Correction of measurement error in a commercial multiple-breath washout device

Abstract

Rationale: Nitrogen multiple breath washout (N2MBW) is an established technique to assess functional residual capacity (FRC) and ventilation inhomogeneity in the lung. Accurate gas sensors are essential for the appropriate calculation of clinical outcomes. Objectives: We investigated the accuracy of oxygen and carbon dioxide sensors used for the indirect measurement of nitrogen in the Eco Medics Exhalyzer D N2MBW device and characterized the impact of potential sensor errors on FRC and the lung clearance index (LCI). Methods: Technical gas mixtures and mass spectrometry were used to evaluate sensor accuracy. We assessed the impact of potential sensor errors and correction on FRC and LCI in a dataset of healthy children and children with cystic fibrosis using custom analysis software. Results: We found a systematic error in the gas sensors of the Exhalyzer D device involving inadequate correction for the cross sensitivity between the oxygen and carbon dioxide sensors. This error results in an overestimation of expired nitrogen concentration, and consequently FRC and LCI outcomes. Breath-by-breath correction for this sensor error non-systematically reduced mean (SD) FRC by 8.9 (2.2)% and LCI by 11.9 (4.0)%. It also resulted in almost complete disappearance of the tissue nitrogen signal at the end of the measurement. Conclusions: An error in the cross sensitivity correction between the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of FRC and LCI. Correction of this error is possible but needs to be applied breath-by-breath by re-analysing the measurements in an updated software version.

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

“…accessed the correction factors and the equations from Eco Medics AG, which have also been published by us in preprint form (28). They applied the equations in a custom-made software version to measurements of healthy infants and toddlers (20).…”

Differential effects of ELX/TEZ/IVA on organ-specific CFTR function in two patients with the rare CFTR splice mutations c.273+1G>A and c.165-2A>G

“…MBW testing was performed with the Exhalyzer D system (Eco Medics), and 100% oxygen was used to wash out resident nitrogen from the lungs with a mouthpiece as interface (Stahl et al, 2017). All measurements were using spiroware 3.3.1 (Eco Medics) (Stahl et al, 2020;Graeber et al, 2021;Wyler et al, 2021). The upper limit of normal (ULN) was determined as 7.1 (Wyler et al, 2021).…”

“…All measurements were using spiroware 3.3.1 (Eco Medics) (Stahl et al, 2020;Graeber et al, 2021;Wyler et al, 2021). The upper limit of normal (ULN) was determined as 7.1 (Wyler et al, 2021).…”

“…Both patients were compound heterozygous for the rare splice mutations c.273+1G>C and c.165-2A>G. At baseline, B1 was 10.2 years old and B2 was 7.2 years, both of them presented with the phenotype of pancreatic insufficient cystic fibrosis (PI-CF). Prior to ETI, the sweat chloride concentrations were in the typical PI-CF Dashed lines indicate published limits of normal for QPIT (Nährlich et al, 2013), LCI 2.5 (Wyler et al, 2021), nPD Sermet Score (Sermet-Gaudelus et al, 2010) and SST (Pallenberg et al, 2022).…”

“…FIGURE 1Effects of ETI on QPIT (A), LCI 2.5 (B), nPD basic potential (C), nPD Amiloride response (D), nPD cumulative depolarization response to chloride-free solution and isoproterenol (E), nPD Sermet Score (F), response to forskolin/IBMX and carbachol in ICM (G) and SST (H) in brother 1 (triangle) and brother 2 (circle) compared to the median effect on pwCF with one or two p.Phe508del alleles (white square) and reference values for healthy controls (HC, star). Dashed lines indicate published limits of normal for QPIT(Nährlich et al, 2013), LCI 2.5(Wyler et al, 2021), nPD Sermet Score(Sermet-Gaudelus et al, 2010) and SST(Pallenberg et al, 2022).…”