Sleep Disorders Related to Chronic Gastroesophageal Reflux Disease (GERD): Determining Their Prevalence in the European and American General Population


Scope of the Meeting


Goal

We plan to design a project to investigate the relationship between chronic Gastroesophageal Reflux Disease (GERD) and Sleep. This project is based on a previous longitudinal study of the general populations of the United Kingdom, Germany, Spain and USA.

We have already shown the strong link between nocturnal awakenings and GERD. We have shown how GERD disturbs Sleep and how Sleep aggravates GERD. This research provides the impetus for further investigations in terms of remission, recurrence, and chronicity. Treatment resistance is one of the keys to understand how the evolution of Sleep and GERD could interact. Full, partial and non-responders to treatment need to be defined on the basis of their clinical features. Identifying and describing evolution predictors and risk factors are our objectives. 

The first phase of this project will be to gain consensus and clarity on the role of subsets of comorbidities and links between Sleep Disorders and Chronic GERD. The aim for this phase is to establish a consensus on what we know and what we still need to know in order to advance the research and treatment of chronic GERD.

Objectives

  1. To identify the clinical keys for screening the general population for GERD.
  2. To identify the main parameters of quality of life for patients suffering of GERD
  3. To define the key comorbid pathologies related to chronic GERD
  4. To understand the key clinical symptoms of chronic GERD and their link with sleep disorders
  5. To identify and eventually predict the response to treatment for GERD and sleep

Program

Friday, February 10, 2017

08:30 - 08:40 Maurice Ohayon, MD, DSc, PhD
Welcome and Opening Remarks
 
08:40 - 09:30 Maurice Ohayon, MD, DSc, PhD
The Relationship between Chronic GERD and Sleep in a Longitudinal Survey of the US General Population
 
09:30 - 09:40 Discussion
 
09:40 - 10:30 George Triadafilopoulos, MD
GERD and Sleep: Refractory GERD
 
10:30 - 10:40 Discussion
 
10:40 - 10:50 Break
 
10:50 - 11:30 Ronnie Fass, MD
The Bilateral Relationship between Sleep and GERD - An Eye Opening Experience
 
11:30 - 11:40 Discussion
 
11:40 - 12:05 Krisel Ruth Saldívar Hernández, MD
Gastro-esophageal Reflux Disease and its Relationship with Mental Disorders
 
12:05 - 12:15 Discussion
 
12:15 - 13:15 Lunch
 
13:15 - 13:55 Adam Farmer, MD, PhD
The Role of the Vagus Nerve in Esophageal Hypersensitivity in Gastro-Esophageal Reflux Disease and Functional Esophageal Disorders – A Potential Therapeutic Target?
 
13:55 - 14:05 Discussion
 
14:05 - 14:45 Frank Tortorice, MD
A Functional Medicine Approach to GERD and Sleep Disorders
 
14:45 - 14:55 Discussion
 
14:55 - 15:15 Kyungyeol Bae, MD, PhD
Health-related Quality of Life of Patients with GERD
 
15:15 - 15:25 Discussion
 
15:25 - 15:40 Break
 
15:40 - 16:20 Michael Vitiello, PhD
GERD and Chronicity in the Elderly Populations
 
16:20 - 16:30 Discussion
 
16:30 - 17:10 Michelle Dossett, MD, PhD, MPH
Non-Pharmacologic Approaches to GERD Management
 
17:10 - 17:20 Discussion
 
17:20 - 17:40 Cristina Milesi, PhD
Summary of the Presentations
 
17:40 - 18:00 Maurice Ohayon, MD, DSc, PhD
Group Discussion and Next Steps
 
18:30 Dinner @ Il Fornaio Restaurant
(520 Cowper St, Palo Alto, CA)

