Surgical outcomes and revision rates for velopharyngeal insufficiency (VPI) in syndromic and non-syndromic children: A systematic review and meta-analysis.

PURPOSE: To evaluate pre- and post-operative resonance, surgical technique, revision rate, and revision indication among syndromic and non-syndromic children with velopharyngeal insufficiency (VPI). MATERIALS AND METHODS: A systematic review was conducted through July 2022. Children surgically treated for VPI were included. A meta-analysis of single means, proportions, comparison of proportions, and mean differences with 95 % confidence interval [CI] was conducted. RESULTS: Twenty-three articles (n = 1437) were included in the analysis. The most common surgery was Sphincter Pharyngoplasty (SP), 62.6 % [31.3-88.9] for syndromic and 76.3 % [37.5-98.9] for non-syndromic children. Among all surgical techniques, for syndromic and non-syndromic children, 54.8 % [30.9-77.5] and 73.9 % [61.3-84.6] obtained normal resonance post-operatively, respectively. Syndromic patients obtained normal resonance post-operatively in 83.3 % [57.7-96.6] of Combined Furlow Palatoplasty and Sphincter Pharyngoplasty (CPSP), 72.6 % [54.5-87.5] of Pharyngeal Flap (PF), and 45.1 % [13.2-79.8] of Sphincter Pharyngoplasty (SP) surgeries. Non-syndromic patients obtained normal resonance post-operatively in 79.2 % [66.4-88.8] of PF and 75.2 % [61.8-86.5] of SP surgeries. The revision rate for syndromic and non-syndromic patients was 19.9 % [15.0-25.6] and 11.3 % [5.8-18.3], respectively. The difference was statistically significant, 8.6 % [2.9-15.0, p = 0.003]. Syndromic patients who underwent PF were least likely to undergo revision surgery as compared to SP and CPSP, 7.7 % [2.3-17.9] vs. 23.7 % [15.5-33.1] and 15.3 % [2.8-40.7], respectively. CONCLUSIONS: Syndromic children had higher revision rates and were significantly less likely to obtain normal resonance following primary surgery than non-syndromic patients. Among syndromic children, PF and CPSP have been shown to improve resonance and reduce revision rates more so than SP alone.

Characteristics and outcomes of interventions for pediatric laryngomalacia: A systematic review with meta-analysis.

OBJECTIVES: To analyze characteristics of children treated for laryngomalacia to determine predictive factors and provide an updated meta-analysis on outcomes. METHODS: A systematic review was conducted according to PRISMA guidelines from inception to May 2, 2023, using CINAHL, PubMed, and Scopus databases. Study screening, data extraction, quality rating, and risk of bias assessment were performed by 2 independent reviewers. Data were meta-analyzed using fixed-/random-effects model to derive continuous measures (mean), proportions (%), and mean difference (Δ) with 95% confidence interval (CI). RESULTS: 100 articles were identified with information on outcomes of pediatric patients with laryngomalacia (N = 18,317). The mean age was 10.6 months (range: 0 to 252, 95%CI: 9.6 to 11.6, p = 0.00) with a 1.4:1 male to female ratio. Many patients presented with stridor (87.9%, 95% CI: 69.8 to 98.4), and the most common comorbidity at time of diagnosis was gastroesophageal reflux disease (48.8%, 95%CI: 40.9 to 56.8). Based on the patient population included in our analysis, 86.1% received supraglottoplasty (95% CI: 78.7 to 92.1). A total of 73.6% (95% CI: 65.5 to 81.0) had reported complete resolution of symptoms. For patients with a concurrent diagnosis of sleep disordered breathing receiving supraglottoplasty, the apnea-hypopnea index improved with a mean difference of -10.0 (95%CI: 15.6 to -4.5) events per hour post-treatment. CONCLUSIONS: Laryngomalacia continues to be a common problem in the pediatric population. Supraglottoplasty remains an effective treatment option leading to symptomatic improvement in many cases. For those with concurrent sleep disordered breathing, supraglottoplasty lowers the apnea-hypopnea index.

Does REM AHI Predict Persistent OSA After Pediatric Adenotonsillectomy?

