title: Risk factors for the progression of cystic fibrosis lung disease throughout childhood.
abstract: BACKGROUND
  Previous studies of risk factors for progression of lung disease in cystic fibrosis (CF) have suffered from limitations that preclude a comprehensive understanding of the determinants of CF lung disease throughout childhood. The epidemiologic component of the 27-year Wisconsin Randomized Clinical Trial of CF Neonatal Screening Project (WI RCT) afforded us a unique opportunity to evaluate the significance of potential intrinsic and extrinsic risk factors for lung disease in children with CF.
  
  
  OBJECTIVE
  Describe the most important intrinsic and extrinsic risk factors for progression of lung disease in children with CF.
  
  
  METHODS
  Variables hypothesized at the onset of the WI RCT study to be determinants of the progression of lung disease and potential risk factors previously identified in the WI RCT study were assessed with multivariable generalized estimating equation models for repeated measures of chest radiograph scores and pulmonary function tests in the WI RCT cohort.
  
  
  RESULTS
  Combining all patients in the WI RCT, 132 subjects were observed for a mean of 16 years and contributed 1,579 chest radiographs, and 1,792 pulmonary function tests. The significant determinants of lung disease include genotype, poor growth, hospitalizations, meconium ileus, and infection with mucoid Pseudomonas aeruginosa. The previously described negative effect of female sex was not seen.
  
  
  CONCLUSIONS
  Modifiable extrinsic risk factors are the major determinants of progression of lung disease in children with CF. Better interventions to prevent or treat these risk factors may lead to improvements in lung health for children with CF.
authors.affiliation: 1 Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Don B
authors.initials: DB
authors.lastname: Sanders
authors.forename: Zhanhai
authors.initials: Z
authors.lastname: Li
authors.forename: Anita
authors.initials: A
authors.lastname: Laxova
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rock
authors.forename: Hara
authors.initials: H
authors.lastname: Levy
authors.forename: Jannette
authors.initials: J
authors.lastname: Collins
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.forename: Philip M
authors.initials: PM
authors.lastname: Farrell
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D045823:Ileus / Q000150:complications*; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging*; D008297:Male; D008470:Meconium; D015997:Neonatal Screening; D009748:Nutrition Disorders / Q000150:complications*; D009842:Oligopeptides; D011552:Pseudomonas Infections / Q000150:complications*; D011550:Pseudomonas aeruginosa; D011859:Radiography; D012129:Respiratory Function Tests; D012307:Risk Factors; D055815:Young Adult
chemical_list: C096894:MUT 1 peptide; D009842:Oligopeptides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator