Transcriptomic analysis identifies phosphatases as novel targets for adenotonsillar hypertrophy of pediatric obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) is a highly prevalent disorder in children, in which enlarged adenotonsillar tissues (AT) play a major pathophysiologic role. Mechanisms leading to the proliferation and hypertrophy of AT in children who subsequently develop OSA remain unknown, and surgical extirpation of AT is associated with potential morbidity and mortality. OBJECTIVES: We hypothesized that a computationally based analysis of gene expression in tonsils from children with OSA and children with recurrent tonsillitis without OSA can identify putative mechanistic pathways associated with tonsillar proliferation and hypertrophy in OSA. METHODS: Palatine tonsils from children with either polysomnographically documented OSA or recurrent infectious tonsillitis were subjected to whole-genome microarray and functional enrichment analyses followed by significance score ranking based on gene interaction networks. The latter enabled identification and confirmation of a candidate list of tonsil-proliferative genes in OSA. MEASUREMENTS AND MAIN RESULTS: In vitro studies using a mixed tonsil cell culture system targeting one of these candidates, phosphoserine phosphatase, revealed that it was more abundantly expressed in tonsils of children with OSA, and that pharmacological inhibition of phosphoserine phosphatase led to marked reductions in T- and B-lymphocyte cell proliferation and increased apoptosis. CONCLUSIONS: A systems biology approach revealed a restricted set of candidate genes potentially underlying the heightened proliferative properties of AT in children with OSA. Furthermore, functional studies confirm a novel role for protein phosphatases in AT hypertrophy, and may provide a promising strategy for discovery of novel, nonsurgical therapeutic targets in pediatric OSA.

Postoperative Recurrent Cholesteatoma in Rural Versus Urban Populations.

OBJECTIVE: Chronic ear disease presents a unique challenge to otolaryngologists in both rural and urban settings. Cholesteatoma remains a difficult disease to treat in rural populations due to limited healthcare access and high risk of recurrence. The purpose of this study was to determine if there are differences in surgical outcomes among patients with acquired cholesteatoma residing in rural versus urban settings. STUDY DESIGN: Single-surgeon retrospective case series with chart review. SETTING: Tertiary care private otolaryngology practice. PATIENTS: One hundred twenty-two patients presenting to the Kentuckiana ENT otology and neurotology practice from January 2011 to May 2017. MAIN OUTCOME MEASURES: Surgical outcomes including recurrence, air-bone gap improvement, ossicular integrity, and complications were reviewed and compared between the rural and urban cohorts. RESULTS: Presence of postoperative residual cholesteatoma (OR = 8.667, 95% CI = 2.022-37.141, p = 0.008) and number of surgeries per patient (OR = 5.185, 95% CI = 1.086-24.763, p = 0.024) were significantly increased among patients in rural nonmetropolitan areas. No significant differences were found when comparing risk of recurrence, size of cholesteatoma, presence of complications, air-bone gap improvement, and ossicular chain integrity. There were significantly more second-look surgeries performed in privately insured patients (OR = 8.582, 95% CI = 1.937-38.017, p = 0.001). CONCLUSIONS: Patients in rural communities have an increased number of surgeries and postoperative risk for residual cholesteatoma compared to patients residing in urban settings. This study provides the basis for larger, multicenter, prospective examinations of outcomes among urban versus rural patients, which would enable a better understanding of difference in surgical outcomes between rural and urban cohorts.Level of Evidence: IV.

When worlds collide: Challenges to implementing communication research in community oncology practices.

OBJECTIVE: During a recent trial assessing the effectiveness of an online communication training for community practice oncologists, we encountered multiple barriers. METHODS: We asked oncologists to participate through the American Board of Internal Medicine (ABIM) Maintenance of Certification program. Oncologists collected 25 Clinician and Group Consumer Assessment of Healthcare Providers (CAHPS) surveys from patients and 4 audio-recorded clinic encounters. They then completed either the ABIM Action Plan (control) or the online Study of Communication in Oncologist Patient Encounters (SCOPE) program (intervention). Oncologists collected another 25 CAHPS surveys and 4 audio-recorded encounters as follow-up. RESULTS: We enrolled 146 oncologists in the study. Only 27 completed the study; another 27 actively withdrew, and 94 did not complete the study. We identified four main challenges to participation: commitment discrepancies, burden of research, informed consent, and technology. We introduced efforts to overcome these barriers with success limited by time and resources. CONCLUSION: When conducting research in community practices, investigators must provide significant support, limit burden, increase flexibility, and conduct thorough pilot testing. PRACTICE IMPLICATIONS: To improve patient care, research must translate well into the workflow of actual practices. Assessing our experience, we identified challenges and effective solutions to be used by investigators as they plan and implement future communication interventions.

Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea.

Adenotonsillar hypertrophy is the major pathophysiological mechanism underlying obstructive sleep apnea (OSA) and recurrent tonsillitis (RI) in children. The increased expression of various mediators of the inflammatory response in tonsils of patients with OSA prompted our hypothesis that the enhanced local and systemic inflammation in children with OSA would promote tonsillar proliferation. Mixed cell cultures from tonsils recovered during adenotonsillectomy in children with OSA and RI were established, and proliferative rates were assessed. Cells were also cultured to determine the levels of proinflammatory cytokines and antioxidant protein levels and mRNA expression. Global cell proliferative rates from OSA tonsils were significantly higher than RI (p < 0.01), with CD3, CD4, and CD8 cell proliferation being higher in OSA (p < 0.05). Moreover, proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-1alpha, were highly expressed in OSA-derived tonsils. Furthermore, thioredoxin (TRX), an antioxidant protein, was also highly expressed in OSA tonsils at the mRNA and protein levels (p < 0.01). Thus, T cells are in a highly proliferative state in the tonsils of children with OSA and are associated with increased production of proinflammatory cytokines and TRX, when compared with children with RI.

Relationship between obstructive sleep apnea and difficulty of anesthesia induction in children undergoing tonsillectomy.

OBJECTIVE: To determine whether anesthesiologists need to rely on polysomnography (PSG) when predicting need for airway intervention during induction in patients with sleep-disordered breathing (SDB). METHODS: Prospective case-control observational study at a tertiary care pediatric hospital. Children between the ages of 2-17 undergoing tonsillectomy were divided into three groups: those presenting with OSA observed by history and/or physical examination alone (SDB; n = 33), those with OSA determined by preoperative PSG (OSA; n = 32), and a control group (n = 35) undergoing tonsillectomy for recurrent tonsillitis. An anesthesiologist ranked each case on the level of intervention required to maintain ventilation. RESULTS: Age, height and BMI were associated with greater induction difficulty (r's > .225, p's < .025). Compared to controls, induction difficulty was significantly greater for the SDB group (mean difference = -0.751, 95% confidence interval [CI] = -1.241, -0.261, p = .003), but not for the OSA group (p = .061). No significant difference in induction difficulty was observed between SDB and OSA groups. In a subgroup analysis of the OSA group, an apnea-hypopnea index (AHI) > 10 correlated with increased level of intervention during induction (r = .228, p = .022). Race was also associated with AHI >10 (odds ratio = 3.859, 95% CI = 1.485, 10.03, p = .006). CONCLUSION: Children with OSA undergoing tonsillectomy require more airway intervention during induction than children with recurrent tonsillitis. Age and BMI were correlated with greater induction difficulty, suggesting that PSG data should be considered in light of these clinical characteristics to ensure an optimal postoperative course for children undergoing tonsillectomy.

Otolaryngology practice patterns in pediatric tonsillectomy: The impact of the codeine boxed warning.

OBJECTIVES/HYPOTHESIS: To determine if otolaryngologists at a single children's hospital were adherent to the boxed warning for codeine use in post-tonsillectomy patients and the implications for practice patterns. STUDY DESIGN: Case series with chart review. METHODS: Charts from all patients undergoing adenotonsillectomy at a single children's hospital from January 1, 2010 through December 31, 2015 were analyzed and stratified according to date (pre- or post-boxed warning) and practitioner type (academic otolaryngologists [AO] vs. nonacademic otolaryngologists [NAO]). Demographic data, surgical technique, method of removal, narcotic prescriptions (dosage and drug), and complications were recorded. Fisher exact test was used to determine the level of significance in prescription rates pre- and postwarning. SPSS version 22 was used for statistical analysis, with P < .05 indicating statistical significance. RESULTS: There were 2,749 children undergoing adenotonsillectomy during the study period, with 1,239 AOs and 1,510 NAOs. There was a distinct downward trend in codeine prescriptions before and after the warning, with the AO group reaching zero sooner than the NAO group. There was a 5% decrease in discharge narcotic prescriptions given postwarning (P < .001), but no significant difference in postoperative emergency department visits or pain-related complications when comparing the two time periods. CONCLUSIONS: Codeine use for management of pediatric post-tonsillectomy pain was essentially zero after issuance of the boxed warning. Total narcotic use decreased significantly without increase in pain- or medication-related complications. Future research should focus on identifying markers of increased susceptibility to adverse medication events and determining the safest options for pain management. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:264-268, 2018.

