Pathophysiology, diagnosis, and pharmacological treatment of gastro-esophageal reflux disease

ABSTRACT

Introduction

Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic, relapsing disorder, whose knowledge has increased in last years thanks to the advent of new sophisticated techniques, such as 24-h impedance-pH monitoring and high-resolution manometry, for the study of esophageal functions.

Areas covered

This review provides an overview of our advancements in understanding the complex pathophysiology, improving the diagnosis and defining the modern pharmacological therapeutic approach to GERD.

Expert opinion

The growing clinical application of impedance-pH testing has allowed us to know the diversity of patients with non-erosive reflux disease (NERD), who nowadays represent about 70% of the whole population with reflux symptoms. We have realized that NERD has to be considered as an umbrella term covering various subgroups with different pathophysiologies. The development of new impedance metrics, in particular mean nocturnal baseline impedance, seems to be promising in the improvement of the diagnostic process of this disease. There are no particularly innovative features in the pharmacological therapy of GERD, unless the interest toward drugs is able to increase the defense properties of esophageal mucosa and/or its protection. These compounds can be of help in combination with proton pump inhibitors in NERD patients with partial response to antisecretory drugs alone.

KEYWORDS:

• Gastroesophageal reflux disease
• pathophysiology
• diagnosis
• impedance-pH monitoring
• pharmacological treatment

Article highlights

• Pathophysiology of GERD is multifactorial and involves esophageal alterations, disruption of EGJ, gastric factors, and visceral hypersensitivity.

• There is no pathogenetic role for gastric acid hypersecretion.

• A consistent subgroup of patients with heartburn pertain to esophageal functional disorders, including both reflux hypersensitivity and functional heartburn.

• Twenty-four-hour impedance-pH monitoring is the best method to diagnose GERD and has allowed us to identify various subsets of NERD patients with different pathophysiology.

• The adoption of new impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave, is able to increase the diagnostic yield in NERD patients.

• PPIs remain the mainstay of the medical therapy of GERD, while prokinetics and reflux inhibitors are not recommended.

• The reinforcement of mucosal resistance is a new therapeutic target, overlooked in the past. Several compounds have been shown to improve symptom relief and quality of life, when used in combination with PPIs.

Declaration of interest

V. Savarino has served as a consultant and paid speaker for Reckitt Benkiser, Alfasigma, Takeda, Malesci, Crinos, Teofarma. E. Savarino has served as a consultant and paid speaker for Takeda, Janssen, MerkSharpDohme, Abbvie, Malesci, Reckitt Benkiser, and Medtronic. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.