Key points

Introduction

Gastroesophageal reflux disease (GERD) is a chronic disorder characterized by typical bothersome symptoms such as heartburn and acid regurgitation. A population-based study estimated that 20% of adults in the United States experience GERD symptoms at least weekly. A recent report demonstrated that GERD is the most common gastrointestinal (GI) diagnosis, accounting for approximately 9 million patient visits in the United States in 2009. Heartburn occurs at any time throughout the day, whereas heartburn during sleep occurs only during conscious awakenings. Nighttime GERD is associated with more severe disease than daytime GERD, including worsened quality of life, impairment of work productivity, extraesophageal symptoms (hoarseness, wheezing, and coughing), daytime sleepiness, sleep disturbances, and esophageal complications (stricture, Barrett’s esophagus, and esophageal adenocarcinoma).

Recent studies have further explored the epidemiology, pathophysiology, diagnostic modalities, and therapy in GERD-related sleep disturbances. This review attempts to provide a summary of the current knowledge about GERD and sleep.

Introduction

Gastroesophageal reflux disease (GERD) is a chronic disorder characterized by typical bothersome symptoms such as heartburn and acid regurgitation. A population-based study estimated that 20% of adults in the United States experience GERD symptoms at least weekly. A recent report demonstrated that GERD is the most common gastrointestinal (GI) diagnosis, accounting for approximately 9 million patient visits in the United States in 2009. Heartburn occurs at any time throughout the day, whereas heartburn during sleep occurs only during conscious awakenings. Nighttime GERD is associated with more severe disease than daytime GERD, including worsened quality of life, impairment of work productivity, extraesophageal symptoms (hoarseness, wheezing, and coughing), daytime sleepiness, sleep disturbances, and esophageal complications (stricture, Barrett’s esophagus, and esophageal adenocarcinoma).

Recent studies have further explored the epidemiology, pathophysiology, diagnostic modalities, and therapy in GERD-related sleep disturbances. This review attempts to provide a summary of the current knowledge about GERD and sleep.

Epidemiology

A national survey demonstrated that 74% of the individuals who experienced GERD symptoms at least once a week also reported nighttime GERD symptoms. These symptoms occurred when patients lay down to sleep at night (69%), awoke from sleep at night (54%), woke up in the morning (40%), and awoke at night because of coughing or choking due to fluid, an acidic or bitter taste, or food in the throat (29%). Another nationwide survey by the Gallup Organization demonstrated that 79% of the 1000 adults who experienced heartburn at least once a week had nighttime heartburn. Among these individuals, 75% reported that these symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, 40% believed that sleep difficulties caused by nighttime heartburn impaired their ability to function the following day, 42% stated that they accepted they could not sleep through the night, 39% reported that they took naps whenever possible, 34% reported sleeping in a chair or in a seated position, and 27% reported that their heartburn-induced sleep disturbances kept their spouses from having a good night’s sleep. In a large cohort evaluated by the Sleep Heart Health Study, 3806 of 15,314 subjects (25%) reported having heartburn that caused them to awaken from sleep 2 or more times per month. Heartburn that occurred during sleep was strongly associated with increased body mass index (BMI), consumption of carbonated soft drinks, snoring and daytime sleepiness, insomnia, hypertension, asthma, and benzodiazepine usage. College education was associated with a reduced risk for reporting heartburn during sleep. A patient-reported survey conducted in 2006 among the general United States population revealed that 89% of participants experienced nighttime symptoms, 68% experienced sleep difficulties, 49% had difficulty falling asleep, and 58% reported difficulty in maintaining sleep. These epidemiologic studies strongly indicate that nighttime GERD is very common and that most United States adults with GERD suffer from several types of GERD-related sleep abnormalities.

