A multicenter study analyzing the impact of pre-existing comorbidities on laryngotracheal reconstruction (LTR) outcomes.

INTRODUCTION: Comorbidities such as chronic lung disease and gastroesophageal reflux (GERD), prematurity, and numerous other conditions may impact the success of LTR. Single-center studies are limited in terms of patient numbers and may be underpowered. OBJECTIVES: To analyze the impact of specific comorbidities on the operation-specific and overall surgical success of LTR in a large multicenter cohort and validate a predictive model for surgical success. METHODS: A large retrospective multicenter 10-year review was undertaken to validate the data of a previous single-center study (Wertz et al. Laryngoscope 2020) which identified specific predictive comorbidities which impacted LTR outcomes. A Monte Carlo simulation based on the previous data set suggested that 300-400 cases would be needed to optimize the statistical power of a Bayesian model developed from the single-center data to predict surgical success. An IRB-approved data-sharing agreement was executed for 4 large U.S. CENTERS: A virtual REDCap® data entry form inquired about patient characteristics that best predicted surgical success in the single-center model. These included demographics, surgical approaches, cardiac, airway, genetic, endocrine, musculoskeletal, gastrointestinal, and pulmonary comorbidities; details of the surgical procedures, and results of esophagogastroduodenoscopy (EGD), esophageal pH/impedance and flexible bronchoscopy with bronchioalveolar lavage (BAL) were included. Surgical success defined as successful decannulation or resolution of airway symptoms was recorded as single surgery success and overall success following open surgical revision surgery. Multivariate Bayesian analysis, logistical regression, and Kaplan-Meier analysis were performed. RESULTS: 542 patients were identified, including 165 from the single-center study and an additional 377 patients from the multicenter group. The median age was 36 months at the time of the most recent surgery. 70.9% of the LTRs were double-staged procedures. The overall success rate was 86.4% and operation-specific success rate was 69.2%. The specific comorbidities and aerodigestive test results that impacted success based on univariate analysis included staging, bronchiectasis, pulmonary hypertension, GERD, ASD, PDA, grade of stenosis, advanced levels of stenosis, Trisomy 21, MRSA, prior open surgery at another hospital, and gross appearance on EGD. Bayesian model averaging with backward selection was used to validate and refine a predictive model for surgical success with favorable receiver operating curve characteristics - AUC values of 0.827 for single surgery success and 0.797 for overall success. DISCUSSION: With over 500 patients reviewed, this was the largest multicenter study of LTR to date, which elucidated the impact of comorbidities on success with LTR and was able to improve upon the predictive modeling based on single-center data. Patient factors are most critical in the outcome of LTR. Stage and levels of stenosis, as well as pulmonary and GI conditions most strongly impact the likelihood of success. Future prospective case-control studies will be performed to further optimize the current model for outcome prediction and patient management.

Anesthesia for laryngotracheal reconstruction in children: A narrative review.

Laryngotracheal stenosis, congenital or acquired, is a common cause of pediatric airway obstruction. Acquired subglottic stenosis frequently results from prolonged neonatal intubation. The clinical presentation of subglottic stenosis is variable, ranging from biphasic stridor and frequent upper respiratory infections to acute airway compromise. Optimal patient care requires clinical coordination within a multidisciplinary subspecialty team. Medical management includes optimizing respiratory status, gastroesophageal reflux, speech, feeding, nutrition therapies, and providing psychosocial support. If surgical intervention is required, the otolaryngologist, anesthesiologist, and perioperative team must collaborate closely to ensure successful operative outcomes. This narrative review of laryngotracheal stenosis will discuss the pathophysiology, clinical evaluation, medical management, and surgical interventions, and focus on the perioperative anesthetic considerations for children undergoing laryngotracheal reconstruction.

Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas.

Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.

Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia.

OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients. METHODS: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model. CONCLUSIONS: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.

Prophylactic inhaled corticosteroids for the management of recurrent croup.

