title: Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn.
abstract: BACKGROUND
  Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI.
  
  
  METHODS
  Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed.
  
  
  RESULTS
  The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30 %, 1378 Ω) than in HE (51 %; 2274 Ω) and in both of them as compared with FH (76 %; 3445 Ω) (P = 0.0001). Both the PSPW index (adjusted odds ratio 0.863, P = 0.001) and the MNBI (adjusted odds ratio 0.998, P = 0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62 %), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92 %; P < 0.0001).
  
  
  CONCLUSIONS
  HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.
authors.affiliation: Digestive Pathophysiology Unit, Baggiovara Hospital, Viale Giardini, 1355, 41100, Modena, Italy. marziofrazzoni@gmail.com.
authors.forename: Marzio
authors.initials: M
authors.lastname: Frazzoni
authors.affiliation: Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: de Bortoli
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Frazzoni
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Manuele
authors.initials: M
authors.lastname: Furnari
authors.affiliation: Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Martinucci
authors.affiliation: General and Bariatric Surgery Unit, Department of Surgery, 2nd University of Napoli, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Tolone
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Farioli
authors.affiliation: Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Santino
authors.initials: S
authors.lastname: Marchi
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fuccio
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savarino
authors.affiliation: Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Savarino
mesh_terms: D000328:Adult; D000368:Aged; D017097:Electric Impedance; D050782:Esophageal pH Monitoring; D004947:Esophagus / Q000503:physiopathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D006356:Heartburn / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010528:Peristalsis / Q000502:physiology*; D011237:Predictive Value of Tests; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016037:Single-Blind Method
chemical_list: D054328:Proton Pump Inhibitors
keywords: Functional heartburn; GERD; Hypersensitive esophagus; pH Impedance monitoring