| Title: | Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study |
| Author(s): | Fenn D; Lilien TA; Hagens LA; Smit MR; Heijnen NFL; Tuip-de Boer AM; Neerincx AH; Golebski K; Bergmans D; Schnabel RM; Schultz MJ; Maitland-van der Zee AH; Brinkman P; Bos LDJ; |
| Address: | "Amsterdam UMC location University of Amsterdam, Department of Pulmonary Medicine, Amsterdam, Netherlands. Amsterdam UMC location University of Amsterdam, Laboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam, Netherlands. Amsterdam UMC location University of Amsterdam, Department of Paediatric Intensive Care, Amsterdam, Netherlands. Amsterdam UMC location University of Amsterdam, Department of Intensive Care, Amsterdam, Netherlands. Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands. School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands. Amsterdam UMC location University of Amsterdam, Department of Experimental Immunology, Amsterdam, Netherlands" |
| DOI: | 10.1183/23120541.00427-2022 |
| ISSN/ISBN: | 2312-0541 (Print) 2312-0541 (Electronic) 2312-0541 (Linking) |
| Abstract: | "BACKGROUND: Changes in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking. METHODS: In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (H(2)O(2)), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres. Exposed and unexposed cells were compared using targeted and untargeted analysis. Breath samples of invasively ventilated intensive care unit patients (n=489) were collected on sorbent tubes and associated with the inspiratory oxygen fraction (F (IO(2)) ) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry. RESULTS: In the cell, headspace octane concentration was decreased after oxidative stress (p=0.0013), while the other VOCs were not affected. 2-ethyl-1-hexanol showed an increased concentration in the headspace of cells undergoing oxidative stress in untargeted analysis (p=0.00014). None of the VOCs that were linked to oxidative stress showed a significant correlation with F (IO(2)) (R(s) range: -0.015 to -0.065) or discriminated between patients with F (IO(2)) >/=0.6 or below (area under the curve range: 0.48 to 0.55). CONCLUSION: Despite a comprehensive translational approach, validation of known and novel volatile biomarkers of oxidative stress was not possible in patients at risk of pulmonary oxidative injury. The inconsistencies observed highlight the difficulties faced in VOC biomarker validation, and that caution is warranted in the interpretation of the pathophysiological origin of discovered exhaled breath biomarkers" |
| Notes: | "PubMed-not-MEDLINEFenn, Dominic Lilien, Thijs A Hagens, Laura A Smit, Marry R Heijnen, Nanon F L Tuip-de Boer, Anita M Neerincx, Anne H Golebski, Korneliusz Bergmans, Dennis C J J Schnabel, Ronny M Schultz, Marcus J Maitland-van der Zee, Anke H Brinkman, Paul Bos, Lieuwe D J eng England 2023/03/24 ERJ Open Res. 2023 Mar 20; 9(2):00427-2022. doi: 10.1183/23120541.00427-2022. eCollection 2023 Mar" |
