Gastroesophageal reflux disease (GERD) is classified into erosive reflux disease (ERD) and non-erosive reflux disease (NERD). NERD includes three phenotypes: true NERD, functional heartburn (FH) and reflux hypersensitivity (RH). The management of these NERD phenotypes differs. We aimed at studying the spectrum of high-resolution manometry (HRM) and 24-hour impedance-pH findings in Indian patients with NERD, classifying the phenotypes and assessing the response to phenotype-based treatment. We prospectively studied the clinical characteristics, endoscopy, HRM, 24-hour impedance-pH findings, symptom association and response to phenotype-specific treatment in patients with NERD. Of 53 patients with NERD, the following phenotypes were diagnosed namely: 35(66%) true NERD, 12(22.7%) RH and six(11.3%) FH. The esophagogastric junction-contractile integral (EGJ-CI) was low in 60.4% and ineffective esophageal motility (IEM) was present in 53% of patients. The respective median values for true NERD, RH and FH groups were as follows: proximal mean nocturnal baseline impedance (P-MNBI) 2250Ω, 2241Ω, 2550Ω, (p = 0.592), distal (D-MNBI) 1431Ω, 2887.5Ω, 2516Ω (p < 0.001), post-reflux swallow-induced peristaltic wave index (PSPWI) 11.1%, 16%, 18.7% (p = 0.127). Receiver operating characteristic (ROC) curve analyses showed that D-MNBI and PSPWI discriminated FH and RH from true NERD, respectively, with a cut-off of 2376.5Ω (area under curve [AUC]:0.919, p < 0.001), 22.6% (AUC:0.671, p = 0.184) and 2318Ω (AUC:0.919, p = < 0.001), 16.2%(AUC:0.671, p = 0.079). The median P-MNBI was lower in patients with GERD-associated cough than other symptoms 1325 (1250, -). Fifty (94.3%) patients showed significant improvement in symptom severity scores (p < 0.001) following phenotype-specific treatment. In NERD patients, EGJ-CI and IEM were low. D-MNBI and PSPWI could effectively discriminate true NERD from FH and RH, whereas P-MNBI could help diagnose GERD-associated cough. The phenotype-specific treatment provides better symptom relief for patients.
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