Correcting for tissue nitrogen excretion in multiple breath washout measurements

Nitrogen excreted from body tissues impacts the calculation of multiple breath nitrogen washout (MBW(N2)) outcomes. The aim of this study was to determine the effect of tissue N(2) on MBW(N2) outcomes in both healthy subjects and patients with CF and to assess whether it is possible to correct for tissue N(2). The contribution of tissue N(2) to MBW(N2) outcomes was estimated by comparing MBW(N2)-derived functional residual capacity (FRC(N2)) to FRC measured by body plethysmography (FRC(pleth)) and by comparing MBW outcome measures derived from MBW(N2) and sulfur hexafluoride MBW (MBW(SF6)). Compared to plethysmography and MBW(SF6), MBW(N2) overestimated FRC and lung clearance index (LCI). Application of mathematical tissue N(2) corrections reduced FRC(N2) values closer to FRC(pleth) in health and reduced LCI(N2) in both health and CF, but did not explain all of the differences observed between N(2)-dependent and -independent techniques. Use of earlier washout cut-offs could reduce the influence of tissue N(2.) Applying tissue N(2) corrections to LCI(N2) measurements did not significantly affect the interpretation of treatment effects reported in a previously published interventional trial. While tissue N(2) excretion likely has an impact on MBW(N2) outcomes, better understanding of the nature of this phenomenon is required before routine correction can be implemented into current MBW(N2) protocols.