OBJECTIVE: The utility of REM AHI in managing pediatric obstructive sleep apnea (OSA) is not fully understood. This study aimed to evaluate the relationship of preoperative REM AHI to postoperative persistence of OSA in children who underwent adenotonsillectomy. METHODS: This retrospective chart review identified children under the age of 18 years that received an adenotonsillectomy for OSA and a preoperative and postoperative polysomnogram. Children with craniofacial or neuromuscular disorders or a tracheostomy were excluded. The primary outcome was the postoperative persistence of OSA, defined as a postoperative obstructive apnea-hypopnea index (oAHI) ≥ 1.5 events/hour. REM-predominant OSA was defined as a ratio of REM/NREM AHI ≥ 2. REM AHI minus NREM AHI and REM AHI minus oAHI helped to identify patients with a larger distribution of REM AHI. RESULTS: A total of 353 patients were included. Postoperative persistent OSA was seen in 232 (65.7%) children. The preoperative REM AHI, REM AHI minus NREM AHI, and REM AHI minus oAHI of children with persistent OSA did not differ significantly from children with resolution of OSA. Rates of persistence were not different between those with REM-predominant OSA and REM-independent OSA (63.8% vs 70.7%, P = .218). CONCLUSION: This study suggests that preoperative REM AHI may be a poor predictor of OSA persistence after adenotonsillectomy. Further study is needed to help characterize how pre-operative REM AHI should impact clinicians' decision making, family counseling and recommendations.

Is there an OAHI or O2 nadir that predicts the need for preoperative echocardiogram prior to adenotonsillectomy for children with severe obstructive sleep apnea?

PURPOSE: To investigate threshold values for obstructive apnea-hypopnea index (OAHI) and nadir oxygen saturation (NspO2) in children with severe obstructive sleep apnea (OSA) to identify children most appropriate for preoperative echocardiography. METHODS: A multi-institutional retrospective chart review was performed on children who underwent echocardiography and polysomnogram within a year. Children with severe OSA as defined by OAHI > 10 or NspO2 < 80% were included. Receiver operator curves and Youden's J index were used to assess the discriminatory ability and threshold values of OAHI and NspO2 for right heart strain (RHS) on echocardiography. RESULTS: A total of 173 prepubertal (< 10 years) children and 71 postpubertal (≥ 10 years) children of age were included. RHS was seen in 9 (5%) prepubertal children and 4 (6%) postpubertal children. In prepubertal children, OAHI and NspO2 were poor predictors of RHS (area under the curve [AUC] 0.53 [95%CI 0.45-0.61], p = 0.748; AUC 0.56 [95%CI 0.48-0.64], p = 0.609). In postpubertal children, threshold values of 55 events/hour and 69% were strong predictors for RHS (AUC 0.88 [95%CI 0.78-0.95], p < 0.001; AUC 0.92 [95%CI 0.83-0.97], p < 0.001). CONCLUSION: In children with severe OSA, evidence of RHS is low. Postpubertal children with OAHI > 55 and NspO2 < 69% appear most appropriate for echocardiography. Clinicians should weigh the risks and benefits of preoperative echocardiography for each child with these threshold values in mind.

Preoperative Imaging in Patients with 22q11 Deletion Syndrome Undergoing Velopharyngeal Surgery.

