Vaezi.qxp 15/10/07 9:19 am Page 76
Gastroesophageal Reflux Disease
Figure 1: Combined Multichannel Intraluminal Impedance and pH
symptoms had a positive SI (45% for non-acid reflux, 10% for acid reflux),
whereas only 25% of patients with atypical symptoms had a positive SI (23%
for non-acid reflux, 2% for acid reflux). A different study evaluated symptom
association through 24-hour ambulatory MII–pH in 74 symptomatic
untreated patients and 60 patients with symptoms while on acid suppression
UES
with PPIs.
17
By adding measurement of non-acid reflux, MII–pH increased the
17
diagnostic yield and enabled better symptom analysis than pH-metry alone,
15
c
m)
mainly in patients on PPI therapy. Symptom association probability (SAP) was
used to establish a relationship between reflux and symptoms. The study
2cm 9
found a positive SAP in 37% of 60 patients on treatment. The SAP study was
c
e above LES (
7
positive due to non-acid reflux in 17%, acid reflux in 5%, and acid plus non-
pH electrode
5 acid reflux in 15%. The symptoms most frequently associated with non-acid
Distan
Impedance
3 reflux were regurgitation and cough. The lower rate of positive symptom
electrode
association in the second study may be explained by the use of the SAP, a
LES more stringent measure than the SI. An additional study evaluated 22
patients with unexplained chronic cough, using MII–pH monitoring off acid
suppression. An association between reflux and cough based on the SAP was
found in 45% of patients; this was related to non-acid reflux in 13%, acid
The combined multichannel intraluminal impedance–pH catheter is a thin, flexible 2.1mm polyvinyl catheter (Sandhill
Scientific Inc., Denver, Colorado) similar to a standard pH catheter. On this catheter are six impedance-measuring reflux in 23%, and acid plus non-acid reflux in 9%.
18
segments (four distal and two proximal) and a pH sensor. The catheter is placed into the esophagus transnasally and
positioned so that the pH sensor is 5cm above the lower esophageal sphincter (LES). The impedance measuring
segments are located on the catheter so that, when properly placed in the esophagus, impedance at 3, 5, 7, 9, 15, The studies mentioned above suggest that, with the exception of cough, a
and 17cm above LES is measured.
positive association between non-acid reflux and atypical symptoms appears
Omeprazole did not achieve a significant reduction in the total number of to be relatively rare. Rather than showing dismay at this finding, it must be
reflux episodes (acid and non-acid reflux combined). However, after taken as useful information in the evaluation of these patients, in whom
omeprazole treatment the percentage of acid reflux decreased from 45 to non-reflux causes of symptoms should be sought out. It is also very
3%, while non-acid reflux increased from 55 to 97%. Heartburn and acid important to note that, in the absence of controlled outcome trials, the
taste were more commonly linked to acid reflux, but were also produced by prevalence studies summarized above cannot establish causality. However,
non-acid reflux. Regurgitation was unchanged by acid suppression, as it was these data suggest a role for non-acid reflux as a cause of symptoms in
frequently caused by non-acid reflux in the treated state. This was the first roughly one-third of treated GERD patients, as well as in 22% of untreated
study to demonstrate ongoing non-acid reflux as a potential cause of patients with cough.
symptoms in acid-suppressed patients. A subsequent study by the same
group of investigators, also using two-hour MII–pH recordings in The only outcome data available for treatment of non-acid reflux come
refluxogenic conditions, assessed the effect of pharmacological inhibition of from uncontrolled trials. It is worth mentioning these studies as
transient lower esophageal relaxations (TLESRs) on acid and non-acid hypothesis-generating information. Two reviews of patients with
reflux.
16
In this study, 18 subjects (nine GERD patients and nine healthy symptomatic non-acid reflux (defined by a positive SI) were performed by
volunteers) were tested on placebo and, after a single 40mg dose of the same group. A retrospective study identified six patients with
baclofen, a gamma-aminobutyric acid B (GABAB) agonist that inhibits persistent cough despite PPIs in whom ambulatory MII–pH revealed a
TLESRs. Baclofen resulted in a significant decrease of both acid and non-acid positive association between non-acid reflux and cough (based on the
reflux. Additionally, this GABAB agonist also reduced the median number of SI).
19
After undergoing Nissen fundoplication, all six patients remained
acid-related and non-acid-related symptoms. Of note, this medication also asymptomatic and off acid suppression when followed for a median of
caused significant and frequent side effects, mainly nausea and 17 months (range: 12–27). A prospective study was based on telephone
somnolence. It is very important to keep in mind that these studies involved interview to follow 18 subjects who underwent Nissen fundoplication for
short-term MII–pH monitoring in conditions designed to maximize reflux, the treatment of symptomatic non-acid reflux detected by MII–pH
and the findings may not reflect what happens in prolonged ambulatory monitoring performed while on therapy with PPIs.
20
Fourteen patients
conditions. However, they helped establish MII–pH as a useful tool to with a variety of symptoms (heartburn, regurgitation, cough, throat
measure symptomatic acid and non-acid reflux in treated patients. clearing, hoarseness) had a positive SI for non-acid reflux, and four had
a positive SI for acid reflux (three complained of heartburn, one had
The role of acid and non-acid reflux in patients with persistent symptoms nausea). One patient was lost to follow-up. Of the remaining 17 patients,
despite acid suppression has recently been examined. A multicenter study all but one were asymptomatic or markedly improved after a mean
that used 24-hour ambulatory MII–pH in 144 patients with symptoms follow-up of 14 months (range: 7–25). Both studies lacked a control arm
despite twice-daily PPIs found that, on therapy, 11% of patients had a and were based on subjective end-points with limited follow-up.
positive symptom index (SI) for acid reflux while 37% had a positive SI for Therefore, this information should be regarded as hypothesis-generating.
non-acid reflux.
5
In the remaining 52% of patients, there was no association Hopefully, well-designed, prospective, controlled trials will provide us
between reflux (either acid or non-acid) and symptoms. A positive SI was a with solid information that can guide us in choosing patients who may
lot more common in patients with typical symptoms (heartburn, benefit from treatment of symptomatic non-acid reflux. While data on
regurgitation, and chest pain). Fifty-five percent of patients with typical treatment of non-acid reflux are scant, theoretically this can be
76 US GASTROENTEROLOGY REVIEW 2007
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100