Abstracts

The Relationship between Chronic GERD and Sleep in a Longitudinal Survey of the US General Population
Maurice Ohayon, MD, DSc, PhD
GERD is a digestive disease originating from the spilling of gastric acid from the stomach into the esophagus. The objective of this study was to assess the prevalence of GERD in the US general population and analyze its association with sleep, medical and psychiatric conditions. The survey is longitudinal and allowed to follow the evolution of sleep disorders associated with GERD and was completed by a representative sample of the US general adult population. 12,218 subjects were interviewed at wave 1 (W1) and 10,830 subjects were interviewed at wave 2 (W2). The analyses were carried on the subjects who participated in both interviews (N=10,930). On average, three years separated the two interviews. All the interviews were using the SleepEVAL system.
We found that 10.6% of the sample reported having seen a physician for GERD and/or were taking a medication for GERD at W1. At W2, this prevalence increased to 12.4%. GERD was chronic for 3.9% of the sample interviewed. The prevalence of GERD increased with age until 55 y.o. GERD chronicity increased with age, with individuals between 45 and 64 being at greater risk.
Subjects affected by GERD reported significantly higher nocturnal awakenings and were significantly more often diagnosed with obstructive sleep apnea and restless leg syndrome, while insomnia disorders were significantly higher only among subjects with chronic GERD.
Subjects affected by GERD were more likely to report other medical conditions, such as hypercholesterolemia, diseases of the musculoskeletal system and connective tissue and hypertension, than people that never experienced GERD. Individuals with chronic GERD were also significantly more likely to be affected by a major depressive disorder.
Sleep disorder symptoms such as nocturnal awakening are highly prevalent among GERD patients and can often lead into a sleep disorder diagnosis when they are not treated.

The bilateral relationship between sleep and GERD - An eye opening experience
Ronnie Fass, MD, FACG
Gastroesophageal reflux disease (GERD) is a chronic disorder and the most common disease that affects the esophagus. A population-based study estimated that 20% of the U.S. adult population experience GERD-related symptoms at least once a week [1]. GERD can lead to esophageal mucosal injury in a subset of patients as well as bothersome symptoms, such as heartburn and acid regurgitation that may affect patients’ reported quality of life.
Recent studies have suggested a bidirectional relationship between GERD and sleep [2]. GERD has been shown to adversely affect sleep by awakening patients from sleep during the night or more commonly by leading to multiple short amnestic arousals, resulting in sleep fragmentation. At the same time, sleep deprivation per se can adversely affect GERD by enhancing perception of intraesophageal acid (esophageal hypersensitivity) [2]. In fact, there is a potential “vicious cycle” in which GERD leads to poor quality of sleep, which then in turn enhances perception of intraesophageal stimuli that further exacerbates GERD [3].
Nighttime reflux has been demonstrated to be more commonly associated with the development of GERD-related symptoms, complications and extraesophageal manifestations of GERD [4]. Patients with reflux during sleep are more likely to develop esophageal inflammation, peptic stricture, esophageal ulceration, Barrett’s esophagus, and even adenocarcinoma of the esophagus [5, 6]. In addition, these patients have a higher prevalence of oropharyngeal, laryngeal, and pulmonary manifestations [7, 8]. Poor quality of sleep and a variety of sleep disturbances have been recently added to the growing list of extraesophageal manifestations of GERD.
The two pivotal underlying mechanisms for reduced quality of sleep and sleep disturbances in patients with GERD are heartburn that awakens patients from sleep during the night and short, amnestic arousals that lead to sleep deprivation. Between 47%–57% of the GERD patients reported having heartburn that awaken them from sleep during the night [1, 9, 10]. In the general population, about a quarter of the subjects reported heartburn that awakened them from sleep.
Overall, therapeutic studies using PPIs have shown good control of nighttime heartburn. In early studies that used the ambiguous end point of nighttime heartburn, the latter appears to be more responsive to PPI therapy than daytime heartburn. Furthermore, a PPI prior to dinner appears to be more efficacious in controlling nighttime heartburn than a PPI prior to breakfast in GERD patients with primarily nighttime symptoms [11].


Gastro-esophageal Reflux Disease and its Relationship with Mental Disorders
Krisel Ruth Saldívar Hernández, MD
Gastro-esophageal reflux disease (GERD) is a common health problem in the general population. The link between GERD and mental disorders is bi-directional. Nationwide-population studies confirm this theory. Subjects with GERD predict the appearance up to three times of major depressive disorder (MDD), anxiety disorders (AD), and sleep disorders during the course of the disease. MDD is comorbid in different GERD subgroups: erosive reflux disease, non- erosive reflux disease, hypersensitive esophagus and functional heartburn. Subjects without GERD that suffer from Major Mood Disorder have a 70% probability to develop GERD in the course of their psychopathology. This could be explained by medications with an anticholinergic or miorelaxant effect (OR= 1.45-1.71). The presence of MDD or AD has been reported to affect poorly the outcome of medical treatment for GERD and the improvement of mental disorders contribute to a higher response to treatment. The presence of MDD or AD also affects the outcome of the antireflux surgical treatment. These patients have referred less satisfaction with the results of the surgery than patients without a psychiatric disorder because they expected less postoperative pain, symptom relief, swallowing difficulties, and had more residual symptoms like chest pain, bloating and dysphagia, than patients without psychopathology.

