title: Lung clearance index predicts pulmonary exacerbations in young patients with cystic fibrosis.
abstract: BACKGROUND
  The lung clearance index (LCI) is a promising endpoint for use in cystic fibrosis (CF) clinical trials, but correlations with validated clinical endpoints have not yet been established.
  
  
  OBJECTIVE
  This study aimed to demonstrate that, in young patients with CF, baseline LCI predicts subsequent pulmonary exacerbation (PE) and correlates with the respiratory domain of the CF Questionnaire-Revised (CFQ-Rresp).
  
  
  METHODS
  Baseline LCI, forced expiratory volume in 1 s (FEV1), CFQ-Rresp and PEs over the subsequent year were prospectively recorded in 63 patients aged 5-19 years. The ability of baseline LCI to predict PE was assessed using negative binomial regression models and Kaplan-Meier plots.
  
  
  RESULTS
  Twenty-six patients (41%) experienced 48 PEs. Baseline LCI and FEV1 were predictors of PE. Compared with the quartile with the lowest LCI, the annual PE rate in increasing LCI quartiles was 2.9 (95% CI 0.5 to 16.5, p=0.238), 5.4 (95% CI 1.0 to 29.0, p=0.045) and 13.6 (95% CI 2.8 to 67.1, p=0.001). Similarly, time to first PE decreased with worsening LCI quartiles (log-rank test for trend, p<0.001). Furthermore, LCI correlated with CFQ-Rresp (r=-0.43, p<0.001). In the subgroup of 53 patients with normal FEV1, LCI was a predictor of PE. In this subgroup, LCI also correlated with CFQ-Rresp (r=-0.282, p=0.043).
  
  
  CONCLUSIONS
  Baseline LCI predicts PE in young patients with CF and correlates with CFQ-Rresp, a validated patient-reported outcome, even in the subgroup with normal FEV1. These data further support the use of LCI as a surrogate outcome measure in CF clinical trials.
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Centre, University Hospital Leuven, , Leuven, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Vermeulen
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.forename: Mieke
authors.initials: M
authors.lastname: Boon
authors.forename: Trudy
authors.initials: T
authors.lastname: Havermans
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D013147:Spirometry; D014797:Vital Capacity; D055815:Young Adult
keywords: Cystic Fibrosis