Rationale The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and clinically relevant changes in LCI during routine clinical surveillance. Objectives To evaluate long-term variability of LCI and propose a threshold for a clinically relevant change. Methods Children with CF aged 4-18 years performed LCI measurements every three months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for clinically relevant changes. Results Repeated LCI measurements of acceptable quality (N= 858) were available in 100 patients with CF. Variability of repeated LCI measurements over time expressed as coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. Conclusion We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered clinically relevant. These findings will help guide clinical decisions according to LCI changes.

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.