Are proton pump inhibitors effective in asthmatics with gastroesophageal reflux disease?

Effects of proton pump inhibitors in asthmatics with gastroesophageal reflux disease (Korean J Gastroenterol 2011;58:178-183).     

Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach

Lifestyle modifications are first-line therapy for patients with gastroesophageal reflux disease (GERD). We applied an evidence-based approach to determine the efficacy of lifestyle measures for GERD management. We used PubMed and Ovid to perform a search of the literature published between 1975 and 2004 using the key words heartburn, GERD, smoking, alcohol, obesity, weight loss, caffeine or coffee, citrus, chocolate, spicy food, head of bed elevation, and late-evening meal. Each study was reviewed by 2 reviewers who assigned one of the following ratings: evidence A, randomized clinical trials; evidence B, cohort or case-control studies; evidence C, case reports or flawed clinical trials; evidence D, investigator experience; or evidence E, insufficient information. We screened 2039 studies and identified 100 that were relevant. Only 16 clinical trials examined the impact on GERD (by change in symptoms, esophageal pH variables, or lower esophageal sphincter pressure) of the lifestyle measure. Although there was physiologic evidence that exposure to tobacco, alcohol, chocolate, and high-fat meals decreases lower esophageal sphincter pressure, there was no published evidence of the efficacy of dietary measures. Neither tobacco nor alcohol cessation was associated with improvement in esophageal pH profiles or symptoms (evidence B). Head of bed elevation and left lateral decubitus position improved the overall time that the esophageal pH was less than 4.0 (evidence B). Weight loss improved pH profiles and symptoms (evidence B). Weight loss and head of bed elevation are effective lifestyle interventions for GERD. There is no evidence supporting an improvement in GERD measures after cessation of tobacco, alcohol, or other dietary interventions.     

Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy: Is gastroparesis a factor?

AIM:To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH(MII-pH)is linked to gastroparesis(GP).METHODS:A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease(both typical and atypical symptoms)despite acid suppression therapy.MII-pH technology was used over 24 h to detect reflux episodes and record patients’symptoms.Parameters evaluated in patients with documented GP and controls without GP by scintigraphy included total,upright,and supine number of acid and non-acid reflux episodes(pH<4 and pH>4,respectively),the duration of acid and non-acid reflux in a 24-h period,and the number of reflux episodes lasting longer than 5 min.RESULTS:No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events,total number and duration of non-acid reflux events or the duration of longest reflux episodes.The number of nonacid reflux episodes with a pH>7 was higher in subjects with GP than in controls.In addition,acid reflux episodes were more prolonged(lasting longer than 5min)in the GP patients than in controls;however,these values did not reach statistical significance.Thirty-five patients had recorded symptoms during the 24 h study and of the 35 subjects,only 9%(n=3)had a positive symptom association probability(SAP)for acid/non-acid reflux and 91%had a negative SAP.CONCLUSION:The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.     

Is there a role for proton pump inhibitor prophylaxis in haematology patients?

While proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy‐induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14‐month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.     

Does the addition of a prokinetic to proton pump inhibitor therapy help reduce duodenogastro-oesophageal reflux in patients with Barrett's oesophagus?

OBJECTIVE: The metaplastic change of Barrett's oesophagus is linked to both acid and duodenal reflux together with impaired motility. Proton pump inhibitors (PPI) reduce acid reflux, but no treatment is available that reduces duodenogastro-oesophageal reflux (DGOR). The aim of this study was to investigate whether adding a prokinetic to PPI treatment could improve oesophageal motility and subsequently reduce reflux. METHODS: Two groups of patients with Barrett's oesophagus on PPI therapy (prokinetic, n = 12; placebo, n = 11) were investigated. At visit 1, ambulatory oesophageal manometry was performed, and peristaltic and simultaneous wave percentage and characteristics were measured. DGOR and pH measurements were also performed. After treatment with either the prokinetic cisapride or placebo, all investigations were repeated (visit 2). Analysis of covariance and Spearman's correlation coefficients of changes from visit 1 to visit 2 were used to compare data. RESULTS: There was no significant difference between the two groups with respect to DGOR, DGOR characteristics, or the percentage of peristalsis and simultaneous waves and their characteristics. There was no correlation between DGOR and motility changes. Although no significant differences existed between acid reflux in the two groups, five patients with high supine acid reflux showed a significant reduction after treatment with cisapride. CONCLUSIONS: Addition of cisapride to PPI treatment does not appear to improve oesophageal motility or reduce DGOR in patients with Barrett's oesophagus.     

Is reflux cough due to gastroesophageal reflux disease or laryngopharyngeal reflux?

