title: GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation.
abstract: BACKGROUND
  Combinations of reflux parameters (acid exposure time, AET; symptom association probability, SAP) on pH-impedance monitoring describe varying confidence in reflux evidence. We compared outcomes between phenotypes with distinct pre-identified reflux parameters.
  
  
  METHODS
  In this observational cohort study, patients undergoing pH-impedance testing over a 5-year period were phenotyped by strength of reflux evidence as strong (abnormal AET, positive SAP), good (abnormal AET, negative SAP), reflux hypersensitivity (RH, normal AET, positive SAP), and equivocal evidence of reflux, and compared to two historical institutional pH monitoring cohorts. Symptom burden (dominant symptom intensity, DSI; global symptom severity, GSS) was assessed by questionnaire at baseline and on prospective follow-up and compared between phenotypes.
  
  
  RESULTS
  Of 94 patients tested off proton pump inhibitor (PPI) therapy, baseline symptom burden was highest with strong reflux evidence and lowest when equivocal (DSI: p = 0.01; GSS: p = 0.03 across groups). After 3.1 ± 0.2 years follow-up, symptomatic improvement with surgical or medical therapy was highest with strong or good evidence, and lowest when equivocal (DSI: p = 0.008; GSS: p = 0.005 across groups). This was most pronounced for typical symptoms (DSI: p = 0.001; GSS: 0.016 across groups), but not atypical symptoms (DSI: p = 0.6; GSS: p = 0.2). For testing on PPI therapy, only GSS followed a similar trend (GSS: p = 0.057, DSI: p = 0.3). Compared to historical cohorts with pH monitoring alone, equivocal evidence for reflux was partly replaced by RH, especially off PPI (p < 0.0001).
  
  
  CONCLUSIONS
  Phenotyping gastroesophageal reflux disease by the strength of reflux evidence on pH-impedance testing off PPI efficiently stratifies symptomatic outcome, especially for typical symptoms, and could be useful in planning management.
authors.affiliation: Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.affiliation: Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA.|Division of Gastroenterology, John Cochran VA Medical Center, Saint Louis, MO, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Sayuk
authors.affiliation: Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Kushnir
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Chan
authors.affiliation: Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Gyawali
mesh_terms: D015331:Cohort Studies; D017097:Electric Impedance; D050782:Esophageal pH Monitoring; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000145:classification* / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors
keywords: gastroesophageal reflux disease; pH-impedance testing; strength of reflux evidence; symptom-reflux association