EDITORIAL
Redeeming Clinical Value of
Esophageal pH Impedance
Monitoring
sophageal ambulatory pH impedance monitoring
E showed much promise in the new millennium as a
novel approach to quantifying reflux events irrespective
of pH or antisecretory therapy.1 It was widely believed
then that pH-impedance monitoring would become the
standard for reflux monitoring, and would be performed
on antisecretory therapy without the need for discontin-
uation of acid suppression.2 The method has been proven
to identify higher proportions of reflux events compared
with pH monitoring alone even in studies performed off
antisecretory therapy, and to diagnose unusual syn-
dromes such as rumination, supragastric belching, and
aerophagy.3,4 However, there were problems within its
primary role: evaluation of gastroesophageal reflux dis-
ease (GERD). Identification and characterization of reflux
events had to be confirmed manually, and could be time
consuming. The studies also were difficult to interpret,
with even experts disagreeing on occasion on what
constituted a reflux event, especially proximal esopha-
geal events.5,6 Although normative data were collected
and reported, there was scant information on whether
impedance parameters predicted outcome.7 Many
studies were performed on antisecretory therapy in pa-
tients with reflux symptoms but without prior confirma-
tion of reflux; therefore, the true impact of a negative
impedance study on management decisions was difficult
to assess. In contrast, pH testing concurrently moved to-
ward a less-cumbersome wireless system with the capa-
bility of collecting up to 96 hours of pH data. In the
changing role of reflux monitoring, now often performed
to rule out rather than quantify reflux, the easier and
better-tolerated prolonged wireless pH probe started
gaining value as a tool to assess reflux symptoms.8
Finally, outcome studies began to be published. It was
clear that the number of reflux events could be reduced
by antireflux surgery, but reflux patterns identified on
pH-impedance monitoring did not necessarily translate
into better patient outcomes.4,9 Reflux exposure time,
bolus contact time, and bolus clearance time fell by the
wayside as useful reflux parameters, and even symptom
reflux correlation was questioned as not being repre-
sentative because of the significant impact of uncon-
trolled patient factors in symptom reporting during
monitoring.10 In fact, acid-based parameters from pH-
impedance studies provided the best evidence for ther-
apeutic success rather than the impedance portion of the
study.4 In evaluation of reflux symptoms, the best value
for impedance monitoring appeared to be limited to
identification of reflux events for symptom-reflux
association, adding confidence to the diagnosis of reflux
disease in patients who were incompletely responsive to
antisecretory therapy.
The study by Frazzoni et al published in this issue of
Clinical Gastroenterology and Hepatology is a redemption
of sorts for pH-impedance monitoring, adding to its niche
value in the evaluation of reflux symptoms. It has been
known for some time that baseline mucosal impedance
correlates with esophageal mucosal integrity, hence
values can be low in severe reflux disease11; alterna-
tively, motor disorders with a fluid-filled, dilated
esophagus also can decrease values.12 Frazzoni et al13
have standardized measurement of baseline impedance
by calculating the mean nocturnal baseline impedance
(MNBI) across three 10-minute periods between 1 AM
and 3 AM, away from daytime esophageal physiologic
activity. The second measure reported by Frazzoni et al
makes even more physiologic sense. After a reflux event,
the refluxate is mostly cleared by a secondary peristaltic
wave in response to esophageal distension, but neutral-
ization of mucosal acidity is facilitated by a reflex pri-
mary swallow that brings salivary bicarbonate into the
esophagus.14 Therefore, the postreflux swallow-induced
peristaltic wave (PSPW), identified by a panesophageal
antegrade decrease in impedance within 30 seconds of a
reflux event, indirectly assesses esophageal motor peri-
staltic reserve.15 Esophageal motor function in this
context is relevant in reducing retention of the refluxate
(by secondary peristalsis), and in chemical clearance (by
inducing primary peristalsis). The PSPW index proposed
by Frazzoni et al13 consists of the ratio of PSPW to the
total reflux events identified, and therefore adds an
additional dimension to the assessment of the number of
reflux events during a pH impedance study.
