Neurogastroenterology & Motility
Neurogastroenterol Motil (2012) 24, 432–e210
Predictors of acid suppression success in patients with
chronic laryngitis
A. J. WANG ,*,  M. J. LIANG ,à A. Y. JIANG ,à J. K. LIN ,* Y. L. XIAO ,* S. PENG ,* J. CHEN ,* W. P. WEN à
*Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
àDepartment of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Abstract
Background Up to 50% of the patients suspected of
reflux laryngitis syndrome failed to respond to acid
suppression therapy. However, predictors of acid
suppression success have not been determined.
Methods Consecutive patients with chronic laryngitis
were enrolled prospectively. All the patients under-
went laryngoscopy, esophagogastroduodenoscopy and
24-h multichannel intraluminal impedance and pH
(MII-pH) monitoring before receiving rabeprazole
10 mg b.i.d. for 3 months. Patient was considered as a
responder to acid suppression if the chief laryngeal
complaint score during the last week since last inter-
view had decreased by at least 50% after the start of
therapy compared with baseline. Cox regression
analysis was used to determine the independent pre-
dictors of acid suppression success. Key Results Of 92
patients (age 42.4 ± 14.3 years, 50 women), 42 (45.7%)
responded to acid suppression after 3 months. Gas-
troesophageal reflux disease was defined in 22
patients, of whom 19 patients had pathological distal
esophageal acid exposure and 5 were defined as ero-
sive esophagitis. The time to response showed a sig-
nificant hazard ratio for patients with increased distal
esophageal acid exposure time (b: 0.93; HR: 2.55; 95%
CI: 1.24–5.24; P = 0.011) and increased laryngopha-
ryngeal bolus exposure time (BET; b: 0.96; HR: 2.61;
95% CI: 1.36–5.00; P = 0.004). The latter had the best
Youden Index (0.34) and accuracy (68.5%). Conclu-
sions & Inferences The success of acid suppression on
chronic laryngitis could be predicted using reflux
Address for Correspondence
Min Hu Chen, Department of Gastroenterology, The First
Affiliated Hospital of Sun Yat-sen University, Guangzhou
510080, China.
Tel: 0086-20-87755766 Ext. 8172; fax: 0086-20-87332916;
e-mail: chenminhu@vip.163.com
Received: 14 November 2011
Accepted for publication: 27 December 2011
432
doi: 10.1111/j.1365-2982.2011.01873.x
& M. H. CHEN *
parameters detected by MII-pH, among which
increased laryngopharyngeal BET is the best.
Keywords gastroesophageal reflux disease,
impedance, laryngitis, laryngopharyngeal reflux, pH
monitoring, predictor, proton pump inhibitor.
INTRODUCTION
Gastroesophageal reflux disease (GERD) has been
recognized as a cause of chronic laryngitis, which is
often referred to as reflux laryngitis syndrome (RLS).1
Reflux laryngitis syndrome has been considered as a
causative role in 60–70% of the Western population
with laryngopharyngeal symptoms. About 20% of
patients suspected with RLS were identified to have
pathological esophageal acid exposure by 24-h pH
monitoring.2–5
The recommended treatment in patients suspected of
RLS is an empirical therapy with 3- to 6-month course of
double-dose proton pump inhibitor (PPI).6 However, up
to 50% of the patients suspected with RLS do not
respond to aggressive acid suppression.7 Two meta-
analyses reveal that treatment of RLS with PPIs has
shown no benefit over placebo.8,9 Overprescribing PPI is
quite prevalent in managing these patients, which could
bring some side effects.10–13 It is more advisable to
administer a long term and aggressive acid suppression
to patients who would respond to PPI therapy than to all
patients with suspected RLS. Consequently, the predic-
tors of PPI therapy success of chronic laryngitis are
deserved to explore to reduce the medical cost of
laryngitis and avoid overuse of PPI.
The current practice in most studies is to detect
increased esophageal acid exposure by a pH probe
with dual sensors, one placed 5 cm above the upper
border of the lower esophageal sphincter (LES) deter-
mined by manometry and a second placed in the
proximal esophagus near the lower border of upper
 2012 Blackwell Publishing Ltd
Volume 24, Number 5, May 2012
esophageal sphincter. However, laryngopharyngeal
epithelium is far more susceptible to reflux-related
injury than esophageal epithelium, thus nonacid
reflux (pH > 4), which cannot be detected by pH
monitoring, may also lead to damage of laryngeal
mucosa.14 Pepsin was also detected in the laryngeal
epithelium of RLS patients, which could result in
local inflammatory reaction.15 Pepsin retains some of
its peptic activity at pH levels as high as 6.5.16
Therefore, it is necessary to evaluate both acid and
nonacid laryngopharyngeal reflux (LPR) in patients
with suspected RLS. Combined multichannel intralu-
minal impedance and pH (MII-pH) monitoring could
detect both acid and nonacidic reflux episodes and
help determine the proximal extent of the refluxate. It
has also been observed that addition of MII to pH
monitoring increased two-fold of the diagnostic yield
for detecting gastroesophageal reflux.17 We have set
out to study a carefully selected group of patients
with chronic laryngitis by MII-pH monitoring, to
initially identify the clinical and reflux parameters
that best predict the success of acid suppression in
patients with chronic laryngitis.
SUBJECTS AND METHODS
Consecutive patients aged between 18 and 70 years attending
the Otorhinolaryngology Clinic of the First Affiliated Hospital
of Sun Yat-sen University were recruited if they had chief
complaint of sore throat, throat clearing, throat burning, throat
dryness, globus or hoarseness of voice ‡3 days week)1 for at
least 3 months. They were referred to a single-experienced
otorhinolaryngologist for a complete examination of the nose,
pharynx and larynx. Patients’ medical and surgical history was
taken. Patients were excluded if they were professional voice
users (e.g., singer and teacher), an exposure to occupational or
environmental pollutants or any contraindication to rabepraz-
ole, such as known or suspected allergy or sensitivity to any
PPI.; or had a history of respiratory or gastrointestinal malig-
nancy, peptic ulcer disease, a radiation therapy to the head and
neck, lung, or gastrointestinal tract, a significant gastroesoph-
ageal, laryngeal or tracheal surgery, chronic sinusitis, chronic
rhinitis, an allergic cause of laryngitis, an acute traumatic event
near the larynx; or had tobacco or alcohol abuse in the past
year. Other exclusion criteria included presence of an infectious
cause of laryngitis in the past 3 months; any PPI, theophylline,
or any other investigational compound or participation in
another investigational drug study in the past 1 month; need
for continuous therapy within 1 week of enrollment with
diazepam, phenytoin, mephenytoin, warfarin, anticholinergics,
antineoplastics, prostaglandin analogs, H2-receptor antagonists,
steroids (inhaled, oral, or intravenous), promotility drugs, and
sucralfate. Women were required to be nonpregnant and non-
lactating and to maintain effective contraception if of child-
bearing potential. All enrolled patients were also required to
have laryngoscopically proven laryngitis, which was diagnosed
in the same way as previously described.18 This study protocol
was approved by the Ethics Committee of the First Affiliated
Hospital of Sun Yat-sen University. Written informed consent
was obtained from all the participants.
