Obstructive Sleep Apnea Children Research Articles

Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea

BackgroundIntrinsic variance of the urine proteome limits the discriminative power of proteomic analysis and complicates potential biomarker detection in the context of paediatric sleep disorders. Methods and resultsUsing a rigorous workflow for proteomic analysis of urine, we demonstrate that gender and diurnal effects constitute two important sources of variability in healthy children. In the context of disease, complex pathophysiological perturbations magnify these proteomic differences and therefore require contextualised biomarker analysis. Indeed, by performing biomarker discovery in a gender- and diurnal-dependent manner, we identified ∼30-fold more candidate biomarkers of paediatric obstructive sleep apnoea (OSA), a highly prevalent condition in children characterised by repetitive episodes of intermittent hypoxia and hypercapnia, and sleep fragmentation in the context of recurrent upper airway obstructive events during sleep. Remarkably, biomarkers were highly specific for gender and sampling time as poor overlap (∼3%) was observed in the proteins identified in boys and girls across morning and bedtime samples. ConclusionsAs no clinical basis to explain gender-specific effects in OSA or healthy children is apparent, we propose that implementation of contextualised biomarker strategies will be applicable to a broad range of human diseases, and may be specifically applicable to paediatric OSA.

Obstructive sleep apnea and obesity are associated with reduced GPR120 plasma levels in children

Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promote increased food intake. GPR120 is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects from insulin resistance and systemic inflammation. Thus, we hypothesized that GPR120 levels would be reduced in children with OSA, particularly among obese children. 226 children (mean age: 7.0 ± 2.1 years) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, HOMA-IR and hsCRP assays, monocyte GPR120 expression and plasma GPR120 levels were assessed using qPCR and ELISA kits. Obese children and OSA children had significantly lower GPR120 monocyte expression and plasma GPR120 levels. Furthermore, when both obesity and OSA were concurrently present, GRP120 levels were lowest. Linear associations emerged between GRP120 plasma levels and BMI z score, as well as with AHI, SpO2 nadir, and respiratory arousal index, the latter remaining statistically significant when controlling for age, ethnicity, gender, and BMI z score ( p < 0.001). Similarly, HOMA-IR was significantly associated with GRP120 levels, but neither LDL nor HDL cholesterol or hsCRP levels exhibited significant correlations. GPR120 levels are reduced in pediatric OSA and obesity, particularly when both are present, and may play a role in modulating the degree of insulin resistance. The short-term and long-term significance of reduced GPR120 in food intake and glycemic deregulation remains undefined. Supported by National Institutes of Health grants HL-65270, HL-086662, and HL- 107160.

T Regulatory Lymphocytes and Endothelial Function in Pediatric Obstructive Sleep Apnea

BackgroundObstructive sleep apnea (OSA) is a low-grade inflammatory disease affecting the cardiovascular and metabolic systems. Increasing OSA severity reduces T-regulatory lymphocytes (Tregs) in OSA children. Since Tregs modulate endothelial activation, and attenuate insulin resistance, we hypothesized that Tregs are associated with endothelial and metabolic dysfunction in pediatric OSA.Methods50 consecutively recruited children (ages 4.8–12 years) underwent overnight polysomnography and fasting homeostatic model (HOMA) of insulin resistance was assessed. Percentage of Tregs using flow cytometry, and endothelial function, expressed as the time to peak occlusive hyperemia (Tmax), were examined. In a subgroup of children (n = 21), in vitro Treg suppression tests were performed.ResultsCirculating Tregs were not significantly associated with either BMI z score or HOMA. However, a significant inverse correlation between percentage of Tregs and Tmax emerged (p<0.0001, r = −0.56). A significant negative correlation between Tregs suppression and the sleep pressure score (SPS), a surrogate measure of sleep fragmentation emerged (p = 0.02, r = −0.51) emerged, but was not present with AHI.ConclusionsEndothelial function, but not insulin resistance, in OSA children is strongly associated with circulating Tregs and their suppressive function, and appears to correlate with sleep fragmentation. Thus, alterations in T cell lymphocytes may contribute to cardiovascular morbidity in pediatric OSA.

