Effect of Unilateral Cordotomy on Perception of Dysphagia.

OBJECTIVES: CO2 laser medial transverse cordotomy is a permanent static procedure performed to achieve adequate functional airway in cases of posterior glottic stenosis and bilateral vocal fold paralysis. Although it is the preferred method to manage long-term bilateral vocal fold immobility, it is widely believed that cordotomy has the potential to cause aspiration. The minimal existing data on the effect surgical enlargement of the glottic airway on swallowing function is heterogeneous. Through investigation of dysphagia after cordotomy, we hope to better understand the influence of glottic function and its role in dysphagia. The Eating Assessment Tool (EAT-10), is a validated dysphagia symptom-specific outcome measure. We hypothesized that EAT-10 scores would not change after CO2 laser cordotomy despite causing glottic insufficiency. METHODS: Retrospective review was performed on sequential patients having undergone unilateral CO2 laser cordotomy with complete pre- and postoperative EAT-10 questionnaire data available for evaluation. RESULTS: Fifteen patients were available for analysis; 10 patients underwent primary unilateral medial transverse cordotomy, 5 patients underwent revision cordotomy, and 20 unique procedures were included in the dataset. The median EAT-10 score during the visit prior to surgery was 3.5, whereas the post-surgery median score was 2. Furthermore, the median difference of 0 was statistically non-significant (P = .91). CONCLUSION: CO2 laser cordotomy does not contribute to patient-reported dysphagia despite creating glottic incompetence. This suggests vocal fold apposition may play a less significant role in normal swallowing function than widely believed.

Chemical receptors of the arytenoid: A comparison of human and mouse.

OBJECTIVES/HYPOTHESIS: The larynx is a highly responsive organ exposed to mechanical, thermal, and chemical stimuli. Chemicals elicit responses both in intraepithelial nerve fibers and in specialized chemosensory cells, including scattered solitary cells as well as taste cells organized into taste buds. Activation of both chemosensory cells and taste buds in the larynx elicit cough, swallow, or apnea with exposure to sour or bitter substances, and even by water or sweet-tasting chemicals. In an effort to begin understanding their function, we sought to compare the distribution, density, and types of chemosensory cells and chemoresponsive nerve fibers in laryngeal epithelium of humans and mice. STUDY DESIGN: Animal and human laboratory analysis. METHODS: Using immunohistochemistry, we identified taste cells and polymodal nociceptive nerve fibers in the arytenoid area of the laryngeal epithelium of the following: 1) infants undergoing supraglottoplasty for laryngomalacia, and 2) a cadaveric specimen procured from a 34-year-old donor. We then compared these findings to both preweanling and mature mouse tissue. RESULTS: Arytenoid tissue from both human and mouse contained many taste buds containing type II taste cells-bitter, sweet, or umami sensing-which were innervated by nerve fibers expressing P2X3 type adenosine triphosphate receptors. Type III cells (acid responsive) were also present, but they were fewer in human tissue than in equivalent tissue from mice. In both species, the epithelium was densely innervated by free nerve endings. CONCLUSIONS: Our findings suggest that from a standpoint of chemosensation, human and mouse larynges are biologically similar. This suggests that a murine model can be used effectively in laryngeal chemosensory research. LEVEL OF EVIDENCE: NA Laryngoscope, 130:423-430, 2020.

Voice therapy associated with a decrease in the reflux symptoms index in patients with voice complaints.

