Presentation and Epidemiology of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated mortality is rare. The prevalence of GERD symptoms appeared to increase until 1999. Risk factors for complications of GERD include advanced age, male sex, white race, abdominal obesity, and tobacco use. Most patients with GERD present with heartburn and effortless regurgitation. Coexistent dysphagia is considered an alarm symptom, prompting evaluation. There is substantial overlap between symptoms of GERD and those of eosinophilic esophagitis, functional dyspepsia, and gastroparesis, posing a challenge for patient management. Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated mortality is rare. The prevalence of GERD symptoms appeared to increase until 1999. Risk factors for complications of GERD include advanced age, male sex, white race, abdominal obesity, and tobacco use. Most patients with GERD present with heartburn and effortless regurgitation. Coexistent dysphagia is considered an alarm symptom, prompting evaluation. There is substantial overlap between symptoms of GERD and those of eosinophilic esophagitis, functional dyspepsia, and gastroparesis, posing a challenge for patient management. Joel H. RubensteinView Large Image Figure ViewerDownload Hi-res image Download (PPT) By consensus, gastroesophageal reflux disease (GERD) has been defined as the effortless movement of stomach contents into the esophagus or mouth causing troublesome symptoms or complications.1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar We review the clinical presentation and epidemiology of GERD. The cardinal symptoms of GERD are heartburn and regurgitation. GERD is exceedingly common, ranking as the most frequent gastrointestinal diagnosis associated with outpatient clinic visits in the United States (US), with nearly 9 million visits in 2009.2Peery A.F. Dellon E.S. Lund J. et al.Burden of gastrointestinal disease in the United States: 2012 update.Gastroenterology. 2012; 143: 1179-1187.e3Abstract Full Text Full Text PDF PubMed Scopus (1420) Google Scholar Although complications such as bleeding erosive esophagitis or peptic stricture are becoming less common, individuals with GERD symptoms have a decrement in their quality of life that is similar to patients with inflammatory bowel disease.2Peery A.F. Dellon E.S. Lund J. et al.Burden of gastrointestinal disease in the United States: 2012 update.Gastroenterology. 2012; 143: 1179-1187.e3Abstract Full Text Full Text PDF PubMed Scopus (1420) Google Scholar To accurately diagnose and manage GERD, it is important to recognize the epidemiologic risk factors for GERD, the variety of presenting symptoms and their relative likelihood of representing pathological reflux, and the potential for overlap with other gastrointestinal disorders. Heartburn and acid regurgitation are the classic symptoms of GERD. Patients generally report a burning feeling in the retrosternal area, raising into the chest and radiating toward the neck, throat, and occasionally the back.1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar It occurs post-prandially, particularly after large fatty meals or the ingestion of spicy foods, citrus products, fats, chocolates, or alcohol. The supine position and bending over may exacerbate heartburn. Nighttime heartburn may cause sleeping difficulties and impair next-day function.3Johnson D.A. Orr W.C. Crawley J.A. et al.Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial.Am J Gastroenterol. 2005; 100: 1914-1922Crossref PubMed Scopus (182) Google Scholar Sleep deprivation as well as psychological or auditory stress may lower the threshold for symptom perception.4Kessing B.F. Bredenoord A.J. Saleh C.M. et al.Effects of anxiety and depression in patients with gastroesophageal reflux disease.Clin Gastroenterol Hepatol. 2015; 13: 1089-1095Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar GERD can be diagnosed based on symptoms, such as the occurrence of heartburn 2 or more days a week, although symptoms can be less frequent if they are troublesome and have adverse effects on well-being.1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar The frequency and severity of heartburn does not associate with degree of esophageal damage. Regurgitation has been more inconsistently described in clinical trials and epidemiologic studies on GERD. Per the Montreal consensus statement, regurgitation is defined as the “perception of flow of refluxed gastric contents into the mouth or hypopharynx.”1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar Among patients with daily regurgitation, lower esophageal sphincter pressure is often low; many patients have associated gastroparesis, and esophagitis is common, making this symptom more difficult to treat medically than classic heartburn.5Kahrilas P.J. Jonsson A. Denison H. et al.Impact of regurgitation on health-related quality of life in gastro-oesophageal reflux disease before and after short-term potent acid suppression therapy.Gut. 2014; 63: 720-726Crossref PubMed Scopus (24) Google Scholar The lack of a standard for the diagnosis of GERD has made it difficult to define the accuracy of the typical reflux syndrome of troubling heartburn and/or regurgitation. The Diamond Study from the United Kingdom attempted to address this question in patients presenting to family practitioners with complaints of upper gastrointestinal symptoms.6Dent J. Vakil N. Jones R. et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: The Diamond Study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (221) Google Scholar GERD was present in 203 of 308 patients (66%), based on endoscopic esophagitis and/or abnormal acid exposure or a positive symptom association probability from 24-hour pH tests. Only 49% of patients with GERD selected either heartburn or regurgitation as their most troublesome symptom, followed by dyspepsia, bloating, regurgitation, and abdominal pain or discomfort that was not characterized as dyspepsia. Sensitivity and specificity values for symptom-based diagnosis of GERD were 63% and 63% by family practitioners and 67% and 70% by gastroenterologists, respectively. Questionnaires about reflux symptoms did not perform any better; they identified patients with GERD with only 62% sensitivity and 67% specificity. Nor could response of symptoms to treatment with the proton pump inhibitor (PPI) esomeprazole (40 mg for 2 weeks) increase diagnostic precision (a positive response to the PPI test was observed in 69% of patients with GERD and 51% of patients without GERD).7Bytzer P. Jones P. Vakil N. et al.Limited ability of the proton pump inhibitor test to identify patients with gastroesophageal reflux disease.Clinical Gastroenterol Hepatol. 2012; 10: 1360-1366Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar Similarly, a well-performed meta-analysis cast doubt on the diagnostic accuracy of the PPI trial, finding that it identified patients with GERD with 78% sensitivity and 54% specificity.8Numans M.E. Liu J. de Wit N.J. et al.Short-term treatment with proton pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics.Ann Intern Med. 2004; 140: 518-527Crossref PubMed Scopus (282) Google Scholar Less-common symptoms of GERD include dysphagia, chest pain, water brash, odynophagia, burping, hiccups, nausea, and vomiting. Dysphagia is considered an alarm symptom in patients with GERD that warrants upper endoscopy.9Fransen G.A. Janssen M.J. Muris J.W. et al.Meta-analysis: the diagnostic value of alarm symptoms for upper GI malignancy.Aliment Pharmacol Ther. 2004; 20: 1045-1052Crossref PubMed Scopus (64) Google Scholar Dysphagia usually occurs in patients with long-standing heartburn with slowly progressive dysphagia for solids. Weight loss is uncommon because patients have good appetites. The most common causes are peptic stricture and severe inflammation, but dysphagia can be the first symptom of Barrett’s esophagus with esophageal cancer. The chest pain associated with GERD can be indistinguishable from that of ischemic cardiac pain. GERD is a more frequent cause of non-cardiac chest pain than esophageal motor disorders.1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar The most problematic and controversial symptoms associated with GERD are chronic cough, chronic laryngitis (including hoarseness, globus sensation, and throat clearing), and asthma. Although potential mechanisms of pathogenesis have been identified, trials of medical and surgical anti-reflux treatments have produced uncertain and inconsistent results.1Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (2732) Google Scholar Some patients with GERD are asymptomatic. This is particularly true in older patients, perhaps because of decreased acidity of the reflux material or decreased pain perception. Many older patients present first with complications of GERD because of long-standing disease with minimal symptoms. This is a particular problem for patients with Barrett’s esophagus. European population studies found that 44%–46% of patients did not report symptoms of GERD.10Ronkainen J. Aro P. Storskrubb T. et al.Prevalence of Barrett’s esophagus in the general population: an endoscopic study.Gastroenterology. 