Nocturnal Reflux Research Articles

Review article: putting immediate‐release proton‐pump inhibitors into clinical practice – improving nocturnal acid control and avoiding the possible complications of excessive acid exposure

Nocturnal gastro-oesphageal reflux is an under-appreciated clinical challenge. This condition may cause symptoms such as nocturnal heartburn, or it may be asymptomatic. In addition, patients may experience sleep disturbances that can potentially lead to complications such as erosive oesophagitis and Barrett's oesophagus, and may be a risk factor for development of oesophageal adenocarcinoma. Delayed-release proton-pump inhibitors (PPIs) have traditionally been effective in treating both daytime and night-time reflux symptoms, but are limited in control of nocturnal acidity by their pharmacodynamic characteristics. This narrative review addresses the prevalence, impact and pharmacologic approaches used to control nocturnal acidity. Methods to optimize nocturnal acid control include careful attention to dosing schedule, using higher doses of PPIs, adding an histamine H2-receptor antagonist at bedtime to once or twice daily delayed-release PPI, or using immediate-release omeprazole (Zegerid powder for oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation appears to provide sustained control of intragastric pH at steady state, and when dosed at bedtime, and may be effective in improving control of nocturnal pH and treating night-time GERD.

Introduction

Proton-pump inhibitors (PPIs) represent a major therapeutic advance in the management of acid-related disorders, including gastro-oesophageal reflux disease (GERD) and non-variceal upper gastrointestinal (GI) bleeding, but there still remain unmet needs, which if addressed could improve treatment. The delayed-release PPIs have quite similar pharmacokinetic and pharmacodynamic profiles. Their absorption and onset of action is delayed because they require an enteric-coating as protection against acid degradation in the stomach. To achieve maximum acid inhibition, they all need to be dosed before meals, a time when parietal cells are stimulated. Despite their remarkable ability to suppress acid during the day, delayed-release PPIs do not predictably control acid at night even when dosed twice daily. These characteristics have resulted in several unmet clinical needs specifically relating to inadequate control of nocturnal reflux symptoms, delayed symptom relief with on-demand dosing and suboptimal efficacy in those who forget or do not take their medication before eating. Immediate-release omeprazole [(IR-OME) Zegerid powder for oral suspension; Santarus Inc., San Diego, CA, USA] does not require an enteric-coating because of its unique formulation, which incorporates acid buffering sodium bicarbonate. This facilitates more rapid drug absorption, a quicker onset of action, and superior acid suppression during the night when given at bedtime. The rapid absorption and onset of action of immediate-release omeprazole also makes the medication ideally suited for those who might not comply with mealtime dosing of PPIs or who choose to manage their reflux symptoms with on-demand therapy. In addition, the immediate and prolonged acid suppression seen with single, daily, enteral dosing of immediate-release omeprazole in critically ill patients suggests this formulation is an appropriate alternative to parenteral histamine H2-receptor antagonists (H2RAs) for preventing stress related mucosal bleeding. A group of experts was convened to reflect on current management approaches to GERD and upper GI bleeding. Open discussion centred on current diagnosis and treatment, unmet needs, and strategies to meet these needs with the hope of improving management for the future. I was pleased to moderate this session and trust you will find the comments of these experts as provocative and interesting as I did. Also, I hope the summaries of the discussions presented in this publication prove useful in your day-to-day management of patients.

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole

Background Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. Aim To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. Methods Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole ( n = 16) or 30 mg lansoprazole ( n = 14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. Results Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole ( p = 0.026). Conclusions Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.

