Discussion:
The relationship of LPR with and its potential role in the pathogenesis
of OSAS have not been fully elucidated. The originality of the present
study is the realization of both HEMII-pH and PSG in the same time in
patients with untreated sleep and LPR findings. We found that patients
with LPR and OSAS have different HEMII-pH and clinical patterns compared
with LPR individuals without OSAS. Precisely, OSAS patients had a lower
number of HREs and less severe otolaryngological symptoms compared with
LPR patients. Moreover, there were no significant associations between
nighttime HREs and PSG data and between the severity of LPR and OSAS. We
only observed associations between ESS, RSS and the number of evening
HREs, which supports potential relationship between both conditions
without providing pathophysiological explanations. The association
between pH-study and PSG findings was investigated in many
studies,14-20 which reported controversial results.
Some authors observed that patients with severe OSAS had a significant
higher number of nocturnal proximal or distal esophageal events compared
with patients with mild OSAS,14,16,17 while others did
not find any association between reflux and OSAS
findings.15,18,19,21-23 The inconsistencies may result
from methodological differences across studies.
Some authors used dual- or triple-probe pH monitoring to evaluate reflux
events and did not consider nonacid HREs.18,19 Others
only included patients with GERD (distal probe
findings)14,20,23 or esophagitis.21Among studies reporting gastrointestinal findings, the prevalence of
patients with GERD or GERD and LPR varied from 38.9% to 100% of
cases.14,15,18,20,21 From an epidemiological
standpoint, the use of different inclusion criteria and diagnostic
approaches may have a substantial impact on the results of the study.
First, LPR is defined by the occurrence of acid, weakly acid and nonacid
HREs.10 Nonacid HREs concern more than 50% of LPR
patients and are not detected by pH monitoring without
impedance.4 The lack of consideration of
nonacid/weakly HREs may lead to a bias selection through the exclusion
of patients with nonacid/weakly LPR.
Second, it has been reported that patients with both GERD and LPR have
different profile at the HEMII-pH with higher proportion of nocturnal
and supine HREs in GERD patients.4 Moreover, patients
with GERD may have a significant higher probability to have acid LPR,
while patients without GERD had equal proportions of acid, nonacid and
weakly acid LPR.4 In that respect, the consideration
of GERD as a key inclusion criteria may lead to the introduction of an
important bias because many patients with GERD have no LPR or vice
versa .1,4 To have a representative sample of LPR
population, authors should use HEMII-pH that detects GERD, acid, weakly
acid and nonacid HREs.
Third, the severity of LPR was evaluated through different
patient-reported outcome questionnaires including GERD-related
questionnaires,5,7,15 reflux symptom
index,6,14,17,21,22 or LPR-health-related quality of
life.22 These patient-reported outcome questionnaires
are all validated but do not include similar symptoms and rating
approaches, yielding the comparison across studies difficult. According
to these reasons, the comparison of our results with the literature
remains limited. Only Xiao et al . used HEMII-pH monitoring to
investigate the relationship between HREs and PSG
findings,15 and they did not find significant
objective association, corroborating our observations. Our findings as
well as the observations of Xiao et al . reinforce the controverse
about the pathophysiological link between LPR and OSAS.
