Nitrogen-based lung clearance index: a valid physiological biomarker for the clinic

Multiple breath washout (MBW) testing is increasingly used as a physiological measurement in the clinic, due in part to the availability of commercial equipment and reference values for MBW indices. Commercial N washout devices are usually based on indirect measurement of N concentration ( ), by directly measuring either molar mass and O and CO , or molar mass and CO . We aim to elucidate the role of two potential pitfalls associated with N -MBW testing that could override its physiological content: indirect N measurement and blood-solubility of N . We performed MBW in 12 healthy adult subjects using a commercial device (MBW ) with simultaneous direct gas concentration measurements by mass spectrometry (MBW ) and compared between MBW and MBW . We also measured argon concentration during the same washouts to verify the maximal effect gas solubility can have on N -based functional residual capacity (FRC) and lung clearance index (LCI). Continuous N concentration traces were very similar for MBW and MBW , resulting in comparable breath-by-breath washout plots of expired concentration and in no significant differences in FRC , LCI , S , and S between the two methods. Argon washouts were slightly slower than N washouts, as expected for a less diffusive and more soluble gas. Finally, comparison between LCI and LCI indicates that the maximum impact from blood-tissue represents less than half a LCI unit in normal subjects. In conclusion, we have demonstrated by direct measurement of N and twice as soluble argon, that indirect N measurement can be safely used as a meaningful physiological measurement. The physiological content of N multibreath washout testing has been questioned due to N indirect measurement accuracy and N blood solubility. With direct measurement of N and twice as soluble argon, we show that these effects are largely outweighed by ease of use.