Smith David, Španěl Patrik
Trans Spectra Limited, 9 The Elms, Newcastle under Lyme, United Kingdom.
J Breath Res. 2017 Nov 1;11(4):047106. doi: 10.1088/1752-7163/aa7ab5.
It is argued that shortcomings of certain approaches to breath analysis research based on superficial interpretation of non-quantitative data are inadvertently inhibiting the progression of non-invasive breath analysis into clinical practice. The objective of this perspective is to suggest more clinically profitable approaches to breath research. Thus, following a discourse on the challenges and expectations in breath research, a brief indication is given of the analytical techniques currently used for the analysis of very humid exhaled breath. The seminal work that has been carried out using GC-MS revealed that exhaled breath comprises large numbers of trace volatile organic compounds, VOCs. Unfortunately, analysis of these valuable GC-MS data is mostly performed using chemometrics to distinguish the VOC content of breath samples collected from patients and healthy controls, and reliable quantification of the VOCs is rarely deemed necessary. This limited approach ignores the requirements of clinically acceptable biomarkers and misses the opportunity to identify relationships between the concentrations of individual VOCs and certain related physiological or metabolic parameters. Therefore, a plea is made for more effort to be directed towards the positive identification and accurate quantification of individual VOCs in exhaled breath, which are more physiologically meaningful as best exemplified by the quantification of breath nitric oxide, NO. Support for the value of individual VOC quantification is illustrated by the SIFT-MS studies of breath hydrogen cyanide, HCN, a biomarker of Pseudomonas aeruginosa infection, breath acetic acid as an indicator of airways acidification in cystic fibrosis patients, and n-pentane as a breath biomarker of inflammation in idiopathic bowel disease patients. These single VOCs could be used as non-invasive monitors of the efficacy of therapeutic intervention. The increase of breath methanol following the ingestion of a known amount of the sweetener aspartame impressively shows that accurate breath analysis is a reliable indicator of blood concentrations. However, using individual VOCs for specific disease diagnosis does have its problems and it is, perhaps, more appropriate to see their concentrations as proxy markers of general underlying physiological change. We dedicate this perspective to Lars Gustafsson for his seminal work on breath research and especially for his pioneering work on nitric oxide measurements in exhaled breath in asthma, which best shows the utility and value of the quantification of individual breath biomarkers on which this perspective focuses.
有人认为，基于对非定量数据的肤浅解读，某些呼吸分析研究方法的缺点在不经意间阻碍了非侵入性呼吸分析进入临床实践。本文观点的目的是提出更具临床效益的呼吸研究方法。因此，在论述呼吸研究中的挑战和期望之后，简要介绍了目前用于分析非常潮湿的呼出气的分析技术。使用气相色谱 - 质谱联用（GC - MS）所开展的开创性工作表明，呼出气中包含大量痕量挥发性有机化合物（VOCs）。不幸的是，对这些宝贵的GC - MS数据的分析大多使用化学计量学来区分从患者和健康对照收集的呼吸样本中的VOC含量，并且很少认为有必要对VOCs进行可靠的定量分析。这种有限的方法忽略了临床可接受生物标志物的要求，并且错过了识别个体VOC浓度与某些相关生理或代谢参数之间关系的机会。因此，呼吁做出更多努力，以积极鉴定和准确定量呼出气中的个体VOCs，其在生理上更具意义，呼吸一氧化氮（NO）的定量就是最好的例证。对个体VOC定量价值的支持体现在对呼吸氰化氢（HCN）的选择离子流动管质谱（SIFT - MS）研究中，HCN是铜绿假单胞菌感染的生物标志物；呼吸乙酸作为囊性纤维化患者气道酸化的指标；正戊烷作为特发性肠病患者炎症的呼吸生物标志物。这些单一VOCs可用作治疗干预效果的非侵入性监测指标。摄入已知量的甜味剂阿斯巴甜后呼吸甲醇的增加令人印象深刻地表明，准确的呼吸分析是血液浓度的可靠指标。然而，使用个体VOC进行特定疾病诊断确实存在问题，也许将它们的浓度视为一般潜在生理变化的替代标志物更为合适。我们将本文观点献给拉尔斯·古斯塔夫松，感谢他在呼吸研究方面的开创性工作，特别是他在哮喘患者呼出气中一氧化氮测量方面的开创性工作，这最能体现本文观点所关注的个体呼吸生物标志物定量的实用性和价值。
