Background The advantages of multiple breath washout tests, and in particular lung clearance index (LCI), over conventional spirometry in cystic fibrosis (CF) are now well established. Although the majority of studies have used exogenous sulphur hexafluoride (SF₆) as the tracer gas this has also led to an increased interest in nitrogen washout tests, despite the differences between these methods. Although it is increasingly appreciated that the two systems may produce different results in patients with lung disease, the impact on nitrogen washout progression of body nitrogen excreted across the alveoli has previously been ignored.

Methods A two compartment lung model was developed that included ventilation heterogeneity and dead space (DS) effects, but also incorporated previous experimental data from adults on nitrogen excretion. The model was used to assess the impact of nitrogen excretion on washout progress and accuracy of functional residual capacity (FRC) and LCI measurements at varying degrees of DS and ventilation heterogeneity. An estimate was also made of the effects in children, based upon extrapolation adult clinical data.

Results Excreted nitrogen had a small effect on accuracy of FRC (1.8%) in the healthy adult model. The error in LCI calculated with true FRC was greater (6.3%), and excreted nitrogen contributed 21% of the total nitrogen concentration at the end of the washout. Increasing DS caused further increase in measurement error, whilst increasing ventilation heterogeneity caused a bell shaped curve with initially increasing error falling again as ventilation heterogeneity approached a maximum. LCI was increased by 6–13% in a CF child model, and excreted nitrogen increased the end of washout nitrogen concentration by 24–49%.

Conclusions Excreted nitrogen appears to have complex but clinically significant effects on washout progress, particularly in the presence of abnormal gas mixing. This may explain much of the previously described differences in washout outcomes between SF₆ and nitrogen. Caution should be applied in applying conclusions derived from using one tracer gas to another.