title: Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis.
abstract: BACKGROUND
  In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied.
  
  
  OBJECTIVE
  To assess reflux parameters by impedance-pH monitoring in PPI-resistant reflux oesophagitis.
  
  
  METHODS
  Impedance-pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high-dose PPI therapy of at least 8-week duration.
  
  
  RESULTS
  Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively.
  
  
  CONCLUSIONS
  Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra-gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring results.
authors.affiliation: Nuovo Ospedale S. Agostino, Modena, Italy. m.frazzoni@ausl.mo.it
authors.forename: M
authors.initials: M
authors.lastname: Frazzoni
authors.forename: R
authors.initials: R
authors.lastname: Conigliaro
authors.forename: G
authors.initials: G
authors.lastname: Melotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004351:Drug Resistance; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors