Diagnosis of GERD - Practical Gastroenterology

GERD IN THE 21st CENTURY, SERIES #10
Donald O. Castell, M.D., Series Editor
Diagnosis of GERD:
Ambulatory pH Monitoring
by Amine Hila and Donald O. Castell
Gastroesophageal reflux disease (GERD) is a common condition. Its diagnosis is not
always straightforward. 24-hour esophageal pH monitoring is considered the gold standard
for the diagnosis of acid GERD. Standard pH testing involves the placement of a
pH probe through the nares into the esophagus or attaching a small transmitter assembly
directly onto the mucosa, this allows the identification of acid refluxate into the
esophagus. In analyzing the tracings resulting from ambulatory esophageal pH monitoring,
acid is traditionally detected by the percent time pH drops below 4, both in the
upright and recumbent position. It is also important to include the assessment of symptom
association with reflux in the interpretation of prolonged esophageal pH studies.
Currently, with the wide use of empiric trials of GERD medical therapy, 24-hour
esophageal pH monitoring has its main indication in assessing patients with poor response
to GERD therapy and those in whom an anti-reflux surgical procedure is contemplated.
INTRODUCTION
GERD describes the clinical manifestations of the
pathological movement of acid gastric contents
into the esophagus. The classic symptoms of
GERD, heartburn and acid regurgitation, are common
in the general population. It is estimated that up to
11% of the US population experience heartburn daily
and 30% every 3 days (1). The total cost of caring for
patients with moderate to severe GERD is between
$2,100 and $4,574 per patient per year, and the drugs
Amine Hila, M.D., Department of Gastroenterology
and Hepatology, Medical University of South Carolina,
Charleston, South Carolina. Donald O. Castell, M.D.,
Department of Gastroenterology and Hepatology,
Medical University of South Carolina, Charleston,
South Carolina.
used to treat GERD rank among the highest in sales
among prescription medications (2,3).
The diagnosis of GERD is not always straightforward
because of the wide range of typical, atypical,
and extraesophageal symptoms in patients. A number
of tests have been developed to help the physician
identify patients with GERD: barium swallow, upper
gastrointestinal endoscopy, esophageal acid perfusion,
and ambulatory esophageal pH monitoring.
Prolonged ambulatory monitoring of esophageal
pH is the most reliable method of diagnosing GERD. In
fact, it allows the measurement of the basic pathophysiologic
problem of GERD, namely the exposure time of
the esophagus to excessive acid refluxate. This concept
of recording GER over a prolonged interval, by placing
a small pH sensitive electrode in the distal esophagus,
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Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
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Table 1
Comparison between the transnasal catheter and the wireless probe.
Transnasal Probe
Wireless Transmitter
20 yr data/experience Many unknowns (more GER)
Catheter limits activity
No catheter
Throat irritation
Bolus effect/chest pain
24 hr data 48 hr data
Accurate placement
Placement variable (where is LES?)
Multiple electrodes easy
Multiple electrodes difficult & costly
Easy passage
Nose bleed (nasal placement)
Stop PPI (endoscopic placement)
Detects acid and non-acid GER (with MII) Detects acid GER only
was first reported by Spencer in 1969 (4). In 1974, Johnson
and DeMeester provided a more extensive evaluation
of this technique and expanded its applications (5).
However, these earlier studies were not ambulatory. In
fact, ambulatory esophageal pH monitoring was first
described in 1980 (6). Since then, the technique has
rapidly gained popularity. Light-weight portable data
recorders are available, allowing the patients to be monitored
in their home or work environment.
TECHNIQUE OF AMBULATORY PH MONITORING
There are several types of small pH electrodes available
for intraesophageal monitoring. These include
monocrystalline antimony electrodes, combined glass
electrodes, or ion-sensitive field effect transistor
(ISFET) electrodes. The ideal pH probe should be
small so it can be easily passed through the nose into
the esophagus, and it should be firm so that it remains
in a certain position for the entire study. The number of
electrodes in the pH probe is variable. Single electrode
probes contain only one pH electrode located at the
distal end of the catheter. Dual, triple and 4 electrode
probes are available, with standard spacing of 5, 10 or
15 cm between electrodes. These different configurations
allow simultaneous gastric, intraesophageal or
even pharyngeal pH recording, as needed. The most
common configuration includes 2 electrodes 15 cm
apart. This allows 2 types of monitoring depending on
probe positioning: either simultaneous gastric and distal
esophageal monitoring where the proximal electrode
is 5 cm above the lower esophageal sphincter
(LES), and the distal one in the
stomach; or distal and proximal
esophageal monitoring with the
electrodes 5 and 20 cm above
the LES.