Patient Safety/Quality Improvement Primer, Part I: What PS/QI Means to Your Otolaryngology Practice.

Patient safety/quality improvement (PS/QI) is the cornerstone of 21st-century health care. Otolaryngology-Head and Neck Surgery is excited to provide a dedicated PS/QI primer. The overarching goal for this PS/QI series is to provide a comprehensive and practical resource that assists readers, authors, and peer reviewers in understanding PS/QI research, its unique methodology, and the associated reporting standards for trustworthy performance measures. The target audience includes resident and fellows, faculty from the private sector and academia, and allied health professionals. This inaugural primer reviews PS/QI background as it relates to otolaryngology practice. It explores the history, goals, and development of performance measurement. In addition, it highlights opportunities for integrating PS/QI into otolaryngology practice. Payers will drive patients to quality care based on outcomes. Otolaryngologists have a responsibility to embrace a culture of PS/QI. In doing so, we will define optimal, quality otolaryngology care through objective data and metrics.

A parallel group analysis of tonsillectomy using the harmonic scalpel vs electrocautery.

OBJECTIVE: To evaluate efficiency and postoperative morbidity in tonsillectomy using the harmonic scalpel (HS) vs conventional electrocautery (EC). DESIGN: A retrospective medical chart review of all patients who underwent tonsillectomy at a single children's hospital during a 32-month period from January 2001 to August 2003. PATIENTS: The charts of 605 patients who underwent tonsillectomy or adenotonsillectomy were reviewed. The patients were stratified into 2 groups based on the dissecting instrument used (HS vs EC). Each group consisted of 2 subcategories based on age (< or =7 years and >7 years). Data collected included age, sex, operative indication, operative time, postanesthetic recovery room time, pain scale scores, postoperative admissions, and postoperative morbidities. RESULTS: There were significant differences in mean age (P<.001), mean weight (P<.001), and indication for surgery (P<.001) between the 2 methods: HS patients were younger, weighed less, and more often had obstructive symptoms as their primary operative indication compared with the EC group. Average operative times were not significantly different between methods. No differences were noted with respect to recovery time (HS group, P = .10; EC group, P = .30), postoperative oxygen requirements (HS group, P = .07; EC group, P = .09), and postoperative pain scores (HS group, P = .31; EC group, P = .58). There was a significant difference in postoperative admissions between the 2 methods in patients 7 years or younger (P = .005). Finally, we noted a significant difference in postoperative bleeding between the HS (2/292) and EC (13/313) methods when the data were compared per age group (P = .006), but the overall bleeding rate was not statistically significant owing to the small number of total bleeding instances (15/605). CONCLUSIONS: Recent prospective studies indicate that the HS provides advantages over conventional EC with respect to postoperative pain and return to normal activity. This study shows that HS tonsillectomy was as efficient as the conventional EC method. In addition, there was evidence that the rate of postoperative bleeding was significantly reduced by using the HS vs conventional EC.

Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection.

BACKGROUND: Recurrent tonsillitis and sleep apnea are the major indications for tonsillectomy in children. We hypothesized that the recurrent vibration in the upper airway of snoring children would promote inflammatory changes in the tonsillar tissue and would lead to the up-regulation of cysteinyl leukotriene (LT) receptors (Rs). OBJECTIVE: To assess the expression patterns of the human LT-Rs in children undergoing tonsillectomy, and compare those patterns in children having recurrent throat infections (RIs) and children with obstructive sleep apnea syndrome (SA). METHODS: Tonsillar tissue from 17 children with SA and 13 with RIs was subjected to quantitative polymerase chain reaction using specific primers for LT1-R and LT2-R, and to immunohistochemistry and Western blotting for protein expression of LT1-R and LT2-R. RESULTS: Messenger RNA encoding for the expression of LT1-R and LT2-R was detected in the tonsils of all children. Immunoblots revealed significantly higher expressions of LT1-R and LT2-R in the tonsils of children with SA. The topographic pattern of both receptors differed among the tonsils of children with SA and RI. CONCLUSION: LT1-R and LT2-R are expressed in pediatric tonsillar tissue, are more abundant in SA patients, and demonstrate a specific topographic pattern of expression. These findings suggest that an inflammatory process involving LT expression and regulation occurs in children with SA.

Obstructive Sleep Apnea and Surgery: Quality Improvement Imperatives and Opportunities.

