Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated residual chloride secretion does not protect against early chronic Pseudomonas aeruginosa infection in F508del homozygous cystic fibrosis patients

Pediatr Res. 2004 Jan;55(1):69-75. doi: 10.1203/01.PDR.0000100758.66805.CE. Epub 2003 Nov 6.


Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl-) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa (PA). In this study, we investigated whether or not the presence of residual Cl- secretion protects against early chronic PA colonization of patients' airways. Excluding influences on the phenotype caused by different CFTR mutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl- secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n = 14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n = 10). We determined the Cl- transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl- secretion, most likely due to the CFTR Cl- channel, was observed in 63% of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl- secretion determine the age of onset of PA colonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Chlorides / metabolism*
  • Chronic Disease
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Electrophysiology
  • Epithelial Cells / physiology
  • Female
  • Homozygote
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / physiopathology*
  • Respiratory Function Tests


  • CFTR protein, human
  • Chlorides
  • Cystic Fibrosis Transmembrane Conductance Regulator