There is a need for biological markers of the acute respiratory distress syndrome (ARDS). Exhaled breath contains hundreds of metabolites in the gas phase, some of which reflect (patho)physiological processes. We aimed to determine the diagnostic accuracy of metabolites in exhaled breath as biomarkers of ARDS.Breath from ventilated intensive care unit patients (n5101) was analysed using gas chromatography and mass spectrometry during the first day of admission. ARDS was defined by the Berlin definition. Training and temporal validation cohorts were used.23 patients in the training cohort (n553) had ARDS. Three breath metabolites, octane, acetaldehyde and 3-methylheptane, could discriminate between ARDS and controls with an area under the receiver operating characteristic curve (AUC) of 0.80. Temporal external validation (19 ARDS cases in a cohort of 48) resulted in an AUC of 0.78. Discrimination was insensitive to adjustment for severity of disease, a direct or indirect cause of ARDS, comorbidities, or ventilator settings. Combination with the lung injury prediction score increased the AUC to 0.91 and improved net reclassification by 1.17.Exhaled breath analysis showed good diagnostic accuracy for ARDS, which was externally validated. These data suggest that exhaled breath analysis could be used for the diagnostic assessment of ARDS. @ERSpublications Metabolites in the breath of ventilated patients may be used to diagnose the acute respiratory distress syndrome
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).
A large number of videos are captured and shared by the audience from musical concerts. However, such recordings are typically perceived as boring mainly because of their limited view, poor visual quality and incomplete coverage. It is our objective to enrich the viewing experience of these recordings by exploiting the abundance of content from multiple sources. In this paper, we propose a novel Virtual Director system that automatically combines the most desirable segments from different recordings resulting in a single video stream, called mashup. We start by eliciting requirements from focus groups, interviewing professional video editors and consulting film grammar literature. We design a formal model for automatic mashup generation based on maximizing the degree of fulfillment of the requirements. Various audio-visual content analysis techniques are used to determine how well the requirements are satisfied by a recording. To validate the system, we compare our mashups with two other mashups: manually created by a professional video editor and machine generated by random segment selection. The mashups are evaluated in terms of visual quality, content diversity and pleasantness by 40 subjects. The results show that our mashups and the manual mashups are perceived as comparable, while both of them are significantly higher than the random mashups in all three terms.
Identification and prospective stability of eNose derived inflammatory phenotypes in severe asthma.
The diagnosis of hospital-acquired pneumonia remains challenging. We hypothesized that analysis of volatile organic compounds (VOCs) in exhaled breath could be used to diagnose pneumonia or the presence of pathogens in the respiratory tract in intubated and mechanically-ventilated intensive care unit patients. In this prospective, single-centre, cross-sectional cohort study breath from mechanically ventilated patients was analysed using gas chromatography-mass spectrometry. Potentially relevant VOCs were selected with a p-value < 0.05 and an area under the receiver operating characteristics curve (AUROC) above 0.7. These VOCs were used for principal component analysis and partial least square discriminant analysis (PLS-DA). AUROC was used as a measure of accuracy. Ninety-three patients were included in the study. Twelve of 145 identified VOCs were significantly altered in patients with pneumonia compared to controls. In colonized patients, 52 VOCs were significantly different. Partial least square discriminant analysis classified patients with modest accuracy (AUROC: 0.73 (95% confidence interval (CI): 0.57–0.88) after leave-one-out cross-validation). For determining the colonization status of patients, the model had an AUROC of 0.69 (95% CI: 0.57–0.82) after leave-one-out cross-validation. To conclude, exhaled breath analysis can be used to discriminate pneumonia from controls with a modest to good accuracy. Furthermore breath profiling could be used to predict the presence and absence of pathogens in the respiratory tract. These findings need to be validated externally.
An effective quark Lagrangian is derived from first principles through bilocal gluon field correlators. It is used to write down equations for baryons, containing both perturbative and nonperturbative fields. As a result one obtains magnetic moments of octet and decuplet baryons without introduction of constituent quark masses and using only string tension as an input. Magnetic moments come out on average in reasonable agreement with experiment, except for nucleons and $\Sigma^-$. The predictions for the proton and neutron are shown to be in close agreement with the empirical values once we choose the string tension such to yield the proper nucleon mass. Pionic corrections to the nucleon magnetic moments have been estimated. In particular, the total result of the two-body current contributions are found to be small. Inclusion of the anomalous magnetic moment contributions from pion and kaon loops leads to an improvement of the predictions.Comment: 24 pages Revte
IntroductionInfections such as ventilator-associated pneumonia (VAP) can be caused by one or more pathogens. Current methods for identifying these pathogenic microbes often require invasive sampling, and can be time consuming, due to the requirement for prolonged cultural enrichment along with selective and differential plating steps. This results in delays in diagnosis which in such critically ill patients can have potentially life-threatening consequences. Therefore, a non-invasive and timely diagnostic method is required. Detection of microbial volatile organic compounds (VOCs) in exhaled breath is proposed as an alternative method for identifying these pathogens and may distinguish between mono- and poly-microbial infections.ObjectivesTo investigate volatile metabolites that discriminate between bacterial mono- and co-cultures.MethodsVAP-associated pathogens Enterobacter cloacae and Pseudomonas aeruginosa were cultured individually and together in artificial sputum medium for 24 h and their headspace was analysed for potential discriminatory VOCs by thermal desorption gas chromatography–mass spectrometry.ResultsOf the 70 VOCs putatively identified, 23 were found to significantly increase during bacterial culture (i.e. likely to be released during metabolism) and 13 decreased (i.e. likely consumed during metabolism). The other VOCs showed no transformation (similar concentrations observed as in the medium). Bacteria-specific VOCs including 2-methyl-1-propanol, 2-phenylethanol, and 3-methyl-1-butanol were observed in the headspace of axenic cultures of E. cloacae, and methyl 2-ethylhexanoate in the headspace of P. aeruginosa cultures which is novel to this investigation. Previously reported VOCs 1-undecene and pyrrole were also detected. The metabolites 2-methylbutyl acetate and methyl 2-methylbutyrate, which are reported to exhibit antimicrobial activity, were elevated in co-culture only.ConclusionThe observed VOCs were able to differentiate axenic and co-cultures. Validation of these markers in exhaled breath specimens could prove useful for timely pathogen identification and infection type diagnosis.Electronic supplementary materialThe online version of this article (10.1007/s11306-018-1357-5) contains supplementary material, which is available to authorized users.
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