Gastric emptying and different types of reflux in adult patients with cystic fibrosis

Aliment Pharmacol Ther 2011; 34: 799–807

Summary

Background Increased gastro‐oesophageal reflux (GER) is common in patients with cystic fibrosis (CF). Previous studies showed delayed gastric emptying (GE) and a high prevalence of bile acids in saliva suggesting duodenogastro‐oesophageal reflux (DGER). Aim To assess different types of reflux (acid, weakly acidic and bile) and their relationship with rate of GE in adult CF patients. Methods Gastric emptying was assessed in 33 CF patients using breath tests, reflux was monitored in 42 patients using impedance‐pH‐metry and 14 CF patients underwent combined impedance‐pH‐Bilitec monitoring. Results Delayed GE was found in 33%, increased GER (predominantly acid) in 67% and pathological DGER in 35% of the CF patients. There was a significant correlation between oesophageal bile and acid exposure (P < 0.0001, r = 0.85). Patients with increased DGER had a higher proximal extent of reflux compared to those without DGER [17 (9–35) vs. 5 (1–12), P = 0.04]. There was no correlation between GE and reflux parameters, however, in a subgroup of 10 patients studied by impedance‐pH‐Bilitec and GE, there was a strong correlation between GE rate and bile exposure (P = 0.005, r = 0.83). Conclusions Delayed gastric emptying is present in 1/3 of patients with cystic fibrosis. There is a subgroup of these patients with both delayed gastric emptying and increased acidic duodenogastro‐oesophageal reflux with high proximal extent and risk of aspiration. Controlled studies should be performed to evaluate the effect of prokinetics or antireflux surgery on the clinical cystic fibrosis evolution in these patients.     

Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD

Aliment Pharmacol Ther 2011; 34: 67–75

Summary

Background EsophyX is a novel transoral incisionless fundoplication device developed to mimic surgical fundoplication. EsophyX fundoplication improves acid reflux parameters in proton pump inhibitor (PPI)‐responsive GERD patients but its efficacy in refractory GERD has been scarcely studied. Aim To assess reflux parameters before and after EsophyX or laparoscopic fundoplication and their relationship with symptoms in refractory GERD. Methods In an open‐label study, we enrolled prospectively patients with heartburn/regurgitation persisting despite high‐dose PPI therapy. Impedance‐pH monitoring was performed on PPI therapy before intervention and off PPI therapy 3 months after intervention. Results Ten patients chose to undergo EsophyX (EndoGastric Solutions, Redmond, WA, USA) fundoplication while ten chose laparoscopic fundoplication, and the baseline characteristics were comparable. Distal and proximal refluxes were significantly reduced post‐operatively in the surgical but not in the endoscopic group and the median values were significantly lower in the former than in the latter. The oesophageal acid exposure time was normal in 50% of cases after EsophyX and in 100% of cases after surgery (P = 0.033); the number of distal refluxes was normal in 20% and 90% of cases (P = 0.005) and the number of proximal refluxes was normal in 40% and 100% of cases (P = 0.011), respectively. A positive persisting symptom‐reflux association was found post‐operatively in 6/10 patients in the EsophyX group and in 0/10 patients in the surgical group (P = 0.011). Conclusions In patients with refractory GERD, EsophyX fundoplication is significantly less effective than laparoscopic fundoplication in improving reflux parameters and accordingly, in inducing symptom remission.     

Systematic review: role of acid,weakly acidic and weakly alkaline reflux in gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 2010; 32: 334–343

