The use of soluble and surface TREM-1 as markers of Ventilator-associated pneumonia in Intensive Care
File(s)
Author(s)
Grover, Vimal
Type
Thesis
Abstract
Ventilator-associated pneumonia (VAP) is the commonest nosocomial infection in
Intensive Care and is associated with significant morbidity and mortality. Biomarkers
offer the potential to speed up diagnosis and differentiate pulmonary from nonpulmonary
infection. We postulated that measurement of cell surface receptors in
addition to soluble proteins, in dual sites (blood and BAL) and calculation of an index
ratio of BAL / blood would increase the discriminative utility and differentiate
pulmonary from non-pulmonary infection.
Our body of work included paired blood and BALF obtained from 91 patients in a
pilot study: 27 with VAP, 15 ventilated patients with non-pulmonary sepsis, 18
ventilated patients with no evidence of infection and 31 non-ventilated non-infected
patients. In each sample, the monocytic and neutrophilic surface proteins TREM-1,
CD11b and CD62L were assessed using flow cytometry. Soluble proteins (IL-1β, IL-
6, IL-8) were assayed using ELISA in addition to Procalcitonin, CRP and white cell
count.
The levels of soluble TREM-1, IL-1β and IL-8 were significantly raised in the BAL of
patients with VAP. BAL monocytic surface TREM-1 was also significantly higher in
VAP. The BAL / blood ratio increased the discrimination of patients with VAP from
non-VAP. Furthermore, the BAL / blood ratio of patients differentiated VAP from
non-pulmonary infection. Monocytic and neutrophilic TREM-1 were assessed during
the development and resolution phases of VAP. Monocytic surface TREM-1 and its
BAL / blood ratio accurately mirrored the changes with infection, indicating them to
be putative biomarkers of infection.
Finally, we constructed and validated a biomarker panel to discriminate patients with
VAP from non-VAP. The panel comprised the BAL / blood ratios of monocytic
TREM-1 and CD11b, the BAL levels of soluble TREM-1, IL-8 and IL-1β together with
the blood levels of IL-6 and CRP. It had high utility in identifying patients with VAP.
Intensive Care and is associated with significant morbidity and mortality. Biomarkers
offer the potential to speed up diagnosis and differentiate pulmonary from nonpulmonary
infection. We postulated that measurement of cell surface receptors in
addition to soluble proteins, in dual sites (blood and BAL) and calculation of an index
ratio of BAL / blood would increase the discriminative utility and differentiate
pulmonary from non-pulmonary infection.
Our body of work included paired blood and BALF obtained from 91 patients in a
pilot study: 27 with VAP, 15 ventilated patients with non-pulmonary sepsis, 18
ventilated patients with no evidence of infection and 31 non-ventilated non-infected
patients. In each sample, the monocytic and neutrophilic surface proteins TREM-1,
CD11b and CD62L were assessed using flow cytometry. Soluble proteins (IL-1β, IL-
6, IL-8) were assayed using ELISA in addition to Procalcitonin, CRP and white cell
count.
The levels of soluble TREM-1, IL-1β and IL-8 were significantly raised in the BAL of
patients with VAP. BAL monocytic surface TREM-1 was also significantly higher in
VAP. The BAL / blood ratio increased the discrimination of patients with VAP from
non-VAP. Furthermore, the BAL / blood ratio of patients differentiated VAP from
non-pulmonary infection. Monocytic and neutrophilic TREM-1 were assessed during
the development and resolution phases of VAP. Monocytic surface TREM-1 and its
BAL / blood ratio accurately mirrored the changes with infection, indicating them to
be putative biomarkers of infection.
Finally, we constructed and validated a biomarker panel to discriminate patients with
VAP from non-VAP. The panel comprised the BAL / blood ratios of monocytic
TREM-1 and CD11b, the BAL levels of soluble TREM-1, IL-8 and IL-1β together with
the blood levels of IL-6 and CRP. It had high utility in identifying patients with VAP.
Version
Open Access
Date Issued
2013-09
Date Awarded
2014-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Singh, Suveer
Takata, Masao
Kelleher, William
Sponsor
Westminster Hospital. Medical School
National Institute of Academic Anaesthesia
Publisher Department
Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)