Is twice the duration of washout sufficient time between multiple breath nitrogen washout tests?

From the authors:

We read the paper by K.M. Hardaker and co-workers with great interest. Their study confirmed our earlier data: that a washout-derived wait time between measurements of nitrogen-based multiple breath washout (MBW) was not influenced by disease severity, and that on average a wait time of twice the duration of the washout between nitrogen MBW tests eliminated potential measurement artefacts [1].

K.M. Hardaker and co-workers investigated whether our recommendation to wait at least twice the initial washout time between nitrogen MBW measurements was applicable in a larger cohort of children, with a retrospective analysis of clinically obtained data. In our study, we initially used a combination of wait times (5 and 15 min), which were randomised, in children aged 7 years and older. Our protocol was subsequently reviewed for an adult dataset and a wait time based on a function of initial washout time was used. The clinical data set used by Hardaker and co-workers allowed the expression of wait time in relation to washout time, rather than a fixed time, and this was, on average, 1.9 times the previous washout time. We commend their inclusion of preschool-aged children and are pleased that our recommendation is supported in this younger group by their evidence, which showed that a wait time of 1.50–2.27 times the previous washout time was sufficient for repeat measurements of functional residual capacity (FRC) to return reproducible values. A limitation of this retrospective analysis was that, unlike in our study, the time between repeat trials was not randomised and therefore an order effect could not be excluded. Similarly, while their data confirms that a wait time of twice the washout duration was sufficient to avoid artefacts in young children, their study was not designed to specifically test if shorter wait times were appropriate.

Hardaker and co-workers added value to this work by including the lung clearance index (LCI) and found that waiting ∼2 times the previous washout time ensured repeat measurements were reproducible. While our study did not report LCI, we are confident that any potentially detrimental effects of ventilation inhomogeneity on the measured FRC were accounted for by a wait time that was equal to, or exceeded, twice that of the initial washout time. This is supported by our observation in an adult cohort that a wait time based on the patient's own washout time was appropriate in obstructive lung disease. Random-effects regression analysis demonstrated no independent effect of obstructive disease severity on the washout time (p=0.98).

Hardaker and co-workers commented that future work could be done towards pursuing a reduced washout time; however, investigations should proceed with caution as the shorter the time between measurements the greater the risk of effects due to ventilation inhomogeneity. Although no recorded effects were seen on repeat FRC measurement after waiting only once the initial washout time in both our healthy and restricted groups, our obstructive lung disease group exhibited a significant difference in FRC. This suggests that reduced wait times may lead to measurement inaccuracies, although we do advocate further optimisation of lung-function testing protocols to improve the clinical reliability of the test.

The most recent consensus statement for inert gas washout measurements recommends that three technically acceptable FRC measurements are obtained with <10% variation from the minimum to maximum values [2]. The work of Hardaker and co-workers, in addition to our own work, means that this recommendation is attainable within a reasonable time period in a clinical laboratory. We welcome this contribution that has added to the body of work on nitrogen MBW testing procedures by including a younger cohort as well as LCI in the analysis of wait time effect on repeated nitrogen MBW measurements. This work supports our recommendation to wait twice the initial washout time between repeat measurements of FRC and we continue to strongly encourage the development of evidence-based guidelines to inform best practice in the clinical lung-function laboratory.