LAUSR

Background: While lung clearance index (LCI) is acknowledged to be a sensitive measure to detect small airway disease in cystic fibrosis (CF), less is known about its long-term progression. For clinical interpretation, knowledge of longitudinal changes is crucial. Objectives: To describe the longitudinal course of lung clearance index from clinical routine in children with cystic fibrosis and assess influencing factors. Methods: Children with CF aged 3- 18 years performed LCI measurements every three months as part of routine clinical care from 2011-2018. Matching clinical data were recorded at every visit. A multilevel mixed-effect model was used to determine the increase in LCI over time and identify factors that influence LCI course. Measurements and Main Results: Longitudinal data were collected from 1204 visits (3603 MBW trials) in 78 subjects; 907 visits had acceptable LCI measurements. Average increase in LCI for the entire population was 0.29 LCI units/year (95% CI 0.20 - 0.38). LCI was rather stable during early childhood (4-10.5 years; slope 0.1 LCI units/year, (95% CI -0.1 – 0.22)) whereas the increase was pronounced during adolescence (10.5 - 18 years; 0.32 LCI units/year (95% CI 0.21 - 0.43); p for interaction 0.003). Chronic colonization with either Pseudomonas or Aspergillus, intravenous antibiotic treatment, acute exacerbations, CF-related diabetes and bronchopulmonary aspergillosis (ABPA) were associated with a higher increase in LCI over time. Conclusion: LCI measured in clinical routine detects worsening of lung function over time suggestive of underlying pathological processes. Without risk factors, LCI remains surprisingly stable, especially before adolescence.