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This segregation is only possible owing to the use of impedance\u2013pH monitoring. Indeed, weakly acidic reflux represents one of the most common causes of refractory symptoms in patients evaluated off antisecretory therapy and, more importantly, during antisecretory drug treatment. Patients with heartburn who do not have any type of reflux underlying their symptoms (functional heartburn) must be excluded from the category of GERD. The drawbacks of impedance\u2013pH are mainly due to the day\u2010to\u2010day variability of the test and the fact that the accuracy of the symptom\u2013reflux correlation scores is often far from perfect. Some histopathological characteristics, such as dilated intercellular spaces, can be helpful in distinguishing patients with NERD through esophageal biopsies. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to proton pump inhibitor therapy, while those with hypersensitive esophagus to weakly acidic reflux could be treated with reflux inhibitors or surgery, although further controlled studies are required.<\/jats:p>","DOI":"10.1111\/nyas.13169","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T20:46:26Z","timestamp":1477601186000},"page":"218-229","source":"Crossref","is-referenced-by-count":27,"title":["Between GERD and NERD: the relevance of weakly acidic reflux"],"prefix":"10.1111","volume":"1380","author":[{"given":"Nicola","family":"de Bortoli","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Translational Research and New Technology in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ottonello","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology University of Padua Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Zerbib","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology CHU Bordeaux and Bordeaux University Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Sifrim","sequence":"additional","affiliation":[{"name":"Barts and the London School of Medicine and Dentistry Queen Mary University of London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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