Link between pharyngeal acid reflux episodes and the effectiveness of proton pump inhibitor therapy

Background: Diagnosing laryngopharyngeal reflux (LPR) is challenging due to overlapping symptoms. While proton pump inhibitors (PPIs) are commonly prescribed, reliable predictors of their responsiveness are unclear. Reflux monitoring technologies like dual potential of hydrogen (pH) sensors and multichannel intraluminal impedance-pH (MII-pH) could improve diagnosis. Research suggests that a composite pH parameter, defined by ≥ 2 pharyngeal acid reflux (PAR) episodes and/or excessive esophageal acid reflux (EAR), predicts PPI efficacy. The criteria for PAR episodes, a pharyngeal pH drop of ≥ 2 units to < 5 within 30 seconds during esophageal acidification, showed strong interobserver reliability. We hypothesized that PAR episodes alone might also predict PPI responsiveness.

Aim: To investigate whether PAR episodes alone predict a positive response to PPI therapy.

Methods: Patients suspected of having LPR were prospectively recruited from otolaryngologic clinics in three Taiwanese tertiary centers. They underwent a 24-hour esophagopharyngeal pH test using either 3-pH-sensor or hypopharyngeal MII-pH catheters while off medication, followed by a 12-week esomeprazole course (40 mg twice daily). Participants were categorized into four groups based on pH results: PAR alone, EAR alone, both pH (+), and both pH (-). The primary outcome was a ≥ 50% reduction in primary laryngeal symptoms, with observers blinded to group assignments.

Results: A total of 522 patients (mean age 52.3 ± 12.8 years, 54% male) were recruited. Of these, 190 (mean age 51.5 ± 12.4 years, 61% male) completed the treatment, and 89 (47%) responded to PPI therapy. Response rates were highest in the PAR alone group (73%, n = 11), followed by EAR alone (59%, n = 68), both pH (+) (56%, n = 18), and both pH (-) (33%, n = 93). Multivariate analysis adjusting for age, sex, body mass index, and endoscopic esophagitis showed that participants with PAR alone, EAR alone, and both pH (+) were 7.4-fold (P = 0.008), 4.2-fold (P = 0.0002), and 3.4-fold (P = 0.03) more likely to respond to PPI therapy, respectively, compared to the both pH (-) group. Secondary analyses using the definition of ≥ 1 PAR episode were less robust.

Conclusion: In the absence of proven hypopharyngeal predictors, this post-hoc analysis found that baseline ≥ 2 PAR episodes alone are linked to PPI responsiveness, suggesting the importance of hypopharyngeal reflux monitoring.