Sleep problems are also common in the general population. The 2008 National Sleep Foundation Sleep in America Poll demonstrated that approximately half of the participants reported nonrefreshing sleep a few nights per week or more, with 42% reporting frequent awakenings at night and 26% reporting difficulty in falling asleep. Wallander and colleagues performed a longitudinal, population-based cohort study of adults living in the United Kingdom. The investigators found that the diagnosis rate of a new sleep disorder was 12.5 per 1000 person-years, and prior GERD was identified as one of the risk factors for the development of sleep disturbances (odds ratio: 1.4; 95% confidence interval: 1.2–1.7). The latter study suggests that GERD precedes the development of sleep disturbances.

Pathophysiology of nighttime GERD and its related sleep disturbances

There are several differences in GI functions associated with GERD between wakeful and asleep periods. Basal gastric acid secretion is high during the late evening, although no differences in gastric acid secretion have been observed among the different sleep stages. Nocturnal acid breakthrough (NAB), defined as an intragastric pH less than 4.0 lasting for more than 1 hour during the night in patients taking a twice-daily proton-pump inhibitor (PPI), might play a role in the pathogenesis of nighttime GERD, particularly in PPI-refractory cases.

Several physiologic changes have been observed during sleep in comparison with the awake period, including delayed gastric emptying, decrease in frequency of transient lower esophageal sphincter relaxation (TLESR), decrease in basal upper esophageal sphincter pressure, primary and secondary esophageal peristalsis. Changes that occur during sleep with an impact on GERD, apart from those that affect the GI tract, include decreased saliva secretion and swallowing responses. It should be noted that TLESR, which plays a pivotal role in the pathogenesis of GERD, occurs only during arousals from sleep. These physiologic changes that occur during sleep increase the likelihood of nighttime reflux in patients with GERD.

Several pathophysiological mechanisms might explain the bidirectional relationship between GERD and sleep disturbances. Awakening from sleep because of nighttime heartburn commonly results in the initiation of swallowing and a consequent increase in esophageal clearance. Such response is necessary to prevent aspiration of reflux contents into the trachea. However, arousal from sleep is associated with impairment in sleep quality. Recently, several new findings regarding the mechanisms underlying the relationship between GERD and sleep were reported using combined pH monitoring and actigraphy (an actigraph is a wristwatch-like device that has been shown to be highly comparable with a polysomnogram in determining durations of sleep and awakening). Poh and colleagues found that the mean number of conscious awakenings detected by actigraphy was significantly higher in GERD patients than in controls. Of the conscious awakenings, 52% were associated with an acid reflux event in GERD patients, although they were seldom symptomatic. This finding confirmed that the presence of nighttime heartburn during sleep could not explain the full extent of the association between GERD and sleep disturbances.

Allen and colleagues demonstrated that increased acid reflux during recumbency occurred primarily during the recumbent-awake and not the recumbent-asleep period, suggesting that nighttime reflux is associated with difficulty in falling asleep. Therefore, presentation of gastroesophageal reflux (GER) during the recumbent period in bed is different during recumbent-awake compared with the recumbent-asleep period. Poh and colleagues examined the differences in the characteristics of reflux episodes before (up to 1 hour) and immediately after (10 and 20 minutes) awakening from sleep in the morning. The investigators found an increase in the frequency of reflux events in the early morning, termed “riser’s reflux,” in approximately 50% of the GERD patients. These findings might be associated with early awakening in the morning. Dickman and colleagues identified reflux events that are associated with short, amnestic arousals. This type of arousal is likely the precursor of prolonged acid reflux events during sleep. In addition, these types of acid reflux events during sleep might be associated with severe erosive esophagitis because lack of a conscious awakening response results in prolonged acid contact time with the esophageal mucosa. Short, amnestic arousals might also be associated with poorer quality of sleep due to sleep fragmentation. The aforementioned studies revealed that GERD could disturb sleep by causing difficulty in falling asleep, sleep fragmentation caused by multiple short amnestic arousals, or/and conscious awakenings and awakening in the early morning.