The Role of the Vagus Nerve in Esophageal Hypersensitivity in Gastro-Esophageal Reflux Disease and Functional Esophageal Disorders – A Potential Therapeutic Target?
Adam D Farmer PhD MRCP
Gastro-esophageal reflux disease (GERD) is common. GERD is characterized by the involuntary movement of gastric contents into the esophagus. GERD is a normal physiological process that occurs several times a day without symptoms or damage of the esophageal mucosa in most otherwise healthy individuals. GERD is a condition in which reflux of gastric contents into the esophagus produces frequent or severe symptoms that negatively affect an individual’s quality of life or result in damage to the esophagus, pharynx or the respiratory tract. It is estimated that there is an approximate prevalence of 10-20% of GORD in western adult populations.
The typical presentation of GORD is chest burn (often referred to as heartburn) and the regurgitation of sour or bitter liquid, frequently mixed with food, into the proximal esophagus or oropharynx. Subjects may also have non-burning chest pain and difficulty in swallowing. The chest pain is usually located in the middle of the chest and may radiate through to the back. However, symptoms may occur in the absence of demonstrable reflux.
The Rome IV diagnostic criteria delineates five functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus and functional dysphagia. These are a heterogeneous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood.
In this lecture, I will provide the audience with an introductory primer to the structure and function of esophageal perception, including nociception, that forms the basis of the putative mechanisms that may give rise to symptoms in GERD and the functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established and potential management techniques.
One of the most interesting neuro-modulatory techniques that is available is physiological and electrical manipulation of vagal tone. The vagus nerve is a branch of the autonomic nervous system which mediates motility and analgesia in the foregut. GERD is associated with a reduction in vagal activity. However, during sleep vagal activity is known to predominant and moreover higher resting daytime vagal tone predicts sleep quality. Thus, the vagus nerve stimulation could represent a potential therapeutic target in both GERD and the functional esophageal disorders.


Health-related quality of life of patients with gastro-esophageal reflux disease
Kyung-Yeol Bae, MD, PhD
Health-related quality of life (HRQL) includes the areas of physical function, somatic sensation, psychological state, and social interactions that are affected by ones health status. Measurement of HRQL may help physicians to understand the patient’s perspective of the risks and benefits of medical intervention. A lot of instruments have been developed for the evaluation of HRQL of patients with gastro-esophageal reflux disease (GERD). A lot of studies have suggested that GERD has a significant negative impact on near all domains of general HRQL. Previous studies have reported that the clinical factors contributing to the HRQL in patients with GERD may include the symptom severity such as heartburn sensation, nocturnal symptom and so on. The measurement of HRQL in patients with GERD can serve as a complement to traditional outcome measures. Further systematic studies are needed to ascertain the exact effect of GERD on patient’s HRQL.

GERD, SLEEP and AGING
Micheael Vitiello, PhD
Gastroesophageal reflux disease (GERD) is a common, chronic digestive disease. GERD occurs when stomach acid or, occasionally, stomach content, flows back into the esophagus, irritating it’s lining. Gastroesophageal reflux and disturbed sleep are closely associated. Reflux is often more common at night and typically results in awakenings from sleep and difficulty returning to sleep. The prone position typical of sleep results in more fluid pressure against the esophageal sphincter increasing the likelihood of reflux. GERD and sleep disturbance are both quite common in the older adult population. Yet little is known about the interactions of GERD and disturbed sleep, per se, and sleep disorders such as obstructive sleep apnea and how these interactions may be influenced by advancing age. Similarly, the magnitude of potential adverse impact of GERD on cognitive function in older adults, either directly through chronic sleep disturbance and its impact on the glymphatic system, or indirectly by treatment with proton pump inhibitors and resultant effects on Vitamin B12 metabolism is unclear.

Non-pharmacologic approaches to GERD Management
Michelle Dossett, MD, PhD, MPH
While proton pump inhibitors reduce GERD-related symptoms in many individuals, not everyone benefits and long-term use is associated with side-effects. A growing body of evidence suggests that certain non-pharmacologic approaches may improve GERD symptoms. This talk will review the evidence for acupuncture, mind-body therapies, supplements, and the therapeutic effect of the patient-clinician interaction.


This Activity is supported by unrestricted grants from John Arrillaga Foundation, The Bing Foundation, Takeda Development Centre Europe.