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

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\u2013pH 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\u2013pH 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\ua0%, 1378\ua0\u3a9) than in HE (51\ua0%; 2274\ua0\u3a9) and in both of them as compared with FH (76\ua0%; 3445\ua0\u3a9) (P\ua0=\ua00.0001). Both the PSPW index (adjusted odds ratio 0.863, P\ua0=\ua00.001) and the MNBI (adjusted odds ratio 0.998, P\ua0=\ua00.001) 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\ua0%), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92\ua0%; P\ua0<\ua00.0001). 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