Changes in lung clearance index in children with cystic fibrosis -- guidance for clinical practice

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.