Introduction: Recent studies indicate limited utility of nitrogen multiple breath washout (N2MBW) in infancy and advocate for using sulphur hexafluoride (SF6)MBW in this age group. Modern N2MBW systems, such as EXHALYZER D® (ECO MEDICS AG, Duernten, Switzerland), use O2 and CO2 sensors to calculate N2 concentrations (in principle: N2%=100-CO2%-O2%). High O2 and CO2 concentrations have now been shown to significantly suppress signal output from the other sensor, raising apparent N2 concentrations. We examined whether improved Exhalyzer D® N2-signal, accomplished after thorough examination of this CO2 and O2 interaction on gas sensors and its correction, leads to better agreement between N2MBW and SF6MBW in healthy infants and toddlers. Method: Within the same session 52 healthy children aged 1-36 months (mean 1.30 (SD 0.72) years) completed SF6MBW and N2MBW recordings (EXHALYZER D®, SPIROWARE® version 3.2.1) during supine quiet sleep. SF6 and N2 SPIROWARE® files were re-analyzed off-line with in-house software using identical algorithms as in SPIROWARE® with or without application of the new correction factors for N2MBW provided by ECO MEDICS AG. Results Applying the improved N2-signal significantly reduced mean (95% CI) differences between N2- and SF6MBW recorded functional residual capacity (FRC) and lung clearance index (LCI): for FRC, from 26.1 (21.0; 31.2) mL p<0.0001 to 1.18 (-2.3; 4.5) mL p=0.5, and for LCI, from 1.86 (1.68; 2.02) p<0.001 to 0.44 (0.33; 0.55) p<0.001. Conclusion: Correction of N2-signal, for CO2 and O2 interactions on gas sensors resulted in markedly closer agreement between N2MBW and SF6MBW outcomes in healthy infants and toddlers.

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Introduction Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulphur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment and to produce device specific equations if necessary. Method SF6MBW was performed in 327 healthy children aged 0.1-18.4 years (151 [46%] girls), 191 (58.4%) < 3 years. Z-scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression performed to produce device specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF (n=138 test occasions) and 49 adults with lung disease. Results Historical SF6MBW reference equations were unsuitable for EXHALYZER D® data. In contrast to LCI and log10(LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10(FRC). Significant predictors for VDE and log10(FRC), respectively, were log10(age) and gender, and log10(height), gender and posture. Conclusion VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted.

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Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF 6 MBW commonly viewed as the reference method.The use of N 2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N 2 signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF 6 and N 2 MBW,correctedsuch as tidal volume reduction during N 2 washout with pure O 2 .Method: This was a longitudinal multicenter cohort study. SF 6 MBW and N 2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N 2,original and N 2,corrected for comparison with SF 6 MBW.Results: Mean functional residual capacity, FRC N2,corrected was 14.3% lower than FRC N2, original , and 1.0% different from FRC SF6 . Lung clearance index, LCI N2,corrected was 25.2% lower than LCI N2,original , and 7.3% higher than LCI SF6 . Mean (SD) tidal volume decreased significantly during N 2 MBW corrected , compared to SF 6 MBW (−13.1 ml [−30.7; 4.6], p < 0.0001, equal to −12.0% [−25.7; 1.73]), but this tidal

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