Objectives Laryngopharyngeal reflux (LPR) is a common upper airway disease. Salivary pepsin is a proposed marker for LPR; however, the optimal time for collection of specimens for pepsin detection and pepsin's presence in the oral and nasal secretions relative to concurrent multichannel intraluminal impedance‐pH (MII‐pH) monitoring are unknown. Study Design Prospective case‐control study with an experimental design. Methods Patients undergoing MII‐pH testing for evaluation of LPR and asymptomatic control subjects were selected. Nasal lavage and saliva samples were collected in the clinic prior to MII‐pH probe placement. Additional saliva samples were obtained an hour after each meal and upon waking the following morning. Nasal lavage and salivary pepsin were measured by ELISA. Results Twenty‐six patients undergoing MII‐pH testing and 13 reflux‐free control patients were enrolled. Salivary pepsin was detected in 11 of 26 patients with suspected LPR and 0 of 13 controls. Pepsin was most frequently detected in the specimen provided upon waking at an average concentration of 186.9 ng/mL. A significant correlation was observed between salivary pepsin in waking samples to MII‐pH measurements, including reflux bolus duration, and proximal and distal recumbent reflux episodes (P < 0.05). A significant correlation was also observed between salivary pepsin upon waking or sinus lavage and reflux symptom index (P < 0.05). Conclusion Pepsin in salivary and nasal lavage samples demonstrated an association with MII‐pH‐documented LPR. Pepsin detection was most frequent in morning samples, supporting use of morning salivary pepsin levels as a potential noninvasive technique for LPR diagnosis. Level of Evidence 2 Laryngoscope, 130:961–966, 2020

Airway reflux is implicated in the pathophysiology of a wide range of adult and pediatric upper and lower airway diseases. However, the diagnosis of proximal reflux–associated disease remains challenging due to evolving clinical criteria and institutional and regional variances in diagnostic practices. Evidence suggests that nonacidic contents of reflux may serve as both pathologic mediators of and biomarkers for reflux in the upper airway. Furthermore, they offer potential pharmaceutical and surgical intervention targets and are the focus of novel clinical diagnostic tools currently under investigation.

Objectives: Laryngomalacia is a common cause of stridor in infants and is associated with laryngopharyngeal reflux (LPR). Although pepsin in operative supraglottic lavage specimens is associated with severe laryngomalacia, detection of pepsin in oral secretions has not been demonstrated in an outpatient setting. Methods: Children <2 years old with laryngomalacia diagnosed by flexible laryngoscopy and children without stridor were selected. Oral secretion samples were obtained in clinic from all subjects. Pepsin, IL-1β, and IL-8 enzyme-linked immunosorbent assays were performed to determine presence of LPR. Results: Sixteen laryngomalacia and sixteen controls were enrolled. Pepsin was detected more frequently in oral secretions of patients with laryngomalacia (13/16) than in controls (2/16; P < .001). Four patients with laryngomalacia developed symptoms requiring supraglottoplasty. Presence and level of salivary pepsin was not significantly associated with need for surgical management, nor were the levels or presence of IL-1β or IL-8 significantly associated with presence or level of pepsin, diagnosis of laryngomalacia, or need for operative management. Conclusion: Pepsin in saliva appears to be associated with laryngomalacia, suggesting a role for salivary pepsin as a noninvasive marker of LPR in patients with laryngomalacia. Future studies will determine the utility of this test in laryngomalacia.

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Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations inTMC1, a gene encoding the pore-forming subunit of the hair cell mechanotransduction channel, cause DFNA36 and DFNB7/11, respectively, accounting for ∼2% of genetic hearing loss. Previous work has established the efficacy of mutation-targeted RNAi in treatment of murine models of autosomal dominant non-syndromic deafness. However, application of such approaches is limited by the infeasibility of development and validation of novel constructs for each variant. We developed an allele-non-specific approach consisting of mutation-agnostic RNAi suppression of both mutant and WT alleles, co-delivered with a knockdown-resistant engineered WT allele with or without the use of woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to augment transgene expression. This therapeutic construct was delivered into the mature murine model of DFNA36 with an AAV vector and achieved robust hair cell and auditory brainstem response preservation. However, WPRE-enhancedTmc1expression resulted in inferior outcomes, suggesting a role for gene dosage optimization in futureTMC1gene therapy development.