A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo

Abstract

Laryngopharyngeal reflux disease (LPRD) is a chronic inflammatory condition affecting the upper aerodigestive tract due to gastric refluxate. Its relationship with gastroesophageal reflux disease (GERD) remains uncertain, and its pathophysiology is not yet clearly elucidated. Accurate diagnosis of LPRD and appropriate therapeutic approaches, as well as predictors of clinical response, are challenges in daily practice. The present study aims to evaluate whether impairment of the integrity of the laryngeal and hypopharyngeal mucosa during laryngopharyngeal reflux could be a factor related to response to proton pump inhibitors (PPIs). Patients presenting with chronic hoarseness and a Reflux Finding Score (RFS) of ≥7 were evaluated using the Reflux Disease Questionnaire (RDQ) and Reflux Symptom Index (RSI). Upper endoscopy was performed, and samples from the posterior commissure of the larynx were collected to evaluate ex vivo the integrity of the laryngeal mucosa by transepithelial resistance (TER) using an Ussing chamber. All patients underwent 24-hour pH-impedance monitoring (pH-imp-24h), followed by an acid oral exposure test. In vivo, hypopharyngeal integrity was measured using intraluminal impedance of the hypopharynx. Clinical responders were defined as those with an RSI score <13 and a reduction of at least 50% from their initial RSI after 8 weeks of pantoprazole treatment. Eighteen patients completed the protocol. The median scores for RDQ, RSI, and RFS were 14 (0–41), 22.5 (4–34), and 9 (7–20), respectively. Esophagitis was detected in 28% of the patients, and one patient presented with acid exposure above 6%. By the end of the 8-week treatment, 12 patients (66.67%) responded to PPI therapy. Baseline laryngeal TER and TER drops after challenge showed no significant difference between PPI responders and non-responders. Hypopharyngeal basal impedance was similar between responders and non-responders. After the acid oral exposure test, impedance was lower in non-responders than in PPI responders. In conclusion, in dysphonic patients with LPRD, hypopharyngeal mucosal integrity was lower in PPI non-responders. This suggests that weaker laryngopharyngeal mucosa in refractory LPRD may require new therapies aimed at improving barrier function.