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.