Alterations in Circulating T-Cell Lymphocyte Populations in Children with Obstructive Sleep Apnea

Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Cross-sectional. Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Consecutively recruited children being evaluated for habitual snoring. N/A. Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 ≤ AHI < 5/hTST), moderate-severe OSA (AHI ≥ 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29). Pediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.

C-Reactive Protein and Carotid Intima-Media Thickness in Children with Sleep Disordered Breathing

Obesity is a risk factor for sleep disordered breathing (SDB) in children. Plasma levels of high-sensitivity C-reactive protein (Hs-CRP) are predictive of cardiovascular morbidity in adults, and CRP levels are associated with over-weight. Increased carotid intima-media thickness (IMT) is associated with several cardiovascular risk factors. We evaluated the effect of SDB on CRP levels and IMT in lean and obese children not selected for snoring. 101 children (age 5-15 years) attending a weight clinic or scheduled for routine visit. IMT was measured with quantitative B-mode ultrasound scans. The apnea-hypopnea index (AHI) was measured overnight: AHI < 1 defined controls, AHI ≥ 1 to < 5 = mild SDB, and AHI ≥ 5 = obstructive sleep apnea (OSA). AHI was significantly associated with Hs-CRP concentration (r = 0.32, p = 0.002) in all 101 children irrespective of age and sex. Body mass index (BMI) was higher in OSA children than controls (25.5 ± 7.0 vs 22.1 ± 6.9, p = 0.05). Obese children had 3.3 times more probability of having OSA (HR 3.3, 95% CI 1.2-9.3, p = 0.02) than lean children. Hs-CRP values were significantly higher in children with OSA than in children without (p = 0.011), but not when BMI z-score was added as covariate. IMT was not associated with AHI or SDB. The results of this study suggest an association between OSA and Hs-CRP concentrations (mainly mediated by overweight and obesity), but not between OSA and subclinical atherosclerosis. There is scope for prevention in childhood before OSA syndrome causes the irreversible damage to arteries observed in adult patients.

Death, nasomaxillary complex, and sleep in young children

This is an investigation of anatomical and sleep history risk factors that were associated with abrupt sleep-associated death in seven children with good pre-mortem history. Seven young children with abrupt deaths and information on health status, sleep history, death scene report, and autopsy performed in a specialized unit dedicated to investigation of abrupt death in young children were investigated Seven age and gender matched living children with obstructive-sleep-apnea (OSA) were compared to the findings obtained from the dead children. Two deaths results from accidents determined by the death scene and five were unexplained at the death scene. History revealed presence of chronic indicators of abnormal sleep in all cases prior death and history of an acute, often mild, rhinitis just preceding death in several. Four children, including three infants, were usually sleeping in a prone position. Autopsy demonstrated variable enlargement of upper airway soft tissues in all cases, and in all cases, there were features consistent with a narrow, small nasomaxillary complex, with or without mandibular retroposition. All children were concluded to have died of hypoxia during sleep. Our OSA children presented similar complaints and similar facial features. Anatomic risk factors for a narrow upper airway can be determined early in life, and these traits are often familial. Their presence should lead to greater attention to sleep-related complaints that may be present very early in life and indicate impairment of well been and presence of sleep disruption. Further investigation should be performed to understand the role of upper airway infection in the setting of anatomically small airway in apparently abrupt death of infants and toddlers.

Relationship between growth of facial morphology and chronologic age in preschool children with obstructive sleep apnea

The purpose of this study was to evaluate the relationship between facial morphology using cephalometry and chronologic age in preschool children with obstructive sleep apnea (OSA). From a group of lateral cephalometric radiographs taken of 35 children with OSA for diagnostic purposes, 15 were selected for the present investigation based on head position. The subjects consisted of preschool children with both OSA and primary dentition, all of them with a lowest documented SpO(2) <90% and a lowest 0 <AI. The control group included 15 preschool children with primary dentition and without enlarged tonsils or adenoids. The present findings reveal that, compared to the controls, OSA children had a narrower pharyngeal airway space related to OSA. In addition, we found that, although there were direct correlations between heights, nasal floor and corpus length, with chronologic age in the controls, there was no significant correlation between height, nasal floor length or corpus length with age in the OSA children. Obstructive sleep apnea in children may be associated with growth disturbances of the nasal floor and corpus length.