Summary

Background The importance of weakly acidic and weakly alkaline reflux in gastro‐oesophageal reflux disease (GERD) is gaining recognition. Aim To quantify the proportions of reflux episodes that are acidic (pH <4), weakly acidic (pH 4–7) and weakly alkaline (pH >7) in adult patients with GERD, and to evaluate their correlation with symptoms. Methods Studies were identified by systematic PubMed and Embase searches. Data are presented as sample‐size weighted means and 95% confidence intervals. Results In patients with GERD taking a proton pump inhibitor (PPI), 80% (76–84%) of reflux episodes were weakly acidic or weakly alkaline and 83% (78–88%) of reflux symptom episodes were associated with weakly acidic or weakly alkaline reflux episodes. In patients with GERD not taking a PPI, 63% (59–67%) of reflux episodes were acidic and 72% (57–87%) of reflux symptom episodes were associated with acid reflux episodes. Six studies presented data separately for weakly alkaline reflux, which accounted for <5% of all reflux episodes, both on and off PPI therapy. Conclusions Weakly acidic reflux underlies the majority of reflux episodes in patients with GERD on PPI therapy, and is the main cause of reflux symptoms occurring despite PPI therapy.     

Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis

Aliment Pharmacol Ther 2011; 33: 601–606

Summary

Background In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied. Aim To assess reflux parameters by impedance–pH monitoring in PPI‐resistant reflux oesophagitis. Methods Impedance–pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high‐dose PPI therapy of at least 8‐week duration. Results Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively. Conclusions Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra‐gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI‐resistant reflux oesophagitis. Therapeutic interventions in patients with PPI‐resistant reflux oesophagitis should be tailored on the basis of impedance – pH‐monitoring results.     

Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia

Aliment Pharmacol Ther 2011; 34: 146–165

Summary

Background Factors other than acid may play a role in gastro‐oesophageal reflux disease (GERD) and its complications. Aim To assessed the role of bile acids in the pathogenesis of GERD, Barrett’s oesophagus and Barrett’s‐related neoplasia. Methods We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett’s oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia. Results Eighty‐three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett’s epithelial cells to produce inflammatory mediators (e.g., IL‐8 and COX‐2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal‐type cells and caused Barrett’s cells to increase expression of intestinal‐type genes. Conclusions In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett’s metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.     

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Summary

Background

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.

Aim

To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro‐oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms.

Methods

Thirty‐two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24‐h pH‐metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full‐dosage PPI therapy (esomeprazole 40 mg/day) was prescribed.

Results

In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01).

Conclusions

This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

     

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study

Aliment Pharmacol Ther 2011; 33: 225–234

Summary

Background Cough may be a manifestation of gastro‐oesophageal reflux disease (GERD). The utility of acid suppression in GERD‐related cough is uncertain. Aim To assess the impact of high‐dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24‐h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough‐Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. Results Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. Conclusion In subjects with chronic cough and rare or no heartburn, high‐dose proton pump inhibitor does not improve cough‐related quality of life or symptoms.     

The effects of dose and timing of esomeprazole administration on 24-h, daytime and night-time acid inhibition in healthy volunteers

Aliment Pharmacol Ther 2010; 32: 1249–1256

Summary

Background Symptoms of gastro‐oesophageal reflux disease (GERD) may persist despite daily treatment with a proton pump inhibitor (PPI). Aim To compare the pharmacodynamic effect of various esomeprazole dosage and timing regimens in healthy volunteers. Methods The effect of different esomeprazole dosage regimens [20 mg once daily (od) before breakfast or dinner; 20 mg twice daily (b.d.); 40 mg od before breakfast, dinner or at bedtime; and 40 mg b.d.] on 24‐h, daytime and night‐time acid inhibition was evaluated in a randomized, seven‐way crossover study in healthy volunteers. Each regimen was taken for 5 days. Results Over the 24‐h period (day 5), esomeprazole 20 mg b.d. was associated with superior acid inhibition vs. all 20 mg and 40 mg od regimens (P < 0.05), but was less effective than esomeprazole 40 mg b.d. (P < 0.05). Dosing with esomeprazole 20 mg or 40 mg od before breakfast gave improved 24‐h and daytime acid inhibition vs. the corresponding administration before dinner or at bedtime (all P < 0.05). Night‐time acid inhibition was improved when esomeprazole 40 mg od was administered before dinner or at bedtime vs. before‐breakfast dosing (P < 0.05). Conclusion Varying the dose and timing of esomeprazole administration may provide acid inhibition appropriate for the symptom pattern of individual patients with GERD.     

