Comment to "current applications of evolving methodologies in gastroesophageal reflux disease testing".

To The Editor: We read with great interest the review article by Weber et al (1) on current applications of new methodologies in gastroesophageal reflux testing. The Authors assessed almost all the available literature published in this field after the advent of wireless capsule pH and impedance-pH monitoring and discussed the clinical applicability, advantages and limits of these new techniques. In particular, they reported that the major advantage of impedance-pH testing relies in the detection of weakly acidic reflux (WAR), that allows clinicians to identify more patients whose reflux is responsible for their symptoms and quoted several investigations, mainly performed in Gastro-oesophageal Reflux Disease (GORD) patients without endoscopic assessment, in order to support their conclusions (2). However, we believe that the above studies do not represent adequately the entire knowledge we have accumulated in last years on the relevance of impedance-pH in GORD patients. If it is true that the importance of MII-pH testing relies more on establishing the symptom association with both acid and weakly acidic reflux events than on quantifying reflux episodes, it must be underlined that this advantage becomes more and more relevant when evaluating patients with clear evidence of no mucosal breaks at upper endoscopy (Non-Erosive Reflux Disease = NERD) rather than the overall population with GORD (3,4). This appears more relevant if we consider that NERD represents the most frequent phenotypic presentation of GORD, amounting to 60%-70% of overall reflux patients. Indeed, in a recent investigation by our group (3), a series of 150 NERD patients off acid suppressive medication were studied by means of MII-pH and we found that 17% of them presented reflux symptoms associated with WAR alone or combined with acid reflux, despite a normal esophageal acid exposure. The identification of this subgroup of NERD patients whose symptoms were clearly related to WAR is a new finding due to MII-pH and contributes to enlarge substantially the group of NERD with an oesophagus hypersensitive not only to acid but also to WAR (this global subset amounts to 37% in our study). Moreover, it must be stressed that the identification of this new subgroup has also the merit to narrow down the proportion of endoscopy-negative patients who do not have any kind of reflux underlying their symptoms and who may be classified as having functional heartburn (FH) , as also confirmed by a recent investigation assessing the added value of impedance-pH testing to Rome III criteria in distinguishing FH from NERD (5). Also the evidence that patients with FH identified by means of impedance-pH testing presents more frequently functional dyspepsia (FD) than the other subsets supports the concept that impedance testing is able to differentiate NERD from FH patients (4). In conclusion, we believe that all the above features have contributed to improve our knowledge of the complex pathophysiology of GORD, and represent an important step favouring the knowledge and management of endoscopy-negative reflux patients. This has been obtained exclusively by the wide application of impedance-pH in daily clinical practice. We believe that the Authors of the review would have mentioned this important pathophysiological and clinical progress which is one the major results of the new technique