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.

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.

Trends in Subglottic Stenosis Management: Resource Utilization and Pediatric Otolaryngology Training.

OBJECTIVES/HYPOTHESIS: The role for endoscopic management in children with subglottic stenosis (SGS) has grown, but there are no data on resource utilization or the impact on surgical training in pediatric otolaryngology. This study hypothesizes that this shift has increased resource utilization and has impacted surgical training by shifting the focus toward more endoscopic techniques. STUDY DESIGN: Retrospective database review. METHODS: The Kids' Inpatient Database for 2003, 2006, 2009, and 2012 was queried for admissions with the diagnosis of SGS. Surgical caseload was studied using the Accreditation Council for Graduate Medical Education Accreditation data system for 2010 to 2017. RESULTS: Admissions with SGS remained constant between 2003 and 2012. Hospital charges per admission did not change between 2003 and 2009 but increased in 2012. Tracheostomy decreased from 10.5% of admissions in 2003 to 6.8% in 2012. The percentage requiring repair of the larynx did not change; other operations on the larynx increased from 4.5% in 2003 to 11.6% in 2012. The median number of laryngoplasties performed per trainee decreased from 14 to nine between 2010 and 2017, whereas the number of laryngoscopy with intervention procedures increased from 34 to 56. CONCLUSIONS: The evolution of SGS management appears to have led to a decrease in tracheostomy and an increase in certain procedures that may include endoscopic procedures. Recently, there has been a shift in airway surgical training, with trainees logging less open laryngotracheoplasty and more interventional laryngoscopy. Although these trends cannot be directly linked, the changes in trainee surgical experience may be justified by the decrease in larger open procedures and associated resource utilization. LEVEL OF EVIDENCE: 2c Laryngoscope, 132:S1-S9, 2022.

Parental and provider perspectives on social media about ankyloglossia.

OBJECTIVES: To investigate and identify the concerns and opinions expressed in both parental and provider posts on social media about ankyloglossia. METHODS: In this study, posts on Twitter between 1/1/2008 and 12/31/2018 were collected using search terms and hashtags specific to pediatric ankyloglossia. The search terms included a primary phrase to indicate ankyloglossia along with a pediatric identifier. Tweets that met inclusion criteria were analyzed qualitatively via conventional content analysis. After all tweets were categorized, descriptive statistics were completed to determine frequency of each theme. RESULTS: In total, 5951 tweets were retrieved. Parents authored 982 (16.5%) of tweets, and 782 (13.1%) were by providers. The remaining 4187 tweets did not fit criteria for either the parent or provider groups. Amongst parents, the most common themes mentioned were feeding problems (309 tweets [32.4%]), followed by lip tie (215 [22.5%]), anxiety or emotion (207 [21.7%]), and maternal breastfeeding complications (127 [13.3%]). The number of tweets about ankyloglossia and frenotomy in 2018 had increased by 2395% since 2009. Amongst providers, 215 tweets were judged by the coders to provide an opinion on ankyloglossia, of which 94.4% had a pro-frenotomy sentiment. When a specialty was identified, tweets were most often by dentists (250 [31.9%]), followed by lactation consultants and International Board Certified Lactation Consultants (IBCLCs) (157 [29.7%]) and non-otolaryngologist physicians (79 [10.1%]). Otolaryngologists accounted for 8.7% (68 tweets) of posts about ankyloglossia. CONCLUSION: Our findings demonstrate the spectrum of opinions that exist among both parents and providers about ankyloglossia. This can aid in shared-decision making by enabling the counseling provider to guide recommendations based on medical evidence with the understanding that there is a large amount of non-scientific information and opinions disseminated that may be shaping decisions.

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.

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.

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.

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.

Resident and Fellow Engagement in Safety and Quality.

Beyond educational and institutional requirements, there is a need for trainees (residents and fellows) to learn patient safety and quality improvement skills in order to achieve the ultimate goal of providing better patient care. Key steps to engagement include creating a safety and quality culture, supporting faculty development, and selecting appropriate curricular resources. Efforts to align the goals and processes of the graduate medical education institution and teaching hospital can foster a unified mission. Faculty must be prepared to teach and reinforce these topics on a regular basis. Both didactic instruction and experiential learning are necessary components for trainee education.

