Attenuation of Helper T Cell Capacity for TH1 and TH17 Differentiation in Children With Nontuberculous Mycobacterial Infection.

Nontuberculous mycobacteria (NTM) infect children with increasing frequency worldwide. Using blood and lymph node tissue from children with NTM lymphadenitis, and uninfected lymph node tissue from community controls, we evaluated helper T (TH) cells in functional assays of TH1/TH17 differentiation and measured the concentration of their associated cytokines at the site of infection. Circulating TH cells from infected children were attenuated in their TH1/TH17 differentiation capacity and expressed less interferon γ and interleukin 17 after polyclonal stimulation. Similar differences were observed at the site of infection, where most cytokine concentrations were unchanged relative to controls. Our data are consistent with a model wherein TH1/TH17 differentiation is attenuated in NTM-infected children.

Otolaryngologic surgeries are frequent in children with eosinophilic esophagitis.

OBJECTIVE: The aim was to study the prevalence of otolaryngologic surgeries in pediatric patients with eosinophilic esophagitis (EoE). METHODS: Retrospective cohort study at a tertiary care center. The type of otolaryngologic surgeries performed in patients with diagnosis of EoE was recorded during a 5-year period. RESULTS: Seventy-five percent of patients were male, with average age of EoE diagnosis at 7.5 years with an 83% incidence of atopy. Cohort analysis revealed that 33% (119/362) had a total of 275 otolaryngologic surgeries. Surgeries performed on 119 patients are as follows: 20% bilateral myringotomy with tubes, 14% tonsillectomy, 18.5% adenoidectomy, 1.4% sinus irrigation, 3.3% bronchoscopy, and 1.4% laryngotracheoplasty (LTP); 63% of patients underwent multiple procedures. Thirty percent of patients undergoing bilateral myringotomy with tube placement (BMT) needed additional tubes. Four of 5 LTP patients had successful operations. Twelve percent of patients had EoE diagnosis prior to an otolaryngologic surgery. CONCLUSION: Thirty-three percent of children with EoE required otolaryngologic surgical intervention and nearly one-third who underwent BMT required additional ear tubes. A large fraction of children with EoE will undergo an otolaryngologic surgery, only a minority with a preoperative EoE diagnosis. Until the nature of this relationship is clarified, the high coincidence with otolaryngologic surgeries dictates that otolaryngologists should be familiar with diagnosis of EoE in patients.

International pediatric otolaryngology group (IPOG) consensus on approach to aspiration.

OBJECTIVE: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration. METHODS: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step. RESULTS: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children. CONCLUSION: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options.

Use of coblation in resection of juvenile nasopharyngeal angiofibroma.

We present a series of 4 patients with juvenile nasopharyngeal angiofibroma (JNA) who underwent Coblation-assisted endoscopic resection after preoperative embolization, and discuss the use and advantages of endoscopic Coblation-assisted resection of JNA. Our limited case series suggests that Coblation may be used in the resection of JNA after embolization in a relatively safe, efficient, and effective manner. Coblation allows for decreased bleeding, less need for instrumentation, and improved visualization. There are limited published data in the literature to date on the use of Coblation in endoscopic JNA resection. We describe its use in a more extensive tumor than those previously reported. Further studies are needed to fully define the safety and utility of Coblation technology for this application.

Ulcerative lesions as a rare cause of laryngotracheitis in the pediatric population.

OBJECTIVE: The goal of this study is to describe a unique finding of ulcerative lesions of the larynx in two pediatric patients presenting with prolonged acute laryngotracheitis and compare to previously described reports to determine the typical clinical picture, need for intervention, and management model. METHODS: We present two cases of ulcerative lesions of the larynx in immunocompetent children, one with PCR positive HSV, which presented as severe croup requiring intensive care unit admission. Literature review was completed to assess for current knowledge of this entity. Our cases are discussed in the context of previously reported cases of HSV laryngotracheitis. Descriptive analysis was completed focusing on presentation, physical exam findings, treatment, length of therapy, and outcomes. RESULTS: Literature review uncovered six case reports including 10 individual cases of prolonged croup with findings of HSV laryngitis and one retrospective review describing 15 cases of prolonged croup found to be caused by ulcerative laryngitis. All patients underwent direct laryngoscopy and bronchoscopy for evaluation. Analysis was completed comparing the studies to our patients with significant findings including high intubation rate of 77%, ulcerative stomatitis in 63%, and treatment with antiviral medication directed at HSV in 85% with improvement in symptoms. CONCLUSION: It is important to consider HSV as a possible pathogen in cases of prolonged or atypical croup. Laryngoscopy should be used for diagnostic intervention and identification of ulcerative lesions. Stomatitis may be an indication for earlier direct inspection. Treatment with anti-viral therapy and with discontinuation or taper of steroid is suggested.

