Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken 'on-demand'

BACKGROUND: Proton pump inhibitors (PPI) therapy 'on-demand' is often used as an alternative to continuous maintenance therapy in gastro-oesophageal reflux disease (GERD). AIM: We conducted a systematic review with the specific objectives to ascertain whether on-demand PPI therapy was effective in preventing symptomatic relapse and to assess the relative efficacy of on-demand vs. continuous PPI maintenance strategy. METHODS: Randomized-controlled clinical trials comparing on-demand PPI vs. placebo or on-demand vs. continuous PPI therapy in GERD patients were identified by searching the Medline database and the Cochrane Controlled Trials Register. RESULTS: Seventeen studies were found which met inclusion criteria. Out of the 17 studies: five investigated exclusively patients with non-erosive reflux disease (NERD), four patients with NERD and mild oesophagitis, two patients with erosive oesophagitis only, and two patients with uninvestigated GERD symptoms, respectively. Four further studies were not investigating the effectiveness of the therapies but primarily pharmacoeconomic or quality of life parameters. CONCLUSIONS: On the basis of the analysis of 17 studies, we can conclude that on-demand therapy with currently available PPI appears to be effective in the long-term management of patients with NERD or mild and uninvestigated forms of GERD, but not in patients with (severe) erosive oesophagitis.     

Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care--the ProGERD study

Aliment Pharmacol Ther 2012; 35: 154–164

Summary

Background The evolution of gastro‐oesophageal reflux disease (GERD) under current management options remains uncertain. Aim To examine whether, depending on the initial presentation, non‐erosive (NERD) and erosive reflux disease (ERD) without Barrett’s oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition. Methods Patients with the primary symptom of heartburn were included at baseline, and stratified into non‐erosive (NERD) and erosive reflux disease (ERD), LA grades A–D (Los Angeles classification). After a 2‐ to 8‐week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett’s oesophagus after 5 years. Results A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5‐year follow‐up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett’s oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett’s oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett’s oesophagus at 5 years. Conclusion Most GERD patients remain stable or improve over a 5‐year observation period under current routine clinical care.     

The influence of co-morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro-oesophageal reflux disease

Background  A subset of patients with gastro-oesophageal reflux disease (GERD) does not achieve complete symptom resolution with proton pump inhibitor (PPI) therapy. The factors which affect response to PPI therapy in GERD patients remain unclear.
Aims  To determine the prevalence and impact of irritable bowel syndrome (IBS) and psychological distress (PD) on GERD symptoms and disease-specific quality of life (QoL) before and after PPI therapy and to assess the same outcomes before and after PPI therapy in non-erosive reflux disease (NERD) and erosive oesophagitis (EO) GERD patients.
Methods  Patients undergoing oesophago-gastroduodenoscopy (OGD) for heartburn were recruited. Participants completed validated surveys: Digestive Health Symptom Index, Reflux Disease Questionnaire, Quality of Life in Reflux and Dyspepsia and Brief Symptom Inventory (BSI). IBS was defined as >3 Manning criteria and PD as BSI score >63. At OGD, patients were classified as NERD or EO. Patients were treated with rabeprazole 20 mg/day for 8 weeks before completing follow-up surveys.
Results  Of 132 GERD patients enrolled, 101 completed the study. The prevalence rates of IBS and PD were 36% and 41%, respectively. IBS independently predicted worse QoL before and after PPI therapy. PD independently predicted worse GERD symptoms and QoL before and after PPI therapy. There were no differences in symptoms or QoL between NERD and EO patients before or after PPI therapy.
Conclusions  IBS and PD impacted GERD symptoms and QoL before and after PPI therapy. Symptoms and QoL before and after PPI therapy were similar in NERD and EO patients.     

