Differences in salivary secretory function between patients
with erosive esophagitis and those with nonerosive reﬂux
Noriaki Manabe,* Ken Haruma,
and Jiro Hata*
*Division of Endoscopy and Ultrasonography, Department of Laboratory Medicine,
Department of Health Care Medicine, Kawasaki Medical School,
Kurashiki, Departments of
General Internal Medicine 2, and
Health Care Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
continuous-wave Doppler sonography, erosive
esophagitis, gastroesophageal reﬂux disease,
nonerosive reﬂux disease, salivary function.
Accepted for publication 15 September 2017.
Noriaki Manabe, Division of Endoscopy and
Ultrasonography, Department of Laboratory
Medicine, Kawasaki Medical School, 577
Matsushima, Kurashiki, Okayama 701-0192,
Declaration of interest statement: The authors
report no conﬂicts of interest. The authors
alone are responsible for the content and writ-
ing of the paper.
Financial support: This study was supported by
our own institutional funds.
Background and Aim: It has been speculated that impaired salivary ﬂow contributes to
abnormal acid clearance in patients with erosive esophagitis (EE). For easy and objective
assessment of salivary function, we developed a salivary gland blood ﬂow measurement
technique using continuous-wave Doppler sonography. In the present study, we evaluated
the salivary secretory function in patients with EE and those with nonerosive reﬂux disease
(NERD) using this method.
Methods: Doppler waveform analysis was performed on the facial artery to assess blood
inﬂow to the submandibular gland of 30 healthy subjects (HS). Blood ﬂow was com-
pared before and after secretory stimulation with 1 mL of lemon juice. Saliva was
simultaneously collected and weighed before and after stimulation. Continuous-wave
Doppler sonography was also performed in patients with EE and NERD. The size of
the submandibular gland was compared in 26 patients with EE, 41 patients with NERD,
and 86 HS.
Results: The submandibular gland blood ﬂow increased after stimulation in all HS.
Both within-day and day-to-day reproducibility were good. There was a signiﬁcant cor-
relation between the percent increase in the maximum velocity and the percent increase
in salivary secretion. Although the size of the submandibular gland was not signiﬁcantly
different among the three groups, the percent increase in the maximum velocity in pa-
tients with EE was signiﬁcantly smaller than that in HS.
Conclusions: We have established an easy method of assessing salivary function in
daily practice. This study revealed that a decrease in salivary secretory function is in-
volved in the pathology of EE.
Previous research has suggested that erosive esophagitis (EE) is a
multifactorial process involving an imbalance between aggressive
and defensive factors.
After acid reﬂux, clearance of acid from
the esophagus is an important defense mechanism against the
development of EE.
Esophageal clearance of regurgitated gastric
contents occurs by three mechanisms: gravity, propulsive
peristalsis, and salivary secretion. In particular, salivation promotes
esophageal acid clearance not only by eliciting swallowing but also
by enhancing washout, dilution, and neutralization of the acid.
Recent studies have revealed that up to 70% of patients with
gastroesophageal reﬂux disease (GERD) have nonerosive reﬂux
However, few reports have addressed the
functional differences in salivary secretion between NERD and
EE. Although the mechanism of salivary secretion is complex,
some of its aspects are considered to be under autonomic nervous
Parasympathetic stimulation elicits both
secretory and vasodilator responses in the cat submandibular
Some parasympathetically induced secretions are affected
by ﬂuctuations of the arterial blood ﬂow in the dog submandibular
It is important to investigate the relationship between
salivary secretion and the arterial blood ﬂow in humans. However,
this has not yet been performed, in part because of the lack of a
convenient and objective procedure with which to perform such
an evaluation. With ongoing progress in ultrasonographic
techniques, continuous-wave (cw) Doppler sonography is being
used increasingly more frequently to measure microcirculatory
blood ﬂow. This method is cost-effective, noninvasive, easy to
perform, and, most importantly, readily available in the vast
majority of facilities.
In the ﬁrst part of this study, we evaluated whether our newly
developed cw Doppler sonographic method of salivary gland
blood ﬂow measurement can be used to assess salivary secretory
function. In the second part of the study, we compared salivary
secretory function in patients with EE, patients with NERD, and
healthy subjects (HS) by assessing salivary gland blood ﬂow using
cw Doppler sonography.
Journal of Gastroenterology and Hepatology 33 (2018) 807–813
© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd