Ghorbani Ramin, Blomberg Anders, Schmidt Florian M
Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Front Physiol. 2018 Jul 30;9:927. doi: 10.3389/fphys.2018.00927. eCollection 2018.
Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive assessment of oxidative stress and respiratory diseases. Standard end-tidal CO analysis, however, cannot distinguish, whether eCO reflects endogenous CO production, lung diffusion properties or exogenous sources, and is unable to resolve a potential airway contribution. Coupling real-time breath gas analysis to pulmonary gas exchange modeling holds promise to improve the diagnostic value of eCO. A trumpet model with axial diffusion (TMAD) is used to simulate the dynamics of CO gas exchange in the respiratory system and corresponding eCO concentrations for the first time. The mass balance equation is numerically solved employing a computationally inexpensive routine implementing the method of lines, which provides the distribution of CO in the respiratory tract during inhalation, breath-holding, and exhalation with 1 mm spatial and 0.01 s temporal resolution. Initial estimates of the main TMAD parameters, the maximum CO fluxes and diffusing capacities in alveoli and airways, are obtained using healthy population tissue, blood and anatomical data. To verify the model, mouth-exhaled expirograms from two healthy subjects, measured with a novel, home-built laser-based CO sensor, are compared to single-exhalation profiles simulated using actual breath sampling data, such as exhalation flow rate (EFR) and volume. A very good agreement is obtained in exhalation phases I and III for EFRs between 55 and 220 ml/s and after 10 and 20 s of breath-holding, yielding a unique set of TMAD parameters. The results confirm the recently observed EFR dependence of CO expirograms and suggest that measured end-tidal eCO is always lower than alveolar and capillary CO. Breath-holding allows the observation of close-to-alveolar CO concentrations and increases the sensitivity to the airway TMAD parameters in exhalation phase I. A parametric simulation study shows that a small increase in airway flux can be distinguished from an increase in alveolar flux, and that slight changes in alveolar flux and diffusing capacity have a significantly different effect on phase III of the eCO profiles.
呼出气体一氧化碳（eCO）是用于氧化应激和呼吸系统疾病无创评估的候选生物标志物。然而，标准的潮气末CO分析无法区分eCO是反映内源性CO产生、肺扩散特性还是外源性来源，并且无法解决潜在的气道贡献问题。将实时呼吸气体分析与肺气体交换建模相结合有望提高eCO的诊断价值。首次使用具有轴向扩散的小号模型（TMAD）来模拟呼吸系统中CO气体交换的动态以及相应的eCO浓度。采用一种计算成本低廉的线方法例程对质量平衡方程进行数值求解，该方法以1毫米的空间分辨率和0.01秒的时间分辨率提供吸气、屏气和呼气过程中呼吸道内CO的分布。利用健康人群的组织、血液和解剖学数据获得TMAD主要参数的初始估计值，即肺泡和气道中的最大CO通量和扩散能力。为了验证该模型，将使用新型自制基于激光的CO传感器测量的两名健康受试者的口呼出呼气图与使用实际呼气采样数据（如呼气流量率（EFR）和体积）模拟的单次呼气曲线进行比较。在呼气阶段I和III中，对于55至220毫升/秒的EFR以及屏气10秒和20秒后，获得了非常好的一致性，从而得出了一组独特的TMAD参数。结果证实了最近观察到的CO呼气图对EFR的依赖性，并表明测得的潮气末eCO始终低于肺泡和毛细血管中的CO。屏气允许观察接近肺泡的CO浓度，并增加了呼气阶段I对气道TMAD参数的敏感性。参数模拟研究表明，可以区分气道通量的小幅增加与肺泡通量的增加，并且肺泡通量和扩散能力的微小变化对eCO曲线的第三阶段有显著不同的影响。