Randomised clinical trial: a multicentre, double-blind, placebo-controlled study on the efficacy and safety of rabeprazole 5 mg or 10 mg once daily in patients with non-erosive reflux disease

Aliment Pharmacol Ther 2011; 33: 213–224

Summary

Background The efficacy of rabeprazole 5 mg/day for patients with non‐erosive reflux disease (NERD) has not been reported in the literature. Aim To evaluate the efficacy of rabeprazole 5 mg and 10 mg/day in Japanese NERD patients. The influence of baseline characteristics as well as genetic background on efficacy was also analysed. Methods Subjects were grade M (minimal changes) NERD patients. Two hundred and eighty‐eight of these subjects, who were nonresponders to open label antacid therapy, entered in a 4‐week, double‐blind treatment (placebo, rabeprazole 5 mg or 10 mg/day). Results Complete heartburn relief rates were 21% in placebo, 34% in rabeprazole 5 mg and 44% in rabeprazole 10 mg (5 mg vs. placebo P = 0.074, 10 mg vs. placebo P = 0.001). Rabeprazole 5 mg was significantly more effective than placebo in elderly patients and in patients with low heartburn frequency or without hiatal hernia. The efficacy of rabeprazole 10 mg was not influenced by age, BMI, hiatal hernia, Helicobacter pylori infection, frequency and severity of heartburn or CYP2C19 genotypes. Conclusions Rabeprazole 5 mg was effective in a subgroup of Japanese NERD patients. Rabeprazole 10 mg provided more potent heartburn relief than 5 mg and was less fragile to baseline characteristics.     

Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis

BACKGROUND: In numerous clinical trials, proton pump inhibitors have demonstrated potent acid suppression and healing of erosive oesophagitis, as well as successful symptom relief for the entire spectrum of gastro-oesophageal reflux disease. AIM: The 'Future of Acid Suppression Therapy' (FAST) trial evaluated, in actual clinical practice, the timing of symptom relief, changes in symptom severity, health-related quality of life and safety in endoscopically confirmed erosive gastro-oesophageal reflux disease treated with rabeprazole. METHODS: This open-label, multicentre study enrolled 2579 patients to receive rabeprazole treatment using 20 mg once daily for 8 weeks. Between two clinical visits (at enrollment and week 8), patients used an interactive voice response system to rate gastro-oesophageal reflux disease symptoms. Subgroup analyses of efficacy were conducted for gender, age, Hetzel-Dent grade, presence of Barrett's oesophagus and for patients reporting previously ineffective symptom relief with omeprazole or lansoprazole. RESULTS: On day 1, rabeprazole significantly decreased daytime and night-time heartburn severity, regurgitation and belching. Complete relief of daytime and night-time heartburn was achieved in 64.0% and 69.2% of symptomatic patients, respectively, on day 1, and in 81.1% and 85.7% of patients, respectively, on day 7. Patients with moderate or severe heartburn symptoms at baseline achieved an even greater degree of satisfactory symptom relief (none or mild) from day 1 onwards. The median time to satisfactory heartburn relief was 2 days. Subgroup analyses showed no consistent differences in efficacy compared to the overall population treated. Health-related quality of life in patients was significantly lower than that of the US general population and improved significantly after 8 weeks of rabeprazole therapy. Rabeprazole was well tolerated, with headache as the most common adverse event, reported by less than 2% of the study population. CONCLUSIONS: In this large, open-label trial, rabeprazole rapidly and effectively relieved gastro-oesophageal reflux disease symptoms in most patients with erosive oesophagitis. Substantial symptom relief was noted on day 1; improvement continued over the first week and at week 4. By week 8, the health-related quality of life had also improved vs. baseline.     