OBJECTIVES/HYPOTHESIS: Patients with muscle tension dysphonia often demonstrate an elevation in Reflux Symptom Index (RSI) and 10-item Voice Handicap Index (VHI-10) scores, and may be erroneously diagnosed with laryngopharyngeal reflux disease. In this study we assessed the effects of voice therapy on RSI and VHI-10 scores in patients with voice complaints not responsive to antireflux medications. STUDY DESIGN: Retrospective cohort study. METHODS: A study of patients was conducted at a single tertiary-care center over 1 year (January 2012-January 2013). Patients were included if they had dysphonia not responsive to proton pump inhibition, did not have neurologic or neoplastic disease, and participated in at least three voice-therapy sessions in the absence of antireflux therapy. Primary analysis assessed change in RSI scores between the initial and follow-up visits with a laryngologist. RESULTS: A total of 18 patients were included (mean age = 49.9 ± 14.5 years, 89% female, 83% with a primary complaint of dysphonia). From initial to follow-up visit, the median RSI score (18.5 [interquartile range {IQR}, 9.5-22.8] vs. 10.5 [IQR, 4.5-14]; P = .02) and median VHI-10 score (25.5 [IQR, 11.3-30.0] vs. 13.5 [IQR, 9.5-20.8]; P = .03) significantly decreased. A significant inverse correlation was found between the number of voice therapy sessions/month and change in RSI score (r = -0.4; P = .05). CONCLUSIONS: In this study of patients with muscle tension dysphonia or vocal hyperfunction not responsive to antireflux therapy, RSI and VHI-10 scores improved following voice therapy. Results suggest that self-reported symptoms typically attributed to laryngopharyngeal reflux disease may actually be secondary to inefficient voice use patterns or anxiety about dysphonia that are responsive to voice therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1169-1173, 2019.

Factors Associated With Infectious Laryngitis: A Retrospective Review of 15 Cases.

OBJECTIVES: To identify the culturable microbes associated with infectious laryngitis and outline effective treatment strategies. METHODS: This is a retrospective chart review of adult patients with persistent dysphonia plus evidence of laryngeal inflammation who underwent biopsy for culture at a tertiary care medical center. Demographic factors, symptoms as reported on validated patient assessment tools, past medical history, social history, culture results, and treatment duration and response were reviewed. RESULTS: Fifteen patients with infectious laryngitis were included in this study. Culture results demonstrated Methicillin-sensitive Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Serratia marcescens, and "normal respiratory flora." In most patients, multiple courses of prolonged antibiotics were needed to treat MSSA or MRSA. Infections associated with other microbes resolved with a single course of antibiotics. CONCLUSIONS: In this population, infectious laryngitis is defined as colonization with bacteria not found in the previously characterized laryngeal microbiome of benign vocal fold lesions. In suspected cases of infectious laryngitis, culture is recommended, by biopsy if needed. For MSSA- and MRSA-associated laryngitis, an extended course of antibiotics may be necessary for symptom improvement and resolution of laryngeal inflammation. However, the optimal treatment regimen has yet to be defined and will require larger, prospective studies.

Laryngeal T regulatory cells in the setting of smoking and reflux.

OBJECTIVES/HYPOTHESIS: The larynx is a mucosal organ rich in lymphatic tissue that is regularly exposed to a multitude of inhaled, ingested, and refluxed microorganisms and irritants. The first line of mucosal immune defense is the barrier, including resident immune cells. T regulatory (Treg) cells are a specialized subset of CD4+ T cells that suppress or dampen immune responses to prevent damaging immunopathology. As Treg cells have been shown to preferentially accumulate at sites of infection, and Treg responses may contribute to persistence of infection by impairing antibacterial immunity, we sought to quantify these cells in laryngeal tissue exposed to smoking and reflux. STUDY DESIGN: Cross-sectional study. METHODS: Using an epigenetic assay, we quantified Treg and T cells and calculated the ratio of Treg to T cells (i.e., cellular ratio of immune tolerance [ImmunoCRIT]) in disease-free laryngeal biopsies representing four inflammatory states: 1) tobacco-exposed tissue, 2) refluxate and tobacco-exposed tissue, 3) refluxate-exposed tissue, and 4) unexposed tissue. RESULTS: There was epigenetic evidence of Treg cells in all tissues, and we found no differences in Treg cell frequency relative to smoking and reflux in laryngeal tissue collected from 42 non-treatment-seeking participants. There was a decrease in total T cell frequency and an increase in ImmunoCRIT values in smokers regardless of reflux status. CONCLUSIONS: In this study, laryngeal tissue from smokers show decreased overall T cells and increased ImmunoCRIT values. Our findings indicate that laryngeal inflammation is not directly mediated by loss of Treg cells in response to smoking and reflux in local tissue and increased ImmunoCRIT values in smokers implicate a role for this environmental exposure in modulating laryngeal immune homeostasis. More studies are indicated to explore Treg cell dysfunction in the pathophysiology of laryngeal disease. LEVEL OF EVIDENCE: NA Laryngoscope, 127:882-887, 2017.

