Exhaled breath metabolomics as a noninvasive diagnostic tool for acute respiratory distress syndrome

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 (n=101) 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 (n=53) 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.