OBJECTIVE: To evaluate the utility of preoperative imaging before velopharyngeal dysfunction (VPD) surgery in children with 22q11 Deletion Syndrome (22qDS) in evaluating internal carotid artery (ICA) medialization. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: Following PRISMA guidelines, a systematic review was performed. Studies of children with 22qDS who underwent preoperative imaging (MRA or CTA) to identify ICA anomalies were included. High-risk medialized ICAs were defined as either submucosal, retropharyngeal, Pfeiffer Grade III-IV, or <3 mm from the pharyngeal mucosa. Meta-analyses of proportions were performed. RESULTS: Eleven studies met inclusion criteria, comprising 398 patients with 22qDS (weighted mean age 7.6 years). In 372 patients with imaging, the rate of ICA medialization on imaging was 47.1% (95%CI 29.2-65.5), of which 46.3% (95%CI 27.4-65.8) were determined high risk. Operative plans were modified in 19.4% (95%CI 5.7-38.8) of 254 surgeries due to medialized ICA. In studies attempting to use nasopharyngoscopy pulsations to identify medialization for 214 patients, the true-positive rate was 53.9% (95%CI 27.5-79.2) and the false-positive rate was 16.2% (95%CI 7.9-26.8). Nine of eleven studies (81.8%) recommended universal preoperative imaging of the ICAs in children with 22qDS undergoing VPD surgery. No cases of perioperative bleeding secondary to ICA injury were identified. CONCLUSION: Although most studies endorse routine preoperative imaging to assess for ICA medialization in children with 22qDS undergoing VPD surgery, only a minority of these cases led to surgical modification. Additional studies are needed to compare outcomes in children with and without preoperative imaging given the low rates of ICA injury in the literature. LEVEL OF EVIDENCE: N/A Laryngoscope, 2023.

Delayed Sublingual Edema Following Neonatal Mandibular Distraction Osteogenesis.

The authors aim to report a rare sequela following neonatal mandibular distraction osteogenesis (MDO) involving delayed onset sublingual swelling. They performed a retrospective chart review of 3 patients who presented with delayed onset sublingual edema following neonatal MDO. The 3 patients presented at 2, 4, and 12 months following MDO for micrognathia secondary to Robin sequence with intermittent sublingual swelling associated with sialorrhea and feeding difficulties. There was no associated recent illness, fevers, or purulent drainage. All 3 children underwent magnetic resonance imaging which demonstrated asymmetric sublingual gland edema. The edema was located on the left sublingual gland in 2 children and was bilateral in the third. The symptoms continue to recur 25.5±3.3 months (range, 22.3-28.9) postoperatively and all are being managed conservatively. Chronic delayed onset intermittent sublingual edema is a possible long-term complication following neonatal MDO and further studies should explore the incidence and management of this finding.

Pediatric obesity education and counseling in otolaryngology clinics: A survey of ASPO members.

BACKGROUND: Adenotonsillectomy can cure pediatric obstructive sleep apnea (OSA) in 80% of children without obesity but only 20-30% of children with obesity. Despite this, there is a current lack of consistent guidelines and practices around pediatric obesity management in otolaryngology. This study evaluated the extent of counseling, referrals, confidence, and barriers in addressing childhood obesity in pediatric otolaryngology. METHODS: A 20-question electronic survey assessing pediatric obesity practice patterns regarding sleep-disordered breathing (SDB) and OSA was distributed to all American Society of Pediatric Otolaryngology (ASPO) members. Descriptive statistics were performed. Pediatric otolaryngologists were compared using logistic regression models based on their practice type and frequency of counseling and referral. RESULTS: Of all ASPO members, 19.6% (114/583) completed the survey. Half (50.0%) of physicians counsel and 14.0% refer to obesity management >75% of the time. Only 8.8% of physicians are confident their counseling helps reduce their patient's obesity, and 35.9% of physicians are satisfied with their services available for referral. Most physicians cite time/clinical workload (81.6%) and parent/rearing habits (50.0%) as barriers to obesity counseling. Non-academic physicians had lower odds of counseling and referring their patients >50% of the time (aOR 0.23 [95%CI 0.06-0.81], aOR 0.23 [95%CI 0.06-0.83]). Almost all (92.1%) physicians counsel on residual SDB or OSA after adenotonsillectomy >75% of the time if the child is obese. CONCLUSIONS: Most pediatric otolaryngologists do not regularly counsel or refer patients to available obesity management programs, with differences seen between academic and non-academic surgeons. Confidence is low in currently available measures to reduce pediatric obesity. These results highlight the challenges of pediatric obesity and provide context for guideline implementation and additional resource development for pediatric otolaryngologists.

Outcomes of Tympanoplasty After Cleft Palate Repair: A Systematic Review and Meta-analysis.