Transcanal incision and drainage of a parapharyngeal abscess in a pediatric patient: A novel technique.

The disease of parapharyngeal abscess is well known to the otolaryngologist and is commonly managed via transoral, transcervical, or combined incision and drainage. We report a novel approach to an abscess that was drained through the external auditory canal (EAC). An otherwise healthy 2-year-old female presented with a 4-day history of fevers, decreased oral intake, neck stiffness, and voice changes. CT neck with contrast revealed a deep abscess in the left neck extending from the peritonsillar space into the parapharyngeal space in close proximity to the anterior aspect of the EAC. Because the EAC was the closest surface to the abscess collection, we elected to attempt drainage through this route. Successful incision and drainage was performed via transcanal approach. She received intravenous antibiotics and steroids post-operatively and surgical packing was removed. She was discharged home on post-operative day 5 afebrile and tolerating a regular diet and continued to do well at most recent outpatient follow-up.

Treatment of Stress Velopharyngeal Incompetence With Injection of Hyaluronic Acid.

Stress velopharyngeal incompetence (VPI) is a challenging clinical entity that can be managed by a variety of surgical and nonsurgical approaches. We describe the case of a clarinetist who presented with nasal air escape while playing. She had successful improvement in her symptoms after targeted injection of a hyaluronic acid compound to her posterior pharyngeal wall. Our objective is to describe the safety and efficacy of this technique, to emphasize the multidisciplinary management of patients with stress VPI, and to review the importance of both nasopharyngoscopy and videofluoroscopy in their evaluation.

Management trends of infantile hemangioma: A national perspective.

INTRODUCTION: The primary management of infantile hemangioma (IH) has changed since 2008, with the initiation of propranolol. The change that propranolol has affected on resource utilization is unknown. MATERIALS AND METHODS: The Kids' Inpatient Database (KID) in 2003, 2006, 2009, and 2012 was queried for ICD-9 codes for IH in children under age three. The number of patients undergoing the following procedures of interest: tracheostomy, tracheoscopy and laryngoscopy with biopsy, and excision of skin lesion were evaluated. Data was analyzed for demographics and details on the admission. Trends were identified. Weighted statistical analyses were performed with SAS 9.4. RESULTS: The number of qualified admissions significantly increased over the years (9271 in 2003-12029 in 2012, OR 1.042 per year increase, p < 0.001). The mean age at admission ranged from 26 to 28 days but did not vary over time (p = 0.54). The percentage undergoing tracheostomy significantly decreased from 1.05% in 2003 to 0.27% in 2012 (p = 0.0055), and the percentage undergoing tracheoscopy and laryngoscopy with biopsy significantly decreased from 7.29% in 2003 to 4.20% in 2012 (p = 0.011) among those with IH of unspecified or other sites. The percentage undergoing skin lesion excision also significantly decreased from 1.87% in 2003 to 1.03%, in 2012 (p = 0.0038) among those with IH of skin and subcutaneous tissue. These findings suggest a potential impact of propranolol. After adjusting for inflation, the total hospital charges increased from a mean of $17,838 in 2003 to an adjusted mean of $41,306 in 2012 (p < 0.0001). CONCLUSIONS: Total admissions and hospital charges in children with IH has increased from 2003 to 2012. The percentage of patients undergoing tracheostomy, tracheoscopy and laryngoscopy with biopsy, and skin lesion excision significantly decreased in 2012 compared to 2003, suggesting a potential impact of propranolol. Further studies are needed to examine these changes more closely.

Successful Treatment of Invasive Conidiobolus Infection During Therapy for Acute Lymphoblastic Leukemia.

Invasive fungal infections are a serious cause of morbidity and mortality in patients with hematologic malignancies. Conidiobolus species are molds within the order Entomophthorales and may disseminate to become rapidly fatal in immunocompromised individuals. This species of fungal infections are often multidrug resistant (MDR) and present unique therapeutic challenges. Reports of Conidiobolus infections are rare in pediatric oncology. We report the successful treatment of an adolescent male with B-cell lymphoblastic leukemia and MDR invasive sinopulmonary Conidiobolus infection with emphasis on early and aggressive neutrophil support with surgical debridement. The strategies described could be applied to other MDR fungal infections.

Current State of Overlapping, Concurrent, and Multiple-Room Surgery in Otolaryngology: A National Survey.