Systematic review: the association between symptomatic response to proton pump inhibitors and health‐related quality of life in patients with gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 2011; 34: 618–627

Summary

Background Some patients with gastro‐oesophageal reflux disease (GERD) experience persistent reflux symptoms on proton pump inhibitor (PPI) therapy. The relationship between persistent reflux symptoms and health‐related quality of life (HRQoL) is unclear. Aim To assess the relationship between persistent reflux symptoms on PPI therapy and HRQoL in patients with GERD. Methods Systematic searches were conducted in PubMed and Embase. Eligible studies had to have used psychometrically evaluated patient reported outcome instruments to assess HRQoL. Results Nine studies were included; supplementary data were obtained for four of these. The effect of persistent reflux symptoms despite PPI therapy on physical HRQoL was assessed in seven studies and that on mental HRQoL in five studies. Compared with patients whose reflux symptoms responded to PPIs, those with persistent symptoms had, on average, 8–16% lower scores for physical health (five studies) and 2–12% lower scores for mental health (three studies). Three studies included data on the effect of baseline HRQoL on subsequent symptomatic response to PPI therapy. Patients with persistent symptoms had clinically relevant lower psychological well‐being at baseline compared with those whose symptoms responded to PPIs (average score difference: 7%; two studies). High anxiety levels at baseline seemed to be an important aspect of persistent symptoms. Conclusions Persistent reflux symptoms on PPI therapy are associated with reduced physical and mental HRQoL, while reduced mental HRQoL at baseline seems to impair symptomatic response to PPIs. HRQoL may need to be considered alongside reflux symptom frequency and severity when making decisions about disease management.     

Night-time and daytime atypical manifestations of gastro-oesophageal reflux disease: frequency, severity and impact on health-related quality of life

Background Respondents with gastro‐oesophageal reflux disease (GERD) report having a variety of atypical manifestations. The relationship between these manifestations and disease severity, night‐time GERD and functioning has not been determined. Aim To determine if atypical manifestations are related to increased disease severity, night‐time GERD and decreased functioning. Methods A web survey among US adults was conducted, using a validated GERD screener. Frequency of night‐time and daytime typical symptoms (acid regurgitation and heartburn) and atypical manifestations were assessed. Respondents were classified as night‐time GERD or daytime GERD based on typical symptom frequency. Prevalence of frequent atypical manifestations (≥2 days or nights/week) was assessed. Results Gastro‐oesophageal reflux disease cases had a higher prevalence of each atypical manifestation (P < 0.05 for all) compared with controls. Night‐time GERD respondents had a higher prevalence of atypical manifestations compared with daytime GERD respondents (P < 0.05 for most manifestations) and the prevalence of atypical manifestations increased with GERD symptom severity (P < 0.05 for most). Those with atypical manifestations reported lower functioning scores (P < 0.05 for most). Conclusions Respondents with typical GERD symptoms commonly report atypical manifestations, especially those with night‐time symptoms and those with greater underlying GERD severity. Respondents with GERD and atypical manifestations had more impaired functioning than those with typical symptoms only.     

Programme of stepping down from twice daily proton pump inhibitor therapy for symptomatic gastro-oesophageal reflux disease associated with a formulary change at a VA medical center

BACKGROUND: In July 2001, our Veterans' Affairs hospital changed its formulary proton pump inhibitor (PPI) from lansoprazole to rabeprazole. All patients previously receiving lansoprazole 30 mg twice daily were switched to rabeprazole 20 mg once daily. AIM: To determine if patients with gastro-oesophageal reflux disease (GERD), who were previously managed on lansoprazole 30 mg twice daily, could be maintained on rabeprazole 20 mg once daily. PATIENTS AND METHODS: Four hundred and thirty-five patients had received lansoprazole 30 mg twice daily for at least 12 months before the formulary change. Medical records were reviewed for 12 months before and after the formulary change. RESULTS: There were 432 men and three women with a mean age of 66.7 years (range: 38-91). Two hundred and twelve patients were excluded. Of the remaining 223, 111 (50%) were maintained successfully on rabeprazole 20 mg once daily. Twenty-three (10%) stayed off all acid suppression during follow-up. The number of endoscopies and clinic visits did not significantly change during the follow-up. Fifty-six percent who had erosive oesophagitis failed a dose taper compared with 31% of those with endoscopy-negative GERD (P<0.025). CONCLUSIONS: Most patients receiving twice daily PPI therapy for GERD could be maintained on once daily PPI or no acid suppression for 12 months of follow-up. Dose reduction was more successful in those without erosive oesophagitis.     

