Correcting for tissue nitrogen excretion in multiple breath washout measurements

Abstract

Nitrogen excreted from body tissues impacts the calculation of multiple breath nitrogen washout (MBWN2) outcomes. The aim of this study was to determine the effect of tissue N2 on MBWN2 outcomes in both healthy subjects and patients with CF and to assess whether it is possible to correct for tissue N2. The contribution of tissue N2 to MBWN2 outcomes was estimated by comparing MBWN2-derived functional residual capacity (FRCN2) to FRC measured by body plethysmography (FRCpleth) and by comparing MBW outcome measures derived from MBWN2 and sulfur hexafluoride MBW (MBWSF6). Compared to plethysmography and MBWSF6, MBWN2 overestimated FRC and lung clearance index (LCI). Application of mathematical tissue N2 corrections reduced FRCN2 values closer to FRCpleth in health and reduced LCIN2 in both health and CF, but did not explain all of the differences observed between N2-dependent and -independent techniques. Use of earlier washout cut-offs could reduce the influence of tissue N2. Applying tissue N2 corrections to LCIN2 measurements did not significantly affect the interpretation of treatment effects reported in a previously published interventional trial. While tissue N2 excretion likely has an impact on MBWN2 outcomes, better understanding of the nature of this phenomenon is required before routine correction can be implemented into current MBWN2 protocols.

Difference between SF6 and N2 multiple breath washout kinetics is due to N2 back diffusion and error in N2 offset

“…The authors were unable to explain the source of the remaining slope. Our data on NBD and the data on technical offset can explain the observed dFRC/dt in the Kane et al study (13).…”

“…Although we previously identified NBD as one factor (19) contributing to the differences between the two methodologies, we have speculated that NBD alone may be inadequate to account fully for the differences. Other studies (13,17,19,21) have also demonstrated a significant effect of NBD on N 2 washout kinetics, but other factors such as the use of 100% oxygen for washout (16) may also contribute to the difference between SF 6 and N 2 washout kinetics.…”

“…They interpreted the difference as being due to NBD, but our NBD data suggest that it is responsible for only around 40% of the observed difference. Kane et al (13) also investigated the effect of NBD on N 2 FRC and LCI. The authors noted a very similar slope of the breath-by-breath N 2 FRC, dFRC/dt, as observed in our study.…”

Lung clearance index in healthy volunteers, measured using a novel portable system with a closed circuit wash-in

“…They cannot be used to identify normal ranges in subjects performing a nitrogen washout. Commonly deployed nitrogen washout systems seem to generate much higher values of LCI and FRC than SF 6 washouts [13,14] due to differences in the behaviour of the tracer gases [13], the washout of body nitrogen during testing [35,36], and the equipment itself [17]. The data analysis package was developed in-house, and is not the same as that shipped with the Innocor device.…”

Nitrogen offset in N2multiple washout method

“…The authors mention one study [9] that was unable to explain the overreading of functional residual capacity (FRC) of the Exhalyzer by N 2 back diffusion, a study that offered no other explanation. However, the study: 1) did not use back diffusion data from the time interval that is relevant in the MBW test; 2) applied an erroneous equation to correct for back diffusion (see our comment to [9]); and 3) it did not account for the technical offset error.…”