Non-erosive reflux disease (NERD)--acid reflux and symptom patterns

BACKGROUND: Recent reports suggest that patients with non-erosive reflux disease (NERD) treated with anti-reflux medications show lower symptom improvement rates than patients with erosive oesophagitis treated with the same medications. AIM: To determine the acid reflux and symptom patterns of patients with NERD in comparison with those with erosive oesophagitis and Barrett's oesophagus, and to identify different NERD subgroups. METHODS: One hundred and forty-nine consecutive patients seen for classic heartburn symptoms were evaluated for the study. Oesophageal mucosal injury was assessed by upper endoscopy and classified by Hetzel-Dent criteria. Patients with Hetzel-Dent grades 0-1 were considered to have NERD. The extent of oesophageal acid exposure was determined by ambulatory 24-h oesophageal pH monitoring. RESULTS: Seventy-one patients were found to have NERD, 36 erosive oesophagitis and 42 Barrett's oesophagus. Compared with patients with erosive oesophagitis (75%) and Barrett's oesophagus (93%), those with NERD (45%) were significantly less likely to have an abnormal pH test (P = 0.0001). Patients with Barrett's oesophagus had the highest mean number of acid reflux events (210 +/- 17.7), compared with those with erosive oesophagitis (139.7 +/- 15.2) and NERD (95.3 +/- 9.4) (P = 0.0001); however, the rate of perceived acid reflux events was similar and very low in all groups (NERD, 3.6%; erosive oesophagitis, 2.9%; Barrett's oesophagus, 2.17%). NERD-positive patients (abnormal pH test) had a similar extent of oesophageal acid exposure to those with erosive oesophagitis. NERD-positive patients were more likely to demonstrate a symptom index greater than 75% than NERD-negative patients (normal pH test) (61.9% vs. 10.5%; P = 0.0001). In the NERD-negative group, those with a negative symptom index reported having heartburn at pH < 4 only 12.7% of the time, compared with 70.7% of the time in those with a positive symptom index, despite a similar mean number of heartburn episodes. CONCLUSIONS: Patients with NERD commonly demonstrate a negative pH test. Acid reflux characteristics and symptom patterns suggest a heterogeneous group of patients.     

Current understanding of the mechanisms of gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GERD) covers a broad range of signs and symptoms arising from the orad movement of gastric contents into the oesophagus, oropharynx, larynx or airway. Most commonly, contact with and damage to the oesophageal epithelium by acidic refluxate causes micro or macroscopic defects leading to the symptom of heartburn. However, GERD can also give rise to extra-oesophageal manifestations such as pharyngitis, laryngitis, asthma and other disorders, identifiable as acid-mediated events by a favorable response to acid suppression. Only one-third of individuals with heartburn have endoscopic evidence of erosive oesophagitis; the remainder have endoscopy-negative or non-erosive reflux disease (NERD). Improved investigative technologies are increasing our understanding of the pathophysiology of NERD. For example, although a number of microscopic abnormalities have been identified, oesophageal damage in NERD has been shown to be characterized by the presence of 'dilated intercellular spaces' within oesophageal stratified squamous epithelium. Dilated intercellular spaces that reflect damage to the intercellular junctions enable levels of acidity that would be considered innocuous when present in the oesophageal lumen to initiate pathological responses within oesophageal nociceptors when present within the intercellular spaces. This effectively gives rise to the symptom of heartburn. Excessive acidity within the intercellular spaces in NERD also presages its evolution to erosive disease, the latter through inflammation-mediated disruption of the antireflux and luminal clearance mechanisms. Support for this scenario is evident by the ability of effective acid control with proton pump inhibitors both to control symptoms, and lead to resolution of dilated intercellular spaces in patients with both erosive and non-erosive disease. This article examines these concepts and how they shape our current understanding of GERD.     

Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

两种亚型胃食管反流病并发抑郁、焦虑情况及药物疗效观察

目的:观察胃食管反流病(gastroesophageal reflux disease,GERD)的两种亚型非糜烂性反流病(non-erosive reflux disease,NERD)和反流性食管炎(reflux esophagitis,RE)患者的抑郁、焦虑情况及药物治疗效果。方法:按入院时间对两种亚型患者各随机抽取34例,分为NERD组和RE组,均予奥美拉唑20mg,2/d,西沙比利10mg,3/d,口服,疗程为8周,治疗前、后采用综合医院焦虑、抑郁量表(hospital anxiety and depressive scale,HAD)予以评分,于治疗后2、4、6、8周观察胃灼热、反酸、胸骨后痛等症状的缓解情况。结果:治疗2、4、6、8周后症状改善总有效率RE组分别为52.94%、67.65%、82.35%、94.12%,NERD组分别为20.59%、32.35%、41.18%、50.00%,有极显著性差异(P<0.01)。两组治疗前HAD评分有极显著性差异(P<0.01),RE组治疗前后HAD评分有显著差异(P<0.01),NERD组治疗前后HAD评分无明显差异(P>0.05);结论:两种亚型GERD有不同的发病机制,NERD患者抑郁、焦虑症状比RE患者严重,可能是影响疗效的重要因素。     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