 2012 Blackwell Publishing Ltd
PPI response predictors for laryngitis
Screening period
Eligible patients then underwent a 7-day screening period without
treatment, during which they completed a daily diary card on
which they assessed their chief laryngeal complaint and reflux
symptoms over the past 24 h on a 4-point Likert scale (0 = no,
1 = minor, 2 = moderate, 3 = intensive). The patients must have
completed at least 80% of diary entries and had three or more days
with moderate or intensive symptoms (‡2 points) over the last
7 days. The frequency of each symptom was determined by a
5-point scale (0 = none, 1 = 1, 2 = 2–3, 3 = 4–5, 4 = 6–7 day-
s week)1). The score of each symptom was calculated by multi-
plying severity score of each symptom and the frequency score of
the respective symptom.19–21 Mild reflux symptoms (heartburn or
regurgitation) occurred ‡2 days week)1 or moderate/severe symp-
toms occurred ‡1 day week)1 was defined as troublesome reflux
symptoms.1
Esophagogastroduodenoscopy and ambulatory
24-h MII-pH monitoring
All the patients underwent an esophagogastroduodenoscopy
(EGD; Olympus CV 260; Olympus Optical Company, Tokyo,
Japan). The degree of erosive esophagitis (EE) was graded according
to the Los Angeles classification.22 Esophageal manometry (CTD
synectics, Stockholm, Sweden) was performed to determine the
location of LES and UES. Ambulatory 24-h MII-pH monitoring
was performed using a Sleuth System-Multichannel Intraluminal
Impedance Ambulatory System (Sandhill Scientific Inc., High-
lands Ranch, CO, USA), which includes a portable data logger
with impedance-pH amplifiers and a bifurcated impedance-pH
catheter (CZAI-B62C47E; Sandhill Scientific Inc.). Impedance was
recorded with the catheter that consists of two 2.1-mm diameter
polyvinyl subcatheters; one for recording impedance from the
distal esophagus (esophageal subcatheter) and the other for
recording impedance from the proximal esophagus and the larynx
(laryngeal subcatheter). The subcatheter for the distal esophagus
has three electrodes, positioned in such a way that it measured
intraesophageal impedance at 3 and 5 cm above the upper border
of LES. The laryngeal subcatheter had six electrodes positioned in
such a way that the proximal three electrodes measured intrala-
ryngeal impedance at 1 and 0 cm above the upper border of UES
and the distal three electrodes measured intraesophageal imped-
ance at 5.5 and 7.5 cm below the upper border of UES. In addition,
the esophageal subcatheter was incorporated with an antimony
pH electrode (esophageal pH electrode) positioned at 5 cm above
the upper border of LES for monitoring esophageal pH value.
Similarly, the laryngeal subcatheter was also incorporated with a
pH sensor (laryngeal pH electrode) positioned at 0.5 cm above the
upper border of UES for monitoring laryngeal pH value (Fig. 1).
All GER episodes were characterized by pH electrode 5 cm
above the upper border of LES as acid, weakly acidic, or weakly
alkaline in accordance with the consensus.23 LPR was defined if
GER reached proximally to 1 cm above the upper border of UES. If
LPR occurred simultaneously with laryngeal pH < 4.0 and the
corresponding nadir esophageal pH reached a pH value equal to or
lower than the nadir laryngeal pH, it was defined as acidic LPR.
For each reflux episode detected by impedance, bolus exposure
times (BETs) for GER and LPR were calculated as the times
between the 50% drop in impedance to recovery of impedance
baseline for more than 5 s at 5 cm above the upper border of LES
and 1 cm above the upper border of UES, respectively. BET for
GER or LPR was obtained by addition of the corresponding BET
divided by the time of monitoring. Acid exposure time (AET) for
GER or LPR was defined as the time for pH < 4 detected by
433
A. J. Wang et al.
Figure 1 Schematic representation of the recording catheters and their
placement.
corresponding pH electrode associated with bolus reflux divided
by the time of monitoring.
After intubation, subjects were discharged and encouraged to
maintain their normal daily activities, sleep schedules, and
mealtimes. Data stored on the CompactFlash card were down-
loaded onto a personal computer and analyzed visually with the
assistance of dedicated software (Bioview Analysis, version 5.0.9;
Sandhill Scientific, Inc.). Meals were excluded from the analysis.
Increased distal esophageal AET was defined as an intraesophageal
pH of <4 for more than 4% of the recording time. As there is no
consensus on the normal value of other GER and LPR parameters
in the Chinese population, we define 95th percentile value of
these parameters as the upper limit, which was defined in our
previous study.24 The numbers of all reflux >71, acid reflux >50,
LPR and acidic LPR >2 were used to define increased number of all
reflux, acid reflux, LPR and acidic LPR, respectively. The distal
esophageal BET > 1.4%, laryngopharyngeal BET (LPBET)>
0.002% and laryngopharyngeal AET (LPAET)> 0.0003% were
defined as an increased distal esophageal BET, LPBET, and
LPAET, respectively.
