By Inna Husain, MD, VP of Education at RefluxRaft
“Evaluation and Management of Laryngopharyngeal Reflux Disease: An Updated State of the Art Review” by Lechien, Johnston, and colleagues, including me, was published online in Otolaryngology–Head and Neck Surgery on August 26, 2026 (read it here). Our author team spans laryngology, general otolaryngology, gastroenterology, and foregut surgery across five continents. Using a PRISMA-guided search of PubMed, Cochrane, and Scopus, we asked what five years of new evidence means for day-to-day practice.
Our answer is that laryngopharyngeal reflux disease (LPRD) now looks more alkaline, more gaseous, and more multisystem than the acid-centric model most practitioners trained on. That shift affects which questionnaires are used, which signs to look for, which tests are ordered, and what is prescribed first.
The evidence shift: pharyngeal reflux is mostly not acid
The clearest finding of the past five years comes from 24-hour hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH). Across recent studies, most pharyngeal reflux events are weakly acidic or alkaline, and many are gaseous. Among patients with documented pharyngeal events and consistent symptoms and findings, only 10% to 52% have pathologic esophageal acid exposure time. Upper GI endoscopy is normal in up to half of LPRD patients. An acid-only framework will therefore miss a large share of real disease.
The enzyme story has changed to match. Pepsin is still important, both as a biomarker and as a therapeutic target; a phase II trial of fosamprenavir as a pepsin inhibitor is underway. But pepsin appears in saliva only briefly, so even repeated sampling can still miss it. The airway epithelium holds pepsin for about 36 hours, and researchers are using that retention to develop cell-based assays such as brushings.
The newer biomarkers are bile salts and elastase. Both are activated at alkaline pH, and both are found at higher concentrations in the saliva of patients with LPRD than in controls. In recent large methodological studies, salivary elastase combined with cholesterol (an indirect marker of bile salt concentration) had a positive predictive value of 93% and a negative predictive value of 100% for LPRD. These tests are not yet in routine use, and they need external validation. Still, a noninvasive, well-tolerated saliva test is now a realistic goal.
Two other threads deserve attention:
- Microbiome changes. Throat microbial diversity is reduced in LPRD, possibly through enzyme-driven selection of certain species.
- Autonomic dysfunction. Growing evidence links it to sphincter relaxation and gaseous reflux. Higher rates of anxiety, depression, and stress in LPRD patients may reflect this, though whether dysautonomia is a cause or a consequence remains open.
The diagnostic landscape
Moving past the RSI
Only three patient-reported outcome measures (PROMs) have adequate validity and reliability for LPRD: the Reflux Symptom Index (RSI), the Reflux Symptom Score (RSS), and the RSS-12. Recent comparative studies from China and Europe found the full RSS outperformed both the RSI and the shorter RSS-12. The RSS also agreed better with salivary pepsin measured at multiple time points.
The likely reason is scope. The RSS covers digestive and respiratory symptoms as well as throat symptoms, and digestive complaints appear in up to 73% of LPRD patients. That contradicts roughly two decades of teaching that focused on throat complaints alone. It also fits the overlap with gastroesophageal reflux disease (GERD), which is found in about 45% of LPRD populations versus about 30% of the general population. We are clear that no PROM can diagnose LPRD on its own. We also note that, in light of recent FDA guidance, current LPRD outcome measures may not yet meet the bar for regulatory use in trials of new therapies.
Examining beyond the larynx
Sign assessment has moved in the same direction. Instruments that examine the oral cavity and pharynx as well as the larynx, such as the Reflux Sign Assessment (RSA), are now favored over laryngeal-only scoring like the Reflux Finding Score (RFS). Short-form versions may lose accuracy.
A group of atypical findings has also emerged, supported by HEMII-pH results and pepsin detected in tissue:
- a mulberry-appearing posterior inferior turbinate
- nasal dryness and crusting
- nasopharyngeal erythema
- coated tongue
- sticky oropharyngeal mucus
Dry eye, nasal obstruction, and sneezing are among the atypical symptoms worth asking about. None of these findings is diagnostic on its own; the mulberry turbinate currently looks the most specific. Their value is in pattern recognition. When several appear together alongside consistent symptoms, and common mimics have been ruled out, suspicion rises and objective testing becomes more justified.