OBJECTIVE: To analyze graft success rates and hearing outcomes in patients with a history of cleft palate (CP) repair undergoing tympanoplasty. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: Per PRISMA guidelines, the databases were searched from date of inception through December 14, 2021. Studies of patients with previous CP repair who underwent tympanoplasty were included. Meta-analysis of proportions, continuous measures, odds ratios (ORs), and meta-regression were used to analyze graft success and hearing outcomes after tympanoplasty. RESULTS: A total of 323 patients with CP repair and 1169 controls were included. The proportion of graft success was 86.7% (95% CI, 76.1%-94.5%) in patients with CP repair and 88.8% (95% CI, 76.9-96.8) in controls. There was no difference in odds of graft success between patients with CP repair and controls (OR, 1.0 [95% CI, 0.5-1.8]; P = .870). Age was not a significant moderator of graft success in patients with CP repair (r = 0.1 [95% CI, -0.2 to 0.3]; P = .689) or controls (r = -0.0 [95% CI, -0.1 to 0.1]; P = .952). Comparing mean differences between pre- and postoperative air-bone gap was not statistically significant in patients with CP repair and controls (0.2 dB [95% CI, -3.1 to 3.4]; P = .930). Odds of functional success (postoperative air-bone gap <20 dB) were not different between the groups (OR, 0.8 [95% CI, 0.5-1.4]; P = .450). CONCLUSION: This meta-analysis does not endorse anatomic or functional differences between patients with CP repair and controls after tympanoplasty. However, there is a paucity of evidence for younger children. Further studies are warranted to elucidate specific risk factors for tympanoplasty outcomes in young patients with previous CP repair.

Tympanoplasty With and Without Mastoidectomy for Chronic Otitis Media Without Cholesteatoma: A Systematic Review and Meta-analysis.

OBJECTIVE: This study aimed to compare surgical and audiometric outcomes of tympanoplasty alone (T) to tympanoplasty and mastoidectomy (T&M) in patients without cholesteatoma. DATABASES REVIEWED: According to PRISMA guidelines, English articles in PubMed, Scopus, CINAHL, and Cochrane Library databases from inception to 7/29/2021 were searched. METHODS: Studies describing a comparison of patients who underwent T to patients who underwent T&M were included. Studies describing patients with cholesteatoma were excluded. Patient demographics, graft failure rates, and preoperative and postoperative audiological findings were collected. Mean differences (MD) and risk difference (RD) were calculated using RevMan 5.4. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using both version 2 of the Cochrane risk-of-bias tool for randomized trials and Risk of Bias in Non-randomized Studies of Interventions. RESULTS: A total of 27 studies fulfilled eligibility with T (n = 1,711) and T&M (n = 1,186). When pooling the data, mean differences between T versus T&M for air bone gap (-0.3 dB: 95% CI = -1.9 to 1.3, p = 0.730) and pure tone average (1.9 dB: 95% CI = -0.3 to 4.2, p = 0.090) were not statistically significant. Graft failure was higher with T only (16.4% versus 14.2%) than T&M (RD = -0.04, 95% CI = -0.07 to -0.00, p = 0.030, I2 = 35%]. CONCLUSION: This study endorses clinically similar audiological outcomes and a reduced risk difference of graft failure with mastoidectomy. Although these data suggest that adding a mastoidectomy could decrease the risk of graft failure, the risk reduction is minimal. More research on the cost-effectiveness and the specific patient clinical characteristics and comorbidities that would benefit from adding a mastoidectomy is warranted.

Obstructive sleep apnea in children with nonsyndromic cleft palate: a systematic review.