Treatment schedule
All the patients were blinded to the results of EGD and 24-h MII-
pH monitoring. After the completion of all examinations, they
were told their chronic laryngitis were ‘idiopathic’ and probably
caused by GERD. Empirical therapy should be given with a course
of rabeprazole (Pariet, Eisai CO., Ltd, Tokyo, Japan) at a dose of
10 mg 1/2-h preprandial morning and evening meals for
12 weeks.6 The patients used the same daily diary card during
the screening period to assess symptoms each day throughout the
12-week treatment period. Compliance to medication was
assessed by return tablet count of not more than 10% of the
prescribed medications. The patients were interviewed via
434
Neurogastroenterology and Motility
telephone every week for assessment of symptoms and compli-
ance, and were asked to return to hospital with diary cards every
1–2 weeks. The chief laryngeal complaint was considered to be
improved after the start of the acid suppression therapy once the
symptom score had decreased by at least 50% compared with
baseline during the last week since last interview.
Statistical analysis
A Student’s t-test was used to compare the distributions of age,
body mass index (BMI), and the score of chief complaint. The
Mann–Whitney U-test was used to compare the duration of
laryngitis history. The chi-squared tests were used to identify
possible differences in terms of sex, symptom and reflux profiles,
and prevalence of GERD. Fisher’s exact test was used for small
group comparisons of binominal data. A P-value of 0.05 in the
univariate analysis was chosen as a cutoff point to decide whether
a variable could be included in the multivariate Cox regression
analysis of predictors associated with response to PPI. The forward
selection method was used to determine the variables in the final
model. Hazard ratios with 95% confidence intervals (CIs) were
computed. All the statistical comparisons were two-sided using
the 0.05 significance level. Data were processed, and statistical
analysis was performed with a SPSS 13.0 program (SPSS Inc.,
Chicago, IL, USA).
RESULTS
A total of 389 patients with laryngeal symptoms were
recruited from July 2007 to January 2009. One hundred
and nineteen patients were found to have laryngoscop-
ically proven laryngitis and eligible for the study.
Details of enrollment, treatment and follow-up are
shown in Fig. 2. Ninety-two patients agreed to partic-
ipate in the study and completed all the exams.
Seventy-six patients completed 12-week PPI therapy
and 42 patients (45.7%) responded to 12-week acid
suppression therapy with rabeprazole 10 mg b.i.d. The
drop-out rate at the completion of therapy was 17.4%,
and no serious adverse events occurred. Comparison of
baseline between responders and nonresponders to PPI
therapy was summarized in Table 1. Gastroesophageal
reflux disease was defined in 22 patients, of whom 19
patients had pathological distal esophageal acid
Figure 2 Summary of patient flow throughout study.
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Volume 24, Number 5, May 2012 PPI response predictors for laryngitis

exposure and 5 were defined as erosive esophagitis. In
univariate analysis, the response to PPI therapy was
associated with older age, higher BMI, lower chief
complaint severity score, presence of troublesome
regurgitation, increased number of all reflux, increased
distal esophageal BET, AET, LPBET, and LPAET.
Table 2 shows the results of multivariate Cox
regression analysis of factors possibly associated with
the response to PPI therapy. A significant higher hazard
ratio (HR) was found in patients with increased distal
esophageal AET and increased LPBET. Increased
LPBET has the highest sensitivity and the combination
of these two parameters had the highest specificity for
predicting success of acid suppression ther-
apy (Table 3). The former was the best predictor with
the best sensitivity, Youden index and accuracy.
