title: Dilated intercellular space diameter as marker of reflux-related mucosal injury in children with chronic cough and gastro-oesophageal reflux disease.
abstract: BACKGROUND
  The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging.
  
  
  OBJECTIVE
  To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough.
  
  
  METHODS
  Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3 cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups.
  
  
  RESULTS
  A significant difference in mean ISD values was found between GrC patients (0.9 ± 0.2 μm) and controls (0.5 ± 0.2 μm, P < 0.001), whereas there was no difference between GrC and GERD group (1 ± 0.3 μm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 μm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS).
  
  
  CONCLUSIONS
  In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.
authors: Department of Gastroenterology, Neurogastroenterology and Motility Division, Great Ormond Street Hospital and Institute of Child Health, London, UK.
authors: O
authors: O
authors: Borrelli
authors: V
authors: V
authors: Mancini
authors: N
authors: N
authors: Thapar
authors: M
authors: M
authors: Ribolsi
authors: S
authors: S
authors: Emerenziani
authors: G
authors: G
authors: de'Angelis
authors: B
authors: B
authors: Bizzarri
authors: K J
authors: KJ
authors: Lindley
authors: M
authors: M
authors: Cicala
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003371:Cough / Q000473:pathology*; D017097:Electric Impedance; D004945:Esophagoscopy; D005110:Extracellular Space; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male
chemical_list: D015415:Biomarkers