Abstract

The influence of breath sampling on exhaled carbon monoxide (eCO) and related pulmonary gas exchange parameters is investigated in a study with 32 healthy non-smokers. Mid-infrared tunable diode laser absorption spectroscopy and well-controlled online sampling is used to precisely measure mouth- and nose-exhaled CO expirograms at exhalation flow rates (EFRs) of 250, 120 and 60 ml s−1, and for 10 s of breath-holding followed by exhalation at 120 ml s−1. A trumpet model with axial diffusion is employed to fit simulated exhalation profiles to the experimental expirograms, which provides equilibrium airway and alveolar CO concentrations and the average lung diffusing capacity in addition to end-tidal concentrations. For all breathing maneuvers, excellent agreement is found between mouth- and nose-exhaled end-tidal CO (ETCO), and the individual values for ETCO and alveolar diffusing capacity are consistent across maneuvers. The eCO parameters clearly show a dependence on EFR, where the lung diffusing capacity increases with EFR, while ETCO slightly decreases. End-tidal CO is largely independent of ambient air CO and alveolar diffusing capacity. While airway CO is slightly higher than, and correlates strongly with, ambient air CO, and there is a weak correlation with ETCO, the results point to negligible endogenous airway CO production in healthy subjects. An EFR of around 120 ml s−1 can be recommended for clinical eCO measurements. The employed method provides means to measure variations in endogenous CO, which can improve the interpretation of exhaled CO concentrations and the diagnostic value of eCO tests in clinical studies. Clinical trial registration number: 2017/306-31

Highlights

  • Detection of carbon monoxide (CO) in exhaled breath is an established method to assess recent uptake of exogenous CO, such as from smoking [1, 2] or exposure to air pollution [3]

  • In an attempt to contribute to an improved assessment of endogenous exhaled breath carbon monoxide (eCO) and to enhance the information gained from single-exhalations, we have recently introduced an extended breath CO analysis approach, where detection of real-time CO exhalation profiles with laser absorption spectroscopy [21, 22] is combined with pulmonary gas exchange modeling and least-squares fitting of the measured eCO profiles [23, 24]

  • Real-time eCO detection was performed with laser absorption spectroscopy by acquisition of single-exhalation profiles from mouth and nose at three exhalation flow rates and after BH

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Summary

Introduction

Detection of carbon monoxide (CO) in exhaled breath is an established method to assess recent uptake of exogenous CO, such as from smoking [1, 2] or exposure to air pollution [3]. The measurement of endogenous CO production via exhaled breath is less common, but could have high diagnostic and clinical value, for example when it comes to non-invasive assessment of respiratory diseases [4, 5]. To successfully resolve endogenous CO concentrations, sensitive and precise analytical methods, as well as knowledge about the natural and breath samplinginduced variability of exhaled CO, are required. A typical measurement of exhaled breath carbon monoxide (eCO) is today synonymous with acquiring a single experimental value corresponding to the end-tidal (ETCO) or mixed-breath CO concentration. Depending on the CO concentration in the ambient air inhaled during the last day(s), the healthy nonsmoker ETCO levels can vary between 1 and 6 parts per million (ppm), whereas smoking can give rise to tens of ppm

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