2005; 129: 1825-1831Abstract Full Text Full Text PDF PubMed Scopus (749) Google Scholar, 11Zagari R.M. Fuccio L. Wallander M.A. et al.Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano-Monghidoro study.Gut. 2008; 57: 1354135-1354139Crossref Scopus (335) Google Scholar GERD symptoms overlap with those of other syndromes. This poses a challenge to diagnosis and can alter medical and surgical treatments. The issue of how to differentiate eosinophilic esophagitis (EoE) from GERD has confounded clinicians and researchers since the recognition of the disease. This diagnostic dilemma began with a pathology study of pediatric patients in 1982, which found that eosinophils in the esophageal squamous epithelium could be a manifestation of GERD, documented by 24-hour pH tests.12Winters H.S. Madara J.L. Stafford R.J. et al.Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis.Gastroenterology. 1982; 83: 818-823PubMed Google Scholar Pathologists rapidly accepted the concept, and it became common clinical practice to attribute esophageal eosinophilia to GERD. The first report describing EoE as a unique syndrome, characterized by solid food dysphagia and distinct from GERD by esophageal tests, was published in 1993.13Attwood S.E. Smyrk T.C. DeMeester T.R. et al.Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome.Dig Dis Sci. 1993; 38: 109-116Crossref PubMed Scopus (655) Google Scholar Subsequently, EoE was considered a chronic immune- or antigen-mediated esophageal disease. However, many cases still overlapped with GERD, so the PPI trial became the most logical and convenient means to differentiate GERD from EoE. This practice was based on the assumption that the only major effect of PPIs is to inhibit gastric acid production. Accordingly, in 2007, the American Gastroenterological Association’s consensus report defined EoE as a primary disorder characterized by esophageal symptoms, esophageal biopsies with more than 15 eosinophils per high-powered field, and the “absence” of pathologic GERD, evidenced either by normal results from pH tests or lack of response to PPIs.14Furuta G.T. Liacouras C.A. Collins M.H. et al.Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for the diagnosis and treatment.Gastroenterology. 2007; 133: 1342-1363Abstract Full Text Full Text PDF PubMed Scopus (1373) Google Scholar This mutually exclusive paradigm began to fall apart as editorials raised the possibilities of a complex interaction between GERD and EoE. These raised questions such as: does EoE cause GERD? Does GERD cause EoE? Or do these merely co-exist, because GERD is such a common disease?15Spechler S.J. Genta R.M. Souza R.F. Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis.Am J Gastroenterol. 2007; 102: 1301-1306Crossref PubMed Scopus (290) Google Scholar Subsequently, Ngo et al16Ngo P. Furuta G.T. Antonioli A. et al.Eosinophils in the esophagus – peptic or allergic eosinophilic esophagitis? Case series of three patients with esophageal eosinophilia.Am J Gastroenterol. 2006; 101: 1666-1670Crossref PubMed Scopus (275) Google Scholar described 3 patients with EoE and significant mucosal eosinophilia who improved, based on clinical and histologic features, after 2 months of PPI therapy. Several years later, Molina-Infante et al17Molina-Infante J. Ferrande-Lamana L. Ripell C. et al.Esophageal eosinophilic infiltration responds to proton pump inhibitors in most adults.Clin Gastroenterol Hepatol. 2011; 9: 110-117Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar published findings from 35 patients with mucosal eosinophilia (more than 15 eosinophils per high-powered field); 75% responded to rabeprazole (20 mg, twice daily) for 2 months. All 17 of the patients with GERD profile and objective acid reflux, based on endoscopy or pH tests, responded to this treatment. However, 50% of the patients with an EoE-like profile and normal pH test results also responded to the rabeprazole. The recognition of this condition, which was termed PPI-responsive esophageal eosinophilia (PPI-REE), caused further confusion. Studies documented that 23% to 61% of patients with symptomatic esophageal eosinophilia respond to PPI treatment.18Dellon E.S. Yellove V. Andreatta M. et al.Clinical and endoscopic characteristics do not reliably differentiate PPI responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study.Am J Gastroenterol. 