title: Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.
abstract: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease.
  
  
  
  To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF.
  
  
  
  Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease.
  
  
  
  Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values.
  
  
  
  LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.
authors.affiliation: 1 Division of Respiratory Medicine, and.|2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Sanja
authors.identifier: 0000-0001-7931-8051
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: 3 Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Davis
authors.affiliation: 4 Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and.
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
authors.affiliation: 2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Hailey
authors.initials: H
authors.lastname: Webster
authors.affiliation: 3 Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Miriam
authors.initials: M
authors.lastname: Davis
authors.affiliation: 4 Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and.
authors.forename: Robin C
authors.initials: RC
authors.lastname: Johnson
authors.affiliation: 2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Renee
authors.initials: R
authors.lastname: Jensen
authors.affiliation: 2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.|5 Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Pizarro
authors.affiliation: 2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Mica
authors.initials: M
authors.lastname: Kane
authors.affiliation: 3 Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Clem
authors.affiliation: 3 Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Leah
authors.initials: L
authors.lastname: Schornick
authors.affiliation: 1 Division of Respiratory Medicine, and.|2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Subbarao
authors.affiliation: 1 Division of Respiratory Medicine, and.|2 Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Felix A
authors.identifier: 0000-0003-4057-6592
authors.initials: FA
authors.lastname: Ratjen
mesh_terms: D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D012129:Respiratory Function Tests; D013147:Spirometry
keywords: cystic fibrosis; disease progression; lung clearance index; lung function