Discussion
Since Koufman’s double-probe pH monitoring study for gastroesophageal reflux disease, several studies have improved our understanding of LPR.16 However, because 24hr MII-pH monitoring is an uncomfortable test that patients are reluctant to do, we may shorten the test time if we know when pharyngeal reflux occurs frequently. Moreover, it will be helpful in establishing an appropriate treatment strategy by adjusting the timing of drug administration, it also may improve the accuracy of the analysis of the test outcome. Our research may contribute to the diagnosis and treatment of LPR. In a recent study, it was reported that automated analysis overestimates the number of reflux episodes compared to manual analysis.17 In our study, the hourly number of pharyngeal reflux episodes was meaningful because it was based on manual analysis by a skilled otolaryngologist.
In GERD, esophageal reflux typically occurs during the night and is called nocturnal reflux. GERD reflux usually occurs in a recumbent position. Contrasting results were obtained in this study as well (Table 2). The daytime incidence was more than two times higher than the nighttime incidence, and the frequency of pharyngeal reflux was five times higher in the upright position. Our study provides clues as to whether shortening the 24-hour monitoring period is appropriate. However, careful consideration is required in this regard because other studies have reported that nocturnal reflux is associated with disease severity.10 Additionally, our findings lead us to rethink the usefulness of twice-daily proton-pump inhibitors (PPIs) for all LPR patients. A prospective cohort study on western patients showed that twice-daily PPIs is more efficient than once-daily PPIs.18 However, recent another prospective cohort study on Asian patients fails to show the therapeutic advantage of twice-daily PPIs.19 If patients have no nighttime reflux event, the second dose of PPIs may not useful.
We confirmed that pharyngeal reflux increased after meals compared to before meals (Table 3). This is similar to the esophageal reflux pattern induced by TLESR in GERD. TLESR occurs frequently in the post-prandial period, especially within 15 minutes after meals.20 It is correlated that the distal esophageal reflux episodes in GERD typically occur in the post-prandial 1 h.20 Since an acid pocket has formed near the cardia at that time, TLESR can increase gastric acid up to the esophagus and cause heartburn symptoms in GERD patients.21 The incidence of TLESR in GERD patients is more than two times higher than that of normal healthy controls.22 An esophago-pharyngeal regurgitation process is required to induce the laryngopharyngeal symptoms in LPR. A previous study found that transient upper esophageal sphincter (UES) relaxation was related to pharyngeal reflux in post-prandial 3 h.23 The UES relaxation was not related to swallowing activity and was considered transient spontaneous relaxation. Our study also showed a doubling incidence of pharyngeal reflux in the 2 h post-prandial period compared to the pre-prandial 2 h (Figure 2 ). If post-prandial pharyngeal reflux plays an important role in the physiology of LPR, the 24-hour monitoring time could be reduced. In fact, there have been attempts to reduce the study time for GERD. A GERD study reported that post-prandial 3 h MII-pH monitoring could be used as a predictor of gastroesophageal reflux disease.24
Merati et al. reported that pharyngeal reflux episodes were detected in 0-33% of normal subjects in their meta-analysis.25Looking at the studies included in their meta-analysis, the mean number of pharyngeal reflux episodes found in normal subjects was 1-3 times. The pharyngeal reflux pattern of normal subjects involved in those study was similar to that of normal controls of this study. In this study, pharyngeal reflux episodes were detected in 19% of normal controls, and the mean numbers of their pharyngeal reflux episodes were 1.4. There was no study that revealed the timing of pharyngeal reflux in normal subjects. However, the fact that TLESR occurs mainly after meals in normal subjects is comparable to that pharyngeal reflux occurs mainly after meals in normal controls of this study.6,7 There was not statistical difference in the major timing of pharyngeal reflux episodes in LPR patients and normal controls, but the difference in frequency was clear. This suggests the importance of reducing the frequency of post-prandial pharyngeal reflux episode in the treatment of LPR patients.
Some potential shortcomings of this study were its retrospective design. Some patients were inevitably excluded from this study. The causes of exclusion were as follows: (1) unclear start time of 24hr MII-pH monitoring and (2) no raw data files for analysis. The dropout rate of the subjects can cause selection bias. In this study, the mealtimes of the enrolled 69 patients appeared to have a double peak shape (Figure 1 ). This could mean that patients skipped breakfast among three meals per day despite our education to keep common diet To prevent vomiting during the 24hr MII-ph probe insertion process, the insertion was performed in a fasting state. However, skipping breakfast may have resulted in a few failures in monitoring the routine 24 hours of LPR patients. Eight patients had medical history of GERD among enrolled 69 patients. Even if it is assumed that all eight patients have GERD, we thought that it was a small fraction compared to the total number of patients.