The treatment shift: from PPIs to alginate and magaldrate
The treatment implications follow directly from the alkaline biology. An empirical proton pump inhibitor (PPI) trial produces response in only up to about 60% of patients. Prior meta-analyses found no clear PPI benefit over placebo, and long-term use carries risks. Two common habits, switching to a different PPI or raising the dose, did not produce additional relief in the reviewed data.
Alginates and magaldrate work differently:
- Alginates form a raft that reduces reflux episodes reaching the pharynx and bind pepsin. They block reflux events whether they are acidic, weakly acidic, or alkaline.
- Magaldrate is an aluminum-magnesium antacid that buffers acid, protects the mucosa, and binds bile salts. It is not currently marketed in the United States. Long-term use requires monitoring for magnesium and aluminum accumulation and electrolyte changes. It can also reduce absorption of tetracyclines, fluoroquinolones, levothyroxine, iron, and bisphosphonates, which matters most in elderly and renal-impaired patients.
The supporting evidence is encouraging but early:
- In one retrospective study of HEMII-pH-confirmed patients, diet outperformed PPIs, and alginate and magaldrate were non-inferior or partially superior to PPIs.
- Patients with persistent symptoms on long-term PPIs improved after stopping the PPI and starting an alginate.
- In a 2025 study of recalcitrant patients, switching drug class from alginate to magaldrate achieved a 62.5% response rate.
We also point out that no randomized controlled trial comparing PPIs, alginate, magaldrate, and diet has been published in the past five years. The shift is biologically sound but still awaits RCT confirmation.
Diet and lifestyle apply to every patient, not only as an add-on. In a crossover observational study, 74% of patients improved significantly at six weeks on diet alone, and 54% were still successful at three months. Our review supports a 3-month treatment trial followed by reassessment and, if needed, a revised 3-month course.
For patients who do not respond, look again before escalating:
- In one series, 74.8% of recalcitrant patients had an additional diagnosis. The most common were inhaled steroid laryngitis (12.6%), untreated allergy (11.9%), lactose intolerance (10.5%), and chronic rhinosinusitis (7.7%).
- Up to 62.7% of “resistant” patients were not taking their treatment as prescribed.
Practical takeaways
- Use the full RSS rather than the RSI alone, and ask about digestive and respiratory symptoms.
- Examine beyond the larynx. Look at the nose, nasopharynx, tongue, and oropharynx, and ask about dry eye.
- Pursue objective testing whenever feasible, and use HEMII-pH where it is available.
- Consider alginate as a first-line option, and treat diet and lifestyle as core therapy for every patient.
- Don't reflexively escalate PPIs in patients who haven't responded. Instead, check adherence, reconsider mimics, and consider switching drug class.
- Watch the saliva biomarker literature. Elastase plus cholesterol may become a practical noninvasive test.
LPRD evidence is moving quickly, and cost and low awareness remain real barriers to good care. For clinicians who want to go further, our HCP education program covers diagnosis, HEMII-pH interpretation, and alkaline-targeted therapy in more depth: RefluxRaft for Practitioners
Read the full review in Otolaryngology–Head and Neck Surgery
About the author
Inna Husain, MD, is RefluxRaft's VP of Education and a co-author of “Evaluation and Management of Laryngopharyngeal Reflux Disease: An Updated State of the Art Review” (Otolaryngology–Head and Neck Surgery, 2026). She is a board-certified otolaryngologist–head and neck surgeon with subspecialty training in laryngology, focused on voice, airway, and swallowing disorders. Dr. Husain earned her MD at UT Southwestern Medical School, completed residency at Northwestern University's McGaw Medical Center, and completed fellowship at Harvard Medical School.
She spent seven years in academic medicine as an Associate Professor, Section Head of Laryngology, and Associate Residency Program Director. She has published more than 30 peer-reviewed papers and speaks nationally and internationally on LPR. Follow her patient education on Instagram at @innahusainmd, and hear more on atypical LPR in her BackTable ENT episode.
This article is for educational purposes for healthcare professionals and is not a substitute for individual medical advice.
