Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.
OBJECTIVE
Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection.


METHODS
Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions.


RESULTS
Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05).


CONCLUSIONS
Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.
Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Philip
P
Woodland
Chung
C
Lee
Yasotha
Y
Duraisamy
Yasotha
Y
Duraysami
Ricard
R
Farré
Peter
P
Dettmar
Daniel
D
Sifrim
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000464:Alginates / Q000008:administration & dosage*; D001647:Bile Acids and Salts / Q000009:adverse effects; D001706:Biopsy; D016022:Case-Control Studies; D017097:Electric Impedance; D050782:Esophageal pH Monitoring; D004941:Esophagitis / Q000517:prevention & control*; D004947:Esophagus / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D005764:Gastroesophageal Reflux / Q000517:prevention & control*; D006356:Heartburn / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D055815:Young Adult
D000464:Alginates; D001647:Bile Acids and Salts