Esophageal pH increments associated with post-reflux swallow-induced peristaltic waves show the occurrence and relevance of esophago-salivary reflex in clinical setting

Background: Following acid perfusion, esophageal pH is restored by swallowed bicarbonate-containing saliva secreted in response to a vagal esophago-salivary reflex. At impedance-pH monitoring, the post-reflux swallow-induced peristaltic wave (PSPW) index puts into relationship timely post-reflux swallows with the number of reflux events: Low values typify reflux-related heartburn (RRH) and lack of on-therapy improvement characterizes proton pump inhibitor (PPI) failure. Considerable esophageal pH increments associated with PSPWs could demonstrate the occurrence of esophago-salivary reflex in clinical setting, while its relevance could be shown by lower esophageal pH increments in PPI-refractory RRH. Methods: Prospective multicenter study in patients with PPI-refractory or PPI-responsive RRH evaluated with off-PPI impedance-pH monitoring. Increments in pH associated with PSPWs were measured and the mean calculated to obtain the PSPW-associated increment pH. Key Results: The mean PSPW-associated increment pH in 294 RRH patients was 1.2 +/- 0.7 and was lower in 137 PPI-refractory (1.0 +/- 0.6) than in 157 PPI-responsive (1.5 +/- 0.6) cases (p < 0.0001). Lower PSPW-associated increment pH was independently related to PPI failure at multivariable logistic regression analysis (OR 0.16, 95% CI 0.09-0.26). At ROC analysis, comparing PPI-refractory to PPI-responsive cases the AUC for PSPW-associated increment pH was 0.76 (95% CI 0.71-0.82), the best cutoff value being 1.2. Conclusions and Inferences: Considerable PSPW-associated pH increments demonstrate the occurrence of esophago-salivary reflex in clinical setting. Lower increments in PPI-refractory RRH cases show the clinical relevance of esophago-salivary reflex, confirming that PSPW represents a defense mechanism against reflux. PSPW-associated increment pH can efficiently predict PPI response in patients undergoing off-therapy impedance-pH monitoring.