American society of pediatric otolaryngology vascular anomalies task force review of tongue venous malformations: Techniques, pearls, and pitfalls.

Management of tongue venous malformations can be challenging in the pediatric population due to their heterogeneity in presentation, extent of involvement and functional compromise. It is important to recognize the value of various treatment options in order to guide management of each patient in an individualized fashion. Here we describe a series of patients with tongue venous malformations that are managed using diverse modalities to illustrate the relative benefits and risks of each technique. The challenges of venous malformation treatment can be mitigated by tailoring the approach to each individual patient and malformation. This case series also emphasizes the need and importance of working in the setting of a multidisciplinary vascular anomalies team.

Establishment of novel immortalized middle ear cell lines as models for otitis media.

Objective: Otitis media (OM) is among the most frequently diagnosed pediatric diseases in the US. Despite the significant public health burden of OM and the contribution research in culture models has made to understanding its pathobiology, a singular immortalized human middle ear epithelial (MEE) cell line exists (HMEEC-1, adult-derived). We previously developed MEE cultures from pediatric patients with non-inflamed MEE (PCI), recurrent OM (ROM), or OM with effusion (OME) and demonstrated differences in their baseline inflammatory cytokine expression and response to stimulation with an OM-relevant pathogen lysate and cytokines. Herein, we sought to immortalize these cultures and assess retention of their phenotypes. Methods: MEE cultures were immortalized via lentivirus encoding temperature-sensitive SV40 T antigen. Immortalized MEE lines and HMEEC-1 grown in monolayer were stimulated with non-typeable Haemophilus influenzae (NTHi) lysate. Gene expression (TNFA, IL1B, IL6, IL8, MUC5AC, and MUC5B) was assessed by qPCR. Results: Similar to parental cultures, baseline cytokine expressions were higher in pediatric OM lines than in HMEEC-1 and PCI, and HMEEC-1 cells were less responsive to stimulation than pediatric lines. Conclusion: Immortalized MEE lines retained the inflammatory expression and responsiveness of their tissues of origin and differences between non-OM versus OM and pediatric versus adult cultures, supporting their value as novel in vitro culture models for OM.

International Pediatric Otolaryngology Group: Consensus guidelines on the diagnosis and management of non-tuberculous mycobacterial cervicofacial lymphadenitis.

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infection commonly manifests as subacute or chronic cervicofacial lymphadenitis in immunocompetent children. The optimal management of this pathology remains controversial. OBJECTIVES: This international consensus guideline aims to understand the practice patterns for NTM cervicofacial lymphadenitis and to address the primary diagnostic and management challenges. METHODS: A modified three-iterative Delphi method was used to establish expert recommendations on the diagnostic considerations, expectant or medical management, and operative considerations. The recommendations herein are derived from current expert consensus and critical review of the literature. SETTING: Multinational, multi-institutional, tertiary pediatric hospitals. RESULTS: Consensus recommendations include diagnostic work-up, goals of treatment and management options including surgery, prolonged antibiotic therapy and observation. CONCLUSION: The recommendations formulated in this International Pediatric Otolaryngology Group (IPOG) consensus statement on the diagnosis and management of patients with NTM lymphadenitis are aimed at improving patient care and promoting future hypothesis generation.

Association of Pepsin With Inflammatory Signaling and Effusion Viscosity in Pediatric Otitis Media.

OBJECTIVE: Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro. STUDY DESIGN: Cross-sectional study. METHODS: ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR. RESULTS: Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P < .05). Pepsin-negative MEF was more frequently absent of interleukin 8 or mucin 5B (P < .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro, however, pepsin induced IL6, IL8, and TNF at pH 7 (P < .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration. CONCLUSIONS: Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:470-477, 2022.

Management of plastic bronchitis in a child with mild intermittent asthma.

OBJECTIVES: We describe the clinical presentation of a 7 1/2-year-old boy with a history of mild intermittent asthma who presented with left lung collapse and was found to have plastic bronchitis. METHODS: We reviewed the patient chart and imaging results and performed a literature review of plastic bronchitis and its management. RESULTS: Bronchoscopy in our patient demonstrated a large white, friable, cast-like material that obstructed the entire left main stem bronchus and could not be easily suctioned. The cast was removed in a piecemeal fashion by means of serial rigid bronchoscopy over a 6-month period with use of both optical forceps and flexible suction catheters. Microscopic examination of the cast-like material showed a predominance of eosinophils along with neutrophils encased in proteinaceous material. CONCLUSIONS: Plastic bronchitis in children is a rare condition that can mimic foreign body aspiration and can be associated with underlying pulmonary inflammatory disorders or cardiovascular disease. Aggressive bronchoscopic management of the airway obstruction and medical management of the underlying disease process are important for the successful treatment of plastic bronchitis.