Pediatric Periodic Limb Movement Disorder: Sleep Symptom and Polysomnographic Correlates Compared to Obstructive Sleep Apnea

Although periodic limb movements in sleep (PLMS) have been described in multiple pediatric publications, periodic limb movement disorder (PLMD) has not. The aims of this study were to describe the prevalence, sleep-related correlates, and polysomnographic correlates of PLMD in a large pediatric case series, and compare these to pediatric obstructive sleep apnea (OSA). All PLMD cases (defined by International Classification of Sleep Disorders, 2nd edition criteria + respiratory disturbance index [RDI] < 3) and OSA cases (defined by RDI ≥ 3 + PLMS < 5), from a single pediatric sleep practice, over a 2-year time span, were included. Chart, questionnaire, and polysomnographic data were compiled. Of 468 referred children, 66 PLMD cases were identified (14%). The PLMD cases, mean age 8.1 years (range 1-17), were clinically characterized by frequent sleep onset and maintenance problems, difficulty awakening, restless sleep, leg pain/discomfort at night, and parasomnias. Compared to 90 OSA children, those with PLMD had a history of significantly more sleep onset and maintenance problems, leg pain/discomfort at night, parasomnias, getting out of bed at night, and family history of restless legs syndrome. Polysomnographically, PLMD cases had more awakenings, stage 1 sleep, stage shifts, and spontaneous arousals. These data indicate that pediatric PLMD has important clinical and polysomnographic correlates. In addition, PLMD has many characteristics that are different from pediatric OSA, suggesting that PLMD is a distinct pediatric sleep disorder, of which clinicians should be aware.

Cognitive Function in Prepubertal Children with Obstructive Sleep Apnea: A Modifying Role for NADPH Oxidase p22 Subunit Gene Polymorphisms?

Pediatric obstructive sleep apnea (OSA) may lead to neurocognitive dysfunction, but not in everyone affected. The frequencies of NADPH oxidase (NOX) polymorphisms in the p22phox subunit were similar between children with OSA and controls, except for rs6520785 and rs4673, the latter being significantly more frequent among the OSA children without deficits than with deficits (p<0.02). Similarly, 8-hydroxydeoxyguanine urine levels and NOX activity were lower among children without cognitive deficits and particularly among those with the rs4673 polymorphism. Thus, polymorphisms within the NOX gene or its functional subunits may account for important components of the variance in cognitive function deficits associated with OSA in children.

Comparison of Pre‐ and Postoperative Sleep in Pediatric Obstructive Sleep Apnea

Objective: Adenotonsillectomy is a common procedure for treating pediatric obstructive sleep apnea (OSA). It improves child growth as well as his psychological status. The objectives of this study are to compare the results of pre and postoperative polysomnographic data in terms of sleep structure and to identify the difference of each sleep stage. Method: This is a prospective study of sleep structures of pediatric OSA patients, done on 26 children with OSA. Mean age was 4.5 years. It was done in a tertiary university hospital. All children had adenotonsillectomy. Standard over-night polysomnography was performed pre-operatively and one to three months postoperatively. Results: We identified significant improvements of mean apnea hypopnea index (AHI) after the adeno-tonsillectomy from 17.1 to 3.53 ( P &lt; .001). Rapid eye movement (REM) sleep did not change significantly. Both Stage 2 and slow wave stage did not change significantly. We also identified significant improvement in the arousal index from 23 to 11 ( P &lt; .001). Conclusion: We compared pre and post operative sleep structures in OSA children after adenotonsillectomy. We identified significant polysomnographic changes in the sleep structures in form of reduction of sleep stage 1 and arousal index. These polysomnographic parameters may lead to improvement of their physical and psychological conditions after the operation.

Urates in exhaled breath condensate of children with obstructive sleep apnea

Urate levels may be a marker of oxidative stress. The aim of the present study was to find out are there any differences in urate concentrations in exhaled breath condensate (EBC) between children with obstructive sleep apnea (OSA) and healthy children. EBC was collected in children with obstructive sleep apnea (OSA) and clinically healthy children. Urate measurements in EBC and serum were performed by enzymatic color test. The higher concentration of urates in EBC of children with OSA than clinically healthy children indicate the oxidative stress in their airways. Since there was no significant difference in serum concentration of urates between children with OSA and healthy children, it could be considered that urates are sintetized in the airways of children with OSA. The present study indicated that urates in EBC (but not in serum) may be used as a marker of local synthesis of antioxidant compounds, but definitive conclusion must be supported by investigations involving larger number of participants.

