Biologic Therapy in Pediatric Chronic Rhinosinusitis: A Systematic Review.

OBJECTIVE: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed, MEDLINE, Cochrane, and clinical trial registries. REVIEW METHODS: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. CONCLUSIONS: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. IMPLICATIONS FOR PRACTICE: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

Pediatric Foreign Body Aspiration: Time of Occurrence and Factors Affecting Outcomes.

OBJECTIVES: The goal of this study was to assess which factors could affect outcomes in pediatric patients undergoing bronchoscopy for foreign body aspiration (FBA). METHODS: This is a retrospective case series study evaluating patients who underwent bronchoscopies because of FBA at a tertiary pediatric hospital between January 1, 2010, and December 6. 2018. Data collected included demographic information, time of the aspiration event, history of developmental delay, time of the procedure, duration of the procedure, and outcome (discharged, admission to the hospital or pediatric intensive care unit [PICU], or deceased). Statistical analysis was performed using standard regression analysis and analysis of variance. RESULTS: There were a total of 114 patients who underwent bronchoscopy for FBA (61% male and 39% female). The mean ± SD age was 2.8 ± 3.4 years, and 16% had developmental delay. The mean age for patients with developmental delay was 3.43 years, compared with 1.69 years for patients without developmental delay. The age difference between these 2 groups was statistically significant (P = 0.0047). The most commonly aspirated object was food (57%), and patients were usually with their parents at the time of aspiration (78%). Most aspiration events (57%) happened between 4 pm to 4 am. The mean ± SD time of procedure was 38 ± 28 minutes. The probability of admission to the hospital, PICU, and death increased with the duration of the procedure (P < 0.001). Patients with procedures longer than 60 minutes had a 40% probability of admission to the PICU, and patients with cases longer than 120 minutes had 13% probability of mortality. CONCLUSIONS: Most FBA s occurred in the evening while the children were with their parents. Education of families regarding the risk of aspiration is crucial, so they are always attentive to this issue. Although the focus on prevention tends to be with younger patients, it is essential to emphasize the risk of FBA in older patients with developmental delay. Because most episodes of aspiration occur later in the day, it is imperative that tertiary pediatric centers ensure that the evening staff is trained and have the available equipment for these complex cases.

Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1ß positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.

Psychometric Evaluation of the Nasal Obstruction Symptom Evaluation Scale for Pediatric Patients.

OBJECTIVE: To evaluate the psychometric properties of the nasal obstruction symptom scale within a sample of pediatric patients undergoing septoplasty or functional septorhinoplasty. STUDY DESIGN: This was a prospective study with nasal obstruction symptom scale evaluations conducted pre- and postoperatively. SETTING: A tertiary care pediatric hospital. SUBJECTS AND METHODS: Pediatric patients underwent septoplasty or functional septorhinoplasty (FSR) from January 2013 to January 2017. Reliability of the scale was assessed through measures of internal consistency. In addition, item response models of each item were evaluated to assess how well each item captured individuals with varying levels of nasal obstruction. Study authors assessed face validity, and construct validity was assessed by correlation measures between items and exploratory factor analysis. RESULTS: A total of 136 patients, ages 8 to 18 years with a mean age of 15.7 ± 2.1 years, completed pre- and postoperative evaluations. Internal consistency of the scale was high (Cronbach's α = 0.83). Predominantly a unidimensional scale resulted from exploratory factor analyses. Item response models indicate questions capture low to moderate levels of nasal obstruction within this population. Additional analyses show the scale functions similarly between septoplasty and FSR patients. CONCLUSION: The Nasal Obstruction Symptom Evaluation scale is a robust tool that may be incorporated as a subjective evaluation of severity of nasal obstruction among pediatric patients undergoing a septoplasty or functional septorhinoplasty.

Pediatric septoplasty and functional septorhinoplasty: A quality of life outcome study.

OBJECTIVE: This study assessed disease-specific quality-of-life outcomes among pediatric patients undergoing septoplasty or functional septorhinoplasty. The Nasal Obstruction Symptom Evaluation (NOSE) score was obtained pre- and post-operatively. Additional analyses determined whether demographics, nasal trauma, prior nasal surgery, or allergic rhinitis history affected NOSE scores. METHODS: Patients undergoing septoplasty or functional septorhinoplasty were evaluated prospectively at a tertiary children's hospital. NOSE scores were assessed pre- and post-operatively. Change in NOSE score was analyzed using the Wilcoxon Signed Rank test, while multiple regression analysis evaluated factors associated with NOSE score change. RESULTS: 136 patients (mean age 15.7 ±â€¯2.1 years) were evaluated; 52 (38.2%) underwent septoplasty while 84 (61.8%) underwent functional septorhinoplasty. Mean follow-up was 3.6 ±â€¯5.1 months. There was a statistically significant decrease in NOSE score from pre-operative septoplasty and functional septorhinoplasty: median = 75 to post-operative septoplasty: median = 20 (z = -5.9, p < 0.001) and functional septorhinoplasty: median = 15 (z = -7.9, p < 0.001). Gender, age, nasal trauma, prior nasal surgery, and allergic rhinitis did not have a significant effect on NOSE score change for either group. Additional surgery at the time of procedure was not a confounding variable in the relationship between surgery type and NOSE score. A NOSE Scale reliability analysis demonstrated high internal consistency with Cronbach's α of 0.83 across septoplasty and functional septorhinoplasty patients. CONCLUSION: There was significant improvement in disease-specific quality-of-life in pediatric patients undergoing septoplasty or functional septorhinoplasty. Gender, nasal trauma, prior nasal surgery, and allergic rhinitis did not significantly affect NOSE scores in either group.

