Abstract
BackgroundA large body of evidence has now accumulated describing the advantages of multiple breath washout tests over conventional spirometry in cystic fibrosis (CF). 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. The impact of body nitrogen excreted across the alveoli has previously been ignored.MethodsA two-compartment lung model was developed that included ventilation heterogeneity and dead space (DS) effects, but also incorporated experimental data 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 lung clearance index (LCI) measurements.ResultsExcreted 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 and ventilation heterogeneity both caused further increase in measurement error. LCI was increased by 6–13% in a CF child model, and excreted nitrogen increased the end of washout nitrogen concentration by 24–49%.ConclusionsExcreted 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.
Highlights
Over the last ten years a growing body of evidence has demonstrated the value of lung physiology measurements derived from multiple breath washout tests (MBW), in particular the lung clearance index (LCI) [1,2]
cystic fibrosis (CF) adult with functional residual capacity (FRC) = 3L and R = 10L/min as above, but with dead space (DS) = 0.45, and both X and Y equal to 0.7. In both of these cases we looked at the end of the washout, where the expired nitrogen concentration is 1.975% (1/40th of the starting value) to assess the contribution to this signal made by excreted nitrogen
The effect of nitrogen excretion on nitrogen concentration at end of washout, LCI and FRC are summarised in Table 1 for a healthy adult model and for an adult with both ventilation heterogeneity (X = 0.7) and increased DS (0.45)
Summary
Over the last ten years a growing body of evidence has demonstrated the value of lung physiology measurements derived from multiple breath washout tests (MBW), in particular the lung clearance index (LCI) [1,2]. The recent consensus statement on MBW described three different tracer gases that have been used to measure LCI [8]: helium, sulphur hexafluoride (SF6) and nitrogen (N2). Differences in molar mass affect the diffusion front, which lies more distally for SF6 than for the much lighter helium This difference has potential to be exploited to explore the site of lung pathology [9], though in practice the majority of studies on MBW so far have involved either SF6 or nitrogen as the tracer gas. A large body of evidence has accumulated describing the advantages of multiple breath washout tests over conventional spirometry in cystic fibrosis (CF). The majority of studies have used exogenous sulphur hexafluoride (SF6) as the tracer gas this has led to an increased interest in nitrogen washout tests, despite the differences between these methods. The impact of body nitrogen excreted across the alveoli has previously been ignored
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