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 33: 911–921

Summary

Background ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro‐oesophageal reflux events and oesophageal acid exposure in patients with gastro‐oesophageal reflux disease (GERD) and healthy subjects. Aim To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD. Methods This was a double‐blind, placebo‐controlled, multi‐centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2‐week baseline washout period was followed by 2‐week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom‐free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24‐h impedance–pH monitoring was also determined in a subset of 24 patients. Results The full analysis set comprised 103 patients ADX10059 (N = 50), Placebo (N = 53). In treatment week 2, ADX10059 significantly increased GERD symptom‐free days (P = 0.045) and heartburn‐free days (P = 0.037), reduced antacid use (P = 0.017), improved total symptom score (P = 0.048) including subscale heartburn/regurgitation (P = 0.007) and sleep disturbance because of GERD (P = 0.022). ADX10059 significantly reduced total (P = 0.034) and acidic reflux events (P = 0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%). Conclusions Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD (ClinicalTrials.gov, number NCT00820079).     

Systematic review: the treatment of noncardiac chest pain

Aliment Pharmacol Ther 2012; 35: 5–14

Summary

Background Treatment of noncardiac chest pain (NCCP) remains a challenge. This is in part due to the heterogenous nature of this disorder. Several conditions are associated with NCCP including gastro‐oesophageal reflux disease (GERD), oesophageal dysmotility, oesophageal hypersensitivity as well as others. Aim  To determine the currently available therapeutic modalities for NCCP. Methods We performed a systematic review of the literature that was published between January, 1980 and March, 2011. We identified 734 studies; 68 of them met entry criteria. Results Patients with GERD‐related NCCP should receive proton pump inhibitors (PPI) twice daily for at least 8 weeks. Smooth muscle relaxants are only recommended for temporary relief of NCCP with motility disorders. Botulinum toxin injection of the distal oesophagus may be effective in the treatment of NCCP and spastic oesophageal motility disorders. Studies assessing the value of tricyclic antidepressants, trazodone and selective serotonine reuptake inhibitors in NCCP are relatively small, but suggest an oesophageal analgesic effect in NCCP patients that is limited by their side effects profile. The usage of theophylline to treat patients with non‐GERD‐related NCCP should be weighed against its potential toxicity. Use of complementary medicine has been scarcely studied in NCCP. Patients with coexisting psychological morbidity or those not responding to any medical therapy should be considered for psychological intervention. Cognitive behavioural therapy and hypnotherapy may be useful in the treatment of NCCP. Conclusions Patients with GERD‐related noncardiac chest pain should be treated with at least double dose PPI. The primary treatment for non‐GERD‐related noncardiac chest pain, regardless if oesophageal dysmotility is present, is pain modulators.     

Dilated intercellular space in chronic laryngitis and gastro‐oesophageal reflux disease: at baseline and post‐lansoprazole therapy

Aliment Pharmacol Ther 2010; 32: 916–924

Summary

Background Dilation of intercellular spaces is reported to be an early morphological marker in gastro‐oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux‐related chronic laryngitis. Aim To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis. Methods In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12‐weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes. Results There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate‐to‐severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy. Conclusions There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD.     

Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux disease groups

BACKGROUND: Nocturnal gastro-oesophageal reflux diseases (GERD) can lead to oesophageal mucosal injury and extra-oesophageal complications. AIM: To compare distribution of oesophageal acid exposure during sleep time among patients with non-erosive reflux disease and abnormal pH test (NERD-positive), erosive oesophagitis (EO) and Barrett's oesophagus (BO). METHODS: Patients underwent endoscopy followed by 24-h oesophageal pH testing. Oesophageal acid exposure was assessed every 2 h of the sleep period (0-2, 2-4, 4-6 and 6-8 h). Each period of 2 h was evaluated for acid reflux parameters. All groups were matched by age, time from last meal and duration of sleep time. RESULTS: Thirty-eight patients were enrolled (NERD-positive, 16; EO, 1.4; and BO, 8). All GERD groups demonstrated higher oesophageal acid exposure in the first vs. second half of the sleep period as determined by percent time pH <4 (BO: 34.7 vs.11.6, EO: 13.5 vs. 6.9, NERD-positive: 8.8 vs. 2.5, all P < 0.01). In general, patients with BO had a significantly higher distribution of oesophageal acid exposure than those with NERD-positive and EO. CONCLUSIONS: Oesophageal acid exposure generally declines throughout the sleep period regardless of GERD group, but BO patients demonstrated the greatest decline during the sleep period.     

The influence of environmental risk factors in hospitalization for gastro‐oesophageal reflux disease‐related diagnoses in the United States

Aliment Pharmacol Ther 31 , 852–861

Summary

Background The impact of gastro‐oesophageal reflux disease on hospitalization is unknown. Aim To describe the characteristics of patients hospitalized for diagnoses related to gastro‐oesophageal reflux disease (GERD) and find potential environmental influences that affect their hospitalization. Methods Data from the Healthcare Cost and Utilization Project were used to study the demographic characteristics of hospitalizations associated with GERD during 2003–2006. Data from the Centers for Disease Control were used for information about the US prevalence of obesity. Results During 2003–2006, 0.5 million patients with a primary and 14.5 million patients with a secondary GERD‐related diagnosis became hospitalized in the US. Oesophageal reflux and hiatal hernia were more common in female than in male inpatients, whereas Barrett’s oesophagus and oesophageal adenocarcinoma were more common in male than in female inpatients. All GERD‐related diagnoses were more common in white people than non‐white people. Hospitalizations associated with oesophageal reflux, reflux oesophagitis and Barrett’s oesophagus showed resembling geographical distributions among different US states. The prevalence of obesity and the hospitalization for hiatal hernia or reflux oesophagitis were also characterized by similar geographical distributions. Conclusion The large numbers of inpatients with a discharge diagnosis of GERD‐related conditions attest to the frequent occurrence and relevance of GERD in contributing to hospitalization in the US.     

Increasing insulin resistance is associated with increased severity and prevalence of gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 34: 994–1004

Summary

Background The diagnosis of gastro‐oesophageal reflux disease (GERD) is based on reflux symptoms. Although metabolic syndrome has been linked to erosive oesophagitis (EO), the impact of insulin resistance, the core of the metabolic syndrome, on reflux symptoms remains to be elucidated. Aim To assess the effects of insulin resistance on GERD, including both endoscopic findings and symptoms. Methods A total of 743 sonographic noncirrhotic adult subjects, who underwent an upper gastrointestinal endoscopic examination, completed a gastro‐oesophageal reflux questionnaire and had available fasting insulin data were included. Endoscopic findings were classified according to the Los Angeles classification. Homeostatic model assessment‐insulin resistance (HOMA‐IR) index was used to evaluate the status of insulin resistance. Univariate and multivariate approaches were used to evaluate the associations between insulin resistance and GERD. Results Older age, male gender, smoking and alcohol consumption increased the prevalence of EO, but not GERD symptoms. A large waist circumference, high fasting blood glucose levels and high number of metabolic syndrome components were associated with increased prevalence of both EO and GERD symptoms, while high blood pressure was associated with increased prevalence of EO only. Moreover, higher scores in the gastro‐oesophageal reflux questionnaire were associated with higher HOMA‐IR index, and higher HOMA‐IR index was associated with increased prevalence of EO (adjusted odds ratio 1.14, 95% CI 1.03–1.26, P = 0.012). Conclusions Our findings demonstrate clear associations between insulin resistance, metabolic syndrome and GERD. Whether reducing insulin resistance may improve GERD symptoms or EO deserves prospective study.     

