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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.

RationaleWhile lung clearance index (LCI) is a sensitive marker of small airway disease in individuals with cystic fibrosis (CF), less is known about longitudinal changes in LCI during routine clinical surveillance.ObjectivesTo describe the longitudinal course of LCI in children with CF during routine clinical surveillance and assess influencing factors.MethodsChildren with CF aged 3–18 years performed LCI measurements every 3 months as part of routine clinical care between 2011 and 2018. We recorded clinical data at every visit. We used a multilevel mixed-effect model to determine changes in LCI over time and identify clinical factors that influence LCI course.Measurements and Main ResultsWe collected LCI from 1204 visits (3603 trials) in 78 participants, of which 907 visits had acceptable LCI data. The average unadjusted increase in LCI for the entire population was 0.29 LCI units·year−1 (95% CI 0.20–0.38). The increase in LCI was more pronounced in adolescence, with 0.41 units·year−1 (95% CI 0.27–0.54). Colonisation with either Pseudomonas aeruginosa or Aspergillus fumigatus, pulmonary exacerbations, CF-related diabetes, and bronchopulmonary aspergillosis were associated with a higher increase in LCI over time. Adjusting for clinical risk factors reduced the increase in LCI over time to 0.24 LCI units·year−1 (95% CI 0.16–0.33).ConclusionLCI measured during routine clinical surveillance is associated with underlying disease progression in children with CF. An increased change in LCI over time should prompt further diagnostic intervention.

Background Multiple breath washout (MBW) is increasingly used in the clinical assessment of patients with cystic fibrosis (CF). Guidelines for MBW quality control (QC) were developed primarily for retrospective assessment and central overreading. We assessed whether real‐time QC of MBW data during the measurement improves test acceptability in the clinical setting. Methods We implemented standardized real‐time QC and reporting of MBW data at the time of the measurement in the clinical pediatric lung function laboratory in Bern, Switzerland, in children with CF aged 4–18 years. We assessed MBW test acceptability before (31 tests; 89 trials) and after (32 tests; 96 trials) implementation of real‐time QC and compared agreement between reviewers. Further, we assessed the implementation of real‐time QC at a secondary center in Zurich, Switzerland. Results Before the implementation of real‐time QC in Bern, only 58% of clinical MBW tests were deemed acceptable following retrospective QC by an experienced reviewer. After the implementation of real‐time QC, MBW test acceptability improved to 75% in Bern. In Zurich, after the implementation of real‐time QC, test acceptability improved from 38% to 70%. Further, the agreement between MBW operators and an experienced reviewer for test acceptability was 84% in Bern and 93% in Zurich. Conclusion Real‐time QC of MBW data at the time of measurement is feasible in the clinical setting and results in improved test acceptability.

Background: Multiple breath washout (MBW) is increasingly used in the clinical assessment of patients with cystic fibrosis (CF). Guidelines for MBW quality control (QC) were developed primarily for retrospective assessment and central overreading. We assessed whether real-time QC of MBW data during the measurement improves test acceptability in the clinical setting. Methods: We implemented standardized real-time QC and reporting of MBW data at the time of the measurement in the clinical pediatric lung function laboratory in Bern, Switzerland in children with CF aged 4-18 years. We assessed MBW test acceptability before (31 tests; 89 trials) and after (32 tests; 97 trials) implementation of real-time QC and compared agreement between reviewers. Further, we assessed the implementation of real-time QC at a secondary center in Zurich, Switzerland. Results: Before implementation of real-time QC in Bern, only 68% of clinical MBW tests were deemed acceptable following retrospective QC by an experienced reviewer. After implementation of real-time QC, MBW test acceptability improved to 84% in Bern. In Zurich, after implementation of real-time QC, test acceptability improved from 50% to 90%. Further, the agreement between MBW operators and an experienced reviewer for test acceptability was 97% in Bern and 100% in Zurich. Conclusion: Real-time QC of MBW data at the time of measurement is feasible in the clinical setting and results in improved test acceptability.

All authors edited, reviewed, and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are investigated and resolved.

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.

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