Obstructive sleep apnea (OSA) is more common in surgical candidates than in the general population and may increase susceptibility to perioperative complications that range from transient desaturation to catastrophic injuries. Understanding the potential impact of OSA on patients' surgical risk profile is of particular interest to otolaryngologists, who routinely perform airway procedures-including surgical procedures for treatment of OSA. Whereas the effects of OSA on long-term health outcomes are well documented, the relationship between OSA and surgical risk is not collinear, and clear consensus on the nature of the association is lacking. Better guidelines for optimization of pain control, perioperative monitoring, and surgical decision making are potential areas for quality improvement efforts. Many interventions have been suggested to mitigate the risk of adverse events in surgical patients with OSA, but wide variations in clinical practice remain. We review the current literature, emphasizing recent progress in understanding the complex pathophysiologic interactions noted in OSA patients undergoing surgery and outlining potential strategies to decrease perioperative risks.

Substance P and neurokinin 1 receptors as potential therapeutic targets in children with OSA.

BACKGROUND: Increased substance P (SP) levels and abundant expression of neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful in treating OSA. METHODS: The effects of SP and the NK1 antagonist GR-82334 were examined on mixed cell cultures prepared from dissociated tonsils harvested intraoperatively from children with OSA and RI. Proliferation was assessed by [3H]-thymidine or 5-ethynyl-2'-deoxyuridine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-1ß) was assessed in supernatants by enzyme-linked immunosorbent assay. RESULTS: SP elicited dose-dependent increases in tonsillar cell proliferation in mixed cell cultures from children with OSA but not with RI (P < .0001). The NK1 antagonist exhibited dose-dependent reductions in cellular proliferative rates in OSA-derived cell cultures but not in RI-derived mixed cell cultures (P < .00001). SP treatment was associated with increased TNF-α and IL-6 production, and GR-82334 abrogated SP effects, as well as reduced basal cytokine release (P < .0001). CONCLUSIONS: SP pathways appear to underlie intrinsic proliferative and inflammatory signaling pathways in tonsillar tissues from children with OSA but not with RI. Selective disruption of these pathways may provide nonsurgical alternatives for prevention and treatment of pediatric OSA.

Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention.

OBJECTIVE/HYPOTHESIS: To report data on death or permanent disability after tonsillectomy. STUDY DESIGN: Electronic mail survey. METHODS: A 32-question survey was disseminated via the American Academy of Otolaryngology-Head and Neck Surgery electronic newsletter. Recipients were queried regarding adverse events after tonsillectomy, capturing demographic data, risk factors, and detailed descriptions. Events were classified using a hierarchical taxonomy. RESULTS: A group of 552 respondents reported 51 instances of post-tonsillectomy mortality, and four instances of anoxic brain injury. These events occurred in 38 children (71%), 15 adults (25%), and two patients of unstated age (4%). The events were classified as related to medication (22%), pulmonary/cardiorespiratory factors (20%), hemorrhage (16%), perioperative events (7%), progression of underlying disease (5%), or unexplained (31%). Of unexplained events, all but one occurred outside the hospital. One or more comorbidities were identified in 58% of patients, most often neurologic impairment (24%), obesity (18%), or cardiopulmonary compromise (15%). A preoperative diagnosis of obstructive sleep apnea was not associated with increased risk of death or anoxic brain injury. Most events (55%) occurred within the first 2 postoperative days. Otolaryngologists who reported performing <200 tonsillectomies per year were more likely to report an event (P < .001). CONCLUSIONS: This study, the largest collection of original reports of post-tonsillectomy mortality to date, found that events unrelated to bleeding accounted for a preponderance of deaths and anoxic brain injury. Further research is needed to establish best practices for patient admission, monitoring, and pain management. LEVEL OF EVIDENCE: N/A.

Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea.

INTRODUCTION: The abundant expression of leukotrienes (LTs) and their receptors in adenotonsillar tissues of children with obstructive sleep apnea (OSA) suggest that LT antagonists could be useful in treating OSA. METHODS: The effects of LTD4 and of LT receptor antagonists zileuton, montelukast, and BAY u9773 were examined on mixed cell cultures prepared from dissociated tonsils or adenoids harvested intraoperatively from children with polysomnographically diagnosed OSA. Proliferation was assessed by (3)[H]-thymidine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-8, IL-10, and IL-12) was assessed in supernatants using enzyme-linked immunosorbent assay. RESULTS: LTD4 elicited dose-dependent increases in adenotonsillar cell proliferation (p < 0.001; n = 12). All LT antagonists exhibited dose-dependent reductions in adenotonsillar cellular proliferation rates, with montelukast more than BAY u9773 more than zileuton (n = 14/group; p < 0.001). However, BAY u9773 showed partial agonist effects and increased cellular proliferation at higher concentrations (10(-4) mmol/L; p < 0.01; n = 12). LTD4 effects were partially blocked by montelukast and BAY u9773 but not by zileuton. All three antagonists reduced TNF-alpha, IL-6, and IL-12 concentrations, with selective changes in IL-8 and no effects on IL-10 levels. CONCLUSIONS: LT pathways mediate intrinsic proliferative and inflammatory signaling pathways in adenotonsillar tissues from children with OSA, and targeted pharmacologic disruption of these pathways may provide nonsurgical alternatives for prevention and treatment of this disease.