DISCUSSION
The present study was the first prospective cohort
study with a new type of bifurcated MII-pH catheter to
explore the predictors of acid suppression success on
chronic laryngitis in Chinese. It showed the patients
with increased distal esophageal AET and LPBET were
more likely to respond to double-dose PPI therapy,
whereas the latter parameter had the best predictive
value. These results emphasize the value of 24 h
MII-pH testing off antisecretory therapy in predicting
therapeutic outcome in the patients with ‘idiopathic’
chronic laryngitis. It also suggested that chronic
laryngitis in patients with increased distal esopha-
geal AET or LPBET could perhaps be attributed to
GERD.
Currently, there are no objective gold standards by
which a diagnosis of GERD related laryngeal signs or
symptoms can be established with certainty. Symp-
toms such as globus or frequent throat clearing may be
caused by other factors, such as voice abuse, smoking,
or allergy. Physical findings such as posterior laryngeal
cobblestone appearance, arytenoid erythema, and sub-
glottic edema also may be found in the healthy
population. The diagnosis of RLS more often depended
on subjective judgment rather than objective signs or
exams.25,26 Hence, it is difficult to differentiate RLS
from laryngitis of other causes. Therefore, the inclu-
sion criteria in our study are very strict to exclude
laryngitis of other causes and ensure laryngitis is truly
‘idiopathic’. In addition, we did not want to exclude
patients who might benefit from PPI therapy with
negative results in any one of the above tests except
laryngoscopically proven laryngitis, therefore consecu-
tive patients with laryngeal symptoms were enrolled.
The current recommendation to manage patients
with suspected RLS is to use PPI twice daily for

Table 1 Comparison of baseline between responders and nonresponders

Responders (n = 42) Nonresponders (n = 50) P

Age (years) 47.3 ± 12.9 38.5 ± 14.7 0.003*

BMI (kg m)2) 23.4 ± 3.3 21.4 ± 3.1 0.004*
Female (n, %) 26 (61.9) 24 (48.0) 0.18
Laryngitis history duration (median months) 24 13
Symtoms
Chief complaint severity score 9.4 ± 2.9 10.7 ± 2.0 0.015*
Chief complaint (n, %)
Throat pain 6 (14.3) 9 (18.0) 0.63
Throat burning 8 (19.0) 5 (10.0) 0.22
Globus 14 (33.3) 14 (28.0) 0.58
Throat dryness 0 1 (2.0) 0.99
Throat clearing 9 (21.4) 16 (32.0) 0.26
Hoarse of voice 5 (11.9) 5 (10.0) 0.77
With troublesome heartburn (n, %) 15 (35.7) 9 (18.0) 0.05
With troublesome regurgitation (n, %) 30 (71.4) 15 (30.0) <0.001**
Reflux profile
Increased number of all reflux (n, %) 7 (16.7) 2 (4.0) 0.04*
Increased number of acid reflux (n, %) 9 (21.4) 4 (8.0) 0.07
Increased distal esophageal BET (n, %) 13 (31.0) 6 (12.0) 0.03*
Increased distal esophageal AET (n, %) 14 (33.3) 5 (10.0) 0.006*
Increased number of LPR (n, %) 15 (35.7) 10 (20.0) 0.09
Increased number of acid LPR (n, %) 2 (4.8) 0 (0) 0.21
Increased LPBET (n, %) 22 (52.4) 9 (18.0) 0.001*
Increased LPAET (n, %) 21 (50.0) 11 (22.0) 0.005*
Presence of EE 2 (4.8%) 3 (6.0%) 0.79

LPR, laryngopharyngeal reflux; BMI, body mass index; EE, erosive esophagitis; BET, bolus exposure time; AET, acid exposure time; LPBET,
laryngopharyngeal bolus exposure time; LPAET, laryngopharyngeal acid exposure time.
*P < 0.05;**P < 0.001.

 2012 Blackwell Publishing Ltd 435

A. J. Wang et al.
Table 2 Cox regression analysis for predictors for acid suppression
success of laryngitis
b HR CI
Increased distal 0.93 2.55 1.24–5.24
esophageal AET
Increased LPBET 0.96 2.61 1.36–5.00
HR, hazard ratio; CI, confidence interval; AET, acid exposure time;
LPBET, laryngopharyngeal bolus exposure time.