Treatment for Nocturnal Reflux Often Falls Short

Treatment for Nocturnal Reflux Often Falls Short

The effect of gastro‐oesophageal reflux and omeprazole on key sleep parameters

The effect of gastro-oesophageal reflux on sleep and sleep quality is highly controversial. To determine the temporal relationship of abnormal objective sleep parameters to gastro-oesophageal reflux during acid suppression in patients with self diagnosed sleep disorders. Polysomnography during oesophageal pH monitoring was conducted in 16 subjects with and without gastro-oesophageal reflux as determined by a standardized questionnaire. Subjects were studied before and after omeprazole. All reflux events were followed by a sleep arousal or awakening. Nocturnal acid reflux events were not predicted by the Carlsson score. Omeprazole reduced acid reflux-associated arousals from 11.6 +/- 3.8 to 1.5 +/- 0.8 (P < 0.01) and awakenings from 7.7 +/- 1.2 to 3.7 +/- 0.5 (P < 0.05). Sleep efficiency improved from 70.2% to 81.6% in a small subset of subjects with decreased sleep (P < 0.05); rapid eye movement sleep increased from 55.0 +/- 4.5 to 94.5 +/- 18.9 min (P < 0.05); total sleep time increased from 294.0 +/- 15.9 to 345.6 +/- 55.6 min (P < 0.05). Apnoea, hypopnoea and hypoxaemia were not associated with reflux. In subjects with gastro-oesophageal reflux, sleep arousals and awakenings are closely related to acid reflux events. Reflux-related arousals and awakenings are decreased by acid suppression. Acid suppression in selected subjects with reflux events and reduced sleep efficiency is associated with increased total sleep time, rapid eye movement sleep and sleep efficiency.

Prolonged combined biliary and acidic nocturnal reflux episodes develop dysplasia in patients with intestinal metaplasia of the esophagus

The increasing incidence of esophageal adenocarcinoma in the western countries has prompted us to establish the South Hungarian Regional Surveillance Group for the Study of Barrett's Esophagus in 2003. In the present report we made an interim analysis of the data collected so far. The aim of the study was to evaluate the role of acidic and biliary reflux in the development of metaplastic and dysplastic mucosal changes in patients with Barrett's esophagus.

Prevalence of Respiratory Symptoms and Diseases Associated with Gastroesophageal Reflux Disease

Aim: Investigation of the prevalence of respiratory symptoms and diseases associated with gastroesophageal reflux disease (GERD). Patients and Methods: 299 subjects with GERD were submitted to upper gastrointestinal endoscopy and 24-hour esophageal pH monitoring and a symptom analysis. Results: Chronic respiratory symptoms or diseases were present in 18% (56/299). Chronic cough was observed in 42/56 patients, while typical reflux symptoms such as heartburn and acid regurgitation were observed in 30/56 and 24/56 cases, respectively. The prevalence of airway diseases was chronic bronchitis 12/56, asthma 10/56, recurrent pneumonia 10/56, chronic sinusitis 7/56 and chronic laryngitis 1/56. In patients with respiratory complications pathologic acid reflux was established in 29/51 cases on the basis of the DeMeester score, while 17/51 had pathologic postprandial, nocturnal or diurnal reflux events. Upper gastrointestinal endoscopy revealed a normal esophageal mucosa in 6/56, Savary-Miller stage I esophagitis in 23/56, stage II in 15/56, stage III in 5/56 and stage IV in 6/56 patients. Conclusions: These investigations have demonstrated an abnormal 24-hour pH score in about half of the patients with GERD-associated respiratory complications, and indicated that short reflux events are characteristic of the reflux activity in one third of this population.

Nighttime Reflux? Avoid Late Meals and Snacks.

According to a recent Gallup survey, about 80% of adults with gastroesophageal reflux disease (GERD) experience nocturnal symptoms, but few data specifically address the frequency of nocturnal acid reflux. In a retrospective cohort study, researchers in South Carolina reviewed 201 consecutive 24-hour pH studies performed for typical or atypical GERD symptoms. Acid reflux was …

Night-time gastro-oesophageal reflux disease

Patients who complain of symptoms of gastro-oesophageal reflux disease (GORD) that occur at night require special attention. Night-time GORD can profoundly impair quality of life by causing pain, disturbing sleep, and interfering with next-day mental and physical functioning. Sleep impairs oesophageal acid clearance resulting in a prolongation of acid mucosal contact, and nocturnal reflux portends a greater risk of erosive oesophagitis and other significant complications of gastro-oesophageal reflux. Lifestyle changes such as elevating the head of the bed and adjusting the sleeping position can relieve night-time heartburn, and instituting some dietary changes along with occasional use of histamine H2 blockers can also be helpful. Relief of night-time reflux and its attendant symptoms usually requires a medication with acid-suppressing properties that extend into the sleeping interval. In most instances, more powerful acid suppression in the form of proton-pump inhibitors will be required. Clinical studies have shown that 40 mg esomeprazole provides better control of night-time GORD symptoms than 20 mg omeprazole or 30 mg lansoprazole. Furthermore, 40 mg pantoprazole offers even faster relief than 40 mg esomeprazole for night-time GORD symptoms. Of the several proton-pump inhibitors available on the market, esomeprazole and pantoprazole appear to have some advantages, which have been documented in recent studies. Esomeprazole has been shown to be more effective than lansoprazole in relieving GORD symptoms, and esomeprazole and pantoprazole appear to be equally effective in resolving GORD symptoms in a comparative study. Pantoprazole has pharmacokinetic properties that document a longer half-life compared with the other proton-pump inhibitors, and pantoprazole has the slowest inhibition recovery rate. These properties lend credence to pantoprazole as an effective treatment for associated symptoms of night-time reflux.

Symptomatic gastro‐oesophageal reflux, arousals and sleep quality in patients undergoing polysomnography for possible obstructive sleep apnoea

Nocturnal acid reflux is common and could disturb sleep by causing arousals that fragment sleep. To determine the prevalence of gastro-oesophageal reflux symptoms and their association with arousals, stages of sleep and quality of life in patients undergoing evaluation for excessive daytime sleepiness and obstructive sleep apnoea. Ninety-four consecutive patients with excessive daytime sleepiness were prospectively studied. Patients completed the gastrointestinal symptom rating scale, a validated symptom questionnaire for reflux disease and a disease-specific quality of life questionnaire, the sleep apnoea quality of life index and then underwent overnight polysomnography, which was read in a blinded manner. There were 40 males and 54 females with a mean age of 47 +/- 13 years. Reflux symptoms were present in 63 of the 94 (67%) patients. Patients with reflux symptoms had significantly more arousals from sleep 43 +/- 70/h than those without (20 +/- 24/h; P = 0.03). The sleep duration during the second stage of sleep was shorter (44 +/- 21%) for those with reflux symptoms than those without (52 +/- 12%; P = 0.03). Patients with reflux spent significantly shorter periods in stage II sleep (44 +/- 21%) than those without (52 +/- 12%; P = 0.03). The sleep-related quality of life score in patients with gastro-oesophageal reflux (3.1 +/- 1.1) was significantly lower than in patients without reflux (3.7 +/- 1.0; P = 0.02). Regression analysis demonstrated a significant inverse correlation between quality of life and reflux symptom score (P =0.002) and total spontaneous arousals (P = 0.04). Gastro-oesophageal reflux is common in patients with sleep disorders, is associated with increased arousal, decreased durations spent in the deeper stages of sleep and poorer sleep-related quality of life.

Nighttime GERD: Clinical implications and therapeutic challenges

Limited available data specifically addressing nocturnal gastroesophageal reflux indicate its association with more severe injuries such as esophagitis and stricture, adenocarcinoma of the esophagus, respiratory and ENT disorders as well as sleep disturbances, diminished quality of life and undesired changes in activities of daily living. In a recent survey, altogether 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines and 49% of these rated this approach extremely satisfactory. This recent understanding of the prevalence and impact of nighttime heartburn is an indicator of nocturnal acid reflux events and suggests that nighttime heartburn occurs in a large majority of adults with gastroesophageal reflux disease. The fact that expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients can have significant management implications.

Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non-erosive reflux disease.

The reason why less than one-half of patients with gastro-oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking. To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease. Ambulatory 24-h oesophageal pH monitoring was performed in 220 patients with gastro-oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non-erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated. The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non-erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time. Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro-oesophageal reflux disease.

Gastroesophageal reflux disease: symptoms versus pH monitoring results.

The reason why some patients with gastroesophageal reflux disease (GERD) have symptoms of upper aerodigestive system irritation, while others mainly have gastroenterologic symptoms, is not well established. This retrospective case series study was designed to examine the existence of a correlation between symptoms and reflux characteristics, based on data obtained from esophageal pH monitoring. The study population consisted of 139 patients; 97 patients presented with laryngopharyngeal symptoms of GERD, including unexplained hoarseness, throat clearing, chronic cough, laryngospasm, globus, throat pain, and 42 patients presented with gastroenterologic symptoms, including heartburn and regurgitation. The results of 24-hour, double-channel ambulatory esophageal pH monitoring were analyzed comparing 2 symptom groups. The incidence of abnormal acid reflux at the upper and lower esophageal segments and the effects of upright and supine positions on reflux parameters were evaluated. The incidence of laryngopharyngeal reflux was significantly higher in the laryngopharyngeal symptom group than in the other (52% versus 38%). The patients with laryngopharyngeal reflux from both groups showed no significant differences in terms of number of acid reflux episodes, percentage of times pH was 4, and esophageal acid clearance. Upright and supine parameters did not show significant differences between the patient groups. Upright acid reflux episodes were, however, common in both groups at the lower esophageal and laryngopharyngeal segments. Recent studies suggesting that otolaryngologic patients commonly show upright, daytime reflux with normal esophageal clearance and that typical GERD patients commonly have supine, nocturnal reflux with prolonged esophageal clearance are not supported by this study. This study indicates that acid reflux parameters and positional changes are not sufficient to explain why patients with GERD experience different symptoms. The regional symptoms of GERD may be attributed to the impairment of epithelial resistance, motor activity, and buffering systems for the esophageal antireflux barrier.

Gastroesophageal reflux disease: symptoms versus pH monitoring results

Objectives The reason why some patients with gastroesophageal reflux disease (GERD) have symptoms of upper aerodigestive system irritation, while others mainly have gastroenterologic symptoms, is not well established. This retrospective case series study was designed to examine the existence of a correlation between symptoms and reflux characteristics, based on data obtained from esophageal pH monitoring. Methods The study population consisted of 139 patients; 97 patients presented with laryngopharyngeal symptoms of GERD, including unexplained hoarseness, throat clearing, chronic cough, laryngospasm, globus, throat pain, and 42 patients presented with gastroenterologic symptoms, including heartburn and regurgitation. The results of 24-hour, double-channel ambulatory esophageal pH monitoring were analyzed comparing 2 symptom groups. The incidence of abnormal acid reflux at the upper and lower esophageal segments and the effects of upright and supine positions on reflux parameters were evaluated. Results The incidence of laryngopharyngeal reflux was significantly higher in the laryngopharyngeal symptom group than in the other (52% versus 38%). The patients with laryngopharyngeal reflux from both groups showed no significant differences in terms of number of acid reflux episodes, percentage of times pH was 4, and esophageal acid clearance. Upright and supine parameters did not show significant differences between the patient groups. Upright acid reflux episodes were, however, common in both groups at the lower esophageal and laryngopharyngeal segments. Conclusion Recent studies suggesting that otolaryngologic patients commonly show upright, daytime reflux with normal esophageal clearance and that typical GERD patients commonly have supine, nocturnal reflux with prolonged esophageal clearance are not supported by this study. This study indicates that acid reflux parameters and positional changes are not sufficient to explain why patients with GERD experience different symptoms. The regional symptoms of GERD may be attributed to the impairment of epithelial resistance, motor activity, and buffering systems for the esophageal antireflux barrier.

Efficacy of esomeprazole in controlling reflux symptoms, intraesophageal, and intragastric pH in patients with Barrett’s esophagus*

Barrett's esophagus is a metaplastic condition associated with gastroesophageal reflux disease and an increased risk for adenocarcinoma. Acid plays a significant role in the development and progression of Barrett's esophagus and high dose proton pump inhibitor (PPI) therapy is often needed. The aim of this study is to assess the efficacy of esomeprazole, a new potent PPI, on symptom relief and intraesophageal and intragastric acid suppression in patients with Barrett's esophagus (BE). Patients were evaluated by standardized questionnaires and dual sensor 24-h pH monitoring while receiving esomeprazole at a dose (40-80 mg/day) needed for control of symptoms. Analyses of intraesophageal and intragastric pH profiles were then made. Thirteen patients, mostly men, were studied. All tolerated esomeprazole (40-80 mg/day) with good symptom control. Sixty-two percent of patients with BE had abnormal intraesophageal pH profiles despite adequate symptom control on esomeprazole which was associated with significant breakthrough of intraesophageal acid control, particularly at night. Low nocturnal intragastric pH correlated highly with nocturnal intraesophageal acid reflux (P = 0.004) and there was a relative failure of nocturnal intragastric acid control with esomeprazole. A high percentage of patients with BE continue to exhibit pathologic GERD and low intragastric pH despite esomeprazole for reflux symptom control. For an antisecretory treatment aimed at chemoprevention of esophageal adenocarcinoma to be effective, higher PPI dosing confirmed by pH monitoring may be necessary.

Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association

Objective Although a large body of information exists about the prevalence of gastroesophageal reflux disease (GERD) in general, available data specifically addressing nocturnal reflux are limited. Because nocturnal acid reflux is reported to be associated with more severe injuries such as esophagitis and stricture, as well as adenocarcinoma of the esophagus, a better understanding of the prevalence and impact of nighttime heartburn as a sign of nocturnal acid reflux events can have significant potential management implications. The aims of this study were to determine the prevalence of nighttime heartburn and reflux-attributed supraesophageal symptoms among patients with GERD; and the impact of nighttime heartburn on sleep and several activities of daily living that could affect quality of life. Methods A nationwide telephone survey of 1000 adults experiencing heartburn at least once a week was conducted by the Gallup Organization on behalf of the American Gastroenterological Association. Results Altogether, 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, but only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines, and 49% of these rated this approach extremely effective. Conclusions Nighttime heartburn occurs in a large majority of adults with GERD, resulting in sleeping difficulties and impaired next-day function. The expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients.

Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association.

Although a large body of information exists about the prevalence of gastroesophageal reflux disease (GERD) in general, available data specifically addressing nocturnal reflux are limited. Because nocturnal acid reflux is reported to be associated with more severe injuries such as esophagitis and stricture, as well as adenocarcinoma of the esophagus, a better understanding of the prevalence and impact of nighttime heartburn as a sign of nocturnal acid reflux events can have significant potential management implications. The aims of this study were to determine the prevalence of nighttime heartburn and reflux-attributed supraesophageal symptoms among patients with GERD; and the impact of nighttime heartburn on sleep and several activities of daily living that could affect quality of life. A nationwide telephone survey of 1000 adults experiencing heartburn at least once a week was conducted by the Gallup Organization on behalf of the American Gastroenterological Association. Altogether, 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, but only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines, and 49% of these rated this approach extremely effective. Nighttime heartburn occurs in a large majority of adults with GERD, resulting in sleeping difficulties and impaired next-day function. The expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients.

Surgical trial investigating nocturnal gastroesophageal reflux and sleep (STINGERS).

Nocturnal reflux is important in the pathogenesis of esophagitis. The relationship between reflux and sleep is poorly understood, although data support both paradigms of nocturnal reflux causing arousal and nocturnal arousal allowing reflux. Furthermore, the effect of fundoplication on sleep is unknown. Seven volunteers and 11 patients with gastroesophageal reflux disease (GERD) and nocturnal symptoms were studied with esophageal pH and polysomnography at baseline and at 8 to 10 weeks follow-up evaluation, with patients undergoing interval fundoplication. Gastrointestinal and sleep questionnaires were completed before each study. Questionnaire data between the groups showed differences at baseline, which were eliminated by surgery. No objective differences in sleep were observed between the groups at baseline or at follow-up evaluation. However, the patient group significantly increased the fraction of the night spent in deeper sleep (49.6% vs 58.3%; p = 0.022). Reflux events were associated with arousals in sleep. Fundoplication improves both subjective and objective sleep quality in patients with nocturnal GERD symptoms.

Persistent acid reflux and symptoms in patients with Barrett's oesophagus on proton-pump inhibitor therapy.

To assess both acid gastro-oesophageal reflux (GOR) suppression in patients with Barrett's oesophagus on proton-pump inhibitors (PPI) and the predictive value of symptoms. DESIGN A prospective study of patients with Barrett's epithelium (> 3 cm, containing specialized intestinal metaplasia). Forty-five patients with Barrett's epithelium were recruited. Therapy was adjusted to omeprazole 20 mg twice daily. Oesophageal manometry and 24 h pH studies were performed on treatment. Heartburn score was calculated before and after PPI dose adjustment. In patients with persisting acid reflux, omeprazole dose was increased to 20 mg three times daily and pH studies repeated. Adequacy of GOR suppression, assessed by pH monitoring, was related to heartburn score (0-3). Twenty of the 45 patients were symptomatic (mean score 1.9) on pre-study treatment (mainly omeprazole < 20 mg once daily); on omeprazole 20 mg twice daily, only six patients remained symptomatic (mean score 1.6). Ten patients (22%) had persisting GOR on omeprazole 20 mg twice daily (median % total time with pH < 4 was 8%). Abnormal nocturnal reflux was found in nine and abnormal daytime reflux in only four patients. Heartburn persisted in three of these 10 patients (30%). Those remaining symptomatic had more daytime acid reflux than the asymptomatic patients with persistent reflux (median percentage daytime at pH < 4 was 13.6% vs 0.6%, respectively; P < 0.01). By increasing the omeprazole dose to 20 mg three times daily, only three of the 10 had persistent acid reflux. Persistent acid reflux on PPI therapy is common in patients with Barrett's oesophagus. Although nocturnal acid reflux is the most common finding, symptoms tended to occur in those with abnormal daytime reflux. Symptom resolution does not guarantee acid reflux control.

Interaction of sleep disturbances and gastroesophageal reflux in chronic laryngitis

Background: A considerable percentage of patients with reflux laryngitis do not respond to conventional treatment with proton pump inhibitors or prokinetics. At the present time, the reasons for this are not well known. Purpose: To investigate whether nocturnal reflux associated with sleep-related respiratory disorders is the cause of refractory laryngitis. Method: The data from 227 patients (133 women, ages 18 to 75 years, body mass index 17.4 to 38.3, mean 32.1 kg/m2) with LG were analyzed retrospectively. All received laryngoscopy and gastroscopy. All patients initially received 40- to 80 mg omeprazole and underwent a follow-up laryngoscopy after 6 weeks. Of the patients, 202 showed a clear improvement, whereas 25 (11.1%) did not. All underwent 24-hour pH monitoring and cardiorespiratory polysomnography. Results: All of the patients showed laryngoscopic signs of LG. Of the patients, 102 (45%) had a hiatal hernia and 53 (28%) suffered from reflux esophagitis. Forty-two patients (19%) were found to have Helicobacter pylori in the stomach. Among the 25 patients who failed to respond to omeprazole, pH monitoring showed nocturnal acid reflux in 15 (60%). Twenty-four patients (96%) showed a sleep-related respiratory disturbance manifesting as pathologic snoring (16 patients) or obstructive sleep apnea (8 patients, respiratory disturbance index [RDI] 11 to 33, mean 16.3/h). All received nasal continuous positive airway pressure (nCPAP) treatment, 16 with constant mask pressure (4 to 12, mean, 5.6 mbar) and 8 with autoadjusting pressure. One patient abandoned treatment; the other 23 showed clear subjective and objective improvement after 3 months of treatment. Conclusions: Even without pH monitoring evidence of nocturnal reflux, refractory LG is very often associated with sleep-related respiratory disorders and responds well to nCPAP treatment. Prospective studies are needed to clarify the details of this association. (Am J Otolaryngol 2002;23:20-26. Copyright © 2002 by W.B. Saunders Company)