The human laryngeal microbiome: effects of cigarette smoke and reflux.

Prolonged diffuse laryngeal inflammation from smoking and/or reflux is commonly diagnosed as chronic laryngitis and treated empirically with expensive drugs that have not proven effective. Shifts in microbiota have been associated with many inflammatory diseases, though little is known about how resident microbes may contribute to chronic laryngitis. We sought to characterize the core microbiota of disease-free human laryngeal tissue and to investigate shifts in microbial community membership associated with exposure to cigarette smoke and reflux. Using 454 pyrosequencing of the 16S rRNA gene, we compared bacterial communities of laryngeal tissue biopsies collected from 97 non-treatment-seeking volunteers based on reflux and smoking status. The core community was characterized by a highly abundant OTU within the family Comamonadaceae found in all laryngeal tissues. Smokers demonstrated less microbial diversity than nonsmokers, with differences in relative abundances of OTUs classified as Streptococcus, unclassified Comamonadaceae, Cloacibacterium, and Helicobacter. Reflux status did not affect microbial diversity nor community structure nor composition. Comparison of healthy laryngeal microbial communities to benign vocal fold disease samples revealed greater abundance of Streptococcus in benign vocal fold disease suggesting that mucosal dominance by Streptococcus may be a factor in disease etiology.

Correlation between Reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers.

OBJECTIVES/HYPOTHESIS: Although probable causative agents have been identified (e.g., refluxate components, tobacco smoke), the definitive mechanism for inflammation-related laryngeal mucosal damage remains elusive. Multichannel intraluminal impedance combined with pH monitoring (MII/pH) has emerged as a sensitive tool for diagnosis and characterization of gastroesophageal reflux disease with laryngopharyngeal manifestations. To determine the relationship between laryngeal signs and MII/pH, we examined correlations between Reflux Finding Score (RFS) ratings of videostroboscopic laryngeal examinations and findings from MII/pH. STUDY DESIGN: Correlational study. METHODS: Healthy, untreated volunteers (n = 142) underwent reflux diagnosis using data acquired from MII/pH testing. Eight trained clinicians performed RFS ratings of corresponding laryngeal examinations. Averaged RFS ratings were compared to MII/pH data using Pearson correlation coefficients. The relationship between RFS and MII/pH findings and demographic/clinical information (age, sex, smoking status, reflux) was assessed using general linear modeling. Rater reliability was evaluated. RESULTS: Posterior commissure hypertrophy was negatively correlated with minutes of nonacid refluxate (R = -0.21, P = .0115). General linear modeling revealed that 28% to 40% of the variance in ratings of ventricular obliteration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema, posterior commissure hypertrophy, and granulation/granuloma could be explained by main and interaction effects of age, sex, smoking status, and reflux. Intra- and inter-rater reliability for RFS were poor-fair. CONCLUSIONS: These results support the theory that the RFS is not specific for reflux in healthy, untreated volunteers, suggesting there may be alternate explanations for inflammatory clinical signs commonly ascribed to reflux in this population.

Characterization and comparison of bacterial communities in benign vocal fold lesions.

