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polyvinyl catheter embedded by one pH and six imped-
ance sensors at predefined positions. The pH sensors
were calibrated before placement using standardized
buffer solutions at pH 4.0 and 7.0, as recommended by
the manufacturer. The catheter was placed intranasally
so that the esophageal pH sensor was positioned 5 cm
above the manometrically defined upper border of the
lower esophageal sphincter. Intraluminal impedance was
measured at 3, 5, 7, 9, 15, and 17 cm above the lower
esophageal sphincter. Data sampling frequency for both
impedance and pH sensors was 50 Hz. Studies were per-
formed for 24 hours, after which patients returned to the
lab for catheter removal and data review.
Data were downloaded from the recorder and ana-
lyzed using BioView Analysis software (Sandhill
Scientific Inc). Reflux episodes were identified by compu-
terized detection (Autoscan; Sandhill Scientific Inc.) of
proximally directed decreases in impedance. Tracings
were then manually reviewed by an experienced investi-
gator (MFV) to confirm accuracy and correct any errors.
Total, upright, and supine reflux events were recorded.
Acid reflux events were defined as those occurring with
pH less than 4.0, and nonacid reflux events were defined
as those occurring at pH of 4.0 or greater. For imped-
ance parameters, total number of reflux events greater
than 48 was considered abnormal.
19–22
Statistical Analysis
Data were collected and stored at the secure Web-
based Vanderbilt Digestive Disease Center REDCap
(Research Electronic Data Capture) (1 UL1 RR024975
NCRR/NIH). REDCap is an application designed to sup-
port data capture for research studies providing: 1) an
intuitive interface for validated data entry; 2) audit
trails for tracking data manipulation and export proce-
dures; 3) automated export procedures for seamless data
downloads to common statistical packages; and 4) proce-
dures for importing data from external sources. There
was strict control and supervision of the data entry and
access for this study.
Continuous variables were summarized using the
median, 25th, and 75th percentiles. Categorical varia-
bles were summarized using percentages. We used
separate Kruskal-Wallis tests to determine if the total
number of impedance events and the percent total time
pH less than four differed by esophagitis and pH groups.
Spearman’s rank correlation was used to estimate the
overall association between impedance events (on ther-
apy) and percent total time pH less than 4 (off therapy).
Multivariable linear regression was used to assess the
relationship between
on
-therapy impedance parameters
and
off
-therapy pH parameters, manometry findings,
and upper endoscopy findings. All analyses were con-
ducted using the R statistical program.
RESULTS
Demographics and Endoscopic Findings
Seventy-five patients with suspected extraesopha-
geal reflux underwent testing with 48-hour wireless pH
monitoring
off
PPI therapy and 24-hour impedance/pH
monitoring
on
PPI therapy between 2005 and 2012.
Their chief complaints included: cough (53%), asthma
(12%), hoarseness (7%), throat clearing (6%), pulmonary
fibrosis (6%), sore throat (6%), postnasal drip (5%), and
sinusitis (5%). A total of 58/75 (77%) of patients were
female, 71/75 (95%) were Caucasian, with a median
(IQR) age of 55 (45–64) years, and median (IQR) body
mass index of 29 (25–33). Hiatal hernias greater than 1
cm in size were present in 29/75 (38%), of which 61%
were 2 to 3 cm in size, and 39% were 4 cm or greater.
Esophagitis was present in 14/75 (19%) of patients, of
which 90% were grade A or B by Los Angeles Classifica-
tion. None of the patients were found to have endoscopic
evidence of possible Barrett’s esophagus.
Impedance and pH Parameters
Overall.
Median (IQR) total, upright, and supine
impedance events
on PPI therapy
were 39 (20–54), 29
(6–12), and 4 (1–8), respectively. The impedance events
were predominantly mixed gas and liquid of nonacidic
nature (pH
>
4) and were abnormal (greater than 48
reflux events) in 35% of tested subjects. Abnormal acid
reflux was not present in any of the subjects when
tested
on PPI
therapy. Wireless pH testing
off PPI ther-
apy
showed a median (IQR) % time pH
<
4 of 9% (7%–
13%) in total, 11% (8%–16%) in the upright state, and
2% (1%–8%) in the supine state. Eighty-four percent of
patients had abnormal wireless pH testing results
off
therapy.
Subgroups.
Patients were divided into three sub-
groups based on endoscopic and pH findings: Esophagitis,
normal endoscopy but abnormal pH (referred to as ‘‘pH
þ
’’
in Figures 1 and 2), and normal endoscopy with normal
pH (referred to as ‘‘pH ’’ in Figures 1 and 2). Figures 1
and 2 depict individual and group results on the degree of
Fig. 1. Individual and group median (IQR) % total time pH
<
4 for
the three patient subgroups. As expected, acid reflux was signifi-
cantly less in those with normal endoscopy and pH than those
with abnormal pH or esophagitis.
Laryngoscope 123: October 2013
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