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


Between October 2018 and November 2020, 80 EoE patients underwent impedance-pH monitoring at our centres before the start of PPI. The median number of eosinophils for HPF was 34 (interquartile range 25–41). The main baseline characteristics of EoE patients as compared with those of 80 gender- and age-matched typical GERD cases evaluated at our centres during the same period are reported in Table 1. AET was higher than normal in 13 of 80 (16%) cases. As expected, at impedance-pH monitoring AET and number of acid, weakly acidic and total refluxes were significantly higher in the GERD group, whereas mucosal damage as measured with MNBI was significantly more severe in the EoE group at distal and mid oesophagus; considerable and quite similar PSPW-associated ΔpH values (median 1.4 pH units) were detected in both groups.

Histological response 3 months after the start of PPI therapy was detected in 48 (60%) of 80 EoE cases. Mean dysphagia score decreased from 2.2 ± 0.4 to 0.1 ± 0.3 in PPI-responsive cases and from 2.2 ± 0.7 to 1.1 ± 0.9 and PPI-refractory cases, the difference between on-PPI scores being significant (P < 0.0001). Impedance-pH metrics in PPI-responsive and PPI-refractory EoE cases are shown in Table 2. Reflux parameters did not differ between the two groups, whereas significantly higher values of PSPW-associated ΔpH and ΔMNBI were found in PPI-responsive cases, both variables independently associated with histological response at multivariable logistic regression analysis.

Impedance-pH parameters in 48 PPI-responsive and in 32 PPI-refractory GERD cases are reported in Table 3. AET was higher than normal in 76 of 80 (95%) cases. The sole metric characterising PPI response was PSPW-associated ΔpH, in a manner quite similar to EoE (Figure 1).

Figure 1.

Oesophageal pH increments (ΔpH) associated with PSPWs in EoE and GERD. Box plots represent median and interquartile range. EoE, eosinophilic oesophagitis; GERD, gastro-oesophageal reflux disease; PPI, proton pump inhibitor; PSPW, post-reflux swallow-induced peristaltic wave

Median nadir pH of reflux events was quite similar in EoE (2.7, IQR 2.1–3.3) and GERD (2.4, IQR 2.0–2.7) patients (P = 0.15), as well as in PPI-responsive and PPI-refractory cases in both EoE (2.7, IQR 2.1–3.3 vs 2.9, IQR 2.4–3.6, P = 0.12) and GERD group (2.1, IQR 1.6–2.6 vs 2.5, IQR 2.2–2.8, P = 0.75).

At ROC analysis, both PSPW-associated ΔpH (AUC 0.83, 95% CI 0.73–0.92) and ΔMNBI (AUC 0.75, 95% CI 0.64–0.86) efficiently separated PPI-responsive from PPI-refractory EoE cases (Figure 2). The best cut-off values were 1.4 pH units for PSPW-associated ΔpH, and 279 Ω for ΔMNBI. Combined assessment of PSPW-associated ΔpH and ΔMNBI afforded very efficient separation of PPI-responsive from PPI-refractory EoE cases; the AUC was 0.88 (95% CI 0.81–0.96).

Figure 2.

ROC curves and AUC (95% CI) of PSPW-associated pH increments (ΔpH) and of the gradient between MNBI measured at 9 and 3 cm (ΔMNBI) above the LOS in EoE. AUC, area under curve; CI, confidence interval; EoE, eosinophilic oesophagitis; LOS, lower oesophageal sphincter; MNBI, mean nocturnal baseline impedance; PSPW, post-reflux swallow-induced peristaltic wave; ROC, receiver operating characteristics