Abstract
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.
Highlights
Severe community- and hospital-acquired pneumonia (CAP and HAP) represent a major clinical problem associated with a high mortality, and frequently requires admission to the intensive care unit (ICU), intubation, and mechanical ventilation [1]
Hexanal is an example of a volatile organic compounds (VOCs) that has been shown to have potential to discriminate between chronic obstructive pulmonary disease (COPD) patients and healthy controls [28], whereas nonanal is associated with tobacco consumption in healthy volunteers [29]
Results of another study comparing COPD patients and controls, showed that the VOCs that discriminated mostly appeared to be predominantly lower in the COPD patients [24]
Summary
Severe community- and hospital-acquired pneumonia (CAP and HAP) represent a major clinical problem associated with a high mortality, and frequently requires admission to the intensive care unit (ICU), intubation, and mechanical ventilation [1]. Probable Pneumonia vs Controls (Patients without Pneumonia and without Colonized Airways). Concentrations of eleven (7.6%) VOCs were significantly lower in the breath of cases than in that of controls (p-value < 0.05; see Figure 2 for distribution and names). These results were visualized in a volcano plot (Figure 3). Ten of these VOCs showed an area under the receiver operating characteristics curve (AUROC) higher than 0.7. Principal component analysis showed a significantly lower first principal component score (explaining 35.1% of variance) for patients with probable pneumonia (p < 0.001; see Figure 4).
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