The gist of the study findings is that both the MBNI
and PSPW index showed a gradient across 289 GERD
patients and 50 healthy controls, both parameters being
worse in erosive esophagitis compared with nonerosive
reflux disease and healthy controls. Performance char-
acteristics of both these parameters were overall higher
than that of increased acid exposure time, total reflux
events, and bolus exposure time in predicting both
erosive esophagitis and non-erosive reflux disease
(NERD). Frazzoni et al report a modest correlation be-
tween these 2 parameters (Pearson r ¼ 0.657; P < .001).
Finally, the diagnostic gain over conventional impedance
parameters was substantial, especially within the NERD
categories.13
There are several additional points worth mentioning.
First, the interest in bolus exposure time as an impedance-
based reflux parameter is dampened further by this
study’s findings. Bolus exposure time has not lived up to
the performance of acid exposure time, and does not add
much value in reflux assessment.4 Furthermore, the
Clinical Gastroenterology and Hepatology 2016;14:47–49
48 C. Prakash Gyawali
number of reflux events, although needed for the PSPW
index calculation, did not perform well in any disease
category other than erosive esophagitis. The PSPW index
and MNBI, on the other hand, had higher sensitivity and,
with the former, better accuracy than abnormal acid
exposure time in predicting erosive esophagitis. Within
NERD categories, performance characteristics remained
impressive in pH-positive NERD, but not as much in the
remainder of the NERD categories. This adds further
credence to the notion that true NERD is best identified
with abnormal pH parameters; indeed, in the setting of
abnormal pH, NERD outcomes mirror that seen with
erosive esophagitis.16 It generally is accepted that
negative pH parameters with or without symptom reflux
association potentially represent functional hypersensi-
tivity to mechanical or chemical aspects of reflux (reflux
hypersensitivity) or to physiologic events (functional
heartburn). In contradiction to this dogma, Frazzoni
et al13 suggested that true reflux disease may overlap with
these 2 latter categories despite normal pH-impedance
data off antisecretory therapy, on the basis of the 2 new
indices alone in some instances—a stand that may not be
firm yet without further outcome data. Management
outcomes in these difficult and refractory settings will
define the true value of MNBI and PSPW index, not in
erosive esophagitis or NERD with abnormal pH-
impedance parameters where existing metrics are
adequate for directing therapy.
As with existing studies on pH-impedance parame-
ters, there were limitations. The report was a cross-
sectional study describing proportions of patients with
an abnormal MNBI and PSPW index among categories of
GERD patients, using these proportions to project diag-
nostic yield. The true value of these parameters will be
assessed when outcome data are collected prospectively,
comparing those with and without an abnormal MNBI
and PSPW index. Although Frazzoni et al13 reported high
interobserver agreement for both indices, the PSPW
calculation involves a manual review of the entire pH-
impedance study, which is no simple task. The MNBI
also requires manual calculation after identification of
appropriate quiet periods, and is likely to be impacted by
esophageal motor disorders associated with hypo-
motility and esophageal dilation, where the impedance
rings may not be in firm contact with esophageal mucosa.
Finally, the new kid on the block, endoscopic mucosal
impedance measurement, is threatening to limit the need
for ambulatory pH impedance monitoring in the very
situations in which these new metrics have potential (ie,
in assessing the likelihood of reflux-induced symptoms in
refractory symptomatic states).17
Nevertheless, the MNBI and PSPW index make path-
ophysiologic sense, and certainly deserve a chance in
redeeming the clinical value of ambulatory pH-
impedance testing. Further research certainly is needed
to determine if a normal MNBI and PSPW index in the
setting of normal pH and normal conventional imped-
ance parameters would be the benchmark for diagnosis
Clinical Gastroenterology and Hepatology Vol. 14, No. 1
of functional esophageal symptoms. Other confounders
in the assessment of these parameters need to be eval-
uated, for instance, the contribution of abnormal motor
function or esophageal dilation. Finally, software tools
need to be developed by companies marketing pH-
impedance to simplify the calculation of these parame-
ters because both the MNBI and PSPW index need to be
studied rigorously and potentially adapted for clinical
use in the short term.
C. PRAKASH GYAWALI, MD, MRCP
Division of Gastroenterology
Washington University School of Medicine
St. Louis, Missouri
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January 2016 Editorial 49

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Conflicts of interest
The author discloses no conflicts.
Most current article
http://dx.doi.org/10.1016/j.cgh.2015.08.030