Extra-esophageal presentation of gastroesophageal reflux disease: New understanding in a new era

Associations of gastroesophageal reflux disease (GERD) with extraesophageal manifestations, such as chronic cough, asthma, and laryngitis, are reported frequently, and there is a strong evidence of biological plausibility in support of this relationship. On the other hand, extraesophageal reflux disease (EERD) is usually multifactorial in nature with reflux being just one of the several potential contributing cofactors. Moreover, the accuracy of currently available diagnostic tests for EERD is suboptimal, and therefore the causal relationship between GERD and EERD remains far from being conclusively proven. In addition, there is a general paucity of data supporting a beneficial effect of anti-reflux treatments on symptoms of patients with suspected EERD. Therefore, diagnostic as well as therapeutic management of EERD remains largely empirical. Current guidelines suggest an initial empiric trial of proton pump inhibitors in patients without alarm features, who present also typical GERD symptoms. For those patients who improve with PPIs, GERD is presumed to be the etiology. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluating reflux symptoms. In this context, as symptoms ascribable to GERD may depend on other causes, investigations that excludes GERD can help to redirect the diagnostic and treatment efforts to other pathological conditions. The present review intends to discuss the current state of knowledge regarding the challenging diagnostic and therapeutic management of patients with suspected EERD, emphasizing the points of strengths and limitations of currently available diagnostic options, and to provide an update on major diagnostic innovations in this area