RNA Sequencing and Pathways Analyses of Middle Ear Epithelia From Patients With Otitis Media.

OBJECTIVES: Otitis media (OM) is the most common pediatric diagnosis in the United States. However, our understanding of the molecular pathogenesis of OM remains relatively poor. Investigation of molecular pathways involved in OM may improve the understanding of this disease process and elucidate novel therapeutic targets. In this study, RNA sequencing (RNA-Seq) was used to discern cellular changes associated with OME compared to healthy middle ear epithelium (MEE). STUDY DESIGN: Ex vivo case-control translational. METHODS: Middle ear epithelia was collected from five pediatric patients diagnosed with OME undergoing tympanostomy tube placement and five otherwise healthy pediatric patients undergoing cochlear implantation. Specimens underwent RNA-Seq and pathways analyses. RESULTS: A total of 1,292 genes exhibited differential expression in MEE from OME patients compared to controls including genes involved in inflammation, immune response to bacterial OM pathogens, mucociliary clearance, regulation of proliferation and transformation, and auditory cell differentiation. Top networks identified in OME were organismal injury and abnormalities, cell morphology, and auditory disease. Top Ingenuity canonical pathways identified were axonal guidance signaling, which contains genes associated with auditory development and disease and nicotine degradation II and III pathways. Associated upstream regulators included ß-estradiol, dexamethasone, and G-protein-coupled estrogen receptor-1 (GPER1), which are associated with otoprotection or inflammation during insult. CONCLUSIONS: RNA-Seq demonstrates differential gene expression in MEE from patients with OME compared to healthy controls with important implications for infection susceptibility, hearing loss, and a role for tobacco exposure in the development and/or severity of OME in pediatric patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2590-2597, 2021.

Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media.

OBJECTIVES/HYPOTHESIS: Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age-, sex-, and race-associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC-1, derived from an adult without known middle ear disease. In this study, HMEEC-1 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM-pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis. STUDY DESIGN: Case-control series. METHODS: MEE cultures were established from patients aged <6 years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC-1 cells were stimulated with tumor necrosis factor-α, interleukin (IL)-1ß, or nontypeable Haemophilus influenzae lysate. TNFA, IL1B, IL6, IL8, IL10, and MUC5B were assayed via quantitative polymerase chain reaction. IL-8 was assayed by enzyme-linked immunosorbent assay. RESULTS: Gene/protein target expressions were frequently higher in pediatric OM lines than in HMEEC-1 and Peds CI. HMEEC-1 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines. CONCLUSIONS: OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult-derived HMEEC-1 cells differ significantly in baseline expression and response of OM-associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:410-416, 2021.

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.

Use of a Cervicofacial Flap in Closing Large Defects Following Wide Local Excision of Complicated Preauricular Lesions.

PURPOSE: To describe innovative surgical technique for closure of large defect following complicated preauricular cyst excision secondary to prior failed excision attempts, infections, and drainage procedures. Preauricular cysts must be widely excised including any fistulous tracts in order to reduce recurrence rates; however, the resultant large local excision poses cosmetic challenges. METHODS: Retrospective chart review of 3 patient cases who underwent excision of recurrent preauricular lesions involving cervical parotid flap closure. All three cases demonstrate complicated preauricular congenital cysts which were infected and had prior drainage, excision attempts, or sclerotherapy. A cervicoparotid flap was used to close all defects cosmetically with no facial nerve weakness and without distortion to the oral commissure or lateral canthus. RESULTS/CONCLUSIONS: There is a high recurrence rate seen with wide local congenital cyst excisions that have been previously excised, infected, and drained; as well as, cosmetically unfavorable outcomes utilizing traditional repair. Utilizing our closure technique which involves reconstructive local regional flap with cervicoparotid approach our 3 patients have had no reoccurance of cyst or infection. Our approach also maximizes cosmetic outcomes, with reduced scar visibility. Pre and postoperative photos will be shown.

Detection of Pepsin in Oral Secretions of Infants with and without Laryngomalacia.

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-1ß, 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-1ß 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.

Significance of positive tracheal cultures in the 30 days following tracheostomy.

