Correction of sensor crosstalk error in Exhalyzer D multiple-breath washout device significantly impacts outcomes in children with cystic fibrosis

Abstract

Rationale: Nitrogen multiple-breath washout is an established technique to assess functional residual capacity and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes. Objectives: We investigated the accuracy of oxygen and carbon dioxide gas sensor measurements used for the indirect calculation of nitrogen concentration in a commercial multiple-breath washout device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on functional residual capacity and lung clearance index. Methods: High precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on multiple-breath washout outcomes in a dataset of healthy children and children with cystic fibrosis using custom analysis software. Results: We found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently multiple-breath washout outcomes. Breath-by-breath correction of this error reduced the mean (SD) cumulative expired volume by 19.6 (5.0)%, functional residual capacity by 8.9 (2.2)%, and lung clearance index by 11.9 (4.0)%. It also substantially reduced the level of the tissue nitrogen signal at the end of measurements. Conclusions: Inadequate correction for cross sensitivity in the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of functional residual capacity and lung clearance index. Correction of this error is possible and could be applied by re-analyzing the measurements in an updated software version.

Longitudinal lung clearance index and association with structural lung damage in children with cystic fibrosis

“…LCI values derived from different MBW equipment or different inert gases are not considered interchangeable 15. A recent publication in 2021 revealed a systematic software error from the gas sensors of the Exhalyzer D, that is commonly used in many MBW studies 32. This error resulted in an overestimation of LCI when using nitrogen as an inert gas.…”

Contemporary N2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis

“…20 In this study, we prospectively performed both SF 6 and N 2 MBW at the same visit in a large cohort of infants and toddlers with CF, with the aim of determining the differences between SF 6 and N 2 MBW outcomes and mechanisms contributing to the observed differencessuch as tidal volume reduction during N 2 washout with pure O 2 . We included an assessment of the impact of the recently released correction equations for the N 2 signal, 21,22 and its effect on the classification of the presence of abnormal ventilation inhomogeneity, by comparing it to our recently published data on healthy children. We aimed to determine whether the new corrected N 2 MBW method provided equivalent accuracy to SF 6 MBW in infants and toddlers with CF.…”

Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis

“…All MBW trials were analysed with the newest Spiroware version ( i.e. 3.3.1), so that our results are not affected by the recently revealed sensor crosstalk error in the Exhalyzer D device [ 30 ]. Overall, a posteriori effect size calculations yielded study power in the range of 68–100% for the differences between CIIs in CF and controls and the Pearson's correlation coefficients between CIIs and LCI.…”