Journal of Gastroenterology

, Volume 52, Issue 4, pp 444–451 | Cite as

Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn

  • Marzio FrazzoniEmail author
  • Nicola de Bortoli
  • Leonardo Frazzoni
  • Manuele Furnari
  • Irene Martinucci
  • Salvatore Tolone
  • Andrea Farioli
  • Santino Marchi
  • Lorenzo Fuccio
  • Vincenzo Savarino
  • Edoardo Savarino
Original Article—Alimentary Tract



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.


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.


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).


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.


Functional heartburn Hypersensitive esophagus GERD pH Impedance monitoring 


Compliance with ethical standards

Conflict of interest

The study was conducted without any financial support. The authors have no conflict of interest to declare.


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Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  • Marzio Frazzoni
    • 1
    Email author
  • Nicola de Bortoli
    • 2
  • Leonardo Frazzoni
    • 3
  • Manuele Furnari
    • 4
  • Irene Martinucci
    • 2
  • Salvatore Tolone
    • 5
  • Andrea Farioli
    • 3
  • Santino Marchi
    • 2
  • Lorenzo Fuccio
    • 3
  • Vincenzo Savarino
    • 4
  • Edoardo Savarino
    • 6
  1. 1.Digestive Pathophysiology UnitBaggiovara HospitalModenaItaly
  2. 2.Department of Translational Research and New Technology in Medicine and SurgeryUniversity of PisaPisaItaly
  3. 3.Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
  4. 4.Gastroenterology Unit, Department of Internal MedicineUniversity of GenoaGenoaItaly
  5. 5.General and Bariatric Surgery Unit, Department of Surgery2nd University of NapoliNaplesItaly
  6. 6.Gastroenterology Unit, Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly

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