Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study. Relationship between asthma and gastro-oesophageal reflux. No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux. Famotidine vs. omeprazole: a prospective randomized multicentre trial to determine efficacy in non-erosive gastro-oesophageal reflux disease. Cisapride for gastro-oesophageal reflux and peptic oesophagitis. A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux. Double-blind crossover study of ranitidine and placebo in gastro-oesophageal reflux disease. Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride. Cimetidine suspension in patients with stage 0 gastro-oesophageal reflux disease. Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.
Eleven adult patients with nocturnal asthma, and gastro-oesophageal reflux documented by endoscopy or ambulatory oesophageal pH monitoring completed a double-blind cross-over study (4 week treatment, one week run-in and cross-over periods) comparing the effects of omeprazole 20 mg daily and placebo on asthma control assessed by symptoms, peak expiratory flow rate and bronchodilator usage. Omeprazole treatment did not improve asthma symptoms during the day or night, or peak expiratory flow rate readings. There was no difference in bronchodilator inhaler usage during omeprazole therapy. Treatment of gastro-oesophageal reflux with omeprazole in patients with nocturnal asthma and gastro-oesophageal reflux does not improve asthma symptoms or peak expiratory flow rate. This suggests that gastro-oesophageal reflux does not exacerbate bronchoconstriction in nocturnal asthma. Twenty patients with bronchial asthma who also had gastro-oesophageal reflux were investigated. The severity of their reflux was graded using symptom score of heartburn and regurgitation and by the following investigations: barium swallow and meal, fibreoptic endoscopy and biopsy, manometry and pH monitoring of the distal oesophagus, and an acid infusion test. Full lung function studies were performed and patients were entered into a double-blind crossover study using cimetidine to control their reflux in order to assess beneficial effects with respect to their respiratory problems. Eighteen patients completed the study. Significant improvements were seen in reflux and night time asthmatic symptoms, both these indices being measured on a scoring system. Home monitoring of peak flow values showed a statistical improvement for th last peak flow reading of the day. Fourteen patients felt that their chest symptoms had significantly improved during the cimetidine period. Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway hyperresponsiveness through vagally-mediated pathways. We wanted to determine whether elimination of acid reflux could improve symptoms in such patients. In a randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and severe airway hyperresponsiveness despite maintenance treatment with an inhaled corticosteroid and with increased acid gastro-oesophageal reflux, were treated either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints were: airway hyperresponsiveness, as determined by the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow variability; reversibility to inhaled ipratropium bromide as a parameter of vagal activity; asthma symptoms scores; and medication used. Reflux was measured by 24 h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3 months had no beneficial effect on any of the pulmonary parameters, despite its profound effect on acid reflux and improvement of reflux symptoms scores, compared to placebo. The results of this study do not support a role for intensive antireflux therapy to improve pulmonary symptoms and function in patients with asthma and chronic obstructive pulmonary disease, who have severe airway hyperresponsiveness despite maintenance treatment with inhaled corticosteroids. Several studies in Western countries showed that proton-pump inhibitors are superior to histamine2-receptor antagonists or placebo in the treatment of non-erosive gastro-oesophageal reflux disease. The efficacy of acid-suppressive drugs for non-erosive gastro-oesophageal reflux disease in Japan, in which the prevalence of Helicobacter pylori infection is higher compared with Western countries, is unknown.
                To compare the efficacy of famotidine and omeprazole in Japanese patients with non-erosive gastro-oesophageal reflux disease by a prospective randomized multicentre trial.
                A total of 98 patients received either famotidine 20 mg b.d. (n = 48) or omeprazole once daily (n = 50). Frequency of gastro-oesophageal reflux disease symptoms and health-related quality of life were evaluated at baseline and after 4 weeks of treatment. Complete relief was defined as no gastro-oesophageal reflux disease symptoms during the 7-day interval in week 4.