A mixed cell culture model for assessment of proliferation in tonsillar tissues from children with obstructive sleep apnea or recurrent tonsillitis.

BACKGROUND: Recurrent infective tonsillitis (RI) and obstructive sleep apnea (OSA) are the major indications for adenotonsillectomy (T&A) in children. However, little is known on the determinants of lymphadenoid tissue proliferation in the pediatric upper airway. OBJECTIVES: To develop an in vitro culture system allowing for assessment of tonsillar or adenoidal proliferation under basal or stimulated conditions. METHODS: Tonsils surgically removed from pediatric patients with obstructive sleep apnea and recurrent tonsillitis during T&A, were dissociated using standard methods. Whole cell tonsillar cultures were either maintained in normal medium or stimulated with lipopolysaccharide (25 microg/mL) and concanavalin A (10 microg/mL) for 24 hours (stimulated conditions [STIM]). Cellular proliferation was evaluated by [3H]thymidine incorporation. In parallel, supernatants were collected after 48 hours, and concentration of cytokines was measured using standard enzyme-linked immunosorbent assay procedures. RESULTS: Basal proliferative rates were increased in the OSA group (305.2 +/- 40.6 cpm; n = 31) compared to RI group (232.8 +/- 31.9 cpm; n = 26; P < .001). No significant differences in proliferative rates emerged after STIM between OSA and RI. Furthermore, basal TNF-alpha, IL-6, and IL-8 concentrations in the supernatant were increased in OSA-derived cultures compared to RI, but IL-8 was higher after STIM in RI, while IL-6 remained increased in OSA. CONCLUSIONS: The proliferative rates and concentrations of inflammatory mediators in tonsillar cell cultures from children with OSA and RI suggest that lymphadenoid tissue proliferation in these two conditions may be regulated by different mechanisms. This novel method may allow for future development of specific therapeutic interventions aimed at curtailing and reversing tonsillar and adenoidal hypertrophy in children in a disease-specific manner.

Neurotrophins and tonsillar hypertrophy in children with obstructive sleep apnea.

Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p<0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p<0.01), and substance P concentrations in OSA patients were higher than in RI (p<0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.

Leukotriene modifier therapy for mild sleep-disordered breathing in children.

BACKGROUND: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. METHODS: Twenty-four children with SDB completed an open-label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral X-ray films of the neck were obtained before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, immunohistochemistry, and Western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. RESULTS: Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA was similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with obstructive sleep apnea. CONCLUSIONS: Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double-blind, placebo-controlled trials will be needed to corroborate current findings and solidly establish antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.

Glucocorticoid receptor subunit expression in adenotonsillar tissue of children with obstructive sleep apnea.

Tonsillectomy and adenoidectomy (T&A) is a frequent surgical procedure in children with obstructive sleep apnea (OSA). Many symptomatic children who do not fulfill the currently recommended criteria for T&A may benefit from topical intranasal steroid therapy. However, the expression of glucocorticoid receptor (GCR) expression in adenoid and tonsillar tissue is currently unknown. The objective of this study was to assess and compare expression patterns of the human GCR in children who undergo T&A for either recurrent throat infections (RI) or OSA. Adenotonsillar tissues from 36 children with OSA or RI were subjected to quantitative PCR using specific primers for GCR-alpha and GCR-beta and to immunohistochemistry and Western blotting for protein expression of GCR isoforms. mRNA encoding for expression of both GCR-alpha and GCR-beta was detected in the tonsils and adenoids of all children, with markedly higher relative abundance of the GCR-alpha. Furthermore, GCR-alpha mRNA expression was increased in OSA-derived adenoid and tonsil tissues compared with RI, whereas no differences emerged for GCR-beta. Immunoblots confirmed these findings for the protein transcripts of these genes, and immunohistochemistry showed a specific topographic pattern of distribution for both receptors in tonsillar tissue. GCR-alpha and GCR-beta are expressed in pediatric adenotonsillar tissue, are more abundant in OSA patients, and demonstrate a specific topographic pattern of expression. These findings along with the high GCR-alpha:GCR-beta ratio suggest a favorable profile for topical steroid therapy in snoring children with adenotonsillar hypertrophy.