INTRODUCTION: Positive tracheal cultures obtained after tracheostomy are often considered organ/space surgical site infections by the National Surgical Quality Improvement Project. However, the definition of bacterial tracheitis after tracheostomy is not well described. OBJECTIVE: To determine the relationship of positive tracheal cultures in the 30 days following pediatric tracheostomy, antibiotic treatment of these cultures, and signs/symptoms of respiratory infection. METHODS: A retrospective chart review was performed on subjects who underwent tracheostomy from November 2012-September 2017 at a tertiary care pediatric center. The following data was studied: positive tracheal cultures, antibiotic treatment for positive cultures, and other signs/symptoms of infection including fever and elevated white blood cell count. Descriptive data analysis was performed, and relative risk and 95% confidence intervals were calculated. Multivariate logistic regression model was used to assess independent association when applicable. RESULTS: There were 173 subjects who met study criteria. Median age at tracheostomy was 4.6 months. Fifty-one percent (89/173) of subjects had at least one positive tracheal culture in the 30 days following tracheostomy. Of those subjects, 38% (34/89) had fever, 71% (32/45) had an elevated white blood cell count, 31% (22/72) had consolidation on chest imaging, 61% (54/89) had increased tracheal secretions, 70% (62/89) had increased ventilation requirements, and 60% (53/89) were treated with antibiotics for a diagnosis of tracheitis. There was no meaningful difference when comparing fever, increased white blood cell count, lung consolidation, increased tracheal secretions, or increased ventilation requirements in those with and without a positive tracheal culture or in those with and without antibiotic treatment for a positive culture. Multivariate logistic regression analysis showed that increased age at time of tracheostomy, more days on the ventilator after tracheostomy, and an increased number of positive cultures in the year after tracheostomy were related to having a positive tracheal culture within 30 days of tracheostomy. CONCLUSION: For post-operative pediatric tracheostomy subjects, there were no meaningful differences when comparing signs/symptoms of infection between those with and without a positive tracheal culture and between those with and without antibiotic treatment for a positive culture.

Primary tracheocutaneous fistula closure with immediate transition to nocturnal noninvasive positive pressure ventilation in two children with Congenital Central Hypoventilation Syndrome.

Transitioning children with Congenital Central Hypoventilation Syndrome (CCHS) from nocturnal invasive ventilation via tracheostomy to noninvasive positive pressure ventilation (NIPPV) is challenging due to the leak caused by the tracheocutaneous fistula (TCF), resulting in insufficient ventilation. Decannulation and primary closure of the TCF with immediate transition to nocturnal NIPPV was performed in two children with CCHS at a tertiary care children's hospital. Neither child developed significant adverse effects such as pneumomediastinum or pneumothorax. This technique is a novel approach that may improve decannulation outcomes and aid transition to NIPPV in this patient population.

The direct laryngoscopy and rigid bronchoscopy findings and the subsequent management of infants with failed extubations.

INTRODUCTION: There is limited data regarding the role of direct laryngoscopy and rigid bronchoscopy (DLRB) in infants with failed extubations. Pediatric otolaryngologists are frequently consulted to perform DLRB in infants with failed extubations. OBJECTIVE: To determine the DLRB findings in infants with failed extubations and the interventions performed based on these findings. METHODS: A retrospective chart review was performed on infants less than 12 months old undergoing DLRB for failed extubations from January 2013-June 2017 at a tertiary care children's hospital. Data was collected on age, birth weight, perinatal complications, comorbid conditions, number of failed extubations, length of most recent intubation, operative findings, and subsequent interventions, including tracheostomy. Descriptive and comparative analyses were performed. RESULTS: Of the 62 subjects who met study criteria, median age at DLRB was 3.0 months, corrected age was 1.0 months, gestational age was 27.1 weeks, birth weight was 0.97 kg, and number of failed extubations was 2.0. About 80% had respiratory distress at birth requiring intubation, and 76% carried a diagnosis of bronchopulmonary dysplasia (BPD). The median number of days intubated prior to DLRB was 27. Twenty-seven percent of subjects had no significant abnormal findings on DLRB, and 26% had subglottic stenosis. The majority (74%) underwent tracheostomy. Eighteen percent of subjects had an initial intervention for abnormal DLRB finding(s) other than tracheostomy and were able to avoid tracheostomy as a future intervention. Tracheostomy placement was associated with a diagnosis of BPD (RR 1.78, 95% CI 1.02, 3.10), having a birth weight less than 0.71 kg (RR 1.45, CI 1.01, 2.10), and being intubated for 48 or more days prior to DLRB (RR 1.57, 95% CI 1.05, 2.36); it was not associated with the number of failed extubations prior to DLRB. CONCLUSIONS: Infants with failed extubations commonly had abnormal findings on airway evaluation by DLRB. Most children in this population still required tracheostomy placement, but about 20% were able to have an alternate intervention and avoid tracheostomy.