3–6 months after malignancy is excluded by laryngo-
scope and EGD.6,27 However, up to 50% of patients do
not have abnormal esophageal acid exposure or respond
to long-term aggressive acid suppression. In some
studies in which patients with frequent reflux symp-
toms were excluded because of ethical and safety
concerns, PPI is no more effective than placebo in
producing symptomatic improvement.28–30 It is proba-
bly due to the fact that some patients whose laryngeal
symptoms were not caused by RLS would dilute the
overall study populations resulting in reduced study
power to detect a difference between PPIs and placebo.
These could partly explain why PPIs lack efficacy on
suspected extraesophageal reflux symptoms.
Williams et al.18 enrolled 20 consecutive chronic
laryngitis patients and found that neither voice mea-
sures, esophageal AET, symptoms nor severity of
laryngitis predict 12-week acid suppression. All the
patients with acid LPR responded to therapy and
pharyngeal pH-metry may prove useful. Qua et al.31
enrolled 32 consecutive patients and found that the
proportion of patients with marked/moderate improve-
ment in laryngeal symptoms were significantly higher
in patients with GERD compared with those without
GERD defined by EGD and 24-h pH monitoring after
8-week PPI therapy. However, this study failed to
explore the predictive value of reflux parameters in pH
monitoring for acid suppression success. Our study
enrolled consecutive patients with chronic laryngitis
and did not exclude the patients with frequent reflux
symptoms. Our results showed that about 20% of the
patients had pathological distal esophageal acid expo-
sure and about 50% of the patients with chronic
Table 3 Predictive value of reflux parameters for acid suppression success
Sen (%)
Increased distal esophageal AET 33.3
Increased LPBET 52.4
Increased distal esophageal AET and LPBET 23.8
Sen, sensitivity; Spe, specificity; PLR, positive likelihood ratio; NLR, negative likelihood ratio; AET, acid exposure time; LPBET, laryngopharyngeal
bolus exposure time.
Neurogastroenterology and Motility
laryngitis failed to respond to 12-week aggressive acid
suppression, which were consistent with most
published studies.5,31,32
P
The laryngeal symptoms of RLS patients could
0.011 perhaps be caused by either direct contact with reflux-
ate or a neurally mediated reflex, which occurs through
0.004
vagal afferent pathways stimulated by acid reflux into
the distal esophagus.33,34 Recent study indicates that
laryngopharyngeal epithelium is far more susceptible
to reflux-related injury than esophageal epithelium,
thus the nonacid LPR (pH > 4), which could not be
detected by pH monitoring, may also lead to the
damage of laryngeal mucosa.14 Pepsin was also
detected in the laryngeal epithelium of RLS patients,
which could result in local inflammatory reaction.15
Pepsin retains some of its peptic activity at pH levels as
high as 6.5.16 Our previous study also indicated that
pepsin could be detected in both patients with only
acid LPR and those with only nonacid LPR, which
supported the above notion.35 Pepsin present in a
refluxate could bind to the mucosa, remains native, but
inactive after neutralization of the refluxate and be
reactivated by a subsequent reflux event below pH 6.0
or by the passage over the mucosa of an acidic drink.
