Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Mediated Residual Chloride Secretion Does Not Protect against Early Chronic Pseudomonas aeruginosaInfection in F508del Homozygous Cystic Fibrosis Patients

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 CFTRmutations, 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 (n14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n10). 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.