title: Increased Intestinal Permeability in Relatives of Patients With Crohn's Disease Is Not Associated With Small Bowel Ulcerations.
abstract: OBJECTIVE
  Many first-degree relatives of patients with Crohn's disease (CD) have increased intestinal permeability. Video capsule endoscopy (VCE) is the most sensitive imaging test to identify small bowel mucosal lesions that could indicate subclinical CD. We aimed to estimate the association of increased intestinal permeability with small bowel ulcerations detectable by VCE in healthy first-degree relatives of patients with CD.
  
  
  METHODS
  We conducted a cross-sectional study of 223 healthy, asymptomatic first-degree relatives of patients with CD (parents, siblings, and children; 9-45 years old) enrolled at the University of Alberta between 2009 and 2012. Patients were given the lactulose and mannitol test to measure small bowel permeability; we used high-performance liquid chromatography to measure concentrations of lactulose and mannitol in urine samples (increased permeability defined as a ratio of lactulose/mannitol 0.025 or greater). Patients with increased permeability (n = 39) and randomly selected subjects with normal permeability (n = 59) were then examined by VCE for signs of small bowel inflammation and subclinical CD. The prevalence of small bowel lesions was compared among groups. We performed logistic regression analyses to estimate odds ratios for the association of small bowel ulcerations with intestinal permeability.
  
  
  RESULTS
  Among 223 first-degree relatives of patients with CD, 30% were found to have increased intestinal permeability; VCE examination found 24% of subjects to have 3 or more small bowel ulcers. Three or more small bowel ulcers were detected in 28% of patients with increased intestinal permeability and 20% of patients with normal intestinal permeability (P = .37). The adjusted odds ratio for the association of 3 or more small bowel ulcers with increased intestinal permeability was 1.5 (95% confidence interval, 0.6-3.8; P = .46).
  
  
  CONCLUSIONS
  Thirty percent of healthy, asymptomatic first-degree relatives of patients with CD have increased intestinal permeability. However, a strong association of small bowel ulceration seen on VCE with increased intestinal permeability was not observed.
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada; Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Teshima
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodman
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Kalla
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Samina
authors.initials: S
authors.lastname: Turk
authors.affiliation: Section of Pediatric Gastroenterology, University of Manitoba, Winnipeg, Canada.
authors.forename: Wael
authors.initials: W
authors.lastname: El-Matary
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rosica
authors.initials: R
authors.lastname: Valcheva
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ronda
authors.initials: R
authors.lastname: Danchak
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Gordon
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mullins
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wong
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Dina
authors.initials: D
authors.lastname: Kao
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Meddings
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Hien
authors.initials: H
authors.lastname: Huynh
authors.affiliation: Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Alberta, Canada. Electronic address: l.dieleman@ualberta.ca.
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
mesh_terms: D000293:Adolescent; D000328:Adult; D000416:Alberta; D053704:Capsule Endoscopy; D002648:Child; D003424:Crohn Disease / Q000453:epidemiology* / Q000473:pathology*; D003430:Cross-Sectional Studies; D005190:Family; D005192:Family Health; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology*; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014456:Ulcer / Q000453:epidemiology*; D055815:Young Adult
keywords: Family Member; Inflammatory Bowel Disease; Pathogenesis; Risk Factor