Extra-esophageal GERD: clinical dilemma of epidemiology versus clinical practice

Gastroesophageal reflux disease (GERD) is a common disorder. A significant percentage of patients with GERD may experience extra-esophageal manifestations, such as asthma, cough, and laryngitis. Epidemiologic studies consistently demonstrate strong associations between GERD and potential extra-esophageal manifestations. However, randomized controlled studies evaluating the use of proton-pump inhibitors for treatment of extra-esophageal GERD have inconsistent results. In asthma, few randomized controlled studies have shown improvement in objective measures, such as forced expiratory volume or peak flow. For chronic cough, studies are all small and have not demonstrated consistent improvement with acid suppression. Even a recent well-designed large randomized controlled study in laryngitis demonstrated no difference in resolution of symptoms with acid suppression. Given the examples from the literature, the current treatment of extra-esophageal symptoms with acid suppression is controversial. Although improvement in symptoms has been shown in case series, it has not been consistent in randomized controlled studies. We offer potential explanations for the discrepancy between the epidemiologic associations and the lack of response to therapy in clinical trials.