Histamine receptor antagonists, proton pump inhibitors and their combination in the treatment of gastro-oesophageal reflux disease

The medical treatment of gastro-oesophageal reflux disease is accomplished with the appropriate use of anti-secretory therapy, principally H(2)-receptor antagonists and proton pump inhibitors. In fact, there is a direct correlation between the length of time, in terms of the number of hours per day that the intragastric pH is above 4, and the healing of the oesophagitis. Nowadays, H(2)-receptor antagonists are of limited use as primary treatment, being inferior to proton pump inhibitors in both healing and symptom relief. Although the majority of patients can be effectively managed with carefully titrated doses of proton pump inhibitors, a small number will continue to show difficulty in the management of their disease, principally because of inadequate nocturnal acid control. These patients may benefit from a combination of proton pump inhibitors twice daily with an H(2)-receptor antagonist at bedtime. This article reviews the use of H(2)-antagonists, proton pump inhibitors and their combination in the management of the patient with gastro-oesophageal reflux disease.     

Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.     

Control of gastric acid secretion in health and disease

Recent milestones in the understanding of gastric acid secretion and treatment of acid-peptic disorders include the (1) discovery of histamine H(2)-receptors and development of histamine H(2)-receptor antagonists, (2) identification of H(+)K(+)-ATPase as the parietal cell proton pump and development of proton pump inhibitors, and (3) identification of Helicobacter pylori as the major cause of duodenal ulcer and development of effective eradication regimens. This review emphasizes the importance and relevance of gastric acid secretion and its regulation in health and disease. We review the physiology and pathophysiology of acid secretion as well as evidence regarding its inhibition in the management of acid-related clinical conditions.     

质子泵抑制剂与酸反跳

酸反跳(rebound acid hypersecretion)指停用抑酸药物后胃酸分泌增加超过治疗前水平.质子泵抑制剂(proton pump inhibitors,PPIs)作为一代抑酸药物,比H2受体阻滞剂(histamine-2receptor antagonists,H2RA)具有更强的抑酸效果,是治疗酸相关疾病的主要药物.目前研究已经证实,PPIs可致酸反跳发生.PPIs的酸反跳可以再次诱发酸相关症状出现,不仅增加医疗预算,也给PPIs治疗的终止带来问题.高胃泌素血症是导致酸反跳现象的重要机制.正确使用PPIs,严格掌握适应证,探讨在有效治疗酸相关疾病的同时减少酸反跳发生的措施.     

A Double-Blind Randomized Study Comparing Different Dose Regimens of H2-Receptor Antagonists on 24-Hour Gastric Secretion in Normal Subjects and Duodenal Ulcer Patients

Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730-2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2-receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing.     

La deuxième génération des antisécrétoires gastriques: l''oméprazole

Omeprazole is the first representative of a new class of gastric acid secretion inhibitors. It acts by specific and prolonged inhibition of H+K+ ATPase, or proton pump, which is the terminal and compulsory stage of acid secretion by the parietal cells. The drug therefore inhibits both basal and stimulated secretion. It appears from therapeutic trials that omeprazole administered in doses of 20 mg a.m. once a day is superior to the H2-receptor antagonists in the healing of active duodenal ulcers and ulcerated reflux oesophagitis. It is as active or slightly more active than histamine inhibitors in gastric ulcers. Finally, it is the treatment of choice to prevent ulcerations in Zollinger-Ellison syndrome. These are the 4 indications for omeprazole at the moment. The use of that drug for periods of a few weeks has not given rise to any significant side-effect.     

Role of acid suppressants in prophylaxis of NSAID damage

Gastric acid contributes to the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced ulceration via several mechanisms, including conversion of superficial to deeper injury, impairment of haemostasis, and interference with ulcer healing. The suppression of acid secretion has been shown to reduce the severity of NSAID-induced mucosal damage in experimental models and clinical studies. Current evidence indicates that proton pump inhibitors (PPIs) are the preferred treatment for the healing of gastric ulcers when NSAIDs cannot be discontinued. PPIs are superior to standard-dose H(2)-receptor antagonists and equivalent to low-dose misoprostol in preventing NSAID-induced gastric ulcers. Whether there is any significant advantage of PPIs over higher doses of H(2)-receptor antagonists or misoprostol is unknown. The efficacy of PPIs is enhanced in the presence of H. Pylori infection. Omeprazole has been shown to be effective for the secondary prevention of ulcer bleeding in H. pylori -infected NSAID users. The efficacy of PPIs for the prevention of ulcer complications in H. pylori-negative NSAID users remains uncertain.     

