Effects of therapy with lansoprazole on intestinal permeability and inflammation in young cystic fibrosis patients.
BACKGROUND
Defective pancreatic bicarbonate secretion with low intestinal pH or intestinal inflammation of any origin increase intestinal permeability in cystic fibrosis (CF).


METHODS
In this open study, the authors evaluated the effect of a proton-pump inhibitor on intestinal permeability and inflammation in 14 young, pancreatic-insufficient CF patients. Permeability was measured by a three-sugar permeability test before and after 1 year of lansoprazole use, and urinary nitric oxide (NO) oxidation products were assessed before and during that year as a marker of inflammation.


RESULTS
After 1 year of lansoprazole use, median urinary recovery percentages changed from 2.5% to 1.7% (P = 0.064), from 24.9% to 24.5% (no significance), and from 10.5% to 11.1% (no significance) for lactulose, mannitol, and L-rhamnose, respectively. Despite the fact that the median urinary excretion ratios decreased from 0.108 to 0.083 (P = 0.03) and from 0.246 to 0.176 (P = 0.016) for lactulose and mannitol and for lactulose and rhamnose, respectively, they both remained increased. Median urinary NO products-to-creatinine ratios were 0.287 for CF patients before lansoprazole and 0.130 for healthy control participants (P = 0.002). Although there was a tendency toward a decrease in the NO products-to-creatinine ratio during treatment, this was not significant at the end point.


CONCLUSIONS
Intestinal permeability is considerably increased in CF patients and is partly corrected after the use of a proton-pump inhibitor for 1 year, which may point to a harmful effect of the acid luminal contents on the tight junctional related paracellular permeability pathway. The start and end values for the NO products-to-creatinine ratio in CF patients were not significantly different, but were considerably increased when compared with control participants (P = 0.002).
Hendriks
H J
HJ
Department of Paediatrics, University Hospital of Maastricht, Maastricht, The Netherlands. jhe@skin.azm.nl
van Kreel
B
B
Forget
P P
PP
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000293:Adolescent; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007792:Lactulose / Q000378:metabolism; D064747:Lansoprazole; D008137:Longitudinal Studies; D008297:Male; D008353:Mannitol / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000652:urine; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D012210:Rhamnose / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000890:Anti-Infective Agents; D015415:Biomarkers; D064747:Lansoprazole; D009569:Nitric Oxide; D008353:Mannitol; D007792:Lactulose; D009853:Omeprazole; D012210:Rhamnose