Objective Multiple-room surgery has gained attention due to reports in the lay press scrutinizing the activity, with hospitals and the government collecting data on current practice. We studied practices and attitudes toward multiple-room surgery in otolaryngology. Methods A survey was developed by members of the Patient Safety and Quality Improvement Committee of the American Academy of Otolaryngology-Head and Neck Surgery. The survey was distributed to members of the Academy and included questions on demographics, current practices, and opinions regarding multiple-room surgery. The survey was designed to capture the spectrum of multidisciplinary, overlapping, and simultaneous/concurrent surgery practices. Data were collected via SurveyMonkey. Results A total of 907 of 9520 members completed the survey. Of the respondents, 40.4% reported performing some form of multiple-room surgery. Multiple-room surgery is more common amongst subspecialists than general otolaryngologists. Most believed that regulations disallowing multiple-room surgery would result in an increase in late starts (73.5%), an increase in the time to schedule surgery (84.5%), a detriment to residency training (63.1%), and no improvement in patient safety (60%.) Discussion Multiple-room surgery is common among responding otolaryngologists. Most respondents consider the practice to serve a role in facilitating access, efficiency, and training. Implications for Practice Due to recent attention placed on multiple-room surgery, institutions are reviewing policies regarding the practice. This survey suggests that policy changes that restrict multiple-room surgery must consider a potential unintended negative impact on patient care and access.

Anesthetic Management of an Infant With Postnatally Diagnosed Tracheal Agenesis Undergoing Tracheal Reconstruction: A Case Report.

A term infant born cyanotic failed multiple intubation attempts and tracheostomy placement. After esophageal intubation resulted in the ability to ventilate, he was presumed to have tracheal agenesis and distal bronchoesophageal fistula. He was transferred to our institution where he was diagnosed with Floyd Type II tracheal agenesis. He underwent staged tracheal reconstruction. He was discharged to home at 4 months of age with a tracheostomy collar, cervical spit fistula, and gastrostomy tube. He represents the sole survivor-to-discharge of tracheal agenesis in the United States. We describe the anesthetic considerations for a patient with tracheal agenesis undergoing reconstruction.

Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion.

Importance: Persistent, viscous middle ear effusion in pediatric otitis media (OM) contributes to increased likelihood of anesthesia and surgery, conductive hearing loss, and subsequent developmental delays. Biomarkers of effusion viscosity and hearing loss have not yet been identified despite the potential that such markers hold for targeted therapy and screening. Objective: To investigate the association of gel-forming mucins and aquaporin 5 (AQP5) gene expression with inflammation, effusion viscosity, and hearing loss in pediatric OM with effusion (OME). Design, Setting, and Participants: Case-control study of 31 pediatric patients (aged 6 months to 12 years) with OME undergoing tympanostomy tube placement and control individuals (aged 1 to 10 years) undergoing surgery for cochlear implantation from February 1, 2013, through November 30, 2014. Those with 1 or more episodes of OM in the previous 12 months, immunologic abnormality, anatomical or physiologic ear defect, OM-associated syndrome (ie, Down syndrome, cleft palate), chronic mastoiditis, or history of cholesteatoma were excluded from the study. All patients with OME and 1 control were recruited from Children's Hospital of Wisconsin, Milwaukee. The remainder of the controls were recruited from Sick Kids Hospital in Toronto, Ontario, Canada. Main Outcomes and Measures: Two to 3 middle ear biopsy specimens, effusions, and preoperative audiometric data (obtained <3 weeks before surgery) were collected from patients; only biopsy specimens were collected from controls. Expression of the mucin 2 (MUC2), mucin 5AC (MUC5AC), mucin 5B (MUC5B), and AQP5 genes were assayed in middle ear biopsy specimens by quantitative polymerase chain reaction. One middle ear biopsy specimen was sectioned for histopathologic analysis. Reduced specific viscosity of effusions was assayed using rheometry. Results: Of the 31 study participants, 24 patients had OME (mean [SD] age, 50.4 [31.9] months; 15 [62.5%] male; 16 [66.7%] white) and 7 acted as controls (mean [SD] age, 32.6 [24.4] months; 2 [26.6%] male; 6 [85.7%] white). Mucins and AQP5 gene expression were significantly higher in patients with OME relative to controls (MUC2: ratio, 127.6 [95% CI, 33.7-482.7]; MUC5AC: ratio, 3748.8 [95% CI, 558.1-25 178.4]; MUC5B: ratio, 471.1 [95% CI, 130.7-1697.4]; AQP5: ratio, 2.4 [95% CI, 1.1-5.6]). A 2-fold increase in MUC5B correlated with increased hearing loss (air-bone gap: 7.45 dB [95% CI, 2.65-12.24 dB]; sound field: 6.66 dB [95% CI, 6.63-6.69 dB]), effusion viscosity (2.75 mL/mg; 95% CI, 0.89-4.62 mL/mg), middle ear epithelial thickness (3.5 µm; 95% CI, 1.96-5.13 µm), and neutrophil infiltration (odds ratio, 1.7; 95% CI, 1.07-2.72). A 2-fold increase in AQP5 correlated with increased effusion viscosity (1.94 mL/mg; 95% CI, 0.08-3.80 mL/mg). Conclusions and Relevance: Further exploration of the role of MUC5B in the pathophysiology of OME holds promise for development of novel, targeted therapies to reduce effusion viscosity, facilitation of effusion clearance, and prevention of disease chronicity and hearing loss in patients with OME.