The impact of pre-endoscopy proton pump inhibitor use on the classification of non-erosive reflux disease and erosive oesophagitis

Aliment Pharmacol Ther 2010; 32: 1266–1274

Summary

Background Factors associated with non‐erosive reflux disease (NERD) and erosive oesophagitis (EO) are incompletely understood and the overlap between the two entities is debated. Aim To compare clinical, demographic, and endoscopic findings in a large cohort of NERD and EO patients. Methods After they completed a validated GERD questionnaire, patients who presented for index endoscopy were enrolled and categorized as NERD or EO. Analysis was performed using Chi‐square, Mann–Whitney U‐test and multivariate logistic regression. Results A total of 696 GERD patients [455 (65.4%) NERD; 241 (34.6%) EO]; mean age 57 years; 92% men and 82% Caucasian were prospectively enrolled. Using logistic regression, patients on PPI were more likely to be classified as NERD (OR: 3.2; P < 0.001). NERD patients were older (OR: 1.50; P = 0.05), less likely to have nocturnal symptoms (OR: 0.63; P = 0.04) and hiatal hernia (OR: 0.32; P < 0.001). Compared with PPI‐naïve NERD patients, those on PPI were more likely to have nocturnal symptoms (69% vs. 29%, P = 0.048) and less likely to have mild‐moderate symptoms (63% vs. 79%, P < 0.001) – similar to the EO group. Conclusions Pre‐endoscopy PPI usage contributes significantly to the classification of GERD patients into the NERD‐phenotype. NERD patients on PPI therapy demonstrate some features that are significantly different from PPI‐naïve patients, but similar to EO patients. This observation supports the notion that some PPI NERD patients are actually healed EO patients, and that an overlap does exist between the GERD phenotypes.     

A randomized, double-blind, comparative study of standard-dose rabeprazole and high-dose omeprazole in gastro-oesophageal reflux disease

BACKGROUND: Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro-oesophageal reflux disease. AIMS: To assess the relief from heartburn after 3 days of treatment with standard-dose rabeprazole or high-dose omeprazole (primary end-point). Secondary end-points included the decrease in score for other symptoms of gastro-oesophageal reflux disease, healing rates and quantification of antacid use. METHODS: Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double-blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment. RESULTS: Two hundred and seventy-four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76-90%; 83% for omeprazole; 95% confidence interval, 75-89%). There were no significant differences between the treatments in the relief from other gastro-oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night-time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc). CONCLUSIONS: Standard-dose rabeprazole was as effective as high-dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.     

雷贝拉唑对不同类型胃食管反流病疗效和食管黏膜环氧化酶2的影响

目的：观察雷贝拉唑对不同类型胃食管反流病(CERD)的疗效和对食管黏膜环氧化酶2(COX-2)的影响。方法：GERD病人89例,其中反流性食管炎(RE)组51例和内镜检查阴性的胃食管反流病(NERD)组38例,2组均予雷贝拉唑10 mg,po,qd,共8 wk。正常对照组30例。症状和胃镜表现采用分级和记分法记录；抑郁和焦虑采用Hamilton抑郁量表和焦虑量表评价；COX-2应用链霉菌抗生物蛋白-过氧化物酶(SP)免疫组化法检测。结果：治疗前RE组和NERD组的症状评分无显著差异(P＞0.05)。治疗后RE组与NERD组的烧心样胸痛和反酸的评分明显减低,并可明显改善黏膜的损害,使内镜表现积分明显减低。RE组治愈率和总有效率明显高于NERD组(P＜0.01,P＜0.05)；有效率与进步率NERD组明显高于RE组(P＜0.01,P＜0.05)。RE组复发率和伴随抑郁或焦虑均明显低于NERD。治疗后,RE组的COX-2的阳性率明显减低(P＜0.01)。结论：雷贝拉唑对RE治疗的总有效率明显高于NERD组,并可明显地下调RE的COX-2的表达。     

Predictors of heartburn resolution and erosive esophagitis in patients with GERD

ABSTRACT

Objectives: The primary objective was to assess gastroesophageal reflux disease (GERD) symptom resolution rates with esomeprazole by erosive esophagitis (EE) status, and the secondary objective was to evaluate potential predictors of the presence of EE and heartburn resolution.