BACKGROUND: Benign vocal fold lesions, including cysts, nodules, polyps, and Reinke's edema, are common causes of hoarseness and subsequent voice disorders. Given the prevalence of these lesions, disease etiology and pathophysiology remain unclear and their microbiota has not been studied to date secondary to the paucity of available biopsies for investigation. We sought to characterize and compare the bacterial communities in biopsies of cysts, nodules, polyps, and Reinke's edema collected from patients in Germany and Wisconsin. These samples were then compared to the communities found in healthy saliva and throat samples from the Human Microbiome Project (HMP). RESULTS: 454 pyrosequencing of the V3-V5 regions of the 16S rRNA gene revealed five phyla that explained most of the bacterial diversity, including Firmicutes (73.8%), Proteobacteria (12.7%), Bacteroidetes (9.2%), Actinobacteria (2.1%), and Fusobacteria (1.9%). Every lesion sample, regardless of diagnosis, had operational taxonomic units (OTUs) identified as Streptococcus, with a mean abundance of 68.7%. Most of the lesions, 31 out of 44, were indistinguishable in a principal coordinates analysis (PCoA) due to dominance by OTUs phylogenetically similar to Streptococcus pseudopneumoniae. Thirteen lesions not dominated by S. pseudopneumoniae were more similar to HMP throat and saliva samples, though 12 of them contained Pseudomonas, which was not present in any of the HMP samples. Community structure and abundance could not be correlated with lesion diagnosis or any other documented patient factor, including age, sex, or country of origin. CONCLUSIONS: Dominance by S. pseudopneumoniae could be a factor in disease etiology, as could the presence of Pseudomonas in some samples. Likewise, decreased diversity, as compared to healthy saliva and throat samples, may be associated with disease, similar to disease models in other mucosal sites.

Vocal fold fibroblasts immunoregulate activated macrophage phenotype.

Recent evidence suggests that fibroblasts play a critical role in regulating inflammation during wound healing because they express several inflammatory mediators in response to bacteria. The objective of this study was to analyze the effects of lipopolysaccharide (LPS) on the immunomodulatory properties of vocal fold fibroblasts (VFFs) derived from polyps, scar and normal tissue co-cultured with macrophages, to provide insight into their interactions during the inflammatory process. Fibroblasts were co-cultured with CD14+ monocytes and after 7 days, wells were treated with LPS for 24 and 72 h. Culture supernatants were collected and concentrations of TNF-α, IL-6, IL-8, IL-10, IL-12, IL-1ß and MCP-1 were quantified by ELISA. Normal VFF and CD14+ monocultures were used as controls. Twenty-four hours after LPS activation, macrophages co-cultured with polyp VFF had significantly increased expression of TNF-α, IL-1ß, IL-12 and IL-10 compared to controls (p<0.0001). In contrast, macrophages co-cultured with scar VFF had significantly lower expression of TNF-α, IL-1ß and IL-12 with significantly higher IL-10 compared to control (p<0.0001). After 72 h, macrophages co-cultured with polyp VFF increased expression of TNF-α, IL-1ß, IL-10, IL-6, IL-8, MCP-1 and TGF-ß (p<0.01) and macrophages co-cultured with scar VFF significantly decreased their expression of IL-1ß and IL-12 compared to control (p<0.0001). Scar VFF at both time points produced significantly lower levels of IL-8, MCP-1, IL-6 and TGF-ß compared to controls (p<0.05). Based on our findings, VFF and macrophages secrete several inflammatory mediators that modify their diverse functions. Polyp and scar VFF may play a role in regulating abnormal inflammatory responses, which could result in excessive ECM deposition that disrupts the function of the vocal folds.

Neck surface electromyography as a measure of vocal hyperfunction before and after injection laryngoplasty.

OBJECTIVES: The goal of this preliminary study was to determine whether neck surface electromyography (sEMG) is sensitive to possible changes in vocal hyperfunction associated with injection laryngoplasty, particularly with respect to alterations in the degree of vocal hyperfunction. METHODS: Thirteen individuals undergoing office-based injection laryngoplasty for glottal phonatory insufficiency were prospectively studied with a battery of acoustic, aerodynamic, endoscopic, and anterior neck sEMG assessments before the procedure and approximately 1 week afterward. RESULTS: Anterior neck sEMG values were not significantly reduced (p < 0.05) after the procedure; however, perceptual ratings of strain and false vocal fold compression were both significantly reduced, reflecting a decrease in vocal hyperfunction. CONCLUSIONS: The results do not support the use of anterior neck sEMG measures to assess vocal hyperfunction, and place into question the use of some other measures (estimates of anterior-posterior supraglottic compression, quantitative measures of anterior-posterior and false vocal fold supraglottic compression, and acoustic vowel rise times) that have been considered reflective of vocal hyperfunction.