Phase-resolved real-time breath analysis during exercise by means of smart processing of PTR-MS data
Phase-resolved real-time breath analysis during exercise by means of smart processing of PTR-MS data
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DOI：
10.1007/s00216-011-5173-2
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发表时间：
2011-10-01
影响因子：
4.3
通讯作者：
Miekisch, Wolfram
中科院分区：
文献类型：
--
作者：
Schwoebel, Henny;Schubert, Roland;Miekisch, Wolfram
吸气、混合呼气和肺泡空气的分离对于 VOC 呼吸生物标志物的可靠分析是必不可少的。直接质谱仪的时间分辨率通常不足以可靠地解析呼吸周期的阶段。为了通过利用低碎片软电离的直接 MS 实现快速在线呼吸监测，开发了一种数据处理算法，无需任何额外设备即可从 MS 数据中识别吸气相和肺泡相。为了测试该算法，通过四极质子转移反应质谱 (PTR-MS) 对 7 名健康志愿者在固定自行车上锻炼时选定的呼吸生物标志物（丙酮、异戊二烯、乙醛和己醛）进行了测定。将结果与离线参考方法进行比较，该方法包括在 Tedlar (R) 袋中进行受控肺泡呼吸采样、固相微萃取 (SPME) 预浓缩、GC-MS 分离和鉴定。基于数据处理方法，在实验期间的任何时间，甚至在呼吸频率高达 60/min 的情况下，都可以将生物标志物定量归因于吸气相、肺泡相和混合呼气相。通过 PTR-MS 测量，呼吸标记物的肺泡浓度范围为 130 至 2,600 ppb（丙酮）、10 至 540 ppb（异戊二烯）、2 至 31 ppb（乙醛），而己醛的浓度始终低于 3 ppb 的检测限 (LOD)。在生理参数稳定的阶段，在线 PTR-MS 和 SPME-GC-MS 测量之间存在良好的相关性，但在心率和每分钟通气量快速变化时结果出现偏差。这清楚地证明了呼吸分辨质谱仪在快速在线监测呼出的 VOC 方面的优势。
Separation of inspiratory, mixed expired and alveolar air is indispensable for reliable analysis of VOC breath biomarkers. Time resolution of direct mass spectrometers often is not sufficient to reliably resolve the phases of a breathing cycle. To realise fast on-line breath monitoring by means of direct MS utilising low-fragmentation soft ionisation, a data processing algorithm was developed to identify inspiratory and alveolar phases from MS data without any additional equipment. To test the algorithm selected breath biomarkers (acetone, isoprene, acetaldehyde and hexanal) were determined by means of quadrupole proton transfer reaction mass spectrometry (PTR-MS) in seven healthy volunteers during exercise on a stationary bicycle. The results were compared to an off-line reference method consisting of controlled alveolar breath sampling in Tedlar (R) bags, preconcentration by solid-phasemicro extraction (SPME), separation and identification by GC-MS. Based on the data processing method, quantitative attribution of biomarkers to inspiratory, alveolar and mixed expiratory phases was possible at any time during the experiment, even under respiratory rates up to 60/min. Alveolar concentrations of the breath markers, measured by PTR-MS ranged from 130 to 2,600 ppb (acetone), 10 to 540 ppb (isoprene), 2 to 31 ppb (acetaldehyde), whereas the concentrations of hexanal were always below the limit of detection (LOD) of 3 ppb. There was good correlation between on-line PTR-MS and SPME-GC-MS measurements during phases with stable physiological parameters but results diverged during rapid changes of heart rate and minute ventilation. This clearly demonstrates the benefits of breath-resolved MS for fast on-line monitoring of exhaled VOCs.