Carotid artery pseudoaneurysm: A rare complication following tonsillectomy.

Tonsillectomy is one of the most common surgical procedures performed in children. The most frequent complications are dehydration and bleeding. We present the case of a 6 year old child who developed an internal carotid artery pseudoaneurysm following elective tonsillectomy, necessitating urgent coil embolization and stenting. This is the first reported case in the pediatric population of a vascular injury that manifested in a delayed fashion (6 months) after routine tonsillectomy, and is also one of the youngest reported cases. It is imperative for the otolaryngologist to be aware of this rare complication.

Hoarseness as a presenting sign in children with Kawasaki disease.

We noted that many patients with Kawasaki disease (KD) were hoarse at presentation and thus evaluated the frequency of hoarseness in children with acute KD. New onset hoarseness was noted in 86 of 287 (30%) prospectively assessed KD patients. Laryngoscopic examination of 3 hoarse patients with acute KD revealed edema and erythema of the larynx.

The missing tracheoesophageal puncture prosthesis: evaluation and management.

Placement of a tracheoesophageal puncture prosthesis in the post-laryngectomy patient has significantly improved voice rehabilitation in this population. Rarely, the prosthesis may become dislodged, necessitating medical evaluation. We present the case of a 61-year-old man who presented to our Emergency Department with a missing prosthesis. We describe the evaluation and management of this patient and review the relevant literature. We conclude with the following algorithm: When a patient presents with a missing prosthesis, evaluation of the tracheobronchial tree must be performed. Once the pulmonary system is cleared, the prosthesis can be presumed in the gastrointestinal tract and allowed to pass. A new prosthesis or catheter should be placed in the tract to prevent aspiration.

Temporomandibular joint dysfunction after mandibular fracture in children: a 10-year review.

OBJECTIVES: To collect demographic and clinical data on pediatric mandibular fractures and to assess temporomandibular joint (TMJ) dysfunction in patients with condylar and subcondylar (C/SC) fractures. DESIGN: Retrospective case series of pediatric mandibular fractures (1999-2009) with follow-up telephone questionnaire of patients with C/SC fractures. Collected data included age, gender, unilateral vs bilateral C/SC fracture, presence of concomitant fracture, velocity of injury, and treatment modality. SETTING: Tertiary care children's hospital. PATIENTS: Of 164 patients with mandibular fractures, 83 (50.6%) had C/SC fractures, of which 45 (54.2%) completed the questionnaire. MAIN OUTCOME MEASURES: Helkimo Anamnestic Dysfunction Index (A(i)) quantification of TMJ dysfunction after C/SC fracture and treatment modality of C/SC fractures. RESULTS: Of the 164 patients, 122 (74.4%) were male (median age, 10.4 years; age range, 0.6-19.0 years). Of the 83 patients with C/SC fractures, 61 (73.5%) were male (median age, 9.1 years; age range, 1.1-18.7 years); 66 (79.5%) had unilateral fractures and 17 (20.5%) had bilateral fractures. The A(i) distribution of the 45 patients who completed the questionnaire was as follows: 15 (33.3%) none, 6 (13.3%) mild, and 24 (53.3%) severe. Females have more severe dysfunction than do males (95% confidence interval, 1.6-140.0; P = .02). No other significant predictors of treatment modality or TMJ dysfunction were identified. Patients with bilateral fracture are 8.1 times (95% confidence interval, 1.0-66.1 times; P = .05) more likely to have closed reduction than are those with unilateral fracture. CONCLUSIONS: This is one of the largest series of pediatric C/SC fractures reported in the recent literature. Findings are significant for increased severity of TMJ dysfunction in females and higher incidence of closed reduction in patients with bilateral C/SC fracture.

Optical microscopy of the pediatric vocal fold.

OBJECTIVES: To compare and contrast 4 optical imaging techniques for evaluating the developing microstructure of the pediatric vocal fold and to identify the optimal strategy for in vivo imaging. DESIGN: Prospective study. SETTING: Academic medical center. PATIENTS: A total of 6 laryngeal specimens: 5 pediatric (ages 10 months to 16 years) (4 from cadavers and 1 from a living patient immediately after laryngectomy) and 1 cadaveric young adult specimen (age, 23 years). INTERVENTION: Sequential noninvasive optical imaging of pediatric vocal fold specimens using optical frequency domain imaging (OFDI), angle-resolved OFDI (AR-OFDI), spectrally encoded confocal microscopy (SECM), and full-field optical coherence microscopy (FF-OCM), followed by fixation, sectioning, and histologic analysis of the same specimen for comparison. MAIN OUTCOME MEASURE: Correlation between the microstructure observed using the 4 noninvasive optical imaging techniques and with the results of histopathologic analysis for the same specimen. RESULTS: A successful in vivo imaging technique for developmental assessment of the pediatric vocal fold would include visualization of distinct layers (epithelium, lamina propria, and muscularis mucosa) and allow for identification of the individual cells composing the layers. The OFDI and AR-OFDI techniques provide a global assessment of the microstructure of the pediatric vocal fold to a depth of 1200 mum but lack the ability to distinguish cellular and subcellular structures. The FF-OCM technique allows for visualization with improved cellular detail (1-mum resolution), but the image acquisition speed is too slow for clinical use. The SECM technique has a faster acquisition rate and shows good cellular and subcellular detail to a depth of 250 mum. CONCLUSIONS: The OFDI and SECM techniques were identified as promising and complementary candidates for in vivo cellular and subcellular imaging of the epithelium, basement membrane, and lamina propria of the pediatric vocal fold. To further validate the clinical potential of these techniques, a handheld SECM probe has been developed and demonstrated for in vivo evaluation of the pediatric vocal fold.