The use of soluble and surface TREM-1 as markers of Ventilator-associated pneumonia in Intensive Care

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.