Adenotonsillectomy improves slow-wave activity in children with obstructive sleep apnoea

The aim of the present study was to estimate slow-wave activity (SWA), a marker of sleep homeostasis, in children with obstructive sleep apnoea (OSA) before and after adenotonsillectomy (AT) compared with untreated OSA children (comparison group). 14 children with OSA (mean ± sd age 6.4 ± 2.5 yrs; apnoea-hypopnoea index (AHI) 10.0 ± 10.3 events·h⁻¹) who underwent AT were consecutively recruited to the study. The comparison group comprised six retrospectively recruited children (age 5.4 ± 2.2 yrs; AHI 9.4 ± 7.6 events·h⁻¹) with OSA that did not undergo treatment. Electroencephalogram (derivation C3/A2) was analysed using spectral and waveform analysis to determine SWA energy and slow-wave slope. The same procedure was repeated 5.4 and 19 months later for the AT and comparison groups, respectively. AT improved respiration without a change in duration of sleep stages. Following AT, >50% elevation of SWA during the first two sleep cycles (p<0.01) and a more physiological decay of SWA across the night (p<0.0001) were noted. The slow-wave slope increased by >30% following AT (p<0.03). No significant changes were found in SWA in the comparison group. Sleep homeostasis is considerably impaired in pre-pubescent children with OSA. AT restores more physiological sleep homeostasis in children with OSA. SWA analysis may provide a useful addition to standard sleep-stage analyses in children with OSA.

Ambulatory blood pressure before and after adenotonsillectomy in children with obstructive sleep apnea

IntroductionHypertension is found to be associated with obstructive sleep apnea (OSA) in both children and adults. But data on the effect of blood pressure after adenotonsillectomy (AT) for children with OSA are limited and controversial. ObjectiveTo assess the impact of AT on different parameters of 24-h ambulatory blood pressure monitoring in children with OSA. MethodsWe retrospectively reviewed records of OSA children who had undergone AT and a repeated sleep polysomnography after AT from 2001 to 2008. ResultsForty-four children were identified and included in the analysis. The mean apnea-hypopnea index (AHI) dropped from 14.14±15.9 to 3.3±7.1. (p<0.001). Twenty (45%) were cured of OSA. After AT, the diastolic BP load decreased significantly. Six out of eight (75%) hypertensive children became normotensive after surgery. For the pre-AT hypertensive group, both systolic and diastolic blood pressure decreased significantly during sleep after AT. However, eight children who were normotensive before AT became hypertensive after AT. These 10 post-AT hypertensive patients were more likely to have post-AT AHI>1 than the post-AT normotensive group, although the difference did not reach statistical significance. ConclusionIn the current cohort of OSA children, 44% were cured of OSA and a significant decrease in overall diastolic blood pressure load in 24-h ambulatory blood pressure was achieved after adenotonsillectomy for children with OSA. But hypertension may persist or even occur in those previously normotensive children despite the improvement in AHI. Persistence of OSA may be a risk factor and further study is required. Cure of OSA should not be assumed after AT and follow-up PSG should be performed together with 24-h ambulatory blood pressure monitoring. In light of the current findings, long term study of the blood pressure is warranted for children with OSA.