Acid suppression therapy: where do we go from here?

The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK2-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H3-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK2-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK2 antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H2-receptor antagonists (especially soluble or over-the-counter formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppression therapy. Its long half-life (the longest among the available compounds) and longer duration of antisecretory action, with no difference between day and night, will allow the drug to go beyond the intrinsic limitations of currently available PPIs. Thanks to its favorable pharmacokinetics, the sodium salt of S-tenatoprazole is being developed and the preliminary results indicate that this drug has the potential to address unmet clinical needs. Although some decades have elapsed since the introduction of effective and safe antisecretory drugs in clinical practice and their use has stood the test of time, the ongoing research will further provide the clinician with more effective means of controlling acid secretion.     

Histamine H2-receptor antagonists

The first histamine H2-receptor antagonists were developed in the early 1970s, and they have a dominant role in today's management of peptic ulceration. The original regimens using either cimetidine or ranitidine attempted to control acidity across the 24 hours, but more 'modern' regimens use a large single dose of the H2-blocker in the evening, which produces a pulse of decreased intragastric acidity during the night with a normal acidity in the daytime. High-dose regimens using a new generation of extremely potent histamine H2-receptor antagonists may improve ulcer healing rates at 4 weeks, and may be particularly useful for the management of either severe oesophagitis or intractable duodenal ulceration.     

Current role of acid suppressants in Helicobacter pylori eradication therapy

Helicobacter pylori induces chronic active gastritis that may progress to atrophy. Serious clinical consequences are peptic ulcer disease and gastric malignancies. Today, treatment of the infection is an appropriate option and is strongly recommended in various clinical situations. Although many antibiotics are effective against H. pylori in vitro, few substances are suitable for use in vivo. This is because H. pylori lives in a unique environment in which several factors may affect the pharmacokinetic and pharmacodynamic properties of the anti-microbial agents. One of the most important factors is gastric acidity. This article reviews the effects of acid suppression on H. pylori and the associated gastritis, the potential mechanisms by which anti-secretory drugs such as proton pump inhibitors might enhance the activity of anti-microbials in vivo, and the results of clinical trials supporting the current view that proton pump inhibitors are a mainstay in the treatment of this infection.     

Current trends in the treatment of upper gastrointestinal disease

The past 25 years have seen an amazing improvement in the treatment and understanding of acid-related disorders. In particular, the introduction of selective histamine receptor antagonists and proton pump inhibitors has made the medical control of acid secretion an effective means of therapy. The demonstration that infection with Helicobacter pylori is responsible for most cases of peptic ulcer disease resulted in another major improvement in therapy in these areas as a result of the eradication of the organism. Research continues in an attempt to find improved means of acid control and better methods for the eradication of H. pylori based on unique proteins expressed by the organism to resist gastric acidity.     

Overview of medical therapy of peptic ulcer disease

Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns.     

Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs

FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended. The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs. We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens. For the H2 receptor antagonists alone, the most significant correlation with healing rates was with suppression of intragastric acidity at night (r = 0.926; p = 0.0001). When other classes of drug: high dose antacid, omeprazole and a synthetic prostaglandin (enprostil) were included in the analysis, the closest correlation was with suppression of total 24 hour intragastric acidity (r = 0.911; p less than F0.0001). Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night. Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates. No further benefit was obtained with daytime suppression for H2 receptor antagonists; suppression of acidity at night accounted for 86.1% of the observed variation in healing rates among different regimens of H2 receptor antagonists. When all classes of drugs were analysed, inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone. Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials. The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity. For the H2 receptor antagonists, suppression of nocturnal acidity is the most relevant in this context. Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks. Increasing degrees of suppression merely accelerate healing.     

Lansoprazole in the treatment of gastrooesophageal reflux disease in childhood

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.     