STUDY OBJECTIVES: To characterize obstructive sleep apnea in children with nonsyndromic cleft palate based on polysomnographic parameters relative to primary palatoplasty. METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following databases were searched: PubMed, Scopus, CINAHL, and Cochrane. Studies were only considered for inclusion if they examined exclusively patients with nonsyndromic cleft palate and reported polysomnogram data. RESULTS: Seven studies met inclusion criteria, providing information on a total of 151 patients with a weighted mean age of 5.2 ± 5.0 years (range 0.1-12 years). Five studies presented data from either the pre- or postoperative period. Two studies investigated both pre- and postpalatoplasty polysomnogram data, and neither observed a significant change in apnea-hypopnea index (AHI) values following surgery (mean preoperative AHI of 2.7 events/h, mean improvement of 0.6 events/h). The entire cohort had a prepalatoplasty weighted mean AHI of 11.4 events/h (range 1.5-16.1) and postpalatoplasty AHI of 1.5 events/h (range 0.2-5.2). Interpretation of polysomnographic data was limited by heterogeneity; however, the AHI values for children with nonsyndromic cleft palate largely demonstrated mild to moderate obstructive sleep apnea following palatoplasty. CONCLUSIONS: The full effect of cleft palate repair on obstructive sleep apnea in children with nonsyndromic cleft palate remains understudied. While published data are heterogenous, few studies support the worsening of obstructive AHI after palatoplasty in children with nonsyndromic cleft palate. Further studies with standardized polysomnographic parameters are needed to provide guidance for management of this population. CITATION: Jungbauer WN Jr, Poupore NS, Nguyen SA, Carroll WW, Pecha PP. Obstructive sleep apnea in children with nonsyndromic cleft palate: a systematic review. J Clin Sleep Med. 2022;18(8):2063-2068.

A National Analysis of Inpatient Pediatric Adenoidectomy.

OBJECTIVE: Hospital admission following pediatric adenoidectomy without tonsillectomy is not well characterized. The objective of our study is to better characterize risk factors for post-operative complications in younger children undergoing inpatient adenoidectomy. METHODS: A cross-sectional analysis using data derived from the Kid's Inpatient Database (KID) was performed. Study participants included children <3 years of age who underwent an adenoidectomy and were admitted to hospitals participating in the KID for years 1997, 2000, 2003, 2006, 2009, and 2012. Descriptive statistical analysis and a multivariate logistic regression analysis were performed to identify risk factors for post-operative complication. RESULTS: A total of 3406 children (mean age 1.1 ± 0.7 years) were included. The overall post-operative bleeding and respiratory complication rates were 0.6% and 5.4%, respectively. Children less than 18 months of age demonstrated increased rates of post-operative respiratory complications (P = .009), but not bleeding complications (P = .857). Presence of cardiopulmonary congenital malformations (OR 1.54, 95% CI 1.07-2.20), chronic respiratory disease of the newborn (OR 5.03, 95% CI 2.86-8.85), and neuromuscular disorders (OR 1.97, 95% CI 1.09-3.57) were associated with post-operative respiratory distress. CONCLUSIONS: This analysis of a national dataset suggests that otherwise healthy children less than 18 months of age and children 18 months to 3 years of age with certain comorbidities may benefit from overnight observation following adenoidectomy.

Tissue Doppler echocardiography in children with OSA before and after tonsillectomy and adenoidectomy: A systematic review and meta-analysis.

BACKGROUND: When to order an echocardiogram in children with obstructive sleep apnea (OSA) is debated. Studies evaluating the utility of pre-operative standard echocardiography are inconsistent. Tissue Doppler imaging (TDI) is an additional technique that quantifies the velocity of myocardial motion to assess cardiac function. The utility of TDI in pediatric OSA remains unclear. METHODS: A systematic review and meta-analysis were performed in accordance with PRISMA guidelines using PubMed, Scopus, CINAHL, and Cochrane Library databases. Studies of echocardiographic findings using TDI in children with polysomnogram confirmed OSA before and after tonsillectomy and adenoidectomy (T&A) were included. 1,423 studies were screened, and 4 studies met inclusion criteria. Meta-analysis of echocardiographic findings was performed. RESULTS: Data from 560 children were analyzed. Study groups included pre- and post-T&A children with OSA and non OSA controls. Pre-T&A S' wave at the tricuspid annulus (S' RV) was decreased with a mean difference of -1.04 [95% CI -1.57, -0.52, p < 0.001] and E'/A' ratio at the mitral annulus (E'/A' LV) was decreased with a mean difference of -0.74 [95% CI -0.85, -0.64, p < 0.001] when compared to controls. These variables were not statistically different when comparing post-T&A to controls. CONCLUSIONS: TDI appears to successfully detect subclinical changes in cardiac function in children with OSA. However, echocardiography parameters of post-T&A and non OSA control children were similar. Further prospective studies stratified by OSA severity are needed with both TDI and standard echocardiography to define the utility of pre-operative cardiac imaging.