Background: Patients with GERD who have EE have higher reported symptom resolution rates than those with nonerosive reflux disease (NERD) when treated with proton pump inhibitors (PPIs).

Study: This open-label multicenter study included adults with GERD symptoms. Patients were stratified by EE status after endoscopy and received once-daily esomeprazole 40?mg for 4 weeks. Questionnaires determined symptom response rates, and baseline predictors of EE or heartburn resolution were evaluated. Potential predictors, including years with GERD, history of EE, and time to relief with antacids, were examined.

Results: Heartburn resolution rates at 4 weeks were higher for patients with EE than NERD (69% [124/179] vs. 48% [85/177]; p?<?0.0001). Multivariate models had moderate predictive ability for EE (c-index, 0.76) and poor predictive ability (c-index, 0.57) for heartburn resolution. However, faster heartburn relief with antacid use, particularly within 15?min, was predictive of EE and heartburn resolution.

Conclusions: Patients with EE have higher heartburn resolution rates than patients with NERD after treatment, although recall bias may be possible. Fast relief with antacid use is predictive of EE and heartburn resolution with a PPI and suggests that a history of antacid relief may provide corroborative evidence to empiric PPI therapy in determining whether patients with heartburn have acid reflux disease.

Trial registration: ClinicalTrials.gov identifier: NCT00242736.     

雷贝拉唑联合氟哌噻吨美利曲辛治疗非糜烂性胃食管反流病伴焦虑抑郁的临床观察

目的:观察雷贝拉唑联合氟哌噻吨美利曲辛治疗非糜烂性胃食管反流病(NERD)伴焦虑抑郁的临床疗效和安全性。方法:将109例NERD伴焦虑抑郁患者随机分为对照组(52例)和观察组(57例)。对照组患者给予雷贝拉唑钠肠溶片20 mg,晨服,每日1次;观察组患者在对照组治疗的基础上给予氟哌噻吨美利曲辛片1片,晨服,每日1次。两组患者疗程均为6周。观察两组患者的临床疗效,治疗前后临床症状评分及不良反应发生情况。结果:治疗后观察组患者总有效率显著高于对照组,两组比较差异有统计学意义(P<0.05);治疗后两组患者各临床症状评分均显著低于同组治疗前,且观察组低于对照组,差异均有统计学意义(P<0.05)。两组患者治疗期间均未见明显不良反应发生。结论:雷贝拉唑联合氟哌噻吨美利曲辛治疗NERD伴焦虑抑郁较单用雷贝拉唑疗效更显著,且安全性相似。     

Gastro-oesophageal reflux disease in 'difficult-to-control' asthma: prevalence and response to treatment with acid suppressive therapy

BACKGROUND: The causal association between gastro-oesophageal reflux disease (GERD) and difficult-to-control asthma is unclear. AIM: To determine the prevalence of GERD and response to proton pump inhibitor therapy in patients with difficult-to-control asthma. METHODS: Consecutive patients with difficult-to-control asthma as defined by persistent and recurrent symptoms despite on optimal asthmatic medications were recruited for the study. GERD was diagnosed by symptoms, gastroscopy and 24-h oesophageal pH monitoring. All patients were prescribed a course of lansoprazole 30 mg daily for 8 weeks. Improvement to treatment was assessed by a change in pulmonary symptom score and also by patient's subjective assessment of improvement. RESULTS: Seventeen of 30 (56.7%) patients with difficult-to-control asthma were diagnosed with GERD. Pulmonary symptom score improved significantly only in patients with GERD (35.0 to 21.0; P = 0.002). Twelve of 16 (75%) patients with GERD reported an improvement in asthma symptoms; 1 of 11 (9.1%) without GERD reported mild symptom improvement. There was no significant change in peak expiratory flow rate and forced expiratory volume. CONCLUSIONS: More than half of patients with difficult-to-control asthma were diagnosed with GERD. In these patients the severity of asthma improved significantly with potent acid suppression therapy. This underlines the critical role of acid reflux in this subset of patients with difficult-to-control asthma.     

