Development and validation of a point-of-care breath test for octane detection

Laura A. Hagens*, Alwin R. M. Verschueren, Ariana Lammers, Nanon F. L. Heijnen, Marry R. Smit, Tamara M. E. Nijsen, Inge Geven, Marcus J. Schultz, Dennis C. J. J. Bergmans, Ronny M. Schnabel, Lieuwe D. J. Bos*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: There is a demand for a non-invasive bedside method to diagnose Acute Respiratory Distress Syndrome (ARDS). Octane was discovered and validated as the most important breath biomarker for diagnosis of ARDS using gas-chromatography and mass-spectrometry (GC-MS). However, GC-MS is unsuitable as a point-of-care (POC) test in the intensive care unit (ICU). Therefore, we determined if a newly developed POC breath test can reliably detect octane in exhaled breath of invasively ventilated ICU patients. Methods: Two developmental steps were taken to design a POC breath test that relies on gas-chromatography using air as carrier gas with a photoionization detector. Calibration measurements were performed with a laboratory prototype in healthy subjects. Subsequently, invasively ventilated patients were included for validation and assessment of repeatability. After evolving to a POC breath test, this device was validated in a second group of invasively ventilated patients. Octane concentration was based on the area under the curve, which was extracted from the chromatogram and compared to known values from calibration measurements. Results: Five healthy subjects and 53 invasively ventilated patients were included. Calibration showed a linear relation (R-2 = 1.0) between the octane concentration and the quantified octane peak in the low parts per billion (ppb) range. For the POC breath test the repeatability was excellent (R-2 = 0.98, ICC = 0.97 (95% CI 0.94-0.99)). Conclusion: This is the first study to show that a POC breath test can rapidly and reliably detect octane, with excellent repeatability, at clinically relevant levels of low ppb in exhaled breath of ventilated ICU patients. This opens possibilities for targeted exhaled breath analysis to be used as a bedside test and makes it a potential diagnostic tool for the early detection of ARDS.

Original languageEnglish
Pages (from-to)4605-4614
Number of pages10
Issue number14
Publication statusPublished - 21 Jul 2021




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