Cost comparison between surgical and conservative management for pediatric sinogenic subperiosteal abscesses.

BACKGROUND: There remains variation in management of orbital complications of acute bacterial rhinosinusitis (ABRS); specifically, those subperiosteal abscesses that present without immediate surgical indication. Recent systematic reviews on management and proposed treatment algorithms are helpful but do not consider the financial implications for healthcare systems and patients. METHODS: A retrospective chart review of pediatric patients from a tertiary care children's hospital between 2002 and 2020 was performed, identifying patients via ICD coding corresponding to acute bacterial sinusitis and orbital involvement classified as Chandler 3 confirmed by contrasted computed tomography (CT). Two groups of patients were identified: intravenous (IV) antibiotics alone and IV antibiotics plus surgery. Billing records of total hospital charges and physician fees were recorded for financial analysis. Demographic, length of stay, and charges were analyzed. RESULTS: 58 patients with ABRS and Chandler 3 orbital involvement were confirmed by CT imaging. Twenty-nine (50%) were treated with IV antibiotics alone, and twenty-nine (50%) underwent surgery in addition to IV antibiotics. There were no significant differences in patient demographics. The average total hospital charges for the medically managed group were $9262 ± 4831 compared to $30,830 ± 11,397 for the surgical group (p < 0.0001). In the medically managed group, the average hospital fees were $7305 ± 4048 and the average physician fees were $1543 ± 799. In the surgical group, the average hospital and physician fees were also significantly higher at $23,071 ± 7305 (p < 0.0001) and $7763 ± 3335 (p < 0.0001), respectively. Patients who were treated medically and had a longer than average LOS still had significantly fewer charges than those treated with antibiotics plus surgery and a shorter than average length of stay [$15,311 and $27,723, respectively (p = 0.02)]. CONCLUSION: Pediatric ABRS with orbital involvement requires prompt attention and management. Controversy persists over subperiosteal abscess management that present without overt surgical indications. Surgical intervention is expensive. Our subgroup analysis demonstrates the magnitude of this cost difference. Specifically, longer inpatient stays with IV antibiotics alone appear to be significantly cheaper than shorter ones that include surgery. Not all Chandler 3 patients are candidates for non-surgical management; however, clinicians are encouraged to keep these data in mind for those patients where further medical management is safe and may yield less expensive clinical resolution.

Nasal dorsum reconstruction after pediatric nasal dermoid excision.

BACKGROUND: To review our experience with pediatric nasal dermoids, and discuss reconstructive options for the nasal dorsum after pediatric nasal dermoid removal. METHODS: Retrospective review of pediatric nasal dermoid cases from January 1 2005 through October 1 2016. RESULTS: Twenty-five cases (12 males, 13 females) were identified. Median age at time of surgery was 24 months (7-144). Ten nasal dermoids were superficial; eleven, intraosseous; one, intracranial extradural; three, intracranial intradural. Seven were located on the glabella; fifteen, dorsum; three, nasal tip. Twelve underwent vertical midline incision; ten underwent external rhinoplasty; and three combined approach with craniotomy. There was one recurrence four years postoperatively; which was secondarily resected completely via external rhinoplasty approach. Seven cases utilized endoscopic assistance. Conchal cartilage grafting was utilized in nine cases for dorsal reconstruction. A temporoparietal fascial graft was utilized to reconstruct the soft tissue defect in three patients. Median follow-up was 1.17 years (1 month-10 years). CONCLUSIONS: Nasal dermoid is a rare congenital pathology. Recurrence rate is generally low provided that complete surgical excision is achieved. Achieving complete surgical excision means sometimes compromising the upper lateral cartilages and nasal bones. Conchal cartilage grafting is useful in reconstruction for lesions that significantly disrupt the nasal cartilages and/or nasal bones, wherein the defect is significant and osteotomies may not be sufficient. Temporoparietal fascia is a favorable adjunct for reconstructing soft tissue deficits when the skin is thin. Further studies and longer follow up are needed to adequately assess functional and cosmetic outcomes.

