Beyond PPIs: Addressing the Treatment Gap in Laryngopharyngeal Reflux Disease

To the Editor,

The recent systematic review by Lechien et al, “Treatment for Laryngopharyngeal Reflux Disease: A Systematic Review of Controlled Studies,” provides a timely and essential reassessment of pharmacologic management strategies for laryngopharyngeal reflux disease (LPRD). ¹ The authors’ meticulous evaluation of 14 controlled studies exposes a significant gap between current clinical practice and the available evidence. Despite widespread use, proton pump inhibitors (PPIs) continue to show limited efficacy in LPRD treatment and, as the authors rightly note, have not demonstrated superiority over placebo in recent meta-analyses.

A critical strength of this review lies in its emphasis on the fundamental differences between the pathophysiology of LPRD and that of gastroesophageal reflux disease (GERD). While GERD is driven by acidic reflux, LPRD more often involves weakly acidic or nonacidic refluxate, including pepsin and bile salts, that affect the laryngeal and pharyngeal mucosa. Consequently, therapies that merely suppress gastric acid fail to address the broader refluxate composition that characterizes LPRD. Yet, PPIs remain the predominant treatment worldwide, largely due to historical extrapolation from GERD protocols and a lack of robust evidence for alternatives.

Encouragingly, Lechien et al identify several studies suggesting potential benefits from combining PPIs with prokinetics or alginates. These agents address motility disorders and provide mechanical reflux barriers, respectively, and are more mechanistically aligned with the multifaceted pathophysiology of LPRD. However, the heterogeneity in diagnostic criteria, study designs, and outcome measures across the reviewed literature undermines the ability to draw definitive conclusions. Only a minority of the included studies utilized hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring to confirm LPRD—a diagnostic gold standard endorsed by recent international consensus. Without this level of diagnostic specificity, the interpretation of therapeutic response remains confounded by inclusion of patients with mimicking conditions such as allergic rhinitis, chronic laryngitis, or functional voice disorders.

In addition to diagnostic inconsistency, the review highlights a lack of attention to adherence monitoring, dietary intervention standardization, and the use of validated, comprehensive patient-reported outcome tools. For example, while the Reflux Symptom Index (RSI) remains widely used, it fails to capture several relevant LPRD symptoms and may not be sensitive enough for treatment response assessment. Emerging instruments like the Reflux Symptom Score-12 offer better specificity and should be prioritized in future research.

Given the mounting evidence that PPIs alone are inadequate for many LPRD patients, it is time to rethink our therapeutic framework. Otolaryngologists should consider adopting a more nuanced approach that incorporates objective diagnostic confirmation, addresses esophageal motility, and includes therapies that mechanically or chemically neutralize nonacid refluxate. Moreover, future randomized controlled trials should employ rigorous designs, exclude confounding diagnoses, and ensure adequate treatment durations and adherence monitoring.

Lechien et al should be commended for synthesizing an evolving body of literature into a set of clear, evidence-based recommendations for future research. Their work challenges the field to move beyond outdated GERD-centric paradigms and toward treatment strategies grounded in the unique pathophysiology of LPRD. As clinical practitioners and researchers, we must embrace this shift to ensure that our management of LPRD is both scientifically sound and clinically effective.

James R. Burmeister, BS and Ethan Dimock, BS
Department of Foundational Medical Studies,
Oakland University William Beaumont
School of Medicine, Rochester, MI, USA

Ismail Zazay, BS
John Sealy School of Medicine, University of Texas
Medical Branch, Galveston, TX, USA