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GERD is a spectrum disease, i.e., a disease composed by many patient subgroups, ranging from symptomatic disease without mucosal lesions (or NERD) to the complications of erosive esophagitis, such as esophageal stricture, ulceration or Barrett’s esophagus. Almost all the transitions are possible amongst groups, even if the progression from one stage to the other has been described mainly based upon retrospective data. The natural history of the disease is poorly investigated: available data would suggest that symptoms of GERD tend to persist and to worsen with time, independently from the presence and severity of mucosal lesions or the severity of esophageal acid exposure at presentation. As far as the epidemiological features are concerned, the prevalence of at least monthly GERD symptoms ranges between 26% to 44% in western countries, whereas the prevalence of endoscopic esophagitis at open access endoscopy or in symptomatic patients seem to be very high, up to 20%, with an incidence rate in the general population about hundred time lower. The principal complication, e.g., Barrett’s esophagus, has a prevalence of 15–20% of the GERD population, with a rate of adenocarcinoma development of about 0.5% per patient year of follow up. Mortality for uncomplicated GERD is negligible.

Gastroesophageal reflux disease is a common condition in the elderly, and will become more prevalent as the population ages. Elderly patients often do not present with the classic symptoms of heartburn and acid regurgitation, which can delay diagnosis and contribute to the development of complications. Atypical symptoms such as chest pain, pulmonary, and laryngeal symptoms are more common in this group, and reflux should be considered early in the work-up if these symptoms are present. Due to an increase in complications of reflux disease in this population, most elderly patients being evaluated for reflux symptoms should have an upper endoscopy early in the diagnostic process. There are some important age related changes in the esophagus, including decreased secondary peristalsis, decreased salivary secretion, and an increased visceral pain threshold. However, many age-related changes to motility are not thought to be clinically relevant. More aggressive treatment of reflux disease may be required in the elderly population, as they are more likely to present with complicated disease, despite less severe symptoms. Age alone does not significantly impact the usage of PPI’s, and these medications have excellent results in the elderly for symptom relief, healing of esophagitis, and for maintenance therapy. With the advent of laparoscopic surgery, and an increasing life expectancy, this treatment may become more common in the elderly population, as it is associated with excellent results as well as low morbidity and mortality.

Gastroesophageal reflux is the most common esophageal disorder in children, and is responsible for heterogeneous presentations ranging from effortless regurgitation in “happy spitters” to complex esophageal and extra-esophageal GERD. The frequency and noxiousness of refluxate in proportion to the various esophageal defense mechanisms, and genetic, physiological and environmental influences ultimately determine the pathogenicity and complications of the disorder. While most children may be confidently diagnosed solely on the basis of a detailed history followed by appropriate response to therapy, diagnostic tools may be useful to clarify the role of reflux in extra-esophageal, and complicated GERD. Prompt identification and intervention for GERD in children is crucial to the prevention of strictures, Barrett’s esophagus and adenocarcinoma that are associated with long-standing reflux exposure. The first line of anti-reflux therapy in children is conservative therapy emphasizing thickened feeds, smaller volume meals, proper positioning, and elimination of smoke exposure. Proton pump inhibitor therapy has an established role in the management of those with GERD sequelae, and as empiric therapy in those with extra-esophageal GERD. Fundoplication, reserved for children who are refractory to pharmacotherapy, is being performed successfully; results of laparoscopic surgery in children are favorable with respect to shorter hospital stay, and lower complication rate than open fundoplication.

The interesting pathophysiological interaction between Helicobacter pylori infection, type of gastritis, acid secretion and GORD complicated by weakness of study designs with small numbers of patients should not lead to confusion. The risk of gastric carcinogenesis and peptic ulcer formation against the need for possible higher doses of acid suppressive therapy for symptom control after eradication should be balanced carefully and can only lead us to one conclusion: there are more reasons that favour Helicobacter pylori eradication than to leave the bug in the stomach of your patients.

Theories of the mechanism of gastroesophageal junction competence have seesawed between strictly anatomic explanations, focusing on type-I hiatus hernia, and physiologic explanations focusing on the vigor of LES contraction while ignoring the significance of anatomic factors. As detailed above, current thinking recognizes contributions from both sphincteric components. Furthermore, there is an increasing understanding of mechanical elements of the antireflux barrier, inclusive of, but nor restricted to hiatus hernia and the intrinsic LES. Thus, our view of GERD pathogenesis as it pertains to EGJ competence is now focusing on quantifying the mechanical properties of this complex anatomical zone. Future research will likely focus on methods to measure EGJ compliance and elasticity, as these are the mechanical parameters that influence gastroesophageal reflux.

NERD is a real entity and its importance in the spectrum of GERD must be appreciated. Functional heartburn needs to be further differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, albeit “typical” of GERD, and acid exposure. Several aspects of NERD need to be appreciated including the overlap with functional dyspepsia and potential differences in response to such therapeutic interventions as acid suppressive therapy and fundoplication. While definitive studies on this issue are yet to be completed, it remains quite possible that our failure to separate functional heartburn from NERD, in general, has contributed in large measure to diagnostic difficulties and therapeutic disappointment in GERD. This author contends that functional heartburn should be removed from the spectrum of GERD and relocated to the functional gastrointestinal disorders; only then will effective approaches to the assessment and therapy of this challenging disorder emerge.

Endoscopy is relatively insensitive for making the diagnosis of gastro esophageal reflux disease. However, the presence of erosive esophagitis and/or BE is highly suggestive of GERD. The presence of normal mucosa at endoscopy does not rule out the diagnosis of GERD. At present, the role of biopsies in these situations is unsettled and more data are needed. Newer endoscopic techniques such as chromoendoscopy, magnification and high resolution may demonstrate minimal changes in the distal squamous mucosa such as punctate erythema, pinpoint vessels etc. not seen by standard endoscopy. Some of these changes may respond to therapy with proton pump inhibitor. Endoscopy remains the best test to rule out complications of GERD and allows histological confirmation of esophageal pathology such as intestinal metaplasia, dysplasia and adenocarcinoma. Identifying the patient group with severe erosive esophagitis, BE and peptic strictures may help focus aggressive management that may potentially prevent future complications in these patient groups. Finally, endoscopy may be useful to rule out other diseases in the upper gastrointestinal tract.