Response of eosinophilic oesophagitis to proton pump inhibitors is associated with impedance-pH parameters implying anti-reflux mechanism of action

Background Proton pump inhibitors (PPIs) are effective therapies for eosinophilic oesophagitis (EoE), but the mechanism of action is uncertain. At on-PPI impedance-pH monitoring, improvement in oesophageal chemical clearance assessed with post-reflux swallow-induced peristaltic wave (PSPW) index characterises PPI-responsive EoE and reflux disease. Off-PPI, higher efficacy of the oesophago-salivary reflex as measured with PSPW-associated pH increments characterises PPI-responsive reflux disease and could typify PPI-responsive EoE as well. Aim To establish whether PPI responsiveness in EoE is associated with higher efficacy of the oesophago-salivary reflex. Methods Prospective multicentre study in EoE patients investigated with impedance-pH monitoring before starting PPI. Impedance-pH parameters in PPI-responsive and PPI-refractory cases were compared. PPI response was defined histologically. Results Considerable PSPW-associated pH increments (median 1.4 units) were found in 80 EoE patients, with significantly higher values in 48 PPI-responsive than in 32 PPI-refractory cases (1.8 vs 1.0, P = 0.02). Mucosal integrity, as measured with mean nocturnal baseline impedance was more severely impaired in the distal oesophagus in PPI-responsive cases, the gradient between mid and distal oesophagus being significantly higher (546 vs 137 Ω, P = 0.0002). PSPW-associated pH increments and the baseline impedance gradient between mid and distal oesophagus were independently associated with histological response at multivariable logistic regression; at receiver operating characteristic analysis, the area under the curve of PPI response calculated by combined assessment was 0.88. Conclusion Higher efficacy of oesophago-salivary reflex and more severe mucosal damage in the distal oesophagus are associated with EoE response to PPIs, implying an anti-reflux mechanism of action as most likely.