Abstract
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.
Highlights
Endogenous carbon monoxide (CO) is mainly produced by systemic heme oxygenase and eliminated via respiration
Simulated singleexhalation profiles were found in good agreement with measured healthy non-smoker expirograms for different exhalation flow rates and breath-holding
Axial diffusion plays a significant role in distributing the CO molecules in the respiratory tract, in particular during breath-holding
Summary
Endogenous carbon monoxide (CO) is mainly produced by systemic heme oxygenase and eliminated via respiration. Non-smoking population, end-tidal concentrations are in the range 1–3 parts per million (ppm) (Ryter and Choi, 2013). There is evidence that CO can arise due to locally induced heme oxygenase, e.g., in airway tissue (Horváth et al, 1998). CO has been identified as a cellular signaling molecule (Kim et al, 2006), possibly involved in anti-inflammatory and cytoprotective responses (Ryter and Choi, 2013). In the rapidly evolving field of breath gas analysis, exhaled breath CO (eCO) is considered a potential biomarker for non-invasive assessment of oxidative stress and respiratory diseases (Owens, 2010; Amann and Smith, 2013)
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