Pepsin as a biomarker for laryngopharyngeal reflux in children with laryngomalacia.

OBJECTIVES/HYPOTHESIS: Laryngomalacia is a common cause of newborn stridor. Laryngopharyngeal reflux (LPR) has been associated with laryngomalacia. Although pepsin, a component of LPR, has been associated with inflammatory diseases of the aerodigestive tract, its presence in the airways of laryngomalacia patients is unknown. STUDY DESIGN: Prospective case-control study comparing patients under age 3 years with laryngomalacia to children without laryngomalacia. METHODS: Children less than 3 years old undergoing supraglottoplasty for laryngomalacia or surgery unrelated to the airway, without a history of laryngomalacia, reflux, or respiratory disease, were offered enrollment. Supraglottic lavage samples (3 mL) were obtained from all subjects. Two-millimeter arytenoid biopsies were collected from laryngomalacia patients. Pepsin Western blot and enzyme-linked immunosorbent assay were performed. RESULTS: Ten laryngomalacia and five control subjects were enrolled. Pepsin was detected in lavages of laryngomalacia patients (8/10) but absent in controls (0/5; P = .007). Pepsin was observed more frequently in lavages (8/10) than biopsies (4/10; P = .046) of laryngomalacia subjects. Higher median pepsin concentration was observed in laryngomalacia than control lavages (P = .025). CONCLUSIONS: Pepsin in supraglottic specimens demonstrated an association with laryngomalacia, supporting a role for refluxed pepsin in laryngomalacia. These data corroborate previous work implicating pepsin in inflammatory diseases of the upper airways. Further studies are warranted to investigate the contribution of pepsin to the pathophysiology of laryngomalacia. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2413-2417, 2017.

Office-Based Subglottic Evaluation in Children With Risk of Subglottic Hemangioma.

PURPOSE: Children with V3 cutaneous infantile hemangiomas (IH) and PHACE syndrome have a high incidence for airway hemangioma, 29% and 52%, respectively. Therefore, a clinical evaluation for these high-risk children is essential. We report our experience with in-office lower airway evaluation (OLAE) in these high-risk children. RESULTS: Since 2003, 5 children with IH of the V3 cutaneous distribution and 3 children with PHACE syndrome underwent OLAE. Average age of presentation was 2.75 months. Two children had stridor at initial evaluation, and 1 child had subglottic hemangioma. This child was evaluated serially with OLAE to monitor disease progression and treatment response. A total of 10 upper tracheoscopies were performed on the 8 patients without respiratory complications. CONCLUSION: An airway evaluation is essential to evaluate and manage this high-risk population. Typically, operative endoscopy requires general anesthesia. However, in these high-risk children, we have performed OLAE without sedation to evaluate the trachea. High-speed recording and playback is essential in this method. Our series demonstrates that awake OLAE is possible and may be a safe technique to evaluate and monitor disease progression in these high-risk patients. These patients avoided general anesthesia and delay in diagnosis and did not incur any complications during or after OLAE.