The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea
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ABSTRACT:
SUBMITTER: Carrasco A
PROVIDER: S-EPMC8570126 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.
| S-EPMC10239814 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:Pediatric sleep disordered breathing (PSDB) is not only a very frequent condition affecting 2-4% of all children, but is also associated with an increased risk for a variety of manifestations underlying end-organ injury and dysfunction that impose both immediate and potentially long-term morbidities and corresponding inherent elevations in healthcare costs. One of the major problems with the creation of valid algorithms aiming to stratify diagnostic and treatment prioritization lies in our current inability to predict and identify those children who are most at-risk for PSDB-induced adverse consequences. Thus, improved our understanding of the mechanisms governing phenotype variance in PSDB is essential. Here, we examine some of the potential underpinnings of phenotypic variability in PSDB, and further propose a conceptual framework aimed at facilitating the process of advancing knowledge in this frequent disorder.
| S-EPMC3751986 | biostudies-literature
Project description:Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3–6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tags (TMT)-based proteomic analysis was performed in the serum of patients with OSA.
2022-05-20 | PXD032734 | Pride
Project description:BACKGROUND:Inflammation is often considered relating to pediatric obstructive sleep apnea (OSA). We conducted a study investigating cytokines, including Il-17 and Il-23, in children with OSA before and after adenotonsillectomy (T&A), compared with controls. METHODS:Children with OSA between age 4 and 12 receiving T&A were prospectively followed. Evaluation before and reevaluation six months after the treatment were done, including polysomnography (PSG), blood tests, and questionnaires. Blood samples were obtained to determine the values of high-sensitivity-C-reactive-protein (HS-CRP); tumor-necrosis-factor-alpha (TNF-?); and interleukin (IL)-1, 6, 10, 12, 17, and 23. We compared the results with an age-matched control group. RESULTS:We included 55 OSA children and 32 controls. Children with OSA presented significant improvement after T&A in complaints, signs, apnea hypopnea index (AHI) (p < 0.001), mean oxygen desaturation index (p < 0.001), and mean oxygen saturation (p = 0.010). Upon entering this study, children with OSA had significantly higher cytokine levels than the controls and significant changes in HS-CRP (p = 0.013), TNF-? (p = 0.057), IL-1? (p = 0.022), IL-10 (p = 0.035), and IL-17 (p = 0.010) after T&A. Children with improved but persistently abnormal AHI did not have all cytokine levels normalized, particularly IL-23 and HS-CRP. CONCLUSION:Sleep-disordered breathing can persist after T&A and can continue to have a negative inflammatory effect. HS-CRP and IL-23 may serve as blood markers for the persistence of sleep-disordered breathing after T&A.
| S-EPMC7230716 | biostudies-literature
Project description:IntroductionDiagnosis and treatment of obstructive sleep apnea (OSA) in children is often delayed due to the high prevalence and limited physician and sleep testing resources. As a result, children may be referred to multiple specialties, such as pediatric sleep medicine and pediatric otolaryngology, resulting in long waitlists.MethodWe used data from our pediatric OSA clinic to identify predictors of tonsillectomy and/or adenoidectomy (AT). Before being seen in the clinic, parents completed the Pediatric Sleep Questionnaire (PSQ) and screening questionnaires for restless leg syndrome (RLS), nasal rhinitis, and gastroesophageal reflux disease (GERD). Tonsil size data were obtained from patient charts and graded using the Brodsky-five grade scale. Children completed an overnight oximetry study before being seen in the clinic, and a McGill oximetry score (MOS) was assigned based on the number and depth of oxygen desaturations. Logistic regression, controlling for otolaryngology physician, was used to identify significant predictors of AT. Three triage algorithms were subsequently generated based on the univariate and multivariate results to predict AT.ResultsFrom the OSA cohort, there were 469 eligible children (47% female, mean age = 8.19 years, SD = 3.59), with 89% of children reported snoring. Significant predictors of AT in univariate analysis included tonsil size and four PSQ questions, (1) struggles to breathe at night, (2) apneas, (3) daytime mouth breathing, and (4) AM dry mouth. The first triage algorithm, only using the four PSQ questions, had an odds ratio (OR) of 4.02 for predicting AT (sensitivity = 0.28, specificity = 0.91). Using only tonsil size, the second algorithm had an OR to predict AT of 9.11 (sensitivity = 0.72, specificity = 0.78). The third algorithm, where MOS was used to stratify risk for AT among those children with 2+ tonsils, had the same OR, sensitivity, and specificity as the tonsil-only algorithm.ConclusionTonsil size was the strongest predictor of AT, while oximetry helped stratify individual risk for AT. We recommend that referral letters for snoring children include graded tonsil size to aid in the triage based on our findings. Children with 2+ tonsil sizes should be triaged to otolaryngology, while the remainder should be referred to a pediatric sleep specialist.
| S-EPMC8281470 | biostudies-literature
Project description:Study objectivesObstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.MethodsChildren 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.ResultsThe sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing.ConclusionsAbnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.Trial registrationPediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.
| S-EPMC9113015 | biostudies-literature
Project description:Certain common medical conditions are associated with a higher risk of pediatric obstructive sleep apnea (OSA). A lower threshold for screening is therefore indicated for such patient cohorts. In this article, we briefly discuss the high prevalence of OSA in children born prematurely, and in those with Down syndrome, craniofacial disorders, and neuromuscular disorders. Primary care providers should have an increased index of suspicion for OSA in these children, considering the neurocognitive disability that occurs in these high-risk groups when OSA is left untreated. [Pediatr Ann. 2017;46(9):e336-e339.].
| S-EPMC6340293 | biostudies-literature
Project description:Study objectivesObstructive sleep apnea-hypopnea (OAH) diagnosis in children is based on the quantification of flow and respiratory effort (RE). Pulse transit time (PTT) is one validated tool to recognize RE. Pattern analysis of mandibular movements (MM) might be an alternative method to detect RE. We compared several patterns of MM to concomittant changes in PTT during OAH in children with adenotonsillar hypertrophy.MethodsParticipants33 consecutive children with snoring and symptoms/signs of OAH.MeasurementsMMs were measured during polysomnography with a magnetometer device (Brizzy Nomics, Liege, Belgium) placed on the chin and forehead. Patterns of MM were evaluated representing peak to peak fluctuations > 0.3 mm in mandibular excursion (MML), mandibular opening (MMO), and sharp MM (MMS), which closed the mouth on cortical arousal (CAr).ResultsThe median (95% CI) hourly rate of at least 1 MM (MML, or MMO, or MMS) was 18.1 (13.2-36.3) and strongly correlated with OAHI (p = 0.003) but not with central apnea-hypopnea index (CAHI; p = 0.292). The durations when the MM amplitude was > 0.4 mm and PTT > 15 ms were strongly correlated (p < 0.001). The mean (SD) of MM peak to peak amplitude was larger during OAH than CAH (0.9 ± 0.7 mm and 0.2 ± 0.3 mm; p < 0.001, respectively). MMS at the termination of OAH had larger amplitude compared to MMS with CAH (1.5 ± 0.9 mm and 0.5 ± 0.7 mm, respectively, p < 0.001).ConclusionsMM > 0.4 mm occurred frequently during periods of OAH and were frequently terminated by MMS corresponding to mouth closure on CAr. The MM findings strongly correlated with changes in PTT. MM analysis could be a simple and accurate promising tool for RE characterization and optimization of OAH diagnosis in children.
| S-EPMC4410931 | biostudies-literature