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, 114 (3), 414-421

Revisiting Montreal: New Insights Into Symptoms and Their Causes, and Implications for the Future of GERD


Revisiting Montreal: New Insights Into Symptoms and Their Causes, and Implications for the Future of GERD

A Pali S Hungin et al. Am J Gastroenterol.


The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.


Fig. 1
Fig. 1
Suspected gastroesophageal reflux disease (GERD)-related symptoms, their relative likelihood of response to acid-suppressive therapy based on the literature, and the presumed importance of acid reflux for symptom generation based on these findings. Smaller arrows underneath each symptom indicate the direction of the shift in response to acid suppression when patients are selected based on the presence (RE+) or absence (RE−) of reflux esophagitis, or the presence (pH+) or absence (pH−) of pathologic esophageal acid exposure. The relative position of each symptom and the size of the arrows is not to scale. In summary, heartburn is assumed to be the quintessential acid-related symptom and as such correlates the most frequently with pathologic esophageal acid exposure and response to acid-suppressive therapy. The response of heartburn (and regurgitation) to acid suppression is higher in RE+ patients than in RE− patients, concordant with RE being a good proxy for pathologic esophageal acid exposure in lieu of pH-testing. The relative response of symptoms to acid suppression decreases as their dependence on pathologic esophageal acid exposure decreases. However, even for symptoms such as chest pain and cough, response rates to acid suppression can be enhanced by identifying patients who have pathologic esophageal acid exposure (pH+), albeit with a dwindling effect as symptom etiology becomes increasingly multifactorial
Fig. 2
Fig. 2
Relationship between reflux acidity, response of heartburn to acid-suppressive therapy and the role of peripheral and/or central esophageal hypersensitivity in different gastroesophageal reflux disease (GERD) and non-GERD patients with heartburn. Reflux esophagitis (RE) correlates strongly with the presence of pathologic esophageal acid exposure and, concomitantly, healing of RE and heartburn resolution are high with acid-suppressive therapy in these patients. Some patients have heartburn but not RE. Those who have pathologic esophageal acid exposure (pH+) have NERD, and heartburn symptoms respond as well to acid suppression as they do in patients with RE. Those patients with heartburn who do not have pathologic esophageal acid exposure may still have a positive symptom association probability (SAP+) for acid or non-acid reflux, and are thus categorized as having reflux hypersensitivity (acid hypersensitive esophagus (AHE) or non-acid hypersensitive esophagus (NAHE)). Patients without pathologic acid exposure who have a negative SAP are designated as having functional heartburn (FH). The role of peripheral and/or central esophageal hypersensitivity increases as dependence on acid reflux (and response to acid suppression) decreases, in line with heartburn perception occurring despite non-pathologic acid reflux (hyperalgesia) in patients with reflux hypersensitivity, or under physiological reflux conditions (allodynia) in patients with FH

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