Sulfur hexafluoride multiple breath washin and washout outcomes in infants are not interchangeable

<i>Objective.</i>Sulfur hexafluoride (SF₆) multiple-breath washout (MBW) assesses ventilation inhomogeneity, as an early marker of obstructive respiratory diseases. Primary outcomes are customarily washout-derived, and it is unclear whether the preceding SF₆-washin can provide similar estimates. We aimed to assess comparability of primary SF₆-MBW outcomes between washin and washout phases of infant SF₆-MBW data measured with the WBreath (ndd Medizintechnik AG, Zurich, Switzerland) and Spiroware (Eco Medics AG, Duernten, Switzerland) MBW-setups, respectively.<i>Approach.</i>We assessed mean relative differences in lung clearance index (LCI) and functional residual capacity (FRC) between the washin and washout of existing SF₆-MBW data from healthy infants and infants with cystic fibrosis (CF). We assessed whether these differences exceeded the mean relative within-test between-trial differences of washout-derived outcomes, which can be attributed to natural variability. We also explored non-physiological factors using a pediatric lung simulator.<i>Main results.</i>LCI and FRC from washin and washout were not comparable, for both setups. The mean difference (SD) in LCI between washin and washout was 2.3(10.8)% for WBreath and -9.7(8.0)% for Spiroware, while in FRC it was -4.7(8.4)% for WBreath and -2.3(9.7)% for Spiroware. These differences exceeded the within-test between-trial differences in washout-derived outcomes. Outcomes from washin and washout were also not comparable in a pediatric lung simulator.<i>Significance.</i>Outcomes of the washin and washout were not comparable due to an interplay of physiological and non-physiological factors, and cannot be used interchangeably.