Extraesophageal manifestations of GERD.

The association between gastroesophageal reflux disease (GERD) and extraesophageal disease is often referred to as extraesophageal reflux (EER). This article reviews EER, discussing epidemiology, pathogenesis, diagnosis, and treatment with a focus on the most studied and convincing EER disorders-asthma, cough, and laryngitis. Although EER comprises a heterogeneous group of disorders, some general characterizations can be made, as follows. First, although GERD's association with extraesophageal diseases is well-established, definitive evidence of causation has been more elusive, rendering epidemiological data scarce. Secondly, regarding the pathogenesis of EER, 2 basic models have been proposed: direct injury to extraesophageal tissue by acid and pepsin exposure or injury mediated through an esophageal reflex mechanism. Third, because heartburn and regurgitation are often absent in patients with EER, GERD may not be suspected. Even when GERD is suspected, the diagnosis may be difficult to confirm. Although endoscopy and barium esophagram remain important tools for detecting esophageal complications, they may fail to establish the presence of GERD. Even when GERD is diagnosed by endoscopy or barium esophagram, causation between GERD and extraesophageal symptoms cannot be determined. Esophageal pH is the most sensitive tool for detecting GERD, and it plays an important role in EER. However, even pH testing cannot establish GERD's causative relationship to extraesophageal symptoms. In this regard, effective treatment of GERD resulting in significant improvement or remission of the extraesophageal symptoms provides the best evidence for GERD's pathogenic role. Finally, EER generally requires more prolonged and aggressive antisecretory therapy than typical GERD requires.