OBJECTIVES: Croup is characterized by a barky cough, inspiratory stridor, hoarseness and varying degrees of respiratory distress. Acute croup episodes are often treated with oral, inhaled, or intravenous corticosteroids. Recurrent croup, defined as more than 2-3 episodes of acute croup in the same patient, can mimic asthma. We hypothesized that inhaled corticosteroids (ICS) given at the first sign of a respiratory viral prodrome can be a safe treatment to reduce the frequency of recurrent croup episodes in children without fixed airway lesions. METHODS: A retrospective chart review of patients being treated over an 18-month period was performed at a large tertiary care pediatric hospital following Institutional Review Board (IRB) approval. Patients under 21 years old referred to Pediatric Pulmonology, Otolaryngology, or Gastroenterology for recurrent croup were analyzed for their demographics, medical history, evaluation, treatment and clinical improvement. A Fisher's two-tailed exact test was used to compare the number of croup episodes before and after interventions. RESULTS: 124 patients were included in our analysis: 87 male and 34 female with a mean age of 54 months. Of these, 78 had >5 episodes of croup, 45 had 3-5, and 3 had 2 episodes prior to their first visit for recurrent croup. Operative direct laryngoscopy/bronchoscopy was performed in 35 patients (27.8%), with 60% showing a normal exam without fixed lesions. Ninety-two patients (74.2%) were treated with ICS, 24 were lost to follow up. Of the remaining 68 treated patients, 59 (86.7%) saw improvement with reduced severity and overall number of episodes of croup. Additionally, patients with >5 episodes of croup (47) as compared to <5 (12) were more likely to improve with ICS, (p = 0.003). There were no adverse reactions reported with ICS treatment. CONCLUSION: The novel initiation of ICS at the earliest sign of a viral upper respiratory infection shows promise as a safe preventative treatment to mitigate the frequency of recurrent croup episodes.

Social support moderates the relationship between burnout and job satisfaction in aerodigestive team members.

OBJECTIVES: Burnout among healthcare workers is a public health crisis. Burnout is associated with elevated cynicism, emotional exhaustion, and low job satisfaction. Methods to combat burnout have been challenging to identify. Based on positive experiences of pediatric aerodigestive team members, we hypothesized that social support in multidisciplinary aerodigestive teams moderates the effects of burnout on job satisfaction. METHODS: Using a survey of the Aerodigestive Society, members of Aerodigestive teams (N = 119) completed demographics, the Maslach Burnout Inventory, and measures of job satisfaction, emotional, and instrumental social support. In addition to assessing relationships between components of burnout and job satisfaction, six tests were conducted using PROCESS to ascertain the degree to which social support moderated these relationships. RESULTS: Similar to US healthcare base rates, burnout scores in this sample suggest that a third-to-half felt Emotionally Exhausted and Burned Out from work "A few times a month"-to-"Every Day." Simultaneously, however, the majority in sample (60.6%) noted feeling that they "positively impact others' lives" with 33.3% endorsing "Every Day." Job satisfaction was strikingly high at 89%, with most reporting Aerodigestive team affiliation related to higher job satisfaction. Both Emotional and Instrumental social support moderated the effect of Cynicism and Emotional Exhaustion on Job Satisfaction, with higher Job Satisfaction scores in conditions of high support. CONCLUSIONS: These results support the hypothesis that social support from a multidisciplinary aerodigestive team moderates the effect of burnout in its team members. Further work is needed to understand if membership in other interprofessional healthcare teams can help combat the negative effects of burnout.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.

Posterior tracheopexy for preterm infants with severe bronchopulmonary dysplasia and severe tracheobronchomalacia: A case series.

We report a series of four patients with severe bronchopulmonary dysplasia (BPD) who underwent posterior tracheopexy for severe tracheomalacia (TM). While posterior tracheopexy is an established surgical treatment for TM associated with tracheoesophageal fistula, it has not been previously described in TM associated with BPD. There were no significant intraoperative or postoperative complications from the surgeries. Three of the four patients required tracheostomy and mechanical ventilation, which may reflect the degree of lung disease and other multisystem comorbidities in these patients. More investigation is needed to determine whether posterior tracheopexy is an effective surgical option for TM related to BPD.

Outcomes in Pediatric Thyroidectomy: Results From a Multinational, Multi-institutional Database.

