Esophageal Baseline Impedance is Associated with Laryngopharyngeal Reflux and Treatment Response.

OBJECTIVE: To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy. METHODS: This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR. RESULTS: Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 ± 94.8 vs. 2158 ± 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Ω was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response. CONCLUSION: Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4071-4077, 2024.

Evaluation of Social Determinants of Health on Dysphagia Care Pathways at a Tertiary Care Facility.

OBJECTIVES: Limited research exists evaluating the impact of social determinants of health in influencing care pathways for patients with dysphagia. A better understanding of whether these determinants correlate to altered care and resource utilization is essential as it relates to patient outcomes. STUDY DESIGN: Retrospective chart review. METHODS: All adult patients seen at a tertiary midwestern hospital were screened for ICD codes of dysphagia diagnoses from 2009 to 2019. Demographic information was collected from these patients with dysphagia including sex, race, ethnicity, and insurance status. Subgroup analysis was performed to assess referral pattern rates and types of diagnostic interventions ordered (none, videofluoroscopic swallow study, esophagram, and esophagogastroduodenoscopy). RESULTS: A total of 31,858 patients with dysphagia were seen at our institution during the study period, with a majority being female (56.36%), Caucasian (79.83%), and publicly insured (63.16%), at a median age of 60.35 years. There were no significant care delivery pattern differences based on geography/zip code analyses. African American patients were significantly more likely to have imaging or interventions performed (odds ratio [OR] 1.463, p = 0.005). Patients with public insurance also had higher rates of diagnostic study utilization (OR 1.53, p = 0.01). Only 3% of all patients with dysphagia were seen by laryngologists. CONCLUSION: No significant differences were seen in dysphagia evaluation modalities based on zip code analyses surrounding this tertiary care facility. African American patients and those with public insurance had significantly higher utilization of subsequent testing and intervention for dysphagia care. Further studies are necessary to delineate causes and outcome differences for these measurable differences in dysphagia care pathways. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1139-1146, 2024.

The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus.

OBJECTIVE: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. METHODS: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. RESULTS: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. CONCLUSION: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1614-1624, 2024.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.

Oral and Inhaled Fosamprenavir Reverses Pepsin-Induced Damage in a Laryngopharyngeal Reflux Mouse Model.

OBJECTIVE: More than 20% of the US population suffers from laryngopharyngeal reflux. Although dietary/lifestyle modifications and alginates provide benefit to some, there is no gold standard medical therapy. Increasing evidence suggests that pepsin is partly, if not wholly, responsible for damage and inflammation caused by laryngopharyngeal reflux. A treatment specifically targeting pepsin would be amenable to local, inhaled delivery, and could prove effective for endoscopic signs and symptoms associated with nonacid reflux. The aim herein was to identify small molecule inhibitors of pepsin and test their efficacy to prevent pepsin-mediated laryngeal damage in vivo. METHODS: Drug and pepsin binding and inhibition were screened by high-throughput assays and crystallography. A mouse model of laryngopharyngeal reflux (mechanical laryngeal injury once weekly for 2 weeks and pH 7 solvent/pepsin instillation 3 days/week for 4 weeks) was provided inhibitor by gavage or aerosol (fosamprenavir or darunavir; 5 days/week for 4 weeks; n = 3). Larynges were collected for histopathologic analysis. RESULTS: HIV protease inhibitors amprenavir, ritonavir, saquinavir, and darunavir bound and inhibited pepsin with IC50 in the low micromolar range. Gavage and aerosol fosamprenavir prevented pepsin-mediated laryngeal damage (i.e., reactive epithelia, increased intraepithelial inflammatory cells, and cell apoptosis). Darunavir gavage elicited mild reactivity and no discernable protection; aerosol protected against apoptosis. CONCLUSIONS: Fosamprenavir and darunavir, FDA-approved therapies for HIV/AIDS, bind and inhibit pepsin, abrogating pepsin-mediated laryngeal damage in a laryngopharyngeal reflux mouse model. These drugs target a foreign virus, making them ideal to repurpose. Reformulation for local inhaled delivery could further improve outcomes and limit side effects. LEVEL OF EVIDENCE: NA. Laryngoscope, 133:S1-S11, 2023.

