BreathDx – molecular analysis of exhaled breath as a diagnostic test for ventilator–associated pneumonia: protocol for a European multicentre observational study

Abstract

BackgroundThe diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity.Methods/designThe Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption – Gas Chromatography – Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value).DiscussionTo our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity.Trial registrationUKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym ‘BreathDx’ with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).

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“…Prior to desorption, 100 μl of an internal standard (IS; 1 ppmV 4-bromofluorobenzene in N 2 ; Thames Restek, Bucks, UK) was loaded onto each tube. This compound was used as an IS as it exhibits similar chemical properties and vapour pressure to the analytes of interest whilst it is not naturally present in the samples, with previous use in clinical studies [31]. Metabolites were desorbed from TD tubes at 280˚C for 5 min, cryo-focussed on a cold trap maintained at 0˚C and desorbed from the cold trap onto the GC (Agilent 6890N) column by flash heating to 330˚C for 3 min with a flow path temperature of 200˚C.…”

Nurses' implementation of ventilator‐associated pneumonia prevention guidelines: an observational study in Jordan

“…Ventilator-associated pneumonia (VAP) is a common nosocomial infection that causes significant mortality, morbidity (Spalding et al, 2017), extended hospitalization (Victor et al, 2017) and increase in the cost of care (Van Oort et al, 2017). VAP accounts for 25% of total cases of nosocomial infection in critical care units (Bouglé et al, 2017) and 9-13% of the total deaths in patients with ventilator assistance devices (Larsson et al, 2017).…”

Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia

“…Serial VOC samples are simple to acquire and may allow for preemptive or targeted preventative treatment of early VAP or tracheobronchitis. A large multicenter European study is in progress to evaluate the utility and performance of VOCguided diagnosis for VAP (BreathDx NTR 6114) [81].…”