• Shiqi Zhang, Laura A Hagens, Nanon F L Heijnen, Marry R Smit, Paul Brinkman, Dominic Fenn, Tom van der Poll, Marcus J Schultz, BergmansDennis C J JDCJJDepartment of Intensive Care, Maastricht University Medical Centre+, Maastricht, The Netherlands.Maastricht University Medical Centre+, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, The Netherla, Ronny M Schnabel, BosLieuwe D JLDJAmsterdam UMC, Location AMC, Department of Intensive Care, University of Amsterdam, Meibergdreef 9, Room G3-228, 1105 AZ, Amsterdam, The Netherlands.Amsterdam UMC, Location AMC, University of Amsterdam, Pulmonary Medicine, Amsterdam, The N, and DARTS Consortium.
• Amsterdam UMC, Location AMC, Department of Intensive Care, University of Amsterdam, Meibergdreef 9, Room G3-228, 1105 AZ, Amsterdam, The Netherlands. s.zhang@amsterdamumc.nl.
• Crit Care. 2024 Mar 23; 28 (1): 9696.

BackgroundAcute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation.AimTo evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients.MethodsThis two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS).ResultsA total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance.ConclusionAn exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.© 2024. The Author(s).

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