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 2 washout devices are usually based on indirect measurement of N 2 concentration ( C N2 ), by directly measuring either molar mass and O 2 and CO 2 , or molar mass and CO 2 . We aim to elucidate the role of two potential pitfalls associated with N 2 -MBW testing that could override its physiological content: indirect N 2 measurement and blood-solubility of N 2 . We performed MBW in 12 healthy adult subjects using a commercial device (MBW indirect ) with simultaneous direct gas concentration measurements by mass spectrometry (MBW direct ) and compared C N2 between MBW direct and MBW indirect . We also measured argon concentration during the same washouts to verify the maximal effect gas solubility can have on N 2 -based functional residual capacity (FRC) and lung clearance index (LCI). Continuous N 2 concentration traces were very similar for MBW indirect and MBW direct , resulting in comparable breath-by-breath washout plots of expired concentration and in no significant differences in FRC N2 , LCI N2 , S cond , and S acin between the two methods. Argon washouts were slightly slower than N 2 washouts, as expected for a less diffusive and more soluble gas. Finally, comparison between LCI N2 and LCI Ar 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 2 and twice as soluble argon, that indirect N 2 measurement can be safely used as a meaningful physiological measurement. NEW & NOTEWORTHY The physiological content of N 2 multibreath washout testing has been questioned due to N 2 indirect measurement accuracy and N 2 blood solubility. With direct measurement of N 2 and twice as soluble argon, we show that these effects are largely outweighed by ease of use.