                Complete relief was achieved in 23 (48%) of patients receiving famotidine and 28 (56%) of patients treated with omeprazole. In the famotidine group, complete relief rate in H. pylori-negative patients was significantly lower than H. pylori-positive patients (35% vs. 64%). Both famotidine and omeprazole improved most scales of health-related quality of life. Omeprazole significantly improved reflux score irrespective of H. pylori infection while famotidine significantly improved reflux score in H. pylori-positive patients but not in H. pylori-negative patients.
                Omeprazole is more effective than famotidine for the control of gastro-oesophageal reflux disease symptoms in H. pylori-negative patients, while similar efficacy is observed in H. pylori-positive patients with non-erosive gastro-oesophageal reflux disease. Twenty children (age range 75 days-47 months) with reflux oesophagitis entered a random double blind trial in which they received either Cisapride (Janssen Pharmaceutical Ltd), a new prokinetic agent, or an identical placebo syrup. Diagnosis of gastro-oesophageal reflux was made by measurement of intraluminal oesophageal pH combined with manometry. Oesophagitis was assessed in all patients by histological examination of mucosal specimens taken during oesophagogastroduodenoscopy. Manometry, pH test, and endoscopy with biopsy examination were repeated at the end of the treatment period. Seventeen patients completed the trial, eight of whom were taking the drug and nine the placebo. Mean total clinical score and post-prandial reflux time (% of reflux) significantly improved in patients in the group given Cisapride but not in the group given placebo. Furthermore, there was a significant improvement of the histological oesophagitis score only in the children in the group given Cisapride, whereas placebo was ineffective. It is concluded that Cisapride is a useful agent both for the relief of symptoms of gastro-oesophageal reflux and for the healing of peptic oesophagitis in infancy. In order to study the importance of gastro-oesophageal reflux (GOR) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind, cross-over, placebo-controlled trial over four weeks in 37 children and adolescents (mean age 14 yrs) with bronchial asthma. Ranitidine 300 mg, (150 mg if B.W. was less than 40 kg) was given as a single evening dose during four weeks. In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus. The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma, not related to reduction of GOR. A modest (30%) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR. There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux. Side-effects of ranitidine were negligible. Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR. Further confirmative trials with more potent inhibitors of gastric acid secretion are, however, warranted. The effect of 150 mg ranitidine twice daily was compared with placebo by the double-blind crossover technique (8 weeks twice) in patients with gastro-oesophageal reflux (paired comparison in 38 patients). Ranitidine was superior to placebo with regard to effect on symptoms, improvement of oesophagitis as assessed by endoscopy and biopsy, and decrease of oesophageal acid hypersensitivity. The symptomatic response to ranitidine was, however, unsatisfactory in more than half of the cases. When symptomatic responders taking ranitidine (R) were compared with non-responders (NR), there was no difference with regard to the severity of oesophagitis or frequency of positive acid perfusion tests before or after the 8-week treatment. NR were younger and more often had endoscopic signs of incompetence of the cardia and gastric prolapse. Ranitidine is an efficient drug in patients with reflux disease. It cannot be expected that mechanical problems in the hiatal region will be influenced by ranitidine, which is probably why half the patients did not respond. Few studies have specifically addressed the management of the symptoms of gastro-oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents.
                Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro-oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double-blind, double-dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated.
                At 4 weeks, heartburn was resolved in 65% (95% CI: 57-73%), 56% (48-64%) and 41% (32%-49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride (P < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups (P = 0.002).
                Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life. One hundred and twenty-five patients with symptoms of heartburn and acid regurgitation but without endoscopic abnormalities were randomized to receive 200 mg cimetidine suspension four times daily or placebo for two weeks. Daily dairy cards were kept to evaluate the frequency and degree of symptoms. At two weeks cimetidine was significantly more effective than placebo. It is concluded that placebo suspension has a considerable effect on gastro-oesophageal reflux disease symptoms, but cimetidine suspension provides significantly better relief. As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis.
                Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance.
                On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05).
                Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.
In asthmatic subjects with gastro-oesophageal reflux, (but who were not recruited specifically on the basis of reflux-associated respiratory symptoms), there was no overall improvement in asthma following treatment for gastro-oesophageal reflux. Subgroups of patients may gain benefit, but it appears difficult to predict responders.