Gastroduodenal epithelial transport in patients with cystic fibrosis

Abstract

Cystic fibrosis (CF) is an inherited disease where respiratory failure due to chronic lung infection is the major cause of death. A defective protein, cystic fibrosis transmembrane conductance regulator (CFTR) alters chloride epithelial transport. Exocrine pancreatic insufficiency is found in 90% of the patients, but in spite of pancreatic enzyme supplements, gastrointestinal problems are common. CF patients have evidence of a disturbed intestinal motility and epithelial transport. The aim of this work was to give new insights to the altered function of the CF gut and thereby to improve the understanding of the coupling between the clinical expression and pathology of the disease and the basic defect. We used gastroduodenal manometri combined with intragastric perfusion to investigate fasting motility and motility secretion in 10 CF patients with different genotypes and 12 healthy controls. Eight CF patients showed a normal migrating motor complex. Motility related gastric secretion of acid and bicarbonate did not differ from healthy subjects while gastric net fluid secretion was significantly decreased and bilirubin reflux was significantly increased in the CF patients. Motility related secretion of gastric IgA was studied in ten CF patients and seven healthy controls. The CF patients had significantly lower levels of gastric IgA compared to healthy subjects during phase II and III of the migrating motor complex. Chloride secretion in duodenal biopsies from nine CF patients with different genotypes where investigated in an Ussing chamber. Prostaglandin E2 and acetylcholine induced no changes in chloride secretion in the DF508 homozygotes. In heterozygotes, the induced change in chloride secretion corresponded to the severity of the known mutations. The urinary excretion of orally given lactulose, L-rhamnose and xylose was studied in 19 CF patients and nine healthy controls. Patients who were homozygous or heterozygous for ?F508 had significantly higher lactulose/L-rhamnose excretion ratios, than patients with unidentified genotypes who had excretion ratios in the same range as in healthy controls.Conclusions: Our studies suggest that patients with CF have a normal fasting motility pattern in the upper gastrointestinal tract. Despite this, there were abnormalities in epithelial transport related to genotype, thus indicating a role of CFTR in the transport of fluid, IgA and small molecules. We also found that patients with CF with impaired pancreatic bicarbonate secretion had normal gastric bicarbonate secretion in fasting.