ERJ Open Research · 14 authors, 7 centres
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This study combined lab experiments on lung cells with breath analysis from 489 intensive care unit patients to test if known volatile organic compounds (VOCs) linked to oxidative stress could be validated as reliable biomarkers. The central result was that none of the VOCs investigated, whether previously suggested or novel, could be validated in patients at risk of pulmonary oxidative injury.
This bench-to-bedside study first exposed A549 lung epithelial cells to hydrogen peroxide to induce oxidative stress, analyzing headspace VOCs. It then analyzed exhaled breath from 489 invasively ventilated ICU patients, correlating VOC levels with the fraction of inspired oxygen (FiO2) as a marker for pulmonary oxidative stress. In vitro, octane concentration decreased and 2-ethyl-1-hexanol increased in stressed cells. However, in the patient cohort, none of the tested VOCs correlated significantly with FiO2 or discriminated between patients with high versus low FiO2. The study concludes that known and novel volatile biomarkers of oxidative stress were not validated clinically. Limitations include the use of a 2D cell model, the lack of a biological gold standard for oxidative injury in patients, and potential VOC dilution from ventilator sampling. The implications highlight the difficulties in VOC biomarker validation and urge caution in interpreting the pathophysiological origin of exhaled breath biomarkers.