Systematic review: ageing and gastro-oesophageal reflux disease symptoms, oesophageal function and reflux oesophagitis

Background Gastro‐oesophageal reflux disease (GERD) is thought to become more prevalent with age. Aim To assess systematically how age affects the prevalence of GERD and its oesophageal complications. Methods Systematic PubMed searches were used to identify population‐based studies on the age‐related prevalence and incidence of GERD, and clinical studies on age‐related changes in oesophageal complications in GERD. Results Nine population‐based studies and seven clinical studies met the inclusion criteria. Four of seven prevalence studies observed no significant effect of age on GERD symptom prevalence, two did not report on statistical significance and one observed a significant age‐related increase in symptom prevalence. The two population‐based endoscopic surveys showed no significant effect of age on reflux oesophagitis prevalence. Clinical studies in patients with GERD showed an increase in reflux oesophagitis severity and a decrease in heartburn severity with age, and age‐related increases in oesophageal acid exposure and anatomical disruption of the gastro‐oesophageal junction. Conclusions Epidemiological studies do not show an increase in GERD symptom prevalence with age. However, in individuals with GERD, ageing is associated with more severe patterns of acid reflux and reflux oesophagitis; despite this, symptoms associated with GERD become less severe and more nonspecific with ageing. Thus, the real prevalence of GERD may well increase with age.     

Development of a refractory gastro-oesophageal reflux score using an administrative claims database

Aliment Pharmacol Ther 2011; 34: 555–567

Summary

Background Approximately one‐third of gastro‐oesophageal reflux disease (GERD) patients demonstrate refractory symptoms following treatment with proton pump inhibitor (PPI) therapy. Aim To develop a refractory GERD score that can be applied to predict patients’ healthcare utilisation. Methods We enrolled adults (≥18 years) with a diagnosis of GERD. Refractory GERD was evaluated on an 8‐point scale where 1 point was given for each of the following criteria: doubling, addition, or switching of GERD medication dose, receipt of a GERD‐related endoscopic procedure or surgery, or ≥3 GERD‐related outpatient visits. Refractory GERD was defined as the presence of two or more points. Results A total of 135 139 GERD patients (44% male) were analysed with a mean (±s.d.) age of 52.9 ± 15 years. The mean overall refractory GERD score was 1.12 ± 1.2 (range 0–8 on an 8‐point scale); 31% of patients had refractory GERD with a mean score of 2.56 ± 0.82. Among patients with refractory GERD, 31% doubled their GERD medication, 28% added a new GERD medication, 60% switched GERD medications, 54% had a GERD‐related procedure and 1% had a GERD‐related surgery. Patients with refractory GERD were more likely to be female (59% vs. 55%, P < 0.001) and had a higher co‐morbidity score (0.78 vs. 0.56, P < 0.001). The overall mean costs for refractory patients during the study period were significantly higher compared with treatment‐responsive patients ($18 088 ± $36 220 vs. $11 044 ± $22 955, P < 0.001). Conclusions Refractory GERD was present in approximately one‐third of the GERD patients. We created a GERD refractory score that could define need for increased anti‐reflux therapy and predict higher healthcare resource utilisation.     

The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease

BACKGROUND: Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro-oesophageal reflux disease (GERD). METHODS: To investigate the potential clinical utility of tegaserod in GERD, a five-period crossover study (balanced Latin square) was designed to evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour manometry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2-week treatment period in 19 patients with mild-to-moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure. RESULTS: Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistically significant decreasing (P < 0.05) for the entire treatment group (percentage time for which pH < 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose=8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sphincter relaxations frequency decreased in the 1-2.5 h post-dose. CONCLUSIONS: Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.