Background: Traditionally the inter-test reproducibility of the lung clearance index (LCI) has been described in terms of absolute change (e.g. 1 unit), however, if LCI is more variable at higher values, interpretation of absolute changes in LCI may be biased. Aims: We assessed whether inter-test reproducibility depends on the LCI value and whether relative changes are better suited to define reproducibility. Methods: Multiple breath nitrogen washout (MBW) was measured at baseline, 1, 3, 6, 9 and 12 months in children aged 3-6 years with CF, and age-matched healthy controls. Reproducibility of the LCI between each pair of measurements was described using Bland Altman limits of agreement (LA), Coefficient of repeatability (CR), and relative change. Results: 148 children contributed 619 MBW measurements. The within-subject SD of the LCI between paired measurements, a measure of variability, increased as the absolute LCI increased. Therefore, using LA or the CR to determine thresholds of inter-test reproducibility will over-estimate clinically relevant changes in patients with higher LCI values. Using relative changes, a physiologically or clinically relevant change in healthy preschool children was calculated to be +/- 15%, whereas it was +/- 30% in CF children. The average relative change in both health and CF was independent of the time interval between measurements. Conclusions: Since LCI variability is proportional to its mean, interpretation of absolute changes will be biased. Changes in LCI greater than +/- 15% can be considered greater than the biological variability of the test in health and may help to identify patients with clinically relevant changes in lung function
