Fenn 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
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.
ERJ Open Res. 2023 Mar 20;9(2). doi: 10.1183/23120541.00427-2022. eCollection 2023 Mar.
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.
In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (HO), 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 ( ) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry.
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 (R range: -0.015 to -0.065) or discriminated between patients with ≥0.6 or below (area under the curve range: 0.48 to 0.55).
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.
呼出挥发性有机化合物（VOCs）的变化可用于区分呼吸道疾病，碳氢化合物浓度升高通常与氧化应激有关。然而，不同研究中鉴定出的VOCs并不一致，且缺乏转化研究。
在这项从实验室到临床的研究中，我们使用高容量聚二甲基硅氧烷吸附纤维，在暴露于过氧化氢（HO）以诱导氧化应激后的A549上皮细胞顶空中捕获VOCs。通过靶向和非靶向分析比较暴露和未暴露的细胞。在吸附管上收集有创通气重症监护病房患者（n = 489）的呼气样本，并将其与吸入氧分数（ ）相关联，以反映肺部氧化应激。使用气相色谱和质谱分析顶空样本和呼气样本。
在细胞中，氧化应激后顶空辛烷浓度降低（p = 0.0013），而其他VOCs未受影响。在非靶向分析中，2-乙基-1-己醇在经历氧化应激的细胞顶空中浓度升高（p = 0.00014）。与氧化应激相关的VOCs均未与 显示出显著相关性（R范围：-0.015至-0.065），也无法区分 ≥0.6或低于该值的患者（曲线下面积范围：0.48至0.55）。
尽管采用了全面的转化方法，但在有肺部氧化损伤风险的患者中，无法对已知和新型氧化应激挥发性生物标志物进行验证。观察到的不一致性凸显了VOC生物标志物验证面临的困难，并且在解释发现的呼气生物标志物的病理生理起源时应谨慎。
