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

Abstract

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

Biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise

“…In general, bacterial colonization of the airways occurs frequently in mechanically ventilated patients and neutrophil infiltration is a hallmark of ARDS. The 3-methylheptane is produced through lipid peroxidation, similar to octane (18). Thus, the exhaled gas seems to be mainly influenced by the oxidative stress in the lungs and affected by the inflammatory and infectious responses.…”

“…Several studies have been published using analysis of VOCs by gas-chromatography and mass-spectrometry in ventilated patients (18,70), and three potential VOCs have been identified as potential markers of ARDS: octane, acetaldehyde and 3-methylheptane. These VOCs discriminated ARDS from controls, improving the discrimination when combining with the use of lung injury prediction score (18). Octane is an end-product of lipid peroxidation, one of the processes caused by oxidative stress.…”

“…Investigators have identified several candidate biomarkers for ARDS that have been investigated in blood, pulmonary edema fluid, and exhaled air, but currently they are not reliable enough for clinical use or have not yet been validated (16)(17)(18). In this article, we will briefly review the present understanding on some appealing biomarkers that could be used for identifying patients with ARDS, for enrolling ARDS patients into clinical trials, or for better monitoring of patient's management ( Table 1).…”

“…In this article, we will briefly review the present understanding on some appealing biomarkers that could be used for identifying patients with ARDS, for enrolling ARDS patients into clinical trials, or for better monitoring of patient's management ( Table 1). For a more detailed analysis we recommend a number of more in-depth reviews (16)(17)(18).…”

23rd International Symposium on Infections in the Critically Ill Patient

“…Inaccurate diagnosis or inappropriate antimicrobial therapy, including the treatment of tracheobronchial colonisation, should be avoided. In time, newer technology may allow us to diagnose VAT and VAP in more sophisticated ways (Douglas IS, 2015;Bos LD, 2014), and determine which patients may be at an increased risk of progression from VAT to VAP based on immunological factors. This may enable targeted therapy towards those patients with VAT at the greatest risk of progression to VAP, with improved survival and a minimal excess use of antimicrobials.…”