Cephalometric evaluation of children with nocturnal sleep-disordered breathing

The present study aimed to assess the cephalometric features in children with sleep-disordered breathing (SDB). The subjects were 70 children (34 boys and 36 girls, mean age 7.3, SD 1.72, range 4.2-11.9 years) with habitual snoring and symptoms of obstructive sleep disorder for more than 6 months. On the basis of overnight polygraphic findings, the subjects were further divided into subgroups of 26 children with diagnosed obstructive sleep apnoea (OSA), 17 with signs of upper airway resistance syndrome (UARS), and 27 with snoring. A control group of 70 non-obstructed children matched for age and gender was selected. Lateral skull radiographs were taken and cephalograms were traced and measured. The differences between the matched groups were studied using t-test for paired samples. Differences between the subgroups were studied using analysis of variance followed by Duncan's multiple comparison method. Children with SDB were characterized by an increased antero-posterior jaw relationship (P = 0.001), increased mandibular inclination in relation to the palatal line (P = 0.01), increased total (P = 0.019) and lower (P = 0.005) anterior face heights, a longer (P = 0.018) and thicker (P = 0.002) soft palate, smaller airway diameters at multiple levels of the naso- and oropharynx, larger oropharyngeal airway diameter at the level of the base of the tongue (P = 0.011), lower hyoid bone position (P = 0.000), and larger craniocervical angles (NSL-CVT, P = 0.014; NSL-OPT, P = 0.023) when compared with the non-obstructed controls. When divided into subgroups according to the severity of the disorder, OSA children deviated significantly from the control children especially in the oropharyngeal variables. Children with UARS and snoring also deviated from the controls, but the obstructed subgroups were not confidently distinguishable from each other by cephalometric measurements. Logistic regression analysis indicated that UARS and OSA were associated with decreased pharyngeal diameters at the levels of the adenoids (PNS-ad1) and tip of the uvula (u1-u2), an increased diameter at the level of the base of the tongue (rl1-rl2), a thicker soft palate, and anteriorly positioned maxilla in relation to the cranial base. Lateral cephalogram may thus reveal important predictors for SDB in children. Attention should be paid to pharyngeal measurements. Systematic orthodontic evaluation of SDB children is needed because of the effects of obstructed sleep on the developing craniofacial skeleton.

Obstructive sleep apnoea is associated with impaired pictorial memory task acquisition and retention in children

The aim of our study was to evaluate whether obstructive sleep apnoea (OSA) is associated with impaired acquisition and recall of a pictorial-based memory tasks in children. 54 children with OSA and 17 controls matched for age, sex and ethnicity underwent a sleep study (overnight polysomnogram). Before the sleep study subjects completed a 15-min pictorial memory task acquisition consisting of four trials, followed by a free-recall period to assess retention after 10 min and the following morning upon awakening. Children with OSA had a higher obstructive apnoea/hypopnoea index (6.3+/-1.5 events.h(-1) TST) than controls (0.6+/-0.1 events.h(-1) TST) (p<0.0001). Mean learning scores in controls over the four consecutive trials were incrementally better than in children with OSA for the four-trial set (p<0.0001). Both immediate (p<0.0001) and overnight recall performances were worse among OSA children (p<0.0001), who also exhibited declines in recall performance that was absent in controls (p<0.001). Differences in pictorial task acquisition trajectories suggest that children with OSA require more time and an increased number of learning opportunities to reach immediate and long-term recall performances that are reduced compared with controls. Thus, both acquisition and retention of newly learned material are compromised. These findings confirm and expand on the presence of known cognitive deficits in children with OSA.

Dental arch morphology in children with sleep-disordered breathing

The aim of the present study was to examine the effects of nocturnal breathing disorders such as obstructive sleep apnoea (OSA) and snoring on developing dental arches. The study group comprised 41 children (22 males, 19 females, mean age 7.2 years, standard deviation 1.93) with diagnosed OSA. Age- and gender-matched groups of 41 snoring and 41 non-obstructed control children were selected. Orthodontic examination was carried out and dental impressions were taken. Malocclusions were diagnosed clinically and 13 linear variables were measured from the dental casts. The differences between the dental arch measurements of the OSA, snoring, and control groups were studied using analysis of variance followed by Duncan's multiple comparison method. Children with diagnosed OSA had a significantly increased overjet, a reduced overbite, and narrower upper and shorter lower dental arches when compared with the controls. Snoring children had similar but not as significant differences as OSA children when compared with the controls. There were more children with an anterior open bite (AOB) in the OSA group (P=0.016) and with a Class II or asymmetric molar relationship in the groups of OSA (P=0.013) and snoring (P=0.004) subjects compared with the non-obstructed controls. There were more subjects with mandibular crowding (P=0.002) and with an AOB (P=0.019) with an increasing obstructive apnoea-hypopnoea index (AHI). These findings are in agreement with previous studies of the effects of increased upper airway resistance on dental arch morphology and can be explained by long-term changes in the position of the head, mandible, and tongue in order to maintain airway adequacy during sleep.

