Randomized clinical trial of laparoscopic Nissen fundoplication compared with proton-pump inhibitors for treatment of chronic gastro-oesophageal reflux. Chronic non-asthmatic cough is not affected by inhaled beclomethasone dipropionate. A controlled double blind clinical trial. Treatment of postnasal drip with proton pump inhibitors: a prospective, randomized, placebo-controlled study. Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized placebo-control trial. Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis. Efficacy of a pre-thickened infant formula: a multicenter, double-blind, randomized, placebo-controlled parallel group trial in 104 infants with symptomatic gastroesophageal reflux. Inhaled corticosteroid for persistent cough following upper respiratory tract infection. [Nocturnal spasmodic cough in the infant. Evolution after antireflux treatment]. A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough.
Both laparoscopic Nissen fundoplication (LNF) and proton-pump inhibitor (PPI) therapy are established in the treatment of gastro-oesophageal reflux disease (GORD). The aim of this study was to compare these two treatments in a randomized clinical trial.
                Between July 1997 and August 2001, 340 patients with a history of GORD for at least 6 months were investigated by endoscopy, 24-h pH monitoring and manometry. Of these, 217 were randomized, 109 to LNF and 108 to PPI therapy. The two groups were well matched for age, sex, weight and severity of reflux. Twenty-four-hour pH monitoring and manometry were performed 3 months after treatment, and quality of life was assessed in both groups using the Psychological General Well-being Index and the Gastrointestinal Symptom Rating Scale at 3 and 12 months after treatment.
                At 3 months there was an improvement in lower oesophageal sphincter pressure from 6.3 to 17.2 mmHg in the LNF group but no change in the PPI group (8.1 and 7.9 mmHg before and after treatment respectively) (P < 0.001). The mean DeMeester acid exposure score improved from 42.7 to 8.6 (P < 0.001) in the LNF group and from 36.9 to 17.7 in the PPI group (P < 0.001). The mean gastrointestinal symptom and general well-being scores improved from 31.7 and 95.4 respectively before treatment to 37.0 and 106.2 at 12 months after LNF, compared with changes from 34.3 and 98.5 to 35.0 and 100.4 respectively in the PPI group. The differences in both of these scores were significant between the two groups at 12 months (P = 0.003).
                LNF leads to significantly less acid exposure of the lower oesophagus at 3 months and significantly greater improvements in both gastrointestinal and general well-being after 12 months compared with PPI treatment.
                Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Thirty-one patients with a dry cough for at least 1 h duration in more than half of the last 30 days and with no recent respiratory infection participated in a clinical trial to evaluate the effect of inhaled beclomethasone dipropionate (BDP). Lung function was normal and reversibility was excluded by spirometry before and after bronchodilator and by no diurnal variation in home peak flow monitoring. Only one had significant eosinophilia and only three were mildly hyperreactive by bronchial provocation with histamine. After a 1-week run-in period the patients were randomly allocated to receive either BDP 4 puffs of 50 micrograms b.i.d., or placebo. After 2 weeks the patients were crossed over and received the alternative treatment for another 2-week period. The degree of cough, disturbance of night sleep and peak expiratory flow morning and evening were recorded daily in a diary. Spirometry was performed at each control visit. A significant period effect from run-in to period 1 and/or from period 1 to period 2 was demonstrated for cough and disturbance at night but not for peak flow or spirometry. However, no significant treatment effect was found for any of the measured variables. Patients commonly present with complaints of postnasal drainage (PND) without objective evidence to support a sinonasal or infectious etiology. PND has been attributed to extra-esophageal reflux (EER), and an empiric trial of antireflux medication often is used to treat PND and associated symptoms. This study was performed to (1) evaluate the relationship between symptoms of EER and PND and (2) assess the efficacy of proton pump inhibitors (PPIs) in the management of PND.
                Patients with a chief complaint of PND without objective evidence of sinonasal inflammatory disease were enrolled in a prospective, double-blinded, randomized placebo-controlled trial using rabeprazole, 20 mg, orally twice daily or placebo for 90 days. Subjects completed two-site 24-hour pharyngeal pH probe monitoring before treatment. Outcome measures included pre- and posttreatment visual analog scales for PND symptoms, reflux symptom index, and reflux finding score (RFS).
                Forty-seven patients were enrolled (mean age, 55 years)-21 patients in the PPI group and 26 in the placebo group. Fifty-six percent of subjects had pH probe confirmed EER using a cutoff of pH < 5.0. Baseline symptom measures between subjects with and without EER were not different. Compared with placebo, subjects receiving rabeprazole reported significant reduction in PND frequency (p = 0.0180), hoarseness (p = 0.0164), and chronic cough (p = 0.0204). The RFS decreased slightly in the placebo group (p = 0.1490) whereas it increased slightly in the PPI group (p = 0.5235). This difference between groups was significant (p = 0.0272).
                Although 50% of subjects had evidence of EER, there was no difference in baseline symptoms between subjects with and without. Our findings support the potential benefit of PPI therapy for reducing PND frequency, hoarseness, and chronic cough, and confirm a placebo effect for other laryngopharyngeal reflux symptoms. The effect on laryngeal findings is mixed and patients may experience symptomatic improvement before changes in laryngoscopic appearance. To determine the efficacy of proton-pump inhibitor (PPI) therapy for chronic laryngo-pharyngitis treated with lifestyle modification.
                Double-blind, randomized trial comparing two-month Rabeprazole (20 mg b.i.d.) to placebo control.
                Compared to baseline, both PPI and control patients had significant improvement in total reflux symptoms (P = 0.002 and P = 0.03 respectively), with significant improvement in "laryngo-pharyngeal" but not "typical" reflux symptoms. No significant difference was noted for change in reflux symptoms between PPI-treated and control patients (P = 0.44). Significant global improvement was noted by 50% of control and 53% of PPI-treated patients (P = 1.0). No significant differences were noted within or between treatment groups for change in health status or videostrobolaryngoscopy grade. Lifestyle modification compliance correlated significantly with global improvement.
                Compared to baseline, lifestyle modification for 2 months significantly improved chronic laryngo-pharyngitis symptoms. When compared to control, treatment with a PPI failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance. The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.
                The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period.
                One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies.
                Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. Measurements and results: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.
                The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI. To evaluate a pre-thickened formula (Enfamil AR) for regurgitant gastroesophageal reflux, 104 infants were enrolled in a 5-week, multicenter, double-blind, randomized, placebo-controlled parallel group trial. The Enfamil AR group showed greater symptom reduction by the end of the first week: percent feedings with any regurgitation (p = 0.045), total regurgitation volume score (p = 0.035), and percent feedings with choke-gag-cough (p = 0.004). The most symptomatic infants at baseline had a reduction in trouble sleeping significantly with Enfamil AR by the end of the study (p = 0.030). This formula flows through a standard nipple, reduces regurgitation and choking-gagging-coughing within a week, and improves sleep in the most symptomatic babies by 5 weeks, without causing constipation. The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR).
                This was a prospective, randomized, double-blinded, placebo-controlled study conducted at a university hospital. A total of 30 non-asthmatic, non-smoking patients who were >15 years old and who had persistent post-URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 microg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night-time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment.
                The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P=0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P=0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P=0.23). No difference between groups was found in the mean changes in FEV(1), FVC, and FEF(25--75%) after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline.
                Inhaled corticosteroid is ineffective in treating persistent post-URTI cough in previously healthy individuals. Several studies have shown the relationship between gastro-oesophageal reflux, bronchial asthma and chronic nocturnal cough and this should not be neglected, particularly in patients who present an unfavourable development in spite of conventional treatment. For diagnosis of gastroesophageal reflux, amongst other investigations, esophageal gammagraphy of swallowing, that detects alterations in the mobility of the oesophagus, secondary to a possible oesophagitis. The objective of this study was to evaluate the clinical progress and gammagraphy of a group of children with chronic predominantly nocturnal cough (with or without bronchial asthma) with initially pathological esophageal gammagraphy, after three months of treatment with gastrokinetic drugs (cisapride against domperidone) and postural dietetic limits, in comparison with a reference group who, although having followed the limits in question had not received the pharmacological treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases without significant statistical differences between the two groups. Gammagraphy became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55. Although there was no significant difference, gammagraphy development was better in children who received domperidone. The agreement between clinical progress and gammagraphy was 60% with a large number of false positives in the gammagraphy. We believe that the simple introduction of the postural-dietetic measures may improve the clinical control in the type of patients who present with a chronic nocturnally predominant cough that does not yield to conventional treatment. Recent studies suggest an association between chronic cough and gastroesophageal reflux. Our study aims were 1) to define the prevalence of acid reflux induced cough in the general community, 2) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough, and 3) to assess the utility of omeprazole in a chronic cough algorithm.
                Patients with chronic cough of unknown etiology, who were mostly from the community, were evaluated. Subjects underwent a chest x-ray, methacholine challenge test, and empiric trial of postnasal drip therapy, and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a graded scale of 0-4 (combined maximum 8). After excluding other causes of cough, the remaining patients underwent esophageal and pH testing. Those testing positive were randomized to omeprazole 40 mg b.i.d. or placebo for 12 weeks. Follow-up was 1 yr.
                A total of 71 patients were screened; 48 were excluded. Twenty-three patients were evaluated for gastroesophageal reflux disease; six (26%) were eventually determined to have an acid-related cough. Of these patients, 17 had a positive pH test, six (35%) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr. Six had a negative pH test, none of whom responded to omeprazole therapy. No significant differences were seen between responders (n = 6) and nonresponders (n = 11) for demographic factors, baseline symptom frequency and duration, or physiological parameters (motility/pH).
                Acid-related chronic cough was present in 26% (six of 23) of patients evaluated for gastroesophageal reflux disease. Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy. We suggest that the best diagnostic and therapeutic approach, after excluding asthma and postnasal drip syndrome, is empiric treatment for 2 wk with a high dose proton pump inhibitor.
PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.