Correlation of Esophageal Mean Nocturnal Baseline Impedance With Markers of Laryngopharyngeal Reflux.

OBJECTIVES: Mean nocturnal baseline impedance (MNBI) is a measure of the esophageal epithelial barrier function calculated via high-resolution impedance manometry and can be used as a diagnostic tool and treatment response predictor for gastroesophageal reflux disease (GERD). However, its utility for laryngopharyngeal reflux (LPR) has been minimally studied. We aimed to investigate the relationship of MNBI between patients with suspected LPR, healthy controls, and their 24-h multichannel intraluminal impedance-pH (MII-pH) study results. METHODS: Retrospective patient series analysis was performed of patients with suspected LPR and healthy controls who underwent 24-h MII-pH monitoring. MNBI values were calculated from impedance channels at the level of the hypopharynx, proximal esophagus, and distal esophagus. We compared these MNBI values between the subject groups with secondary analysis on MII-pH results, reflux symptom index, reflux findings score, DeMeester score, and salivary pepsin levels. RESULTS: Twenty-three patients with suspected LPR and 14 healthy controls were enrolled. Decreased distal esophageal MNBI was found to be significantly decreased in patients with suspected LPR compared with healthy controls (p < 0.01) and in subjects with positive MII-pH studies compared to negative MII-pH studies (p < 0.01). There were no significant correlations of MNBI at the hypopharynx or proximal esophagus. CONCLUSION: Distal esophageal MNBI has significant correlations with many phenotypic and biological markers of LPR. These findings indicate that MNBI has the potential to be applied to LPR, similar to its emerging use as a diagnostic tool and treatment response predictor for GERD. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1927-1932, 2023.

Best Practices in Treatment of Laryngopharyngeal Reflux Disease: A Multidisciplinary Modified Delphi Study.

BACKGROUND: Laryngopharyngeal reflux (LPR) is a common otolaryngologic diagnosis. Treatment of presumed LPR remains challenging, and limited frameworks exist to guide treatment. METHODS: Using RAND/University of California, Los Angeles (UCLA) Appropriateness Methods, a modified Delphi approach identified consensus statements to guide LPR treatment. Experts independently and blindly scored proposed statements on importance, scientific acceptability, usability, and feasibility in a four-round iterative process. Accepted measures reached scores with ≥ 80% agreement in the 7-9 range (on a 9-point Likert scale) across all four categories. RESULTS: Fifteen experts rated 36 proposed initial statements. In round one, 10 (27.8%) statements were rated as valid. In round two, 8 statements were modified based on panel suggestions, and experts subsequently rated 5 of these statements as valid. Round three's discussion refined statements not yet accepted, and in round four, additional voting identified 2 additional statements as valid. In total, 17 (47.2%) best practice statements reached consensus, touching on topics as varied as role of empiric treatment, medication use, lifestyle modifications, and indications for laryngoscopy. CONCLUSION: Using a well-tested methodology, best practice statements in the treatment of LPR were identified. The statements serve to guide physicians on LPR treatment considerations.

Demographic differences in the treatment of unilateral vocal fold paralysis.