Therefore, it is necessary to evaluate both acid and
nonacid LPR in patients with suspected reflux-related
laryngitis. As the space between upper esophageal
sphincter and LES was varied among different patients,
early studies were limited by the fact that the dual-
probe pH catheter used had two sensors located 15-cm
apart, which results in variability in the location of the
proximal sensor in relationship to the UES when the
distal probe is positioned 5 cm above the LES. In our
study, we used a new type of bifurcated impedance-pH
catheter to allow esophageal pH electrode positioned
5 cm above the LES and laryngeal pH electrode posi-
tioned 0.5 cm above the UES simultaneously. Our
results showed that patients with increased distal
esophageal AET and LPBET were more likely to
respond to PPI therapy, which was not reported by
other studies. These findings confirmed the theory that
both acid and nonacid reflux could cause laryngeal
symptoms. It suggested that 24-h combined MII-pH
Spe (%) Youden Index Accuracy (%) PLR NLR PLR/NLR
90.0 0.23 64.1 3.33 0.74 4.50
82.0 0.34 68.5 2.91 0.58 5.01
94.0 0.18 62.0 3.97 0.81 4.90
436  2012 Blackwell Publishing Ltd
Volume 24, Number 5, May 2012 PPI response predictors for laryngitis

monitoring could be more promising to diagnose PPI-
responsive laryngitis than 24-h pH biprobe or triprobe
monitoring. Unfortunately, we did not establish an
association with acidic LPR and acid suppression
success. Perhaps, it may be attributed to few patients
with acidic LPR in our study. In addition, our results
indicated impedance-pH monitoring had a low sensi-
tivity, but a relatively high specificity. It probably
means impedance-pH monitoring is a useful tool to
define patients with laryngitis who could benefit little
from PPI therapy, but is not a sensitive way to identify
those that would respond to the acid suppression
therapy. Furthermore, we should emphasize our results
could perhaps be suitable to a specific group of patients
whose laryngitis was idiopathic as our exclusion
criteria were very strict. In the clinical practice,
chronic laryngitis could be caused by many other
causes except GERD. Hence, it is inappropriate to give
high dose and long-term PPI therapy to treat patients of
chronic laryngitis before other possible causes are
excluded. Finally, most laryngeal symptoms such as
globus or hoarse of voice are persistent rather than
episodic in nature, it is difficult to discern the chrono-
logical relationship between reflux and symptoms.
Hence, we could not determine the predictive value
of parameters such as symptom index or symptom
association probability.
Our study has some limitations. Firstly, it was not a
placebo-controlled trial. Perhaps, our results could
overestimate the efficacy of acid suppression on
chronic laryngitis. However, the patients were blinded
to the results of EGD and 24-h MII-pH monitoring. All
of them were told their laryngitis was ‘idiopathic’ and
probably caused by GERD. The placebo effect may play
a similar role between responders and nonresponders.
Secondly, this study was conducted in a single center,
therefore selection and referral bias might exist. Nev-
ertheless, our study had the largest sample size of all
the similar studies in which patients with chronic
laryngitis were evaluated by laryngoscope, EGD and
24-h MII-pH monitoring.
There is a controversy over whether patients should
take an empirical trial of PPI therapy or pH monitoring
as the first step in patients with unexplained chronic
laryngitis since 24-h pH monitoring has little predic-
tive value for acid suppression success of RLS patients.
Most gastroenterologists recommend an empirical trial
of PPI therapy for at least 3 months as the first step
after malignancy has been ruled out by laryngoscopy
and EGD. However, our results suggest that there was
an advantage to evaluate both acid and nonacid reflux
around LES and UES for predicting acid suppression
success. Ambulatory 24-h MII-pH appears to be clin-
ically useful in managing patients with suspected RLS
and avoiding abuse of PPI.
ACKNOWLEDGMENTS
We are indebted to Ms. Wei Chen for the maintenance of multi-
channel intraluminal impedance ambulatory system. We also
thank Professor Benjamin Chun-Yu Wong for assisting in the
preparation of the manuscript.
FUNDING
No funding declared.
DISCLOSURES
No competing interests declared.
AUTHOR CONTRIBUTION
Anjiang Wang participated in designing and conducting the study
and drafting and revising the manuscript; Minhu Chen was
responsible for designing and conducting the study and critically
reviewing the manuscript; Maojin Liang and Jie Chen participated
in designing and conducting the study; Jinkun Lin, Aiyun Jiang
and Weiping Wen were involved in conducting the study; Ying-
Lian Xiao and Sui Peng provided the statistical analysis.

3 Smit CF, van Leeuwen JA, Mathus- gopharyngeal reflux in Chinese

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