To the Editor:Nocturnal intragastric pH < 4.0 lasting over 1 hour during proton pump inhibitor (PPI) administration has been defined as “nocturnal gastric acid breakthrough” (NAB). 1 The additional administration of H2 receptor antagonist (H2RA) at bedtime demonstrated to be effective for prevention of NAB. 2,3 However, Fackler et al recently reported that the efficacy of bedtime H2RA on NAB was disappeared after 4-weeklong coadministration of PPI and H2RA. 4 We analyzed the clinical course of 10 patients with reflux esophagitis, who were examined by intragastric pH monitoring during standard PPI treatment (20 mg omeprazole, 30 mg lansoprazole, or 20 mg rabeprazole once a morning). As shown in Table 1, all 5 patients whose esophagitis was refractory to PPI treatment had high-grade esophagitis (Los Angeles grading C or D) and had observed NAB. On the other hand, 2 patients who showed NAB and whose esophagitis was responsive to PPI treatment had low-grade reflux esophagitis (grading A and B). These observations could be explained by the results of our previous study, which demonstrated that nocturnal gastroesophageal reflux frequently occurs in only patients with high-grade esophagitis. 5 Five patients with NAB and PPI refractory reflux esophagitis were treated by coadministration of PPI in the morning and H2RA (20 mg famotidine or 150 mg ranitidine) at bedtime for more than 9 months. Endoscopy performed 2 months after the coadministration of PPI and H2RA showed healing of the esophagitis in 4 of 5 patients. In addition, follow-up endoscopy in these 4 patients revealed that the esophageal healing lasted for more than 7 months. If the efficacy of additional bedtime H2RA for the control of NAB disappears after 4 weeks of continuous administration, as demonstrated by Fackler et al, 4 then reflux esophagitis may recur during long-term follow-up. Our present findings appear to corroborate those of Xue et al, who demonstrated that bedtime H2RA was effective for control of NAB for more than 1 month when coadministered with PPI. 6 Improvement of esophageal motor function after healing of esophageal mucosal injury, which is demonstrated by Deprez and Fiasse, 7 also has some role on the efficacy of bedtime H2RA, since the healing of esophageal mucosal injury may occur for a relatively short period by combination therapy for H2RA and PPI. A large-scale prospective study appears warranted to establish whether H2RA administration with PPI is effective for the long-term control of NAB and is useful as a maintenance therapy for PPI-resistant reflux esophagitis.