Review article: a conceptual model for the relationship of nocturnal acidity and extra-oesophageal manifestations of gastro-oesophageal reflux disease - where are we now?

A number of extra-oesophageal abnormalities ranging from otolaryngologic disorders and dysphonia to non-cardiac chest pain and sleep disturbances have been attributed to gastro-oesophageal reflux disease. A significant degree of uncertainty and confusion continues to exist with regard to the pathogenesis, diagnosis and treatment of these conditions.

The following conceptual model could be proposed for the pathogenesis of the extra-oesophageal manifestations of gastro-oesophageal reflux disease and, consequently, the likely response to therapy.

This model suggests that these disorders are, in fact, multifactorial and that the contributions of refluxed gastric contents comprise only part of the pathogenesis. In the case of asthma, for example, factors that influence airway resistance and symptom production include basal airway resistance, intra-oesophageal events, such as acid reflux-stimulating vagal afferent fibres and inducing further airway changes, and extra-oesophageal, allergic and other pulmonary factors that can influence airway resistance. This model allows for different degrees of influence from these three main contributors. In this model, if gastro-oesophageal reflux disease-related events contribute minimally to the changes in airway resistance compared with other factors, treating gastro-oesophageal acid reflux would result in minimal or no change in symptoms and vice versa.

At present, as it is difficult to identify prospectively those patients in whom reflux comprises the main pathological factor, and who might therefore respond to acid suppression, a trial of empiric proton-pump inhibitor therapy with reflux precautionary measures seems appropriate and has been suggested by some expert panels.