For a long time, it has been proposed that reflux is thought to be
induced by decreasing intraesophageal pressure during obstructive sleep
apnea, which causes a vacuum-like effect on the gastric contents. This
theory was strengthened by the observation that during sleep, there
would be a delay in the nocturnal acid clearance, facilitated by the
suppression of salivation and esophageal
peristalsis.24 However, recent data supported that
despite a decrease in esophageal body pressure during obstructive apnea
events, compensatory changes in upper esophageal sphincter and
gastroesophageal junction pressures prevent reflux.25The lack of significant association between HREs, AHI and arousal
findings of the present study may strengthen these findings. According
to our observations and those of studies using HEMII-pH or
high-resolution pharyngeal manometry,25 we believe
that there would exist several pathophysiological mechanisms depending
on the lower and upper esophageal sphincter tonicity, the presence of
GERD and the type of HREs (liquid versus gaseous). The
investigation of the type of HREs makes particularly sense because the
supine position would be more favorable for liquid reflux events that
are more aggressive for the laryngopharyngeal mucosa because they
contain more gastroduodenal enzymes.4 In that way and
according to our subgroup analysis, the correlation between reflux and
OSAS severity could particularly concern patients with GERD and liquid
HREs; the overweight being a favoring factor. Naturally, this hypothesis
needs to be confirmed through future studies considering the type
(liquid versus gaseous) and the nature of HRE (acid, weakly acid,
nonacid) and the time of occurrence of HREs.
In our study, we observed significant association between the number of
HREs in the evening, RSS and ESS score. The occurrence of evening HREs
and the deposit of gastroduodenal enzymes into the laryngopharyngeal
mucosa could be associated with the development of a more significant
inflammatory reaction before sleep and related sleep (ESS) disorders.
This hypothesis cannot be confirmed with our data but our findings
support the need to consider daytime and nighttime periods of occurrence
of HREs and not only the nighttime reflux events. Moreover, the
measurement of pepsin saliva in the morning could provide additional
useful analysis in the understanding of the mechanisms underlying the
association between LPR and OSAS.6
With regard to the clinical presentation of patients with OSAS and LPR,
our observations supported that OSAS patients may have less severe
clinical picture than LPR patients. To the best of our knowledge, only
Teklu et al . specifically investigated the symptom profile of LPR
patients with or without OSAS, reporting that patients with OSAS had
worse symptoms as measured by RSI.7 As
above-mentioned, the inclusion of a high number of patients with GERD in
the study of Tekly et al . makes the comparison difficult. Another
finding highlighted in the present study is the higher proportion of
hiatal hernia and potential related esophagitis in LPR group compared
with patients with LPR and OSAS. In the LPR general population,
esophagitis and hiatal hernia concern 20% to 30% of
patients.1 According to our observations, patients
with LPR and OSAS may have a lower proportion and the potential
mechanisms are still unknown.
In this study, we tried to explore the relationship between the
occurrence of arousals/awakenings and HREs. However, we only had 3
patients with nighttime HREs and among them, the sleep events were not
associated with HREs. The low number of patients with nighttime HREs is
not surprising regarding previous data.4 The lack of
association between sleep and reflux events corroborates the findings of
a previous study where authors observed that 82% of reflux events
occurred during a PSG epoch that was classified as
wake.26 Authors also reported that arousals/awakenings
preceded almost all reflux events, whereas fewer had an
arousal/awakening after the event.26
The primary limitations of our study are the low number of patients and
the lack of investigation of laryngopharyngeal signs. In practice, many
patients did not accept to benefit from HEMII-pH and PSG in the same
time and declined one of two examinations. However, the realization of
both examinations in the same period is important to study the
relationship between both conditions. To date, only a few studies
prospectively investigated the relationship between LPR and OSAS through
simultaneous pH-study and PSG.15,16,18,21 This
methodological point is particularly important because the
reproducibility of the HEMII-pH results from one day to the other is not
guaranteed. The number of HREs may depend on the patient
diet,4 or, hypothetically, on the patient stress the
day of the testing that may be both associated with esophageal sphincter
relaxations.1 The primary strengths of the study are
the prospective design and the use of HEMII-pH for the diagnosis. The
consideration of acid, nonacid and weakly acid HREs led us to include
all patients with LPR and not only a subgroup of individuals (acid LPR).
Moreover, in this study we deliberately use the full and not the short
version of RSS (RSS-12) because the consideration of otolaryngological,
digestive and respiratory symptoms makes sense in patients with OSAS
that commonly includes respiratory and, in some GERD patients, digestive
symptoms.