King Julian, Unterkofler Karl, Teschl Gerald, Teschl Susanne, Koc Helin, Hinterhuber Hartmann, Amann Anton
Breath Research Institute, Austrian Academy of Sciences, Dornbirn.
J Math Biol. 2011 Nov;63(5):959-99. doi: 10.1007/s00285-010-0398-9. Epub 2011 Jan 14.
Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide (NO) have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which may reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways, (ii) the concentrations in the tracheo-bronchial lining fluid, (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, the model illuminates the discrepancies between observed and theoretically predicted blood-breath ratios of acetone during resting conditions, i.e., in steady state. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases and thus is expected to have general relevance for a wider range of blood-borne inert gases. The chief intention of the present modeling study is to provide mechanistic relationships for further investigating the exhalation kinetics of acetone and other water-soluble species. This quantitative approach is a first step towards new guidelines for breath gas analyses of volatile organic compounds, similar to those for nitric oxide.
欧洲呼吸学会和美国胸科学会的特别工作组已制定出用于测定呼出气体中一氧化氮和鼻腔一氧化氮（NO）的推荐标准化程序。这些建议为一氧化氮测量成为特定临床应用的诊断工具铺平了道路。制定关于呼出气体中其他痕量气体采样的类似指南将是可取的，特别是可能反映正在进行的新陈代谢的挥发性有机化合物（VOCs）。呼出气体中水溶性血源物质的浓度受以下因素影响：（i）影响传导气道气体交换的呼吸模式，（ii）气管 - 支气管内衬液中的浓度，（iii）化合物的肺泡浓度和全身浓度。经典的法尔希方程仅考虑肺泡浓度。在测力计挑战下对潮气末呼吸中丙酮的实时测量显示出在法尔希设定内无法解释的特征。在这里，我们开发了一个隔室模型，该模型可靠地捕捉这些特征，并能够将呼吸与丙酮的全身浓度联系起来。通过与实验数据比较，可以推断出呼吸丙酮浓度变化的主要部分（例如，对适度运动或改变的呼吸模式的反应）可归因于气道气体交换，而基础血液和组织浓度的变化最小。此外，该模型阐明了在静息状态下，即稳态时，观察到的和理论预测的丙酮血 - 呼吸比之间的差异。特别是，当前的公式包括经典的法尔希模型和谢德系列非均匀性模型作为特殊的极限情况，因此预计对更广泛的血源惰性气体具有普遍相关性。本建模研究的主要目的是提供机制关系，以进一步研究丙酮和其他水溶性物质的呼出动力学。这种定量方法是朝着制定类似于一氧化氮的挥发性有机化合物呼气气体分析新指南迈出的第一步。