Objective: To determine the impact of patient demographics and social determinants of health on treatment pathways for unilateral vocal fold paralysis (UVFP) at a tertiary laryngology clinic. Study design: Retrospective medical record review. Methods: Patient demographics (age, gender, race, ethnicity, and insurance status) were extracted for adults diagnosed with UVFP between 2009 and 2019. Odds ratios for the associations between sociodemographic factors and UVFP treatment pathways were determined by chi-square analyses. Results: A total of 1490 UVFP diagnoses were identified during the study period with the majority being female (58%), White (85%), non-Hispanic (97%), and publicly insured (54%). Five treatment pathways were identified: observation, injection laryngoplasty, voice therapy, laryngeal framework surgery/thyroplasty, and reinnervation surgery. There were 538 patients who underwent observation, 512 injection laryngoplasty, 366 voice therapy, 136 thyroplasty, and 26 laryngeal reinnervation surgery. Males were more likely to undergo injection laryngoplasty than females (OR 1.32; CI 1.08-1.61), whereas females were more likely to undergo voice therapy (OR 1.39; CI 1.09-1.76). Patients with public insurance (OR 1.48; CI 1.03-2.14) and Hispanics (OR 2.60; CI 1.18-5.72) were more likely to undergo thyroplasty. Patients who underwent reinnervation surgery were younger than those in other treatment pathways (median: 39.1 years vs. 50.7-56.1 years). Conclusions: Gender, ethnicity, and insurance status were significantly associated with specific UVFP treatment pathways. Patients with public insurance were more likely to undergo surgical intervention than voice therapy. This data overall supports differences in care pathway utilization for UVFP based on social determinants of health. Level of evidence: Level IV.

Analysis of socioeconomic factors in laryngology clinic utilization for treatment of dysphonia.

OBJECTIVE: To evaluate the association between patient socioeconomic and demographic factors and tertiary care utilization for dysphonia in a localized metropolitan area of the American Midwest. METHODS: Multivariate regression analysis was used to correlate patient demographics and population level data (e.g., age, gender, race, insurance, median income, education level) with tertiary laryngology utilization for dysphonia care at our institution between 2000 and 2019. Initial analyses characterized tertiary laryngology utilization rates for all regional ZIP codes and correlated these data with census information for household income and education. Dysphonia patient demographics were compared among populations cared for in our entire academic Otolaryngology department, our health system, and the regional population. RESULTS: Among 1,365,021 patients in our health system, there were 7066 tertiary laryngology visits with a diagnosis of dysphonia. Dysphonia patients as compared to the overall health system were older (62.0 vs. 50.8 years), more likely to be female (63.7 vs. 50.2%) and more likely to have insurance (98.4 vs. 87.5%, all p < .001). Patient and population-level factors including insurance status, education, and black race showed positive correlation with laryngology utilization while median income did not. CONCLUSIONS AND RELEVANCE: Insurance status, education level, and race correlated with utilization of tertiary laryngology services for the evaluation of dysphonia in our community, while median income did not. Black patients utilized tertiary laryngology care at higher rates compared to departmental and regional population utilization data. These results underscore important demographic and disease-specific factors that may affect utilization of subspecialty care in Otolaryngology. LEVEL OF EVIDENCE: IV.

Twenty-One for 2021: The Most Influential Papers in Laryngology Since 2000.

OBJECTIVES/HYPOTHESIS: To identify the most influential publications in laryngology since 2000. STUDY DESIGN: Modified Delphi process. METHODS: Samples of laryngologists drawn from editors of leading journals, organization officers, and thought leaders were invited to participate in a modified Delphi identification of influential laryngology papers. Influential was defined as follows: yielding meaningful practice changes, catalyzing further work as a foundation for an important topic, altering traditional views, or demonstrating durability over time. Quality and validity were not among the selection criteria. Each participant nominated 5 to 10 papers in Round 1. These nominations, augmented with papers from bibliometric analysis, were narrowed further in Round 2 as participants identified their top 20. The 40 papers with the most Round 2 votes were discussed by video conference and then subjected to Round 3 voting, with each participant again selecting their top 20 most influential papers. Final results were collated by the number of Round 3 votes. RESULTS: Sixteen of 18 invited laryngologists participated overall (all 16 in Rounds 1 and 3; 14 in Round 2). Twenty-one papers were identified as most influential. One paper appeared on all 16 Round 3 lists; three papers with eight (50%) votes each were lasted to make the list. Eleven of these 21 focused on voice; three each related to cancer, airway, and swallowing; and one encompassed all of these clinical areas. CONCLUSIONS: This list of 21 influential laryngology papers serves to focus further research, provides perspective on recent advances within the field, and is an educational resource for trainees and practicing physicians. LEVEL OF EVIDENCE: NA Laryngoscope, 132:406-412, 2022.