Recently, a new wireless
esopahgeal pH recording device
was introduced. It consists of a
pH-sensitive capsule that is
attached to the esophageal
mucosa. Data are sent from the
capsule to a receiver/data logger
by means of radio transmission.
This probe does not require a
transnasal catheter, thus offering a possible comfort
advantage. However, the wireless pH capsule must be
placed endoscopically or blindly through the mouth,
which may be a major drawback. Also, the lack of precision
when placing this probe relative to its location in
relation to the LES could induce interpretation errors in
the real amount of esophageal acid exposure. Table 1
provides a comparison between the transnasal catheter
and the wireless probe.
Standard esophageal pH monitoring involves the
placement of a thin (2 mm diameter) pH probe through
the nares, with the distal esophageal electrode placed 5
cm above the manometrically determined LES location.
The normal values for distal esophageal acid
exposure have been defined using an electrode 5 cm
above the manometrically defined proximal border of
the LES, thus the accuracy of the placement is very
important. After it is placed, the probe is connected to
a small light weight data logger worn on a waist band
or shoulder strap. There are different types of commercially
available data loggers, but all contain one or
more event markers that allow the patient to indicate
when symptoms occur, when they are eating, and
when they are in a recumbent position. Patients are
also usually required to enter this data on a diary.
After the probe is placed and connected, the
patient is usually monitored for approximately 24
hours, often 48 hours using the wireless capsule.
Patients are encouraged to eat, drink and go about their
daily activity as close as possible to their usual routine.
They are also encouraged to consume meals that usu-
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Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
(continued from page 36)
ally produce their GERD symptoms. Unless the goal
of the study is to assess response of GER to anti-secretory
therapy, all medications that affect the pH of the
stomach or the motility of the foregut should be
stopped before the study.
The 24-hour pH monitoring yields a high sensitivity
as a diagnostic test (7,8). A 24-hour pH monitoring
allows study of circadian patterns of reflux by including
a nightime or recumbent period. It also allows
monitoring the effects of physiological activity.
Although a 24-hour recording period is standard, we
have shown that a shorter period yields good results,
especially if it includes the recumbent period (9).
Thus, a 16-hour study, from 4 P.M. to 8 A.M., has a sensitivity
of 97% and a specificity of 95% compared to a
24-hour study period, and would allow patients to have
the probe placed late on the first day and removed
early on the second day, potentially minimizing the
possible work time loss. The same study showed that a
shorter 12-hour period, from 4 pm to 4 am, has a sensitivity
of 93% and a specificity of 92% compared to a
24-hour study period, and thus it is reasonable to
advise the rare patient unable to sleep because of the
pH probe, to remove it at 4 am, and thus get a few
hours of sleep.
INTERPRETATION OF AMBULATORY
pH MONITORING
1. Reflux Criteria
Johnson and DeMeester defined reflux by a fall in
intraesophageal pH to less than 4 with the episode persisting
until the pH returned to greater than 4 (5). This
threshold of pH 4.
C. Initial studies revealed a good association
between symptoms of GERD and intraesophageal
pH

Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
(continued from page 38)
Figure 1: Abnormal upright reflux with normal recumbent
reflux (shaded area).
Figure 4: Three hour segment of a prolonged distal
esophageal recording demonstrating the typical pattern of
upright reflux with multiple episodes of short duration.
Figure 2: Recumbent reflux (shaded area) with normal
upright reflux.
Figure 5: Three hour segment of a prolonged distal
esophageal recording demonstrating the typical pattern of
recumbent reflux with a prolonged episode of acid exposure
due to lack of effective clearing mechanisms while sleeping.
