Response of Eosinophilic Oesophagitis to Proton Pump Inhibitors Is Associated With Impedance-pH Parameters Implying Anti-reflux Mechanism of Action

Marzio Frazzoni; Leonardo Frazzoni; Nicola De Bortoli; Salvatore Russo; Salvatore Tolone; Elena Arsiè; Rita Conigliaro; Roberto Penagini; Edoardo Savarino


Aliment Pharmacol Ther. 2021;53(11):1183-1189. 

In This Article

Materials and Methods

Adult patients referred for solid food dysphagia and/or food impaction were considered for enrolment in this prospective multicentre study. Diagnosis of EoE was based on the detection of oesophageal eosinophilia, that is, ≥15 eosinophils per high-power field (HPF), taken as the peak concentration in the specimens examined.[1,2] Cases with fibrotic strictures were excluded. The study was conducted in accordance with the Declaration of Helsinki after approval by the institutional review boards. A specific written informed consent was always required before each investigation.

Impedance-pH monitoring was performed before the start of PPI therapy, and was always preceded by oesophageal manometry for accurate location of the lower oesophageal sphincter (LOS) and exclusion of achalasia and obstructive motor disorders.[18] A probe allowing detection of intraluminal impedance at 3, 5, 7, 9, 15 and 17 cm and of pH at 5 cm above the LOS was used. Tracings were manually assessed with the aid of commercial software, distinguishing acidic (nadir pH <4.0) from weakly acidic (nadir pH between 4.0 and 7.0) and weakly alkaline (nadir pH not below 7.0) refluxes, meal times excluded.[19] AET, number of total, acid, weakly acidic and weakly alkaline refluxes, as well as PSPW index and MNBI were assessed.

MNBI was assessed during night-time recumbent period: three 10-minute time periods (around 1.00 AM, 2.00 AM and 3.00 AM) were selected avoiding swallows, refluxes and pH drops below 4.0, and the mean was calculated.[20] MNBI was measured 3 and 9 cm above the upper LES border in order to calculate the gradient between mid and distal oesophagus, that is, ΔMNBI.[15]

PSPW was defined as an antegrade 50% drop in impedance, originating in the proximal oesophagus within 30 seconds after the end of a reflux event and reaching the distal lumen; PSPW index was calculated dividing the number of PSPWs by the number of refluxes.[13] The increment in pH (ΔpH) associated with each PSPW was assessed starting from the pH immediately preceding the PSPW, that is, after the end of the reflux episode up to the highest pH value associated with the PSPW; single ΔpH values were summed up and divided by the number of PSPWs to obtain the PSPW-associated ΔpH.[17] Moreover, nadir pH of reflux events was measured for all reflux events followed by a PSPW to evaluate its possible influence on PSPW-associated ΔpH.

Three months after the start of standard dosage (20 mg) esomeprazole administered twice daily, patients underwent repeat oesophago-gastro-duodenoscopy with six oesophageal biopsies at distal, mid and proximal oesophagus. According to current guidelines,[1] PPI response was objectively defined by histological criteria, that is, less than 15 eosinophils per HPF. Dysphagia was scored before starting PPI and at the time of repeat oesophago-gastro-duodenoscopy using a validated 4-grade Likert-type scale administered by a senior investigator.[15]

Impedance-pH parameters in patients with EoE were compared with those detected in gender- and age-marched patients with typical GERD, that is, reflux-related heartburn referred to our centres during the same period. Diagnosis of typical GERD was based on abnormal AET[21] and/or positive heartburn-reflux association as established by concordant positivity of symptom-association probability (SAP) and symptom index (SI).[19] A validated structured questionnaire,[22] based on a 4-grade Likert-type scale, was administered by a senior investigator to evaluate heartburn response to PPI therapy.