Nerd: an umbrella term including heterogeneous subpopulations

ABSTRACT Nonerosive reflux disease (NERD) represents the more common phenotypic presentation of GERD and comprises patients who have typical symptoms without any mucosal breaks at endoscopy.

However, these patients are markedly heterogeneous from a pathophysiological point of view and should be correctly classified by means of 24 h impedance–pH testing, which enables detection

of both acidic and weakly acidic reflux and correlation with symptoms. This technique is able to identify two subsets of NERD (that is, patients with an excess of acid or with a

hypersensitive oesophagus to both acid and weakly acidic reflux) and patients with functional heartburn (who do not have any kind of reflux underlying their symptoms and must be excluded

from the realm of GERD). The mechanisms of symptom generation are not clear in patients with NERD, but the presence of microscopic oesophagitis, including the dilation of intercellular

spaces, seems to have a relevant role. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to PPI therapy, while those with hypersensitive oesophagus to

weakly acidic reflux need to be treated with reflux inhibitors or surgery, although the experience in this field is very scant. Patients with functional heartburn should undergo therapy with

pain modulators, but large placebo-controlled trials are necessary. KEY POINTS * Nonerosive reflux disease (NERD) represents the more common phenotypic presentation of GERD and includes

patients who are heterogeneous from a pathophysiological and clinical point of view * 24 h impedance–pH testing has enabled subdivision of patients with NERD into several subgroups according

to their oesophageal acid exposure time and symptom association analysis to acid and/or weakly acidic reflux episodes * This technique has identified a new subgroup of patients with NERD

who have hypersensitive oesophagus to weakly acidic reflux, which contributes to narrowing down the population of patients with functional heartburn * The mechanisms of symptom generation

are not completely understood in patients with NERD, but the presence of microscopic oesophagitis seems to have a relevant role * Treatment of NERD is based on the use of PPIs, which are

successful in patients in whom acid has a pathogenetic role; pain modulators can be used in patients with hypersensitive oesophagus * Patients with functional heartburn should be treated

with pain modulators, but clinical trials aimed at assessing the efficacy of these drugs in this well-defined group are lacking at this time Access through your institution Buy or subscribe

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GASTRO-OESOPHAGEAL REFLUX DISEASE Article 29 July 2021 CLINICAL SIGNIFICANCE OF GASTROESOPHAGEAL REFLUX DISEASE WITH MINIMAL CHANGE: A MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY Article

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367–372 (2000). Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Gastroenterology, Department of Surgical, Oncological and

Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128, Padua, Italy Edoardo Savarino * Division of Gastroenterology, Department of Internal Medicine, University of

Genoa, Viale Benedetto XV 6, 16132, Genoa, Italy Patrizia Zentilin & Vincenzo Savarino Authors * Edoardo Savarino View author publications You can also search for this author inPubMed 

Google Scholar * Patrizia Zentilin View author publications You can also search for this author inPubMed Google Scholar * Vincenzo Savarino View author publications You can also search for

this author inPubMed Google Scholar CONTRIBUTIONS All authors equally contributed to all aspects of this manuscript. CORRESPONDING AUTHOR Correspondence to Edoardo Savarino. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Savarino, E.,

Zentilin, P. & Savarino, V. NERD: an umbrella term including heterogeneous subpopulations. _Nat Rev Gastroenterol Hepatol_ 10, 371–380 (2013). https://doi.org/10.1038/nrgastro.2013.50

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