PT  - JOURNAL ARTICLE
AU  - Bettina S. Frauchiger
AU  - Severin Binggeli
AU  - Sophie Yammine
AU  - Ben Spycher
AU  - Linn Krüger
AU  - Kathryn A. Ramsey
AU  - Philipp Latzin
TI  - Longitudinal Course of Clinical Lung Clearance Index in Children with Cystic Fibrosis
AID  - 10.1183/13993003.02686-2020
DP  - 2020 Jan 01
TA  - European Respiratory Journal
PG  - 2002686
4099  - http://erj.ersjournals.com/content/early/2020/12/10/13993003.02686-2020.short
4100  - http://erj.ersjournals.com/content/early/2020/12/10/13993003.02686-2020.full
AB  - Rationale While 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.Objectives To describe the longitudinal course of LCI in children with CF during routine clinical surveillance and assess influencing factors.Methods Children 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 Results We 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).Conclusion LCI 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Frauchiger has nothing to disclose.Conflict of interest: Dr. Binggeli has nothing to disclose.Conflict of interest: Dr. Yammine reports grants from Swiss National Science Foundation, outside the submitted work.Conflict of interest: Dr. Spycher reports grants from Swiss National Science Foundation, grants from Swiss Cancer League, outside the submitted work.Conflict of interest: Dr. Krüger has nothing to disclose.Conflict of interest: Dr. Ramsey reports grants from Swiss National Science Foundation, outside the submitted work.Conflict of interest: Dr. Latzin reports grants from Vertex, during the conduct of the study; personal fees from Vertex, personal fees from Novartis, personal fees from Roche, personal fees from Polyphor, personal fees from Vifor, personal fees from Gilead, personal fees from Schwabe, personal fees from Zambon, personal fees from Santhera, grants from Vertex, outside the submitted work.