role of acid, weakly acidic and weakly alkaline reflux in gastroesophageal reflux disease

49 Pages·2017·2.27 MB·English

Systematic review: role of acid, weakly acidic and
weakly alkaline reflux in gastroesophageal reflux disease
Guy E Boeckxstaens, Smout J Smout
To cite this version:
Guy E Boeckxstaens, Smout J Smout. Systematic review: role of acid, weakly acidic and weakly
alkaline reflux in gastroesophageal reflux disease. Alimentary Pharmacology and Therapeutics, 2010,
32 (3), pp.334. ￿10.1111/j.1365-2036.2010.04358.x￿. ￿hal-00552573￿
HAL Id: hal-00552573
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Alimentary Pharmacology & Therapeutic

Systematic review: role of acid, weakly acidic and weakly
alkaline reflux in gastroesophageal reflux disease

Journal: Alimentary Pharmacology & Therapeutics
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Manuscript ID: APT-0257-2010.R3
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Manuscript Type: Systematic Review
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Date Submitted by the
12-May-2010
Author:
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Complete List of Authors: Boeckxstaens, Guy; Academic Medical Centre, Department of
Gastroenterology and Hepatology; Catholic University of Leuven,
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Department of Gastroenterology, University Hospital
Smout, Smout; Academic Medical Centre, Department of
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Gastroenterology and Hepatology
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GERD or GORD < Disease-based, Oesophagus < Organ-based,
Keywords:
Acidity (oesophageal) < Topics, X keyword = no topic
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Page 1 of 47 Alimentary Pharmacology & Therapeutic
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Systematic review: role of acid, weakly acidic and weakly
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alkaline reflux in gastroesophageal reflux disease
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12 Guy Boeckxstaens*† & André Smout*
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14 *Department of Gastroenterology and Hepatology, Academic Medical Centre,
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16 Amsterdam, The Netherlands;
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†Department of Gastroenterology, University Hospital Leuven, Catholic University of
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21 Leuven, BelgiumF.
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Correspondence to:
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28 Dr Guy E. Boeckxstaens, Department of Gastroenterology, University Hospital
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Leuven, Catholic University of Leuven, Herestraat 49, Leuven 3000, Belgium.
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Phone: [phone]
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35 E-mail: [email protected]
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40 Short title: Weakly acidic and weakly alkaline refluxi in GERD
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Smout and Boeckxstaens Aliment Pharmacol Ther 1
Alimentary Pharmacology & Therapeutic Page 2 of 47
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SUMMARY
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6 Background
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The importance of weakly acidic and weakly alkaline reflux in gastroesophageal
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11 reflux disease (GERD) is gaining recognition.
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13 Aim
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To quantify the proportions of reflux episodes that are acidic (pH < 4), weakly acidic
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18 (pH 4–7) and weakly alkaline (pH > 7) in adult patients with GERD, and to evaluate
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their correlation with symptoms.
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Methods o
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25 Studies were identified by systematic PubMed and Embase searches. Data are
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27 presented as sample-size wePighted means and 95% confidence intervals.
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30 Results
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32 In patients with GERD taking a protonr pump inhibitor (PPI), 80% (76–84%) of reflux
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episodes were weakly acidic or weakly alkaline and 83% (78–88%) of reflux
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37 symptom episodes were associated with weakly acidic or weakly alkaline reflux
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39 episodes. In patients with GERD not taking a PPIv, 63% (59–67%) of reflux episodes
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were acidic and 72% (57–87%) of reflux symptom episodes were associated with acid
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44 reflux episodes. Six studies presented data separately for weakly alkaline reflux,
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which accounted for < 5% of all reflux episodes, both on and off PPI therapy.
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Conclusions
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51 Weakly acidic reflux underlies the majority of reflux episodes in patients with GERD
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on PPI therapy and is the main cause of reflux symptoms occurring despite PPI
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56 therapy.
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INTRODUCTION
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6 Gastroesophageal reflux disease (GERD) is a chronic disease that affects 10–20% of
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adults in the USA and Europe (1), and its cardinal symptoms are heartburn and
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11 regurgitation (2). GERD develops when the reflux of stomach contents causes
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13 troublesome symptoms or complications (2). Episodes of gastroesophageal reflux
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occur mainly during transient lower esophageal sphincter relaxations (TLESRs)
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18 (3).The frequency and duration of TLESRs is similar between individuals with and
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without GERD. However, as a group, individuals with GERD have an increased risk
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of reflux occurring douring such episodes (3, 4).
