Proton pump inhibitors (PPI) have greatly improved the treatment of gastroesophageal reflux disease. However, recent investigations have revealed that reflux symptoms persist in a substantial number of patients. Therefore, treatment strategies beyond PPI are urgently required. One such strategy may involve more reliable acid suppression, e.g., with new acid inhibitory drugs. Furthermore, the rapid appearance of an acidic compartment in the proximal stomach after a meal, which is largely responsible for postprandial heartburn, requires a specific kind of therapy in addition to PPI which still needs to be established. Pharmacological augmentation of the lower esophageal sphincter may represent another approach to diminish reflux, but the clinical efficacy of compounds tested so far is limited. Altered e-sophageal perception represents a major component involved in the generation of reflux symptoms, particularly in non-erosive reflux disease, but effective pharmacological intervention is largely lacking. Presumed reflux-induced respiratory symptoms (cough, laryngitis, etc.) in the absence of typical esophageal symptoms (e.g., heartburn) remain a hot topic, but recent research points towards a hypersensitivity syndrome and only a minor role of gastroesophageal reflux. Treatment options for this condition are still pending.
Keywords: Acid pocket; Acid suppression; Esophageal perception; Extraesophageal manifestations; Sphincter augmentation.