Reflux is a common cause of chronic cough. Surveys of patients with chronic cough point to a high association with gastroesophageal disease. Because of our bipedalism and speech, humans are prone to both reflux and aspiration. Whether the reflux of stomach contents into the esophagus alone is sufficient to cause cough or whether reflux into the upper airway is required is unknown. In 50 consecutive patients with chronic cough, symptoms of laryngopharangeal reflux (LPR) paralleled those of gastroesophageal reflux, suggesting no unique syndrome of LPR but that it is part of the protean manifestations of reflux disease.     

Is a proton pump inhibitor necessary for the treatment of lower-grade reflux esophagitis?

The efficacy of histamine H2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) therapies in healing reflux esophagitis was compared in a prospective randomized case-control comparative study. A total of 71 patients with grade A to D esophagitis (Los Angeles classification) were given either famotidine 20 mg twice a day (Fam; n = 35) or omeprazole 20 mg once daily (Ome; n = 36) for 8 weeks. Endoscopy was performed to assess healing in 57 patients. Healed patients were followed-up without H2RA or PPI therapy for 3 months. At the end of follow-up, endoscopy was able to be performed in 33 patients. Healing rates for patients in the Fam and Ome groups were 58.6% (17/29) and 97.4% (27/28), respectively (P < 0.001), and when limited to grade A to B, healing rates were 60.9% (14/23) and 100% (25/25), respectively (P < 0.001). Concerning Helicobacter pylori infection, healing rates for the Fam and Ome groups in H. pylori (+) patients were 90.0% (9/10) and 90.9% (10/11), respectively (P = 1.00). Remission rates in the Fam and Ome groups were 45.0% (9/20) and 33.3% (6/18), respectively (P > 0.4). In regard to alcohol drinking, remission rates of daily and social drinkers were 7.7% and 42.4%, respectively (P < 0.03). Thus, PPI should be the drug of choice even for healing lower-grade reflux esophagitis, especially in H. pylori (−) patients. Treatment with H2RA may be an alternative choice in H. pylori (+) patients. After healing, most patients cannot sustain remission without maintenance therapy. Received: July 13, 1998 / Accepted: February 26, 1999     

Is the esophageal squamous epithelial barrier function impaired in patients with gastroesophageal reflux disease?

BACKGROUND: A disturbed epithelial barrier function has been promoted as one factor in the pathogenesis of gastroesophageal reflux disease (GERD). We therefore studied the effect of acid perfusion on the transmural potential difference (PD) of the distal esophagus in relation to onset of reflux symptoms. METHODS: PD was assessed during perfusion with saline and with 0.1 M HCl in healthy controls (n = 17) and in GERD patients without (n = 15) or with esophagitis (n = 6) and in remission after a fundoplication (n = 10). Heartburn and other upper GI symptoms were recorded concomitantly. Endoscopy-negative patients were studied before and after omeprazole treatment. RESULTS: HCl perfusion induced more lumennegative peak PD values in patients with active GERD, regardless of the presence or absence of esophagitis, than in healthy controls. After successful therapy, the PD response to acid perfusion equalled that of healthy subjects. Acid perfusion was associated with the onset of heartburn in most patients with active GERD but in none of the healthy subjects, and less frequently after medical and surgical therapy. CONCLUSIONS: The epithelial permeability to hydrogen ions differs between healthy subjects and patients with active GERD. Effective treatment, such as omeprazole or fundoplication, might improve the barrier function.     

Is Helicobacter pylori eradication associated with gastroesophageal reflux disease?

OBJECTIVES: A recent report has suggested an association between Helicobacter pylori eradication and the development of gastroesophageal reflux disease (GERD). We therefore assessed the incidence of GERD among comparable patients having undergone successful versus failed H. pylori eradication in a controlled trial. We also compared the H. pylori strains in the subjects that developed GERD to those that did not. METHODS: Patients with a history of proven duodenal ulcer and H. pylori infection were randomised into a H. pylori eradication study. Patients subsequently underwent gastroscopy with gastric biopsies every 3 months for 1 yr. At each visit, the presence of GERD symptoms and endoscopic esophagitis were noted, and the incidence of these variables among patients in whom H. pylori eradication was successful was compared to those in whom it was not. In a subgroup, the presence of the cagA, cagE, and vacA genotypes and of cagA antibodies were determined. RESULTS: Of 98 patients randomized into this study, 11 dropped out before determination of H. pylori eradication, leaving 87 patients with analyzable results. H. pylori eradication was successful in 63 (72%). By the end of the follow-up period, patients with GERD symptoms or endoscopic esophagitis were more prevalent in the successful than in the failed eradication group (37% [95% CI: 25-50%] vs 13% [95% CI: 3-32%], p = 0.04, 95% CI for the difference: 6-42%), as were patients with GERD symptoms alone (29% [95% CI: 18-41%] vs 8% [95% CI: 1-27%], p = 0.04, 95% CI for the difference: 4-36%) or esophagitis alone (21% [95% CI: 12-33%] vs 4% [95% CI: 0-21%], p = 0.10, 95% CI for the difference: 4-29%, respectively). Multivariate analysis revealed no significant association between the incidence of symptoms or esophagitis and age, gender, Quetelet index, caffeine or alcohol intake, smoking, weight change, or the presence of a hiatus hernia. There were also no differences in the prevalence of H. pylori genotypes from patients who developed GERD as compared to those who did not. CONCLUSIONS: In this patient population, the incidence of new GERD-type symptoms or endoscopic esophagitis was greater in patients in whom successful eradication was achieved. This difference does not appear to be attributable to weight gain, habits, or specific H. pylori strains.     

Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett's esophagus: acid reflux, bile reflux, or both?

OBJECTIVES:   Studies using ambulatory pH and esophageal bile reflux monitoring (Bilitec^®) have shown that both acid reflux and duodeno-gastro-esophageal reflux (DGER) frequently occur in patients with gastroesophageal reflux disease (GERD). A subset of patients with GERD has persistent reflux symptoms in spite of standard doses of proton pump inhibitors (PPIs). The aim of the present study was to investigate the role of acid and DGER in patients with reflux disease poorly responsive to PPIs.
METHODS:   Sixty-five patients (32 men, 44 ± 2 yr) without Barrett's esophagus and with persistent heartburn or regurgitation during standard PPI doses were studied. They underwent upper gastrointestinal endoscopy and simultaneous 24-h ambulatory pH and Bilitec^® monitoring while PPIs were continued.
RESULTS:   Thirty-three patients (51%) had persistent esophagitis. Seven patients (11%) had only pathological acid exposure, 25 (38%) had only pathological DGER exposure, and 17 (26%) had pathological exposure to both acid and DGER. Acid exposure under PPI was positive in only 37%, but adding Bilitec^® increased the diagnoses of persistent reflux to 75%. Patients with persistent esophagitis had similar acid exposure, but significantly higher DGER exposure than those without esophagitis. The highest prevalence of esophagitis was found in patients with pathological exposure to both acid and DGER; symptoms did not differ according to the type of reflux.
CONCLUSIONS:   Combined pH and Bilitec^® monitoring is superior to pH monitoring alone in demonstrating ongoing pathological reflux in patients with medically poorly responsive reflux disease.     

Is telemetry useful in evaluating chest pain patients in an observation unit?

Since the development of coronary care units (CCUs), telemetry has rapidly become the standard of care in evaluating patients with suspected acute coronary syndromes, regardless of the probability for ischemia. However, there is no data to support this practice. Our objective was to evaluate the utility of routine cardiac monitoring in a chest pain observation unit. We prospectively studied the utility of routine cardiac monitoring in 249 consecutive patients admitted to an observation unit in an academic Emergency Department over a 6-month period. All the patients presented with chest pain thought to be cardiac ischemia. Observation included serial cardiac enzymes, ECG cardiac monitoring, and exercise testing in a designated chest pain observation unit. These patients were determined to be at low risk for an acute coronary event by two criteria: first, the symptoms had resolved by the time of observation unit admission, and second, the initial ECG was normal, unchanged or non-diagnostic for acute ischemia. Adverse outcomes included cardiac arrest, hospital admission secondary to cardiac dysrhythmia, or alteration in the patient’s medical therapy upon discharge from the observation unit, secondary to cardiac dysrhythmia. There were 249 patients included with a median age of 52 with 60% women. Fifteen percent of the patients were, subsequently, admitted to the hospital for further evaluation of ischemia based on enzyme, ECG, and exercise testing results. One patient with known Tachy-Brady syndrome was noted to have 1.5–2 s pauses while sleeping, and discharged with instructions to hold beta blocker therapy pending results of a continuous loop recorder. Of the remaining 248 patients, no patient suffered a cardiac arrest, no patient was admitted to the hospital secondary to cardiac dysrhythmia, and no alteration in a patient’s medical therapy was made secondary to cardiac dysrhythmia. No patient returned to the Emergency Department within 72 h with cardiac arrest, acute dysrhythmia or acute myocardial infarction. Although telemetry may be the standard of care in evaluating the patients with suspected acute coronary syndromes, regardless of the probability of an acute ischemic syndrome, in those patients with a normal or non diagnostic ECG and resolved symptoms, routine cardiac monitoring is unnecessary.