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25 The study of gastro esophageal reflux has been revolutionized by the
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27 development of combined 2P4-h esophageal pH and multichannel intraluminal
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impedance (MII) monitoring (5, 6). MII detects gastroesophageal reflux episodes
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32 based on changes in resistance to alterrnating electrical current between a series of
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paired electrodes. One of the first studies to combine esophageal pH-monitoring with
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37 MII in humans was conducted about a decade ago in a small group of healthy
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39 volunteers (7). The investigators noted that only avbout half of all reflux episodes
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detected by MII were also detected by pH-metry, concluding that the remainder were
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44 due to relatively pH-neutral reflux.
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Combined esophageal MII and pH-monitoring allows for the timed correlation
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of esophageal pH changes with reflux events, and achieves high sensitivity for the
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51 detection of acid (pH < 4), weakly acidic (pH 4–7) and weakly alkaline (pH > 7)
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reflux episodes. Use of this technology is bringing into focus the potential role of
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56 weakly acidic and weakly alkaline reflux in GERD and in the production of
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58 symptoms that are associated with reflux episodes (8). However, available data on the
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Alimentary Pharmacology & Therapeutic Page 4 of 47
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proportion of reflux episodes that are acidic, weakly acidic or weakly alkaline in
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patients with GERD have not been evaluated using a systematic approach before.
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8 This systematic review of the literature assesses the proportions of reflux
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episodes that are acidic, weakly acidic or weakly alkaline in patients with GERD, and
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13 evaluates how these episodes are associated with use of PPIs and symptoms.
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METHODS
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Systematic literature searches
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Investigational studioes of adult patients with GERD on or off PPI therapy were
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25 identified by systematic se arches of the literature to September 2009 in PubMed and
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27 EMBASE. A flow chart of tPhe systematic searches and search strings used is shown in
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Figure 1. To be eligible for inclusion, studies needed to provide data on the
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32 proportions of acid (pH < 4), weakly arcidic (pH 4–7) and weakly alkaline (pH > 7)
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reflux episodes, based on esophageal pH-metry and MII monitoring. Studies reported
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37 in a language other than English were excluded, as were studies that did not report on
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39 the proportion of acid versus weakly acidic and/orv weakly alkaline reflux episodes, or
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did not provide data sufficient for these proportions to be calculated (e.g. studies
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44 providing only data on the median [not mean] number of episodes per patient, or
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studies reporting only on the proportion of time that esophageal pH was acidic and
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weakly acidic and/or weakly alkaline). Studies on the effects of surgery on reflux
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51 were not included in this review.
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56 Statistical analysis
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58 Sample-size-weighted means and sample-size-weighted 95% confidence intervals
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(CI) were calculated for all pooled prevalence data (9).
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RESULTS
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The literature searches identified 21 studies involving 664 patients with GERD that
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11 fulfilled the inclusion criteria for this review (Figure 1). Twelve of the studies
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13 reported the data of 374 patients taking a PPI and 16 studies reported the data of 382
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patients not taking a PPI. The majority of the identified studies recruited patients who
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18 had a history of reflux symptoms despite taking a PPI. Information on study design is
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summarized in Table 1. More details on the patient populations and reflux−symptom
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correlation data are porovided in the online supplementary Tables S1, S2 and S3.
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25 Seven of the studie s reported data for patients on and off PPI therapy (271
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27 patients in total). InformatioPn on the study population, and mean number of reflux
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episodes and symptom episodes, is shown in Table 2. Overall, the number of reflux
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32 episodes did not differ significantly bertween patients on and off PPI therapy, although
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one study that reported only on reflux during sleep observed a decrease in the number
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37 of reflux episodes with PPI treatment (10). Reflux symptom frequency was 20–70%
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39 higher in patients off PPI therapy than in those onv PPI therapy in studies of patients
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who had reflux symptoms despite PPI treatment. The effect was even more
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44 pronounced in a study that included only patients with a history of favorable response
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to PPI therapy, in which the frequency of reflux symptom episodes in those on PPI
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49 treatment was 14 times that in patients off PPI therapy (11).
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Patients with GERD taking a PPI
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56 The majority of reflux episodes in patients with GERD taking a PPI were of pH > 4,
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proportion of reflux episodes were acidic (mean: 20%; 95% CI: 16–24%) (Figure 2).
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Three studies presented data separately for weakly alkaline reflux, which accounted
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for less than 5% of all reflux episodes (Table S1). The proportion of reflux episodes
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the 24-h recording period compared with the postprandial period following an
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13 evening meal in a study that assessed the two time periods separately (overall: 18%
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15 acidic vs 82% weakly acidic/alkaline; postprandial: 20% acidic vs 80% weakly
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acidic/alkaline) (12).