Figure 3: Abnormal reflux in both the upright and recumbent
(shaded area) positions.
sure (Figure 3). Different authors (8,15) found that
patients with combined reflux or patients with supine
reflux alone demonstrated greater acid exposure and
more severe esophagitis than did patients with upright
reflux alone. In upright refluxers, the predominant
mechanism of reflux is an increased frequency of transient
LES relaxations with relatively preserved acid
clearance from the distal esophagus (16). In patients
with supine reflux, the major abnormality is a marked
impairment in acid clearance (17), resulting in prolonged
reflux episodes from the distal esophagus due to
a combination of factors such as elimination of gravity,
sleep, and decreased salivary secretion and swallowing.
Combined refluxers probably exhibit both abnormalities
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Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
Figure 6: A segment from the upright portion of a 24-hour
esophageal pH recording demonstrating positive symptom
association for both regurgitation and chest pain.
and is at least as important as the amount of
esophageal acid exposure. Symptom-GER association
may be particularly important in patients with atypical
or extraesophageal symptoms.
Based on the patient’s diary, and confirmed by the
event marker, each symptom reported by the patient
can be evaluated for a temporal relationship with a fall
in esophageal pH to < 4. In our laboratory, the timing
for a positive symptom association with reflux requires
that the reflux episode occurs within a time window of
5 minutes before the identification of the symptom by
the patient. Figure 6 shows an example of positive
symptom association with reflux.
In 1988, Weiner, et al (18) proposed a parameter
that expresses the relationship between symptoms and
reflux episodes, named symptom index (SI). The following
formula mathematically defines the SI:
Number of times symptom occurs
with a pH drop below 4
———————————————————— × 100
Total number of times the symptom was reported
Figure 7: A segment from a distal and proximal pH recording
showing no symptom-GER association.
and, thus, may have erosive mucosal disease. The difference
in esophageal acid clearance dependent on gravity
is illustrated by the varying patterns of upright and
recumbent reflux shown in Figures 4 and 5.
2. GER–Symptom Association
Prolonged esophageal pH monitoring provides information
both about esophageal acid exposure and the
temporal association between the occurrence of GER
and symptoms as reported by the patient. This relationship
between symptoms and reflux constitutes an
integral part of the 24-hour pH study interpretation,
In this study, they found that the SI had a bimodal
distribution. The SI was high (>75%) in 98% of
patients with heartburn or chest pain and pathological
GER, and low (

Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
of a symptom index of 100% in a patient with only a
single reflux episode per 24 hours is different from that
in a patient with more than 100 reflux episodes per 24
hours. To circumvent this, the symptom sensitivity
index (SSI) was developed, defined as the percentage of
symptoms associated reflux episodes divided by the
total number of reflux episodes, and not the total number
of symptoms, as in the SI (21). SSI values of 10% or
higher are considered to be positive. However, the SSI
fails to take into account the total number of symptom
episodes, rendering its use of limited value.
Other indexes, such as the symptom association
probability (SAP), have been developed. However,
there is no clear data showing the superiority of any
one over the others. Therefore, we use the symptom
index in our laboratory because of the ease of its calculation,
by keeping a running tally of symptom /
reflux relationships while reading the pH study.
3. Is 24-hour Esophageal pH Monitoring the
Gold Standard for Diagnosis of GERD?
Although 24 hour esophageal pH testing has been
accepted as the gold standard for diagnosing GERD, it
is not perfect. It has a sensitivity of 77%–100%
(8,10,22,23). Thus, it is important to recognize that
false negative results may occur. The frequency with
which false negative results occur will vary depending
on how effectively the patient attempts to reproduce
their usual daily activities. Also, normal acid exposure
values have been recorded in 17% to 24% of patients
with otherwise typical reflux esophagitis (24,25). On
the other hand, esophageal pH monitoring should
achieve a specificity of 100%. That is, false positive
results would not be expected, except in the case of the
artifacts produced by ingestion of acidic food, which is
the reason meal times should be excluded before the
final analysis of the study (26–28). Reproducibility of
this test has been shown; the classification of normal or
abnormal acid exposure changes in less than 10% of
patients when they are studied a second time (29,30).