Principes thérapeutiques du reflux gastroœsophagien

Gastroesophageal reflux is a common disease. Its chronic course, even if mild, is sometimes complicated by erosive oesophagitis. Drug therapy acts against gastric acidity and motility disorders. Treatment of gastroesophageal reflux disease has three aims: improvement of symptoms and quality of life, healing erosive lesions and prevention of symptomatic and endoscopie relapses. Non-drug measures are always useful, even if their efficacy is not well established. Initial therapy of a symptomatic reflux or mild oesophagitis is most of the time effective (antacids, prokinetics, H₂ receptor antagonists). Proton-pump inhibitors are also effective in healing and preventing severe oesophagitis. Questions about long-term treatment adverse events with powerful acid inhibitors, such as hypergastrinemia and the risk of gastric carcinoid tumours seem to be resolved. Studies are requested to define the optimal long-term maintenance treatment with cisapride, H₂ receptor antagonists or proton-pump inhibitors at low doses in prevention of symptomatic and mild oesophagitis relapses.     

Short and long-term PPI treatment for GERD. Do we need more-potent anti-secretory drugs?

Because the reflux of the acidic gastric content into the esophagus plays a major role in the pathogenesis of symptoms of GERD and lesions of erosive esophagitis, acid suppression with a proton pump inhibitor (PPI) is currently the mainstay of anti-reflux therapy. There is a strong correlation between the degree of acid suppression provided by a given drug and its efficacy. The superiority of PPIs over other drugs (antacids, prokinetics and H(2)-receptor antagonists) has now been established beyond doubt, both for short- and long-term treatment. However, there are still some unmet therapeutic needs in GERD; hence, patients with non-erosive reflux disease (NERD) are less responsive to PPIs than those with erosive esophagitis. Moreover, the efficacy of PPIs in patients with atypical symptoms is frequently limited to the relief of associated heartburn or regurgitation. With respect to safety, although most studies on short- and long-term PPI use have provided reassuring data, recent reports have drawn attention to potential side effects or drug-drug interference. Better healing rates in the most severe forms of esophagitis, or a faster onset of symptom relief, may require optimization of acid suppressive therapy with regard to the daily course of acid secretion, especially during the night. Different pharmacological approaches can be considered, with the ultimate goals of achieving faster, stronger and more-sustained acid inhibition. How a better pharmacological profile may translate into clinical benefit should now be tested in appropriate, controlled studies.     

Importance of pH control in the management of GERD

The degree of esophageal mucosal injury that occurs in patients with gastroesophageal reflux disease depends on duration of exposure and pH of the refluxate. Evidence suggests that an intraesophageal pH of less than 4.0 directly correlates with the degree of mucosal injury. The advent of acid secretory inhibitors such as the histamine2-receptor antagonists (H2RAs) and, more recently, the proton pump inhibitors (PPIs) has revolutionized the treatment of patients with reflux disease. However, the evidence linking the degree of mucosal damage to pH of the refluxate has prompted investigators to reevaluate the effectiveness of these agents. The PPIs are significantly more effective than the H2RAs in achieving and sustaining an intragastric pH above 4.0. The results of clinical trials performed with the PPIs indicate a faster rate of healing of erosive esophagitis and of symptom relief than treatment with H2RAs.     

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis： A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.     

Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.     

Proton Pump Inhibitors Improve Acid-Related Dyspepsia in Gastroesophageal Reflux Disease Patients

It has been reported that proton pump inhibitors are more effective than H2 receptor antagonists in patients with functional dyspepsia. Dyspeptic symptoms that respond to proton pump inhibitors are classified as acid-related dyspepsia. A new questionnaire for assessing gastroesophageal reflux disease (GERD), the Frequency Scale for Symptoms of GERD, covers the 12 most common symptoms of GERD patients. A quantitative assessment of the changes of reflux symptoms and acid-related dyspepsia was made in GERD patients receiving proton pump inhibitor therapy. Sixty-eight GERD patients receiving proton pump inhibitor therapy completed the questionnaire before and after treatment for 8 weeks. There is a significant positive correlation between reflux symptoms and acid-related dyspepsia before and after therapy (r = 0.569 and r = 0.569; both P's < 0.001) and acid-related dyspepsia in patients with both nonerosive and erosive GERD. We conclude that GERD patients suffer not only from reflux symptoms, but also from acid-related dyspepsia, and proton pump inhibitors improve both types of symptoms.