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the paucity of high-quality studies examining the clinical
relevance of impedance findings. Thus, the aim of our
study was to determine if
on
therapy impedance values
assessing for nonacid reflux can be predicted from the
traditionally recognized and commonly employed clinical
markers of reflux based on
off
therapy upper endoscopy,
manometry, or pH monitoring.
MATERIALS AND METHODS
The study was performed in accordance with the Declara-
tion of Helsinki, Good Clinical Practice, and applicable
regulatory requirements. The Vanderbilt Institutional Review
Board approved this clinical trial (IRB# 090872).
STUDY DESIGN AND PATIENT POPULATION
The study population consisted of patients with sus-
pected reflux-associated extraesophageal symptoms
refractory to PPI therapy referred to the Esophageal Motility
Center at Vanderbilt University Medical Center for evalua-
tion and treatment. Refractory symptoms were defined as
less than 50% improvement in the chief complaint after at
least 12 weeks of twice-daily PPI therapy. This group was
chosen since they represent the patient population for whom
pH and/or impedance monitoring is currently indicated.
14,15
In order to assess the severity and frequency of their extrae-
sophageal symptoms, patients were asked to complete a
questionnaire previously described in the literature.
16
The
following information were collected for all patients: pres-
ence, severity, and frequency of GERD symptoms (heartburn
6
regurgitation) and extraesophageal symptoms (cough,
hoarseness, throat clearing, sore throat, globus sensation,
postnasal drip symptoms, chest pain), current medications,
demographic data (age, sex, race, body mass index), history
of alcohol and tobacco use, and presence of voice/laryngeal
and nasal symptoms.
Patients underwent esophagogastroduodenoscopy
(EGD), wireless 48-hour pH monitoring, and esophageal
manometry
off
acid suppression to assess the baseline
esophageal mucosal integrity, motility, and acid expo-
sure. They also underwent 24-hour impedance/pH
monitoring while
on
twice daily PPI therapy to deter-
mine the presence of acid and nonacid reflux in the
setting of acid suppression. The presence and size of a
hiatal hernia were determined at endoscopy; the pres-
ence and severity of esophagitis was graded by the Los
Angeles Classification; and the presence of Barrett’s
esophagus was also noted.
17
Inclusion criteria were age
greater than 18 years and chronic EER symptoms re-
fractory to PPI therapy. Patients were excluded from the
study if they were unwilling to undergo testing, were
pregnant, had undergone surgery for reflux or peptic
ulcer disease, or if they had a serious illness that would
interfere with study participation.
Wireless pH Monitoring
Ambulatory pH monitoring was performed for 48
hours using a wireless monitoring device (Given Imag-
ing, Duluth, GA). Patients were instructed to stop
taking all PPIs and H2-receptor antagonists (H2RAs) for
at least 7 days prior to undergoing testing. Wireless
capsules were calibrated by submersion in buffer solu-
tions at pH 7.0 and pH 1.0, and then activated by
magnet removal. Patients underwent EGD with con-
scious sedation for visual anatomic inspection and
distance measurements from the incisors to the squamo-
columnar junction (SCJ). Capsules were then placed
using the manufacturer’s delivery system at 6 cm above
the SCJ and attached with vacuum suction. Capsule
placement was confirmed with endoscopy. After success-
ful placement, patients were given wireless pH recorders
to wear about their waists, or to keep within 3 feet to 5
feet at all times. Recording devices receive pH data sam-
pling transmitted by the capsule at 433 Hz with 6
second sampling intervals. Patients were instructed to
perform their normal daily activities and dietary prac-
tices. Distal esophageal pH recording was conducted for
a total of 48 hours. During this time patients kept dia-
ries of meal times, symptoms, and supine positioning.
After completion of the 48-hour study, data were
downloaded from recording devices to dedicated com-
puters. Patient diary information was manually entered
into the computer-based record. Measurements of the
total, upright, and supine percentage time when esopha-
geal pH was below 4 were determined over day 1 and
day 2 of the wireless study. Total acid exposure time (%
total time pH less than 4) greater than 5.5% was consid-
ered abnormal, while greater than 8.2% was considered
abnormal for the upright state and greater than 3.0%
was considered abnormal for the supine state.
18
Esophageal Motility Testing
High-resolution manometry (Given Imaging, Duluth,
GA) was used to measure the location of the lower esoph-
ageal sphincter prior to placement of the impedance-pH
catheter. A solid-state assembly with 36 circumferential
sensors spaced at 1-cm intervals (outer diameter 4.2 mm)
was used. This device detects pressure over a length of
2.5 mm in each of the 12 radially dispersed sectors of the
36 pressure-sensing elements. The sector pressures are
averaged, making the sensors a circumferential pressure
detector. Prior to recording the transducers were cali-
brated at 0 and 100 mm Hg using externally applied
pressure. Using this device the lower esophageal sphinc-
ter was measured and the proximal location noted for
placement of the impedance-pH catheter.
Combined Impedance-pH Monitoring
Patients underwent impedance-pH monitoring while
on
at least twice daily PPI therapy for 1 month prior to
evaluation. They were instructed to fast for 4 hours before
testing. Each patient’s primary symptom complaint was
recorded as part of the preprocedure evaluation. Patients
were given diaries to record the timing of initiation and
completion of meals and position changes (upright or
supine) during 24-hour impedance and pH monitoring.
Impedance testing was performed using a combined
impedance-pH monitoring device (Sandhill Scientific Inc;
Highlands Ranch, CO) comprising a data recorder (Sleuth
System; Sandhill Scientific Inc.) and a 2.1-mm diameter
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