# Efficacy of Potassium-Competitive Acid Blockers to Treat Chronic Cough Associated With “Proven” Laryngopharyngeal Reflux Disease: A Preliminary Study

## TL;DR

This study shows that potassium-competitive acid blockers may help treat chronic cough in patients with confirmed laryngopharyngeal reflux disease, even when traditional acid suppressants fail.

## Contribution

The study evaluates P-CAB efficacy in PPI-refractory chronic cough with HEMII-confirmed LPRD, revealing potential benefits and limitations.

## Key findings

- P-CAB therapy significantly improved cough and reflux symptoms in PPI-refractory patients with HEMII-confirmed LPRD.
- Over half of the patients had normal acid exposure, suggesting limitations of conventional pH-metry for LPRD diagnosis.
- More than half of responders experienced cough recurrence within six months after stopping P-CAB therapy.

## Abstract

Introduction: Laryngopharyngeal reflux disease (LPRD) is thought to be a potential etiology of chronic cough (CC). A three-month empirical acid suppressive therapy has been recommended as a first-line diagnostic and therapeutic approach to treat patients with CC who are suspicious of LPRD, however its efficacy and benefit remain controversial. Since there has been no objective testing to accurately diagnose LPRD, patient cohorts in the previous studies are thought to be very heterogeneous. Therefore, the “true” efficacy of acid suppressive therapy for patients with CC and “proven” LPRD remains unknown. The objectives of this study were to assess the efficacy of potassium-competitive acid blocker (P-CAB) for “proven” LPRD-related CC and to see if P-CAB could be effective and beneficial in this setting.

Materials and methods: Patients with CC and LPRD as measured by hypopharyngeal-esophageal multichannel intraluminal impedance (HEMII), in whom empirical proton pump inhibitor (PPI) therapy previously failed, were enrolled, and daily P-CAB was given for 12 weeks. Cough Severity Index (CSI) and Reflux Symptom Index (RSI) scores were evaluated. Responders were defined as those who showed a 50.0% or more decrease in the CSI score.

Results: From February 2017 to December 2020, a total of 24 PPI-refractory patients with CC and LPRD were enrolled and analyzed. Of them, 15 patients (62.5%) had a normal acid exposure time. The CSI and RSI scores significantly improved from pre-P-CAB therapy (19.6 ± 9.8 and 18.5 ± 11.2, respectively) to post-P-CAB therapy (11.8 ± 11.1 and 14.1 ± 11.5, p = 0.003 and 0.024, respectively). Of 24 subjects, 14 (58.3%) subjects were responders, however, six (42.9%) subjects had abnormal RSI. Among responders to three-month P-CAB therapy, all subjects who discontinued P-CAB, and 50.0% of subjects who stayed on P-CAB, had recurrent cough within six months.

Conclusions: This preliminary study suggested that three-month P-CAB therapy appears to be a reasonable option for patients with CC and proven LPRD diagnosed by HEMII, even if PPI therapy fails and RSI is normal, however a long-term continuous P-CAB therapy may be required. More than half of patients had normal acid exposure, which may be missed by conventional pH-metry. Since a conventional pH-metry and RSI-based diagnosis of LPRD is insufficient, HEMII may be essential to evaluate patients with CC who are suspicious of LPRD.