author = "Hellyer, {Thomas P.} and Morris, {Andrew Conway} and McAuley, {Daniel F.} and Walsh, {Timothy S.} and Anderson, {Niall H.} and Suveer Singh and Paul Dark and Roy, {Alistair I.} and Baudouin, {Simon V.} and Wright, {Stephen E.} and Perkins, {Gavin D.} and Kallirroi Kefala and Melinda Jeffels and Ronan McMullan and O'Kane, {Cecilia M.} and Craig Spencer and Shondipon Laha and Nicole Robin and Savita Gossain and Kate Gould and Marie-Helene Ruchaud-Sparagano and Jonathan Scott and Browne, {Emma M.} and MacFarlane, {James G.} and Sarah Wiscombe and Widdrington, {John D.} and Ian Dimmick and Laurenson, {Ian F.} and Frans Nauwelaers and Simpson, {A. John}",

year = "2015",

month = jan,

doi = "10.1136/thoraxjnl-2014-205766",

language = "English",

volume = "70",

pages = "41--47",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group",

number = "1",

}

Hellyer, TP, Morris, AC, McAuley, DF, Walsh, TS , Anderson, NH, Singh, S, Dark, P, Roy, AI, Baudouin, SV, Wright, SE, Perkins, GD, Kefala, K, Jeffels, M, McMullan, R, O'Kane, CM, Spencer, C, Laha, S, Robin, N, Gossain, S, Gould, K, Ruchaud-Sparagano, M-H, Scott, J, Browne, EM, MacFarlane, JG, Wiscombe, S, Widdrington, JD, Dimmick, I, Laurenson, IF, Nauwelaers, F & Simpson, AJ 2015, 'Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia', Thorax, vol. 70, no. 1, pp. 41-47. https://doi.org/10.1136/thoraxjnl-2014-205766

TY - JOUR

T1 - Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

AU - Hellyer, Thomas P.

AU - Morris, Andrew Conway

AU - McAuley, Daniel F.

AU - Walsh, Timothy S.

AU - Anderson, Niall H.

AU - Singh, Suveer

AU - Dark, Paul

AU - Roy, Alistair I.

AU - Baudouin, Simon V.

AU - Wright, Stephen E.

AU - Perkins, Gavin D.

AU - Kefala, Kallirroi

AU - Jeffels, Melinda

AU - McMullan, Ronan

AU - O'Kane, Cecilia M.

AU - Spencer, Craig

AU - Laha, Shondipon

AU - Robin, Nicole

AU - Gossain, Savita

AU - Gould, Kate

AU - Ruchaud-Sparagano, Marie-Helene

AU - Scott, Jonathan

AU - Browne, Emma M.

AU - MacFarlane, James G.

AU - Wiscombe, Sarah

AU - Widdrington, John D.

AU - Dimmick, Ian

AU - Laurenson, Ian F.

AU - Nauwelaers, Frans

AU - Simpson, A. John

PY - 2015/1

Y1 - 2015/1

N2 - Background Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.Objectives We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.Methods A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1 beta), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination.Results Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (pConclusions Low BALF IL-1 beta in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

AB - Background Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.Objectives We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.Methods A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1 beta), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination.Results Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (pConclusions Low BALF IL-1 beta in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

KW - BRONCHOALVEOLAR LAVAGE FLUID

KW - PROGNOSTIC VALUE

KW - BRONCHOPNEUMONIA

KW - PROCALCITONIN

KW - INFECTION

KW - OUTCOMES

KW - PROTEIN

KW - MARKER

KW - LUNG

U2 - 10.1136/thoraxjnl-2014-205766

DO - 10.1136/thoraxjnl-2014-205766

M3 - Article

SN - 0040-6376

VL - 70

SP - 41

EP - 47

JO - Thorax

JF - Thorax

IS - 1

ER -

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Abstract

Keywords / Materials (for Non-textual outputs)

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PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY

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