Optimized algorithm for speed-of-sound-based infant sulfur hexafluoride multiple-breath washout measurements

<bold>Introduction</bold> - Methodological issues with the existing algorithm (WBreath) used for the analysis of molar mass-based infant sulfur hexafluoride (SF6) multiple-breath washout (MBW) measurements can lead to implausible results and complicate the comparison between different age groups and centers. <bold>Methods</bold> - We developed an optimized algorithm for speed-of-sound-based infant SF6 MBW measurements (OASIS). This algorithm uses known context of the measurements to replace the dependence of WBreath on model input parameters. We validated the functional residual capacity (FRC) measurement accuracy of this new algorithm in vitro, and investigated its use in existing MBW datasets from different infant cohorts from Switzerland and South Africa. <bold>Results</bold> - In vitro, OASIS managed to outperform WBreath at FRC measurement accuracy, lowering mean (SD) absolute error from 5.1 (3.2) % to 2.1 (1.6) % across volumes relevant for the infant age range (n = 60, p < 0.001), in variable temperature, respiratory rate, tidal volume and ventilation inhomogeneity conditions. OASIS produced more plausible results than WBreath in longitudinal tracking of lung clearance index (LCI) in infants with cystic fibrosis, reducing average absolute differences between measurements at 6 weeks, 1 year and 6 years from 38.3 (16.2) % to 11.8 (6.5) % (n = 21, p < 0.001). OASIS also reduced differences in mean LCI between centers from 16.7 % to 2.1 % in healthy 6-week-old infants. <bold>Discussion</bold> - This new algorithm represents a meaningful advance in obtaining results from a legacy system of lung function measurement by allowing a single method to analyze measurements from different age groups and centers.