OBJECTIVE: Traditionally, data regarding thyroidectomy were extracted from billing databases, but information may be missed. In this study, a multi-institutional pediatric thyroidectomy database was used to evaluate recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. STUDY DESIGN: Retrospective multi-institutional cohort study. SETTING: Tertiary care pediatric hospital systems throughout North America. METHODS: Data were individually collected for thyroidectomies, then entered into a centralized database and analyzed using univariate and multivariable regression models. RESULTS: In total, 1025 thyroidectomies from 10 institutions were included. Average age was 13.9 years, and 77.8% were female. Average hospital stay was 1.9 nights and 13.5% of patients spent at least 1 night in the pediatric intensive care unit. The most frequent pathology was papillary thyroid carcinoma (42%), followed by Graves' disease (20.1%) and follicular adenoma (18.2%). Overall, 1.1% of patients experienced RLN injury (0.8% permanent), and 7.2% experienced hypoparathyroidism (3.3% permanent). Lower institutional volume (odds ratio [OR], 3.57; 95% CI, 1.72-7.14) and concurrent hypoparathyroidism (OR, 3.51; 95% CI, 1.64-7.53) correlated with RLN injury on multivariable analysis. Graves' disease (OR, 2.27; 95% CI, 1.35-3.80), Hashimoto's thyroiditis (OR, 4.67; 95% CI, 2.39-9.09), central neck dissection (OR, 3.60; 95% CI, 2.36-5.49), and total vs partial thyroidectomy (OR, 7.14; 95% CI, 4.55-11.11) correlated with hypoparathyroidism. CONCLUSION: These data present thyroidectomy information and complications pertinent to surgeons, along with preoperative risk factor assessment. Multivariable analysis showed institutional volume and hypoparathyroidism associated with RLN injury, while hypoparathyroidism associated with surgical indication, central neck dissection, and extent of surgery. Low complication rates support the safety of thyroidectomy in pediatric tertiary care centers.

Tonsillectomy and hematologic malignancy: Should routine pediatric tonsillectomy specimens be sent to pathology?

OBJECTIVES: Routine pediatric tonsillectomy ± adenoidectomy (T ± A) is one of the most common procedures for children worldwide, accounting for approximately 2000 procedures per year at our institution. To determine the utility of pathologic analysis of routine, nonsuspicious pediatric tonsil specimens, we investigated the incidence of hematologic and lymphoid malignancy diagnosed at the time of or following T ± A. METHODS: Retrospective review of patients 0-18 years undergoing T ± A between 2012 and 2020 with or without pathologic analysis. RESULTS: Included were 14,141 patients who underwent routine T ± A (mean age 11 ± 4.6 years, 48% female). Of these, tonsils of 2464 patients were sent to pathology, where zero were found to harbor malignancy. Seven patients (0.050%) developed malignancy after T ± A. Of these, 4 had unremarkable tonsils per pathology, and 3 did not have tonsils analyzed. There were 5 cases of Acute Lymphocytic Leukemia (ALL, 0.035%), 1 case of Acute Myeloid Leukemia (0.007%), and 1 case of Lymphoma (0.007%). The average length of time from T ± A to diagnosis was 2.4 ± 1.8 years. CONCLUSION: No cases of occult malignancy were identified in specimens from routine T ± A with pathologic analysis, even among patients who later developed malignancy. This study suggests that sending routine pediatric T ± A specimens for formal pathologic analysis is an inefficient use of resources without appreciably improving the quality and safety of patient care.

The risks of polytetrafluoroethylene pledget use in tracheopexy.

Posterior tracheopexy, performed most often for intrinsic tracheomalacia, is a procedure that is gaining in popularity and application. In this procedure, pledgeted sutures are placed between the trachea and a more fixed structure, in order to provide the airway with greater patency. Polytetrafluoroethylene pledgets are readily available but risk migration into adjacent structures over time. We present a case of a pledget migrating in to the airway and presenting as an obstructing lesion that has required multiple repeat interventions. Given that bioabsorbable materials are available, surgeons should consider alternative pledgets for these patients.

The role of CDHR3 in susceptibility to otitis media.

Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. KEY MESSAGES: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.

Slide Tracheoplasty for Tracheal Cartilaginous Sleeve in a Patient With Apert Syndrome.

Apert syndrome is a form of acrocephalosyndactyly involving craniosynostosis, syndactyly, and less commonly, tracheal cartilaginous sleeve (TCS), a potential cause of tracheal stenosis. Slide tracheoplasty is performed in children with tracheal stenosis. No reports exist for its application in stenosis related to TCS. We present a case in which slide tracheoplasty was used for the expansion of long segment tracheal stenosis owing to TCS in a newborn with Apert syndrome. Using this technique, a safe and durable airway was achieved without tracheostomy.

