Congenital Central Hypoventilation Syndrome in Israel-Novel Findings from a New National Center.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal-dominant disorder of the autonomic nervous system that results from mutations in the PHOX2B gene. A national CCHS center was founded in Israel in 2018. Unique new findings were observed. METHODS: All 27 CCHS patients in Israel were contacted and followed. Novel findings were observed. RESULTS: The prevalence of new CCHS cases was almost twice higher compared to other countries. The most common mutations in our cohort were polyalanine repeat mutations (PARM) 20/25, 20/26, 20/27 (combined = 85% of cases). Two patients showed unique recessive inheritance while their heterozygotes family members were asymptomatic. A right-sided cardio-neuromodulation was performed on an eight-year-old boy for recurrent asystoles by ablating the parasympathetic ganglionated plexi using radiofrequency (RF) energy. Over 36 months' follow-up with an implantable loop-recorder, no bradycardias/pauses events were observed. A cardiac pacemaker was avoided. CONCLUSIONS: A significant benefit and new information arise from a nationwide expert CCHS center for both clinical and basic purposes. The incidence of CCHS in some populations may be increased. Asymptomatic NPARM mutations may be much more common in the general population, leading to an autosomal recessive presentation of CCHS. RF cardio-neuromodulation offers a novel approach to children avoiding the need for permanent pacemaker implantation.

Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

Respiratory effects of acute milk consumption among asthmatic and non-asthmatic children: a randomized controlled study.

BACKGROUND: A commonly held public belief is that cow's milk products increase mucus production and respiratory symptoms. Dietary milk elimination is often attempted despite lack of evidence. Our objective was to investigate whether a single exposure to cow's milk is associated with respiratory symptoms and changes in pulmonary functions in asthmatic and non-asthmatic children. METHODS: We conducted a prospective double blind, placebo-controlled trial on non-asthmatic and asthmatic children aged 6-18 years evaluated at a pediatric pulmonology unit. The children were randomly challenged with cow's milk or soy milk substitute. Symptoms, spirometry, fractional-exhaled nitric-oxide (FeNO), and pulse oximetry findings were obtained at baseline and at 30, 60, 90, and 120 min following challenge. A two-way ANCOVA (with repeated measures when required) was used to compare the performances of all groups and subgroups over time. The outcome measures of each participant were compared to his/her own variables over time and in relation to his/her baseline values. In case of missing data points, missingness analysis was performed using Little's missing completely at random (MCAR) test. RESULTS: Fifty non-asthmatic children (26 assigned to the cow's milk group and 24 to the soy substitute group), and 46 asthmatic children (22 in the cow's milk group and 24 in the soy substitute group) were enrolled. Age, gender, and body mass index Z-score were comparable between the two groups. No changes in symptoms, spirometry, FeNO, or oxygen saturation measurements were observed following challenge in any of the participants in both groups, at any time point compared to baseline. CONCLUSIONS: A single exposure to cow's milk is not associated with symptoms, bronchial inflammation, or bronchial constriction in both non-asthmatic and asthmatic children. Our findings do not support the strict elimination of dairy products from a child's diet for the prevention of respiratory symptoms. TRIAL REGISTRATION: This study was approved by the Tel Aviv Sourasky Medical Center Institutional Review Board and the Israeli Ministry of Health review board (Helsinki Committee, NIH #NCT02745899). Registered April 2016 https://clinicaltrials.gov/ct2/show/NCT02745899?cond=milk+asthma&rank=1 .

Eosinophil cell count in bronchoalveolar lavage fluid in early childhood wheezing: is it predictive of future asthma?

Objective: Increased eosinophil level in bronchoalveolar lavage fluid (BALF) characterizes asthma in school-age children and adults and has been suggested as a marker for disease severity and response to treatment. We aimed to investigate the occurrence and yield of BALF eosinophil cell count in preschool children with recurrent wheezing and its possible relation to future diagnosis of asthma. Methods: BALF was retrospectively studied in young wheezy children and its relation to asthma at age 6 years was evaluated. BALF from children aged 1-48 months (mean = 20.4) was analyzed in preschool wheezy children. Children with anatomical airway obstruction and other lower airway/lung diseases who underwent BALF served as controls. Assessment of asthma was accomplished at 6 years. Results: Eighty-two children were included. The mean age during bronchoscopy and BAL was 20.4 ± 14.4 months (range: 1-48 months). Twenty-six patients had recurrent preschool wheezing, 13 anatomical airway obstruction and 43 had other lower airways/lung diseases. Groups were comparable for age during bronchoscopy and gender. No difference was found between groups for any of the BALF cell types. Eosinophils were very low in all three groups [mean (interquartile range): 0 (0-0.4), 0 (0-0.8), and 0.4 (0-1), respectively, p = 0.25]. No difference in eosinophil levels during bronchoscopy was found between asthmatic children to non-asthmatic as defined at age 6 years. Conclusions: Wheezing in preschool children is not associated with increased BALF eosinophils; hence, at this age, the diagnostic yield of BALF for cell count analysis for diagnosing asthma is limited and is not routinely indicated.

Congenital central hypoventilation syndrome: Severe disease caused by co-occurrence of two PHOX2B variants inherited separately from asymptomatic family members.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.

Laryngeal ultrasound for the diagnosis of laryngomalacia in infants.

INTRODUCTION: Laryngomalacia is the most prevalent cause of congenital stridor. Flexible laryngobronchoscopy (FLB) is the gold standard for diagnosis. However, FLB requires venous access, deep sedation or general anesthesia, and is associated with patient's and parental discomfort and a considerable cost. Laryngeal ultrasound (LUS) has been shown to provide good evaluation of the normal anatomy and the dynamic motion of laryngeal structures. We investigated the yield of LUS in the diagnosis of laryngomalacia in infants with congenital stridor compared to FLB. METHODS: A prospective blind study of consecutive infants referred for FLB due to congenital stridor with unknown cause. The presence of arytenoids adduction on LUS during inspiration was used to diagnose laryngomalacia. LUS was followed by FLB under anesthesia. The physician performing the FLB was blinded to the LUS results. RESULTS: Twenty-four patients participated in the study (54% males). Median (IQR) age and weight were 3.5 (1-7.7) months and 5.1 (4-8.4) kg, respectively. LUS was well tolerated in all infants. Compared to FLB, LUS correctly diagnosed laryngomalacia in 11/14 (78.6%) infants. In 10 infants FLB ruled out laryngomalacia of whom LUS concurred in 9 infants and one was falsely diagnosed with laryngomalacia. LUS had a sensitivity of 78.5% (CI 52-95%), specificity of 90% (CI 49-94%), NPV of 75%, and PPV of 92%. ROC analysis demonstrated AUC of 0.84 (P < 0.01, 95%CI: 0.67-1.0). CONCLUSION: We suggest that LUS has a role in screening congenital stridor in otherwise healthy infants when laryngomalacia is highly probable.

Variability in anesthesiologists' approach to the preoperative management of asthmatic children.

OBJECTIVE: No consensus guidelines exist for the preoperative treatment of asthmatic children referred for elective surgery. We investigated the attitude of pediatric anesthesiologists to this issