This review examines the temporal association between nocturnal gastro-oesophageal reflux and sleep-arousal cycles. Most nocturnal gastro-oesophageal reflux events occur during the awake cycle, and arousals precede most nocturnal gastro-oesophageal reflux events, indicating that arousal from sleep predisposes to nocturnal gastro-oesophageal reflux. This sheds light on the complex relationship between nocturnal gastro-oesophageal reflux and sleep, and has implications for managing nocturnal gastro-oesophageal reflux symptoms. The appearance of symptoms and the pathophysiology of nocturnal gastro-oesophageal reflux are influenced by sleep hygiene, sleep disturbances and the misalignment of circadian rhythms. Nocturnal gastro-oesophageal reflux and its related sleep disorders are prevalent and negatively impact the quality of life. There is conflicting evidence on whether nocturnal gastro-oesophageal reflux and sleep disturbances are causally linked, and whether sleep disturbances drive nocturnal gastro-oesophageal reflux. Poor sleep quality increases oesophageal hypersensitivity and overall acid exposure. The nocturnal gastro-oesophageal reflux is linked to the more severe forms of gastro-oesophageal reflux disease, especially with atypical/extra-oesophageal manifestations and complications of mucosal damage such as oesophagitis and stricture, Barret's oesophagus, and oesophageal adenocarcinoma. This review highlights the role of sleep problems in presenting nocturnal gastro-oesophageal reflux, and the potential benefits of treating sleep disturbances in enhancing patient care and quality of life.

Obstructive sleep apnea (OSA) and asthma are common respiratory diseases that can coexist in the same patient. Epidemiological and pathophysiological data suggest an independent link between these two diseases. Specially, OSA is frequently associated with non-eosinophilic and with poorly-controlled asthma. Common comorbidities including obesity, gastroesophageal reflux and rhinitis may promote this association. The impact of OSA treatment on the clinical and functional control of asthma has been extensively investigated. Numerous non-randomized studies suggest that continuous positive pressure treatment is likely to improve asthma symptoms, the control of the disease and quality of life in asthmatics with OSA. However, this impact has not been confirmed in the limited randomized trial available. To date, the optimal treatment approach in asthmatics with OSA is the best treatment of each disease separately and the recognition and treatment of comorbidities. When indicated, obesity surgery has a major impact on both diseases.

Many different subjective tools are being used to measure excessive daytime sleepiness (EDS) but the most widely used is the Epworth Sleepiness Scale (ESS). However, it is unclear if using the ESS is adequate on its own when assessing EDS. The aim of this study was to estimate the characteristics and prevalence of EDS using the ESS and the Basic Nordic Sleep Questionnaire (BNSQ) in general population samples. Participants aged 40 years and older answered questions about sleepiness, health, sleep-related symptoms and quality of life. Two groups were defined as suffering from EDS: those who scored >10 on the ESS (with increased risk of dozing off) and those reporting feeling sleepy during the day ≥3 times per week on the BNSQ. In total, 1,338 subjects (53% male, 74.1% response rate) participated, 13.1% reported an increased risk of dozing off, 23.2% reported feeling sleepy and 6.4% reported both. The prevalence of restless leg syndrome, nocturnal gastroesophageal reflux, difficulties initiating and maintaining sleep and nocturnal sweating was higher among subjects reporting feeling sleepy compared to non-sleepy subjects. Also, subjects reporting feeling sleepy had poorer quality of life and reported more often feeling unrested during the day than non-sleepy subjects. However, subjects reporting increased risk of dozing off (ESS > 10) without feeling sleepy had a similar symptom profile as the non-sleepy subjects. Therefore, reporting only risk of dozing off without feeling sleepy may not reflect problematic sleepiness and more instruments in addition to ESS are needed when evaluating daytime sleepiness.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease.

Sleep dysfunction is an epidemic affecting a large portion of the adult population. Recent studies have linked sleep dysfunction with an upregulation of proinflammatory cytokines (eg, tumor necrosis factor-α, interleukin-1 and interleukin-6), the implications of which can have a profound impact on a variety of gastrointestinal disease. In particular, sleep dysfunction seems to accelerate disease states characterized by inflammation (eg, gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia, chronic liver disease, inflammatory bowel disease, and colorectal cancer). This article evaluates the complex interplay between sleep dysfunction and gastrointestinal health and disease.

The purpose of this study was to investigate cough hypersensitivity and its potential mechanisms in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).

Fifteen OSAHS patients, 12 simple snoring patients, and 15 healthy volunteers received cough sensitivity test and induced sputum cytology. Cough thresholds C2 and C5 (the minimum of capsaicin inducing ≥ 2 and ≥ 5 coughs, respectively), total cell count, cell differentials and the levels of bradykinin, histamine, prostaglandin E₂, substance P, calcitonin gene-related peptide, pepsin, and interleukin-2 in the induced sputum detected by enzyme-linked immunosorbent assay were compared. The linear correlation between lgC2 and lgC5 and apnea hypopnea index, cell differentials, and inflammatory mediators in the induced sputum was calculated in OSAHS patients.

OSAHS patients presented with a significant lower C2 and C5 (P < 0.01), increased lymphocyte but decreased macrophage and neutrophil proportions in the induced sputum (P < 0.01), and higher contents of substance P, calcitonin gene-related peptide and interleukin-2 (P < 0.01) but similar levels of bradykinin, pepsin, prostaglandin E₂, and histamine (P > 0.05) in the supernatant of induced sputum, when compared with simple snoring patients and healthy volunteers. However, theses variable were comparable between simple snoring patients and healthy volunteers (P > 0.05). Finally, lgC2 or lgC5 was negatively related to apnea hypopnea index, lymphocyte percentage, and the levels of substance P, calcitonin gene-related peptide or interleukin-2 in the sputum (P < 0.01). There was a positive linear correlation between lymphocyte percentage and interleukin-2 level in the induced sputum (r = 0.63, P = 0.00).

OSAHS patients have a predisposition of cough hypersensitivity associated with airway inflammation.

This is the first study to compare reflux events during wake and sleep in obese and non-obese individuals with obstructive sleep apnea (OSA) and obese individuals without OSA. The primary aim of the study was to investigate any additive effect of OSA on gastroesophageal reflux (GER) above that of obesity.

Twenty obese individuals (body mass index, BMI > 30 kg/m(2)), 9 non-obese individuals (BMI < 30 kg/m(2)) with moderate-to-severe OSA, and 17 obese control subjects (BMI > 30 kg/m(2)) underwent high-resolution esophageal manometry, 24-h esophageal pH-impedance monitoring, and in-laboratory polysomnography.

Mean body mass index was 40 ± 6 and 27 ± 4 kg/m(2) for the obese and non-obese OSA groups, respectively, and 34 ± 5 kg/m(2) for the obese control group. Apnea-hypopnea index (AHI) was 50 ± 30 and 30 ± 25 per hour for the obese and non-obese OSA groups (p > 0.05), significantly higher than that of the obese control group (3 ± 3 per hour, p < 0.05). The two obese groups did not show any significant differences in the total number of acidic reflux events (41 ± 20 vs 28 ± 16); however, the obese OSA group had a greater number of acidic reflux events compared to the non-obese OSA group (22 ± 12 events, p < 0.05). In multivariate analysis, BMI significantly predicted number of acidic reflux events (r(2) = 0.16, p = 0.01) during the 24-h period; however, AHI showed no significant association with any measure of GER severity.

This study confirms an important role for obesity, rather than OSA per se in the relationship between OSA and GER.

The pathogenetic relationship underlying the high prevalence of gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnea (OSA) remains unclear. In addition, GERD has not been adequately assessed by endoscopy in patients with OSA. The purpose of this study was to use endoscopy to investigate potential interactions among reflux esophagitis, hiatal hernia (HH) and OSA.

A total of 243 consecutive male Japanese participants who underwent both overnight ambulatory polygraphic monitoring and esophagogastroduodenoscopy were retrospectively evaluated in a cross-sectional study. The prevalence and severity of HH and reflux esophagitis were assessed according to the Los Angeles classification and the Makuuchi classification, respectively. Associations among reflux esophagitis, HH and OSA were examined by univariate and multivariate analyses.

OSA was diagnosed in 98 individuals (40.3%). Endoscopy-confirmed esophagitis (p = 0.027) and HH (p < 0.001) were significantly more prevalent among patients with OSA. Multivariate regression model analysis adjusted for age, body mass index, visceral obesity represented by waist circumference, presence of OSA, concurrence of OSA and HH, smoking, and alcohol consumption yielded OSA as the only variable significantly associated with HH (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.35-4.99; p = 0.004), while concurrence of OSA and HH was related to reflux esophagitis (OR, 3.59; CI, 1.87-6.92; p < 0.001).

OSA was associated with HH and concurrent OSA and HH with reflux esophagitis in male Japanese patients with OSA. Our results support the hypothesis that complicating HH may link reflux esophagitis to OSA.

Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI).

Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history.

Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03).

In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE.

Obstructive sleep apnea (OSA) and asthma are highly prevalent respiratory disorders and are frequently co-morbid. Risk factors common to the two diseases include obesity, rhinitis, and gastroesophageal reflux (GER). Observational and experimental evidence implicates airways and systemic inflammation, neuromechanical effects of recurrent upper airway collapse, and asthma-controlling medications (corticosteroids) as additional explanatory factors. Therefore, undiagnosed or inadequately treated OSA may adversely affect control of asthma and vice versa. It is important for clinicians to be vigilant and specifically address weight-control, nasal obstruction, and GER in these populations. Utilizing validated screening instruments to affirm high risk of co-morbid OSA or asthma in persistently symptomatic patients will allow clinicians to cost-effectively test and treat appropriate patients, potentially improving outcomes. While non-invasive ventilation in acute asthma improves outcomes, the role of chronic continuous positive airway pressure (CPAP; the first-line treatment for OSA) in improving long-term asthma control is not known. Future research should focus on the impact of optimal CPAP therapy and adherence on asthma symptoms and outcomes.

Nocturnal gastroesophageal reflux (nGER) has received increasing interest as a predisposing factor for respiratory diseases and sleep disturbances. The possible role of obstructive sleep apnea (OSA) contributing to nGER is of special interest. The aim of this study was to explore the association between nGER and respiratory diseases, lung function and symptoms of OSA.

Participants in the Burden of Obstructive Lung Disease (BOLD) initiative in Iceland and Sweden, a random sample from the general population of 1325 adults aged 40+ (>70% response rate), were compared by pre- and post-bronchodilator spirometry, answers to questionnaires about OSA and respiratory symptoms, health, and symptoms of GER.

Altogether 102 (7.7%) reported nGER and 249 had used medication against GER. The participants were divided into three groups: 1) No nGER (n = 1040), 2) treated GER without nGER (n = 183) and 3) nGER (n = 102). The nGER group had a significantly higher prevalence of respiratory and OSA symptoms than subjects without nGER. The nGER group also had a higher prevalence of COPD (GOLD stage 1+), (25.0% vs. 15.6%) (p = 0.02) and lower FEV(1)/FVC ratio (95.9% vs. 98.9% of the predicted, p = 0.01). These associations remained significant after adjusting for smoking, weight and other possible confounders. No independent association was found between having treated GER and lung function, respiratory or OSA symptoms.

In our cross-sectional epidemiological study, untreated nGER is strongly associated with both respiratory and OSA symptoms as well as airflow obstruction.

It is has been widely studied and proved that obstructive sleep apnea is a risk factor for cardiovascular diseases, especially hypertension, myocardial infarction and stroke. It is also important to be aware that, due to sleep apnea, hypersomnia increases the risk of accidents and the prevalence of neuropsychiatric complications (cognitive impairments, depression, memory and concentration problems, quality of life decreasing). Sleep apnea has several social and economical consequences. Family physicians have an important role in screening and recognizing sleep apnea. Effective screening methods could prevent severe, irreversible complications and could improve patients' quality of life. Family physicians should collaborate with a specialist from sleep laboratory in the field of the patients' examination, treatment and care.

Obstructive sleep apnea (OSA) is associated with increased nocturnal gastroesophageal reflux (nocturnal GER) events and symptoms. Treatment of OSA with continuous positive airway pressure (CPAP) reduces nocturnal GER in patients with OSA. This study sought to determine the: (1) relationship of nocturnal GER events with apnea/hypopnea and arousal, (2) effect of upper airway obstruction on the barrier function of the lower esophageal sphincter (LES), (3) mechanism of LES failure for each nocturnal GER event and (4) effect of CPAP on LES function during sleep.

Eight patients with OSA and nocturnal GER underwent polysomnography with esophageal manometry and pH monitoring. The first half of the night was spent without CPAP and the second half with 10 cmH(2)O CPAP.

Baseline LES barrier pressure (P (b)) was low in these patients. When patients were off CPAP, there were 2.7 ± 1.8 nocturnal GER events per hour and 70 ± 39 obstructive respiratory events per hour. There was no direct relationship between the occurrence of GER and obstructive events. While upper airway obstruction did not alter P (b), CPAP tended to increase the nadir P (b) during LES relaxation (LESR) and decreased the duration of LESR.

Upper airway obstructive and nocturnal GER events are not directly related. The relatively low P (b) in these OSA patients raises the possibility of weakening of the gastroesophageal junction from repetitive strain associated with obstructed breathing events. The favourable effect of CPAP on nocturnal GER is possibly due to an increase in nadir P (b) and decrease in the duration for which the LES relaxes during swallow-induced and transient LESR.

It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients.

Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed.

Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE.

In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.

Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep.

We studied 15 controls, nine patients with GER disease (GERD) and without OSA, six patients with OSA and without GERD, and 11 patients with both OSA and GERD for 6 to 8 h postprandially during sleep. We concurrently recorded the following: (1) UES, GEJ, esophageal body (ESO), and gastric pressures by high-resolution manometry; (2) pharyngeal and esophageal reflux events by impedance and pH recordings; and (3) sleep stages and respiratory events using polysomnography. End-inspiration UES, GEJ, ESO, and gastric pressures over intervals of OSA were averaged in patients with OSA and compared with average values for randomly selected 10-s intervals during sleep in controls and patients with GERD.

ESO pressures decreased during OSA events. However, end-inspiratory UES and GEJ pressures progressively increased during OSA, and at the end of OSA events were significantly higher than at the beginning (P < .01). The prevalence of GER and EPR events during sleep in patients with OSA and GERD did not differ from those in controls, patients with GERD and without OSA, and patients with OSA and without GERD.

Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent reflux.

Obesity is a risk factor for gastroesophageal reflux disease (GERD) and for obstructive sleep apnea (OSA). Our aim was to evaluate in morbidly obese patients the prevalence of OSA and GERD and their possible relationship.

Morbidly obese patients [body mass index (BMI) >40 or >35 kg/m(2) in association with comorbidities] selected for bariatric surgery were prospectively included. Every patient underwent a 24-h pH monitoring, esophageal manometry, and nocturnal polysomnographic recording.

Sixty-eight patients [59 women and 9 men, age 39.1 +/- 11.1 years; BMI 46.5 +/- 6.4 kg/m(2) (mean +/- SD)] were included. Fifty-six percent of patients had an abnormal Demester score, 44% had abnormal time spent at pH <4, and 80.9% had OSA [apnea hypopnea index (AHI) >10] and 39.7% had both conditions. The lower esophageal sphincter (LES) pressure was lower in patients with GERD (11.6 +/- 3.4 vs 13.4 +/- 3.6 mm Hg, respectively; P = 0.039). There was a relationship between AHI and BMI (r = 0.337; P = 0.005). Patients with OSA were older (40.5 +/- 10.9 vs 33.5 +/- 10.4 years; P = 0.039). GERD tended to be more frequent in patients with OSA (49.1% vs 23.1%, respectively; P = 0.089). There was no significant relationship between pH-metric data and AHI in either the 24-h total recording time or the nocturnal recording time. In multivariate analysis, GERD was significantly associated with a low LES pressure (P = 0.031) and with OSA (P = 0.045) but not with gender, age, and BMI.

In this population of morbidly obese patients, OSA and GERD were frequent, associated in about 40% of patients. GERD was significantly associated with LES hypotonia and OSA independently of BMI.

Patients with obstructive sleep apnea are at risk of mortality and morbidity related to the administration of sedatives, anesthetics, and opioids. Commonly employed sedatives and analgesics promote pharyngeal collapse and alter normal respiratory responses to obstruction and apnea. Literature concerning patients with obstructive sleep apnea undergoing moderate and deep sedation in the endoscopy suite is lacking. The purpose of this article is to provide the reader with a review of normal airway patency, the effects of obstructive sleep apnea on airway patency, and the impact that analgesics and sedatives may impart on the airway of patients with obstructive sleep apnea. The goal of this article is to increase awareness, stimulate discussions within the gastroenterological community, and encourage research regarding sedation in this at-risk population.

Despite being clinically important and highly prevalent, several aspects of gastroesophageal reflux disease are incompletely understood. Research activity remains high, however, and we shall review some highlights from last year's publications.

Community based epidemiological studies have elucidated the risk factors for gastroesophageal reflux disease and demonstrated a significant risk for developing complications over time. New histological parameters such as distended intercellular spaces in the epithelium will detect minor signs of reflux damage. The esophageal endoscopic capsule has been studied as a way of screening for esophageal disease. Wireless pH-metry and impedance-pH-metry have increased our insight into the pathophysiology and improved the diagnostic work-up in atypical and therapy resistant cases. At the molecular level, the role of cytokines has been elucidated and there is increased support for the nitrosative stress theory for epithelial damage at the cardia. Endoscopic therapies have shown disappointing long-term results or safety concerns, leading to withdrawal of several methods.

The last year has brought significant development in diagnostic modalities, and increased our insight in the molecular events involved in the pathogenesis of gastroesophageal reflux disease. Ultimately, this may and must lead to new therapeutic modalities which will supplement proton pump inhibitors in medical therapy for gastroesophageal reflux disease.