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20 Most reflux-related symptom episodes were associated with reflux episodes
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minority of reflux-related symptoms were associated with acid reflux (mean: 17%;
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27 95% CI: 12–22%) (Figure 3P; Table S3) (13-17). The mean proportion of acid reflux
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episodes that were symptomatic was 53% (95% CI: 50–56%), which was similar to
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the mean proportion of weakly acidic or weakly alkaline reflux episodes that were
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34 symptomatic (47%; 95% CI: 44–50%) (13, 15, 17). In a study that assessed heartburn
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and regurgitation separately, and in which participants could report more than one
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39 symptom during each symptom event, symptomatvic acid reflux episodes were just as
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symptomatic weakly acidic or weakly alkaline reflux episodes were more commonly
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46 associated with regurgitation (98%, vs 10% with heartburn) (13).
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Patients with GERD not taking a PPI
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53 In patients with GERD not taking a PPI, the majority of reflux episodes were acidic
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(mean: 63%; 95% CI: 59–67%); the mean proportion of episodes that were weakly
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acidic or weakly alkaline was 37% (95% CI: 33–41%) (Figure 2). Four studies
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presented data separately for weakly alkaline reflux, which accounted for less than
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5% of all reflux episodes (Table S2).
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8 Most reflux-related symptom episodes were associated with acid reflux
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episodes (mean: 72%; 95% CI: 57–87%); only a minority of reflux-related symptom
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13 episodes were associated with reflux episodes that were weakly acidic or weakly
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15 alkaline (mean: 28%; 95% CI: 13–43%) (Figure 4; Table S3) (11, 13, 14, 18). In a
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study that assessed reflux episodes in the postprandial period, the proportion of reflux
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respectively, overall during the 24-h recording period (12).
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27 The mean proportionP of reflux episodes that were symptomatic was slightly
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higher for acid reflux than for weakly acidic or weakly alkaline reflux (acidic: 60%;
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95% CI: 52–68%; weakly acidic/alkaline: 40%; 95% CI: 32–48%) (13, 18). In a study
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report more than one symptom during each symptom event, both symptomatic acid
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39 reflux episodes and symptomatic weakly acidic orv weakly alkaline reflux episodes
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heartburn: 84%, regurgitation: 56%; weakly acidic/alkaline – heartburn: 71%,
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46 regurgitation, 52%) (13).
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The proportion of reflux episodes that were acidic did not differ between
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patients without reflux esophagitis (mean: 65%; 95% CI: 56–74%) and those with
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53 reflux esophagitis (mean: 63%; 95% CI: 57–69%) in the five studies that reported
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data separately for these two patient groups (Figure 5) (11, 19-22). Similarly, the
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proportion of reflux episodes that were weakly acidic or weakly alkaline did not differ
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with reflux esophagitis (mean: 37%; 95% CI: 31–43%). However, in one study that
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reported separately on patients without or with Los Angeles grade A, B and C/D
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8 reflux esophagitis, and with Barrett’s esophagus, the proportion of reflux episodes
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that were acidic increased with increasing esophageal injury (Table S2); participants
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13 who were on PPI therapy had to discontinue PPI use at least 5 days before the study
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20 DISCUSSION
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Our systematic revieow of data from 664 patients with GERD shows that the
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25 proportion of reflux episod es that are acidic as opposed to weakly acidic or weakly
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not. In patients taking a PPI, 20% (95% CI: 16–24%) of reflux episodes were acidic,
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32 whereas in patients not on PPI therapyr the proportion was 63% (95% CI: 59–67%).
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There is a paucity of data on the proportion of reflux episodes that are weakly acidic
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37 and weakly alkaline in individuals with GERD whose symptoms respond to PPI
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39 treatment, with only one of the studies in this revivew including such a patient
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population (23). The overall number of reflux episodes does not differ between
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44 patients on and off PPI therapy, although PPIs may reduce the number of nocturnal
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reflux episodes (10). However, patients on PPI therapy have a decreased symptom
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frequency compared with those not taking a PPI and, not surprisingly, this is
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51 particularly noticeable in patients who have a history of reduction in reflux symptoms
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in response to PPI therapy (11). The decrease in acid reflux with PPIs results from
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56 their ability to elevate gastric and esophageal pH levels, making them effective in the
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58 treatment of acid-related reflux symptoms and complications (24, 25). Most patients
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with GERD, with or without reflux esophagitis, experience resolution of their reflux
Smout and Boeckxstaens Aliment Pharmacol Ther 8