2013; 108: 1854-1860Crossref PubMed Scopus (192) Google Scholar Furthermore, the clinical, endoscopic, histologic, and even esophageal gene-expression features of PPI-REE and EoE are virtually identical.19Molina-Infante J. Bredenoord A.J. Cheng E. et al.Proton pump inhibitor – responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilia oesophagitis.Gut. 2016; 65: 524-531Crossref PubMed Scopus (205) Google Scholar Therefore, PPI-REE resembles EoE far more than it resembles GERD. An exciting discovery around this controversy has been the recognition that EoE and GERD could each arise via cytokine-mediated esophageal injury. In contrast to the model in which refluxed acid causes a chemical injury that destroys esophageal cells, studies from patients and animal models indicated that the esophageal damage found in patients with GERD was caused by inflammatory cells that are attracted to the esophagus by cytokines produced by esophageal epithelial cells following exposure to refluxed acid and bile.20Souza R.F. Huo X. Mittal V. et al.Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury.Gastroenterology. 2009; 137: 1776-1784Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 21Dunbar K.B. Agoston A.T. Odze R.D. et al.Association of acute gastroesophageal reflux disease with esophageal histologic changes.JAMA. 2016; 315: 2104-2112Crossref PubMed Scopus (122) Google Scholar Studies of cultured esophageal epithelial cells revealed anti-cytokine effects of PPIs that were entirely independent of effects on gastric acid production; these could heal GERD and EoE. Omeprazole was found to block eotaxin-3 secretion stimulated by T-helper 2 cytokines produced by esophageal cells from patients with EoE or GERD22Cheng E. Zhang X. Huo X. et al.Omeprazole blocks eotaxin – 3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GERD.Gut. 2013; 62: 824-832Crossref PubMed Scopus (221) Google Scholar and block secretion of interleukin 8, a mediator of eosinophilic inflammation, after exposure to acid and bile salts in esophageal epithelial cells from patients with GERD.23Huo X. Zhang X. Yu C. et al.In oesophageal squamous cells exposed to acidic bile salt medium, omeprazole inhibits IL-8 expression through effects on nuclear factor-kappa B and activator protein-1.Gut. 2014; 63: 1042-1052Crossref PubMed Scopus (56) Google Scholar The current focus on how to distinguish EoE from GERD may therefore be counterproductive because the 2 diseases often co-exist with complex interactions. Patients with GERD with the typical reflux syndrome associated with erosive esophagitis and hiatal hernia can have mucosal eosinophilia, which often is confined to the distal esophagus. It is not clear what proportion of patients with GERD present with these features, but it is likely to be less than 10%.24Kia L. Hirano I. Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies.Nat Rev Gastroenterol Hepatol. 2015; 12: 379-386Crossref PubMed Scopus (39) Google Scholar The etiology of their mucosal eosinophilia may be secondary to direct acid injury or secondary to the effects of GERD on esophageal barrier function, which renders the epithelium permeable to food antigens and causes antigen-induced esophageal eosinophilia.25Calabrese C. Trese D. Liquori C. et al.Esophageal cell proliferation in gastroesophageal reflux disease: clinical – morphological data before and after pantoprazole.World J Gastroenterol. 2009; 15: 936-941Crossref PubMed Scopus (12) Google Scholar Regardless, PPIs can reduce both mechanisms of pathogenesis; careful separation by esophageal manometry and pH – impedance testing is necessary for only patients who require surgical anti-reflux treatment. Population-based studies have identified GERD and dyspepsia, defined as pain or discomfort centered in the upper abdomen, as some of the most common upper gastrointestinal tract symptoms; estimated prevalence values are approximately 20% for each.26Tack J. Talley N.J. Camilleri M. et al.Functional gastroduodenal disorders.Gastroenterology. 