New developments in the pathophysiology of gastro-oesophageal reflux disease (GERD): implications for patient management.

The spectrum of gastro-oesophageal reflux disease (GERD) has expanded; indeed the majority of individuals with symptomatic GERD do not have erosive reflux disease (ERD); this group has been referred to as nonerosive or negative-endoscopy reflux disease (NERD). There may be important differences between NERD and ERD in terms of pathophysiology and management. Thus, NERD patients appear relatively resistant to proton pump inhibitors and may not be good surgical candidates. The clinician caring for patients with GERD must therefore be aware of the full spectrum of GERD and of the pathophysiological and therapeutic implications of NERD. Recent twin studies have revealed that genetic factors play a role in GERD and form the basis for future studies on the role of inheritance in the various manifestations of GERD. Several recent investigations have reaffirmed the primacy of acid reflux in the pathogenesis of GERD and have also provided insights into the pathophysiology of postprandial heartburn. Transient lower oesophageal sphincter relaxations and hiatal hernias have emerged as major and interacting factors in the genesis of reflux events and in the potentiation of acid exposure; the former are attracting considerable attention as a potential therapeutic target. Nocturnal acid breakthrough, which has been implicated in the failure of some patients to respond to high doses of proton pump inhibitors, appears, on further examination, to be a gastric rather than an oesophageal phenomenon, and may not be of clinical or therapeutic importance.