Abstract
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.
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Abbreviations
- Ca2+:
-
calcium
- cAMP:
-
adenosine 3′,5′-cyclic monophosphate
- CF:
-
cystic fibrosis
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- Cl−:
-
chloride
- DIDS:
-
4,4′-diisothiocyanostilbene-2,2′-disulfonic acid
- FEVPerc:
-
percentiles for predicted forced expiratory volume in 1 s
- ΔIsc net:
-
net change in short-circuit current
- IC:
-
intestinal current
- K+:
-
potassium
- PA:
-
Pseudomonas aeruginosa
- PD:
-
potential difference
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Supported by grants from the CF-Selbsthilfe Braunschweig und Hannover e.V., Germany, and the CF-Forschungsförderung Rhede, Germany.
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Derichs, N., Mekus, F., Bronsveld, I. et al. 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 55, 69–75 (2004). https://doi.org/10.1203/01.PDR.0000100758.66805.CE
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DOI: https://doi.org/10.1203/01.PDR.0000100758.66805.CE