2006; 130: 1466-1479Abstract Full Text Full Text PDF PubMed Scopus (1433) Google Scholar Therefore, it should not be surprising that the distinction between GERD and functional dyspepsia may not be clear cut. More than 33% of patients with functional dyspepsia also report heartburn and acid regurgitation and vice versa. This was well illustrated in the Diamond study, in which 42% of the patients without GERD reported dyspepsia as their first- or second-most troubling symptom, whereas this value was 37% in patients subsequently found to have GERD.6Dent J. Vakil N. Jones R. et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: The Diamond Study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (221) Google Scholar Furthermore, endoscopy and pH tests do not separate these groups with a high level of confidence. A large systematic review of more than 5000 patients with a primary complaint of dyspepsia found endoscopic evidence of esophagitis in 13.4% of patients, followed by peptic ulcers in 8.0%.27Ford A.C. Marwaha A. Lim A. et al.What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2010; 8: 830-837Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Several studies identified patients with functional dyspepsia using Rome II or III criteria and performed 24-hour pH tests. Tack et al28Tack J. Caenepeel P. Arts J. et al.Prevalence of acid reflux in functional dyspepsia and its associated symptom profile.Gut. 2005; 54: 1370-1376Crossref PubMed Scopus (130) Google Scholar reported that 23% of patients with functional dyspepsia had abnormal acid exposure times, and their symptom profile was mainly epigastric pain. A similar study of an Asian population, performed by Xiao et al,29Xiao Y.L. Peng S. Tao J. et al.Prevalence and symptom patterns of pathologic esophageal acid reflux in patients with functional dyspepsia based on Rome III criteria.Am J Gastroenterol. 2010; 105: 2626-2631Crossref PubMed Scopus (75) Google Scholar found that 31.7% of patients had abnormal acid exposure times, with the highest percentage (48.9%) in patients who claimed epigastric burning was their predominate symptom. In this study, the proportion of patients with a response to PPI therapy at 1 month was highest (85%) in those with epigastric burning; the proportions were lower in patients with epigastric pain (51.5%), post-prandial distress with fullness (66.7%), or early satiation (41.1%). A study of 626 patients with erosive GERD treated with pantoprazole to esophagitis healing observed a 62% overlap between GERD and dyspepsia symptoms.30Monnikes H. Schwan T. van Rensburg C. et al.Randomized clinical trial: sustained response to PPI treatment of symptoms resembling functional dyspepsia and IBS in patients suffering from an overlap with erosive gastro-oesophageal reflux disease.Aliment Pharmacol Ther. 2012; 35: 1279-1289Crossref PubMed Scopus (22) Google Scholar Remarkably, the dyspepsia symptoms improved by 50% during PPI treatment and unlike the reflux symptoms, which usually relapsed with treatment cessation, the dyspepsia symptoms showed a trend to further decrease. The importance of delayed gastric emptying in the pathogenesis of GERD is controversial. Early studies indicated that up to 50% of patients with reflux had delayed emptying of solids.31McCallum R.W. Berkowitz D.M. Lerner E. Gastric emptying in patients with gastroesophageal reflux disease.Gastroenterology. 1981; 80: 285-291PubMed Scopus (367) Google Scholar However, more recent studies, using a standardized 4-hour gastric emptying test, found an overlap in 8%–20% of patients.32Camilleri M. Parkman H.P. Shafi M.A. et al.Clinical guideline: management of gastroparesis.Am J Gastroenterol. 2013; 108: 18-37Crossref PubMed Scopus (699) Google Scholar Conceptually, impaired gastric emptying results in a greater volume of material in the stomach, which could be available to directly reflux into the esophagus or generate distension of the proximal stomach, triggering transient lower esophageal sphincter relaxations. Recent studies with impedance-pH testing found that acid reflux values were not increased, but consistent with the reflux of meal contents, the increase was in post-prandial liquid or mixed reflux events and non/weakly acid reflux.33Gourcel G. Benanni Y. Boueyre E. et al.Influence of gastric emptying on gastro-esophageal reflux: a combined pH-impedance study.Neurogastroenterol Motil. 2013; 25: 800-807PubMed Google Scholar Women and diabetics are more likely to have gastroparesis with secondary GERD. Complaints of abdominal bloating, pain, nausea, vomiting, or constipation should be helpful clues and manometry often shows a normal lower esophageal sphincter pressure. Treating the gastroparesis with diet and prokinetics can alleviate the need for PPIs or anti-reflux surgery. The pooled prevalence of at least weekly GERD symptoms reported from population-based studies worldwide is approximately 13%, but there is considerable geographic variation.34Eusebi L.H. Ratnakumaran R. Yuan Y. et al.Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut. 2017; ([Epub ahead of print])Crossref PubMed Scopus (233) Google Scholar Accurate estimates are difficult because of heterogeneity in study designs, but the prevalence of GERD appears to be highest in South Asia and Southeast Europe (more than 25%), and lowest in Southeast Asia, Canada, and France (below 10%) (Figure 1).34Eusebi L.H. Ratnakumaran R. Yuan Y. et al.Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut. 2017; ([Epub ahead of print])Crossref PubMed Scopus (233) Google Scholar There are no data on the prevalence of GERD in Africa. In the US, estimates of the prevalence of GERD symptoms have ranged from 6% to 30%, with heterogeneity related to the particular questionnaire used, including the threshold frequency and duration of symptoms required to be classified as GERD.34Eusebi L.H. Ratnakumaran R. Yuan Y. et al.Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut. 2017; ([Epub ahead of print])Crossref PubMed Scopus (233) Google Scholar The prevalence of at least weekly GERD symptoms in the US is approximately 20%.35El-Serag H.B. Sweet S. Winchester C.C. et al.Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review.Gut. 2014; 63: 871-880Crossref PubMed Scopus (1039) Google Scholar There are approximately 110,000 hospital admissions annually in the US for GERD.36Thukkani N. Sonnenberg A. The influence of environmental risk factors in hospitalization for gastro-oesophageal reflux disease-related diagnoses in the United States.Aliment Pharmacol Ther. 2010; 31: 852-861PubMed Google Scholar Importantly, the prevalence of GERD symptoms in North America, Europe, and Southeast Asia has increased approximately 50% relative to the baseline prevalence in the early to middle 1990s, but has plateaued since then.35El-Serag H.B. Sweet S. Winchester C.C. et al.Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review.Gut. 2014; 63: 871-880Crossref PubMed Scopus (1039) Google Scholar In a population-based longitudinal study of a Norwegian county from 1995 through 2009, the annual incidence of any new GERD symptoms was 3.1%, and of severe GERD symptoms was 0.2%.37Ness-Jensen E. Lindam A. Lagergren J. et al.Changes in prevalence, incidence and spontaneous loss of gastro-oesophageal reflux symptoms: a prospective population-based cohort study, the HUNT study.Gut. 2012; 61: 1390-1397Crossref PubMed Scopus (92) Google Scholar Among individuals with any GERD at baseline and excluding those who were using anti-reflux medications, symptoms resolved spontaneously in 2.3% per year; among those with severe GERD, 1.2% spontaneously resolved per year. The predominant complications of GERD include dysphagia (including from peptic strictures, Schatzki’s rings), bleeding from erosive esophagitis, and esophageal adenocarcinoma (discussed in other sections of this issue). In 3 population-based studies of patients agreeing to undergo endoscopy regardless of symptoms, the prevalence of erosive esophagitis ranged from 6.4% in China to 15.5% in Sweden.38Dent J. Becher A. Sung J. et al.Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in large-scale surveys.Clin Gastroenterol Hepatol. 2012; 10: 863-873.e3Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 39Ronkainen J. Aro P. Storskrubb T. et al.High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report.Scand J Gastroenterol. 2005; 40: 275-285Crossref PubMed Scopus (351) Google Scholar, 40Zou D. He J. Ma X. et al.Epidemiology of symptom-defined gastroesophageal reflux disease and reflux esophagitis: The systematic investigation of gastrointestinal diseases in China (SILC).Scand J Gastroenterol. 2011; 46: 133-141Crossref PubMed Scopus (65) Google Scholar Among individuals without symptoms of GERD, the prevalence of erosive esophagitis ranged from 6.1% in China to 9.5% in Sweden. Erosive esophagitis may frequently be a transient phenomenon. In a prospective, longitudinal study, 26% of individuals with non-erosive reflux disease at baseline were found to have erosive esophagitis on repeat endoscopy 2 years later, and in another similar study, erosive esophagitis was found in 10% of individuals 5 years later.41Ronkainen J. Talley N.J. Storskrubb T. et al.Erosive esophagitis is a risk factor for Barrett's esophagus: a community-based endoscopic follow-up study.Am J Gastroenterol. 2011; 106: 1946-1952Crossref PubMed Scopus (78) Google Scholar, 42Labenz J. Nocon M. Lind T. et al.Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease.Am J Gastroenterol. 2006; 101: 2457-2462Crossref PubMed Scopus (139) Google Scholar And among those with Los Angeles Grade A erosive esophagitis at baseline, 21% had more