Esophageal acid exposure still plays a major role in patients with NERD.

To The Editor: We read with great interest the paper by Zhong et al (1) on the significant correlation between esophageal intraluminal baseline impedance and the severity of acid reflux as well as esophageal mucosal histopathological changes, such as dilated intercellular spaces (ICS) and tight junction alterations. This means that low baseline impedance values reflect microscopic mucosal inflammatory abnormalities, which are mainly induced by acid and increase across the spectrum of GERD. In particular, the Chinese study reports that the mean baseline impedance values in non-erosive reflux disease (NERD) were significantly lower than in controls and, among NERD subgroups, the lowest levels pertained to patients with increased acid reflux events and those with mixed acid/weakly acidic reflux episodes. Analyzing the results more in depth, one can realize that an important information is lacking. In fact, patients with NERD were classified into 4 groups on the basis of normal/abnormal number of reflux episodes (i.e. acid, weakly acidic, mixed acid and weakly acidic, alkaline) without mentioning anything about the level of esophageal acid exposure in them. Previous studies documented that about 40% of NERD patients have abnormal distal esophageal acid exposure time (AET) (2-5). For instance, Martinez et al. reported that 45% of their NERD patients had an increased AET (3), while we observed a rate ranging from 33% to 42% of abnormal AET in large samples of endoscopy-negative patients (2,4,5). Moreover, it has been shown that both patients with abnormal number of weakly acidic or mixed reflux events and those with normal number of acid reflux episodes may have also abnormal AET (6,7). Thus, classifying patients only on the basis of the number of reflux episodes without considering the presence of a normal/abnormal AET may lead to an underestimation or overestimation of the role of acid in these patients. Moreover, this could represent a potential confounding factor for the evaluation of baseline impedance values in both weakly acidic and mixed reflux subgroups, thus questioning the conclusion that also weakly acidic reflux decreases baseline impedance values in NERD patients. It must be also stressed that the number of patients with abnormal number of weakly acidic reflux events is much higher than expected. In fact, the increase in weakly acidic reflux may be the result of PPI therapy (8) and we wonder whether the withdrawal of these drugs had been done for a period long enough to guarantee that impedance-pH testing was not affected by the above treatment. Anyway, the results obtained in this study cannot be easily extrapolated to those we can find in populations of Western countries. Finally, it is very surprising that the authors acknowledged the use of light microscopy (LM) instead of transmission electron microscopy (TEM) as an important limitation of their study. In fact, we have shown that LM is able to demonstrate with very good accuracy all the histopathological alterations characterizing microscopic esophagitis, including the ICS (9,10). This method is not only easier and cheaper than TEM, but also more practical as it can be used routinely during the daily clinical practice. An expert pathologist permits to exploit on biopsy samples the entire diagnostic information contained in each element proper of esophageal microscopic inflammation and, if it is true that finding low baseline impedance values is expression of subtle inflammatory mucosal changes, a good correlation between this new functional marker and the damage of esophageal mucosa would be better found by using LM rather than TEM.