CLINICAL APPLICATIONS
Several recent studies have demonstrated that empirical
therapy of GERD with a proton pump inhibitor (PPI) is
not only a sensitive diagnostic test but it is also fairly
specific, readily available, and cost effective (31–34).
The proven efficacy of the empirical PPI test has placed
the management of patients with GERD, presenting
with typical and atypical symptoms, back in the hands
of primary care providers. However, subspeciality
referrals for 24-hour esophageal pH monitoring are still
required for the evaluation of adequacy of treatment, of
treatment failures and for special indications.
Patients with reflux esophagitis have more reflux
episodes and a higher esophageal acid exposure time
than normal control subjects (35–37), and the severity
of reflux esophagitis is significantly correlated with the
extent of gastroesophageal reflux, or acid exposure time
(36). Once the diagnosis of reflux has been made endoscopically,
there is generally no indication for 24-hour
pH monitoring. Only when the esophagitis or symptoms
fail to respond to medical treatment should a 24-hour
esophageal pH study be considered. Dual pH monitoring
with one electrode in the esophagus and one in the
stomach may be helpful in the management of therapyresistant
patients, as this will assess the efficacy of the
PPI in suppressing gastric acid production (38).
24-hour esophageal pH monitoring has a sensitivity
of 77%–100% and a specificity of 85%–100% in
differentiating between normal controls and patients
with reflux esophagitis (7,8,10,22,23). However, the
role of 24-hour esophageal pH monitoring is more
important in patients with reflux symptoms and without
endoscopic esophagitis. In this group of patients,
the sensitivity and specificity of 24-hour pH monitoring
vary between 61%–71% and 85%–100%, respectively
(10). If heartburn and acid regurgitation are the
dominant complaints, there is good correlation
between symptoms and findings on esophageal pH
testing. However, in patients with symptoms such as
nausea, abdominal pain, belching and odynophagia,
the correlation is poor.
24-hour esophageal pH monitoring is particularly
helpful in patients with persistent symptoms despite
adequate medical therapy with PPI and no evidence of
esophagitis by endoscopy (so called “NERD” patients).
Approximately 25% of these patients have persistent
GER requiring aggressive medical therapy with PPI. If
a patient’s symptoms persist, this suggests that either the
treatment has been insufficient, or the symptoms are not
PRACTICAL GASTROENTEROLOGY • FEBRUARY 2005 47

Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
due to GERD. In these patients, pH monitoring should
be performed when they are on PPI therapy, paying
attention particularly to the association between symptoms
and acid reflux episodes when analyzing the pH
tracings. Many of these patients respond to an increase
in the PPI dose. If the pH study on therapy is normal,
and the SI is negative, then acid reflux is not the cause
of this patient’s symptoms. Thus, if symptoms are not
due to acid reflux, the new technology of multichannel
intraluminal impedance (MII) has the potential to determine
whether they are due to non-acid reflux. MII will
be discussed in detail in another article of this series.
Up to 60% of patients with noncardiac chest pain
are likely to have GERD (39,40). These patients often
respond to acid-suppression therapy. Esophageal
manometry alone or in combination with 24-hour
esophageal pH monitoring has been used to evaluate
patients with noncardiac chest pain. Using both techniques
in these patients, it has been found that GER is
more commonly associated with noncardiac chest pain
than are motility abnormalities. Empirical testing with
high dose PPI appears to be the diagnostic method of
choice in patients with noncardiac chest pain (34).
However, 24-hour esophageal pH monitoring would
be required in patients who have not responded to high
dose PPI. The study must be performed as an outpatient
procedure with normal daily activity, and without
any restrictions. False negative results may occur if
patients change their routine or eat less.
SUMMARY
24-hour esopahgeal pH monitoring is the most appropriate
technique to prove or disprove that symptoms
(typical or atypical) are due to reflux. For quantitative
analysis of the temporal relation between symptoms
and reflux, the SI, the SSI or the SAP can be used. The
indications for 24-hour esophageal pH monitoring are:
– Study of the amount and timing of acid exposure
(pH

Diagnosis of GERD
GERD IN THE 21st CENTURY, SERIES #10
(continued from page 48)
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PRACTICAL GASTROENTEROLOGY • FEBRUARY 2005 51