The FUT2 Variant c.461G>A (p.Trp154*) Is Associated With Differentially Expressed Genes and Nasopharyngeal Microbiota Shifts in Patients With Otitis Media.

Otitis media (OM) is a leading cause of childhood hearing loss. Variants in FUT2, which encodes alpha-(1,2)-fucosyltransferase, were identified to increase susceptibility to OM, potentially through shifts in the middle ear (ME) or nasopharyngeal (NP) microbiotas as mediated by transcriptional changes. Greater knowledge of differences in relative abundance of otopathogens in carriers of pathogenic variants can help determine risk for OM in patients. In order to determine the downstream effects of FUT2 variation, we examined gene expression in relation to carriage of a common pathogenic FUT2 c.461G>A (p.Trp154*) variant using RNA-sequence data from saliva samples from 28 patients with OM. Differential gene expression was also examined in bulk mRNA and single-cell RNA-sequence data from wildtype mouse ME mucosa after inoculation with non-typeable Haemophilus influenzae (NTHi). In addition, microbiotas were profiled from ME and NP samples of 65 OM patients using 16S rRNA gene sequencing. In human carriers of the FUT2 variant, FN1, KMT2D, MUC16 and NBPF20 were downregulated while MTAP was upregulated. Post-infectious expression in the mouse ME recapitulated these transcriptional differences, with the exception of Fn1 upregulation after NTHi-inoculation. In the NP, Candidate Division TM7 was associated with wildtype genotype (FDR-adj-p=0.009). Overall, the FUT2 c.461G>A variant was associated with transcriptional changes in processes related to response to infection and with increased load of potential otopathogens in the ME and decreased commensals in the NP. These findings provide increased understanding of how FUT2 variants influence gene transcription and the mucosal microbiota, and thus contribute to the pathology of OM.

Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.

Vascular and pulmonary comorbidities in children with congenital EA/TEF.

BACKGROUND: Esophageal atresia with tracheoesophageal fistula (EA/TEF) is associated with many congenital and vascular malformations; however, reports utilizing computed tomography (CT) and computed tomography angiography (CTA) are limited. The objective of this study is to review CT scans of the chest from patients with EA/TEF and report their pulmonary and vascular findings. METHODS: We completed a retrospective chart review of children with congenital EA/TEF evaluated in the aerodigestive clinic at Children's Hospital Colorado. Results of the most recent CTA or CT of the chest were investigated. Demographics, medical conditions, and bronchoscopy findings were also recorded. The ratio of tracheal lumen area between inspiratory and expiratory CTA images was measured. RESULTS: Of the patients with congenital EA/TEF seen in the program, 47 patients had a chest CT available for review. Eight patients (17%) had bronchiectasis. Of the contrast CT scans, 15 (58%) had a vascular abnormality and 16 (62%) demonstrated tracheal compression (38% at the level of the innominate artery, 35% from other structures). Nineteen of the CTAs had volumetric expiratory images of the trachea to evaluate tracheomalacia. The mean expiratory:inspiratory area was 0.57 (SD ± 0.23) at the level of the innominate. CONCLUSION: Patients with EA/TEF frequently have vascular abnormalities that may alter airway mechanics as well as pulmonary comorbidities that may affect long-term management. For patients experiencing persistent respiratory symptoms, CTA of the chest should be considered adjunct to bronchoscopy to help with medical and surgical management of these children.

Multi-omic studies on missense PLG variants in families with otitis media.

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.

Pediatric laryngoscopy and bronchoscopy during the COVID-19 pandemic: A four-center collaborative protocol to improve safety with perioperative management strategies and creation of a surgical tent with disposable drapes.

Aerosolization procedures during the COVID-19 pandemic place all operating room personnel at risk for exposure. We offer detailed perioperative management strategies and present a specific protocol designed to improve safety during pediatric laryngoscopy and bronchoscopy. Several methods of using disposable drapes for various procedures are described, with the goal of constructing a tent around the patient to decrease widespread contamination of dispersed droplets and generated aerosol. The concepts presented herein are translatable to future situations where aerosol generating procedures increase risk for any pathogenic exposure. This protocol is a collaborative effort based on knowledge gleaned from clinical and simulation experience from Children's Hospital Colorado, Children's Hospital of Philadelphia, The Hospital for Sick Children in Toronto, and Boston Children's Hospital.

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.