Role of Esophageal Motility, Acid Reflux, and of Acid Suppression in Nonobstructive Dysphagia Mentore Ribolsi, MD, PhD, Dario Biasutto, MD, Antonio Giordano, MD, Paola Balestrieri, MD, and Michele Cicala, MD, PhD Goals: The present study was aimed at evaluating, in dysphagic patients, the role of high-resolution manometry (HRM) findings, presence of gastroesophageal reflux disease (GERD), and proton- pump inhibitor (PPI) therapy on dysphagia perception. Background: A relevant proportion of patients with nonobstructive dysphagia present normal esophageal HRM findings. Patients with GERD often complain of dysphagia and factors, such as hyper- sensitivity, might be involved in its occurrence. Study: In total, 37 nonerosive reflux disease (NERD) patients with only dysphagia (group 1) and 52 patients with both dysphagia and typical GERD symptoms (group 2) were evaluated with symptom scores, HRM combined with impedance and 24 hours impedance- pH monitoring. In total, 44 NERD patients, not presenting dys- phagia, underwent the same protocol. A total of 22/37 group 1 patients [11 with pathologic acid exposure time (AET)] were treated with esomeprazole 40 mg oid for 4 weeks and were reassessed during the last week of therapy. Results: A total of 15/37 group 1 patients (40%), 27/52 group 2 patients (52%), and 19/44 (43%) NERD patients presented pathologic AET [P = not significant (NS)]. Group 1 patients with a pathologic AET showed a significantly lower mean distal contractile integral (DCI) and a signi ficant correlation (ρ = -0.71) between individual DCI and total bolus transit time values. During PPI therapy, in group 1 patients with pathologic AET, the mean dysphagia score value decreased significantly [7.5 (range, 3 to 9) before, 4 (range, 2 to 6) during PPI; P < 0.01)] and mean DCI value increased significantly. Conclusions: In total, 40% of dysphagic patients show a pathologic AET and reduced peristaltic vigor. In these patients, an adequate PPI therapy significantly decreases dysphagia frequency and severity and improves the esophageal peristaltic force. Key Words: nonobstructive dysphagia, esophageal high-resolution manometry, GERD (J Clin Gastroenterol 2017;00:000–000) N onobstructive dysphagia (NOD), defined as the sensa- tion of difficult bolus transit in absence of a detectable obstruction of the esophageal lumen at endoscopy or radi- ology, is a real challenge in clinical practice. Bolus passage through the esophagus is primarily influenced by the balance between the peristaltic propulsive force and the outflow resistance across the esophagogastric junction. 1,2 Therefore, esophageal manometry is considered as the gold standard for the evaluation of patients with NOD. 3–5 However, the large majority of patients with NOD do not present pathologic esophageal manometry and videofluoroscopy findings. 6,7 It has been demonstrated that delayed clearing of both liquid and solid boluses occurs as frequently in NOD patients as in healthy controls, evaluated both with high-resolution manometry (HRM) and videofluoroscopy. 8 However, the authors also found that the esophageal motility pattern only approximately predicts the effectiveness of bolus transit. Not all dysphagic patients present delayed bolus transit or abnor- mal esophageal motility and, therefore, the high accuracy of HRM in evaluating NOD patients seems to be limited to patients with evidence of motor disorders such as achalasia or distal esophageal spasm. Patients with typical gastroesophageal reflux disease (GERD) symptoms often complain of dysphagia. 9 It has been demonstrated that a considerable proportion of GERD patients present impaired esophageal motility, which might explain the occurrence of dysphagia. 10–13 However, the presence of ineffective esophageal motility (IEM) does not discriminate patients with dysphagia and the great majority of GERD patients suffering from dysphagia, do not present evidence of IEM. The lack of agreement between dysphagia perception and esophageal function raises the question whether other factors, such as hyper- sensitivity to normal bolus passage, might be involved in the occurrence of dysphagia in GERD patients. Besides the presence of abnormal motility, the sensation of dysphagia in GERD patients might also be correlated with the stimulation of sensory receptors in the esophageal wall, the activation of vagal and spinal pathways as well as the cortical processing of peripheral informations. 14 It has been demonstrated that, in GERD patients, presensitization of esophageal acid-sensitive chemoreceptors is able to reduce pain threshold and to increase pain perception following balloon distension. 15 It is conceivable that repeated acid reflux episodes and/or prolonged acid exposure sensitizes the esophageal mucosa, hence enhancing the perception of food passage mediated by pressure mechanoreceptors. In addition, the cortical response to the stimulus mediated by the intraesophageal content might be altered by psychogenic factors, often reported in GERD patients, as anxiety, stress, and excessive hypervigilance. 16 In this scenario, a study focused on evaluating how HRM findings in NOD patients may relate to bolus transport through the esophagus as well as the role of GERD in dysphagia perception is still lacking and represents the aim of the present investigation. This study is also aimed at evalu- ating the impact of acid suppression on dysphagia perception and on the esophageal motility pattern in a subgroup of NOD patients. Received for publication May 11, 2017; accepted July 6, 2017. From the Digestive Disease Unit, Campus Bio Medico University, Rome, Italy. The authors declare that they have nothing to disclose. Address correspondence to: Mentore Ribolsi, MD, PhD, Digestive Disease Department, Campus Bio Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy (e-mail: m.ribolsi@unicampus.it). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MCG.0000000000000903 ORIGINAL ARTICLE J Clin Gastroenterol  Volume 00, Number 00, ’’ 2017 www.jcge.com | 1 Copyright r 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. This paper can be cited using the date of access and the unique DOI number which can be found in the footnotes.