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

RATIONALE: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). METHODS: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. RESULTS: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. CONCLUSIONS: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Vitamin D deficiency is associated with increased human sinonasal fibroblast proliferation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Vitamin D3 (VD3) is a steroid hormone with known antiproliferative properties. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be VD3-deficient. Moreover, VD3 deficiency is associated with worse disease in patients with CRSwNP. One cell type thought to play a role in chronic rhinosinusitis (CRS) is the human sinonasal fibroblast (HSNF). The aim of this study was to investigate VD3 deficiency and HSNF proliferation in CRSwNP. METHODS: Blood and sinus tissue explants were collected at the time of surgery from patients with CRSwNP (n = 15). Control subjects (n = 12) were undergoing surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. Ex vivo HSNF proliferation was analyzed with flow cytometry using expression of fibroblast-specific protein (FSP) and the proliferation marker Ki67. Plasma levels of 25-hydroxyvitamin D3 (25VD3) were measured by enzyme-linked immunosorbent assay. In vitro analysis of HSNF proliferation after treatment with calcitriol (1,25VD3) was performed using carboxyfluorescein succinimidyl ester (CFSE) and analyzed with flow cytometry. RESULTS: In CRSwNP patients there was an inverse correlation between 25VD3 and proliferating HSNFs (p = 0.0135). This correlation was not seen for control patients (p = 0.3869). In vitro analysis showed that HSNFs from patients with CRSwNP had a higher proliferation index at baseline than HSNFs from control patients (p < 0.01). When treated with 1,25VD3, there was a significant decrease in HSNF proliferation index in patients with CRSwNP (p < 0.01), but not control patients. CONCLUSION: VD3 deficiency is associated with increased HSNF proliferation in CRSwNP. Further investigation into how HSNFs and VD3 impact CRSwNP pathophysiology is warranted.

Fibroblast levels are increased in chronic rhinosinusitis with nasal polyps and are associated with worse subjective disease severity.

BACKGROUND: Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. METHODS: Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. RESULTS: A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). CONCLUSION: Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS.

Reduced sinonasal levels of 1α-hydroxylase are associated with worse quality of life in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25-hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell-specific expression of 1α-hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1α,25-dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1α-hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression. METHODS: Blood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1α-Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22). 1,25VD3 and 25VD3 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with CRSwNP or AFRS have reduced 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1α-hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1α-hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1α-hydroxylase than those without asthma. Total 1α-hydroxylase levels inversely correlated with SNOT-22 in CRSwNP, but not CRSsNP. CONCLUSION: Patients with CRSwNP and AFRS both have reduced sinonasal 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1α-hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP.

Clinical and quality-of-life outcomes following gland-preserving surgery for chronic sialadenitis.

OBJECTIVES/HYPOTHESIS: Gland-preserving salivary surgery utilizing salivary endoscopy has been proposed as a treatment alternative in the management of chronic sialadenitis. This study seeks to determine medium-term clinical and quality-of-life (QOL) outcomes following a gland-preserving approach for chronic sialadenitis. STUDY DESIGN: Cross-sectional survey with retrospective chart review. METHODS: All patients undergoing attempted gland-preserving salivary surgery with salivary endoscopy for chronic sialadenitis at a tertiary, academic salivary referral center between October 2008 and April 2013 were identified from a quality assurance database. A research database was constructed to examine clinical factors of interest. A clinical outcomes and QOL survey was mailed to all eligible patients in order to obtain long-term follow-up data. RESULTS: A total of 206 of 306 (67%) eligible patients returned the survey. The median length of follow-up was 17 months (3-54 months). The majority of patients (89%) endorsed symptom improvement after gland-preserving therapy. Surgical excision was performed on 8% of affected glands. Patients with chronic sialadenitis due to stones reported a greater incidence of symptom resolution (P = 0.0004) and more favorable QOL outcomes (P = 0.0001) than patients with nonstone etiologies. CONCLUSIONS: Patients undergoing gland-preserving salivary surgery with salivary endoscopy for chronic sialadenitis have favorable long-term symptom improvement and gland retention rates. Although patients with stones demonstrated the best outcomes, improvement was documented for all etiologies of chronic sialadenitis. LEVEL OF EVIDENCE: 4.