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.