Poor sleep quality appears to affect GERD-related symptoms. Schey and colleagues examined the role of sleep deprivation on esophageal mucosal acid sensitivity of 10 healthy controls and 10 GERD patients. A crossover study was performed in which the participants were randomized to either sleep deprivation (1 night with ≤3 hours of sleep) or sufficient sleep (3 consecutive days with ≥7 hours sleep per night) as confirmed by actigraphy. Subsequently, the subjects underwent intraesophageal acid infusion in the morning after sufficient sleep or sleep deprivation. The investigators found that sleep deprivation significantly shortened the lag time to symptom generation and enhanced the intensity rating of symptoms in comparison with sufficient sleep in the GERD group but not in the healthy controls. This study suggests that sleep deprivation per se leads to or enhances esophageal sensitivity to acid, and was the first to suggest that poor sleep can exacerbate GERD. Thus, poor sleep can affect GERD and GERD can affect sleep. Fig. 1 summarizes the proposed mechanisms underlying the associations between GERD and sleep disturbances.

The underlying mechanisms of the association between GERD and sleep disturbances.

( Adapted from Fujiwara Y, Arakawa T, Fass R. Gastroesophageal reflux disease and sleep disturbances. J Gastroenterol 2012;47:760–9; with permission.)

Obstructive sleep apnea

The International Classification of Sleep Disorders published by the American Academy of Sleep Medicine suggested that sleep disorders are divided into insomnias, sleep-related breathing disorders, hypersomnia of central origin, circadian rhythm sleep disorders, parasomnias, sleep-related movement disorders, and others. Whereas the relationship between GERD and insomnia has been well substantiated, the association between GERD and other types of sleep disorders is either controversial or has not been fully elucidated.

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by episodes of partial or complete obstruction of the upper airway, thus interrupting or reducing the flow of air. This process leads to transient awakening from sleep during the night. In the United States, the prevalence of OSA is estimated to be 3% to 7% in men and 2% to 5% in women. Untreated OSA is currently recognized as an independent risk factor for the development of certain comorbid conditions such as hypertension, stroke, diabetes mellitus, and perioperative complications.

Epidemiologic studies demonstrated that the prevalence of GERD, GER episodes, and heartburn in patients with OSA is higher than in normal, healthy controls. However, the exact underlying mechanism of the relationship between OSA and GERD remains to be elucidated. Because negative intrathoracic pressure is generated against the closed airway during an apneic event, increases in the transdiaphragmatic pressure gradient could be responsible for GER in patients with OSA. However, a recent study using a combination of high-resolution manometry, pH-impedance monitoring, and polysomnography showed that esophageal body pressure decreased through apneic events, whereas end-inspiratory upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressures progressively increased in patients with OSA. Such compensatory changes in UES and GEJ pressures prevent reflux from occurring. Kuribayashi and colleagues demonstrated that GER events were mainly induced by TLESR that occurred during arousals from sleep in OSA patients with and without reflux esophagitis. Therefore, apneic events in patients with OSA were not directly associated with most GER events. An increase in the transdiaphragmatic pressure gradient during apneic events might play a role in GER of some patients with OSA, especially those with hiatal hernia.

Only a few small studies have evaluated the effect of nasal continuous positive airway pressure therapy (nCPAP) on GER in patients with OSA. Kerr and colleagues demonstrated that nCPAP reduced the percentage of total recording time that esophageal pH was less than 4.0 from 6.3% to 0.1%. Tawk and colleagues showed that nCPAP normalized the esophageal acid exposure in 81% of patients with OSA and GERD. However, Ing and colleagues demonstrated that nCPAP reduced the GER parameters in patients with OSA and those without OSA, suggesting that the effect of nCPAP was likely nonspecific. Morse and colleagues demonstrated that GERD symptoms were unrelated to sleep apnea, and OSA was not influenced by the severity of GERD; they also identified old age (>65 years), male gender, and high BMI (>30 kg/m ² ) as risk factors for sleep apnea.

Because obesity is strongly associated with GERD and OSA, the relationship between OSA and GERD might be simply due to common risk factors. Thus at present there is insufficient evidence of a causal relationship between OSA and GERD, and the disorders are likely associated with each other through similar risk factors.