Obstructive Sleep Apnea and Endothelial Function in School-Aged Nonobese Children

Obstructive sleep apnea (OSA) in children is associated with cardiovascular morbidity such as systemic and pulmonary hypertension. However, it remains unclear whether endothelial dysfunction occurs in pediatric OSA and whether it is reversible on effective treatment of OSA. Consecutive nonobese children (aged 6 to 11 years) who were diagnosed with OSA after overnight polysomnography and control children matched on the basis of age, gender, ethnicity, and body mass index underwent blood draw the next morning for soluble CD40 ligand, asymmetric dimethylarginine (ADMA), and nitrotyrosine levels, as well as 2 iterations of 60-second cuff-occlusion tests for assessment of endothelial function. These tests were repeated 4 to 6 months after adenotonsillectomy. OSA children showed blunted reperfusion kinetics after release of occlusion, which completely normalized in 20 of 26 patients after adenotonsillectomy. All 6 children in whom no improvements occurred had a strong family history of cardiovascular disease (versus 2 of the remaining 20 patients; P<0.04). Plasma nitrotyrosine and ADMA levels were similar in OSA and control children; however, soluble CD40 ligand levels were higher in OSA children and were reduced after treatment, particularly in those with normalized hyperemic responses. Postocclusive hyperemia is consistently blunted in children with OSA, and such altered endothelial function is reversible 4 to 6 months after treatment, particularly if a family history of cardiovascular disease is not present. Although no evidence for either nitric oxide-dependent oxidative/nitrosative stress or for the increased presence of the circulating nitric oxide synthase inhibitor ADMA was found in children with OSA, soluble CD40 ligand levels were increased in OSA and reflected the changes in endothelial function after treatment.

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.

The effect of mode of breathing on craniofacial growth--revisited

It has been maintained that because of large adenoids, nasal breathing is obstructed leading to mouth breathing and an 'adenoid face', characterized by an incompetent lip seal, a narrow upper dental arch, increased anterior face height, a steep mandibular plane angle, and a retrognathic mandible. This development has been explained as occurring by changes in head and tongue position and muscular balance. After adenoidectomy and change in head and tongue position, accelerated mandibular growth and closure of the mandibular plane angle have been reported. Children with obstructive sleep apnoea (OSA) have similar craniofacial characteristics as those with large adenoids and tonsils, and the first treatment of choice of OSA children is removal of adenoids and tonsils. It is probable that some children with an adenoid face would nowadays be diagnosed as having OSA. These children also have abnormal nocturnal growth hormone (GH) secretion and somatic growth impairment, which is normalized following adenotonsillectomy. It is hypothesized that decreased mandibular growth in adenoid face children is due to abnormal secretion of GH and its mediators. After normalization of hormonal status, ramus growth is enhanced by more intensive endochondral bone formation in the condylar cartilage and/or by appositional bone growth in the lower border of the mandible. This would, in part, explain the noted acceleration in the growth of the mandible and alteration in its growth direction, following the change in the mode of breathing after adenotonsillectomy.

APOE ε4 allele, cognitive dysfunction, and obstructive sleep apnea in children

Obstructive sleep apnea (OSA) in children is associated with severity-dependent changes in neurocognitive functioning. However, the severity of OSA accounts for only approximately 40% of the variance in cognitive performance. Thus, genetic determinants of individual susceptibility may also contribute to the morbidity of OSA. Considering the unique susceptibility of apolipoprotein E (ApoE) knock-out mice to an experimental model of OSA, we examined whether the APOE epsilon4 allele contributes to increased neurocognitive morbidity in pediatric OSA. Consecutive habitually snoring and nonsnoring 5- to 7-year-old children underwent overnight polysomnography, neurocognitive testing, and a blood draw the next morning. Children were divided into OSA or no OSA, and OSA children were further subdivided into those with > or =2 abnormal cognitive subtest scores and those with normal cognitive scores. The presence of the APOE epsilon4 allele was determined from blood genomic DNA. Among all children without OSA, APOE epsilon4 was present in 3 of 199 children, whereas in those with OSA, APOE epsilon4 was found in 16 of 146 children (p < 0.0002). Furthermore, 16 of 74 children with OSA and cognitive scores <85% had the APOE epsilon4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002). APOE epsilon4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE epsilon4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.