Dilated intercellular spaces and lymphocytes on biopsy relate to symptoms in erosive GERD but not NERD

Aliment Pharmacol Ther 2011; 33: 1202–1208

Summary

Background Mechanisms of symptom perception among patients with gastro‐oesophageal reflux disease (GERD) remain to be fully elucidated. Aim To correlate quantitative reflux symptom scores with microscopic oesophageal histopathology. Methods Prior to endoscopy, patients with reflux symptoms completed a validated reflux disease questionnaire (score 0–36). Erosive oesophagitis (EO) was graded using the LA classification. Oesophageal biopsies were graded 0–2 for basal cell hyperplasia, papillary elongation, dilated intercellular spaces (DIS), necrosis or erosion, eosinophils and neutrophils by a blinded gastrointestinal pathologist as previously described. Additionally, lymphocyte density was also evaluated. Pearson’s correlation coefficients were computed. Results Thirty‐two EO and 21 non‐erosive reflux disease (NERD) patients were prospectively enrolled. For EO vs. NERD, mean reflux symptom scores (10.7 vs. 8.8, P = 0.35) and histology scores were similar (4.29 vs. 4.25; P = 0.9). However, when symptom scores were compared with histology scores, a correlation was found in the EO group, but not in the NERD group (r = 0.34, P = 0.05 vs. r = 0.22, P = 0.36). On further analysis, DIS was associated with symptom scores in the EO group (P ≤ 0.001), but not in the NERD group (P = N.S.). Similarly, lymphocyte density was associated with symptom scores in the EO group (r = 0.56, P = 0.0009), but not in the NERD group (r = 0.002, P = 0.9). Conclusions Although mean symptom and histology scores were similar in the EO and NERD groups, a significant correlation of symptom scores with histology scores, DIS and lymphocytes was found in the former, but not in the latter. EO and NERD patients may have different symptom perception mechanisms and thus, dissimilar symptom resolution rates with acid suppression.     

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 34: 476–486

Summary

Background Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro‐oesophageal reflux disease (GERD). Aim To assess oesophageal motility and bolus transit in endoscopically defined GERD subgroups. Methods Patients (N = 755) with typical reflux symptoms underwent upper endoscopy, conventional or impedance oesophageal manometry and/or impedance‐pH testing. They were divided into: erosive oesophagitis (EO; N = 340), Barrett Oesophagus (BO; N = 106), non‐erosive reflux disease (NERD; endoscopy?, abnormal pH and/or SAP/SI+; N = 239) and functional heartburn (FH; endoscopy?, normal pH and SAP/SI?; N = 70). Manometric patterns and bolus transit were defined according to previously published criteria. Results Increasing GERD severity was associated with decreased lower oesophageal sphincter resting pressure (P < 0.05) and distal oesophageal amplitude (P < 0.01), higher prevalence of hiatal hernia (P < 0.01) and increased prevalence of ineffective oesophageal motility (P < 0.01). Patients with EO and BO had a significantly lower percentage of complete bolus transit compared with NERD and FH (P < 0.01). Overall, abnormal bolus transit (ABT) for liquid swallows was found in 12% of FH, 20% of NERD, 54% of EO and 56% of BO (P < 0.01). Combined impedance‐manometry showed abnormal oesophageal function in 4% of FH, 4% of NERD, 22% of EO and 21% of BO patients with normal oesophageal manometry. Conclusions Oesophageal motility abnormalities increase in parallel with the severity of GERD from NERD to EO and BO. Bolus transit abnormalities in severe reflux disease underscore the importance of impaired oesophageal function in the development of mucosal injury.

     

Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study

BACKGROUND AND AIMS: Gastro-oesophageal reflux disease (GERD) can be associated with a variety of extra-oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non-erosive reflux disease (NERD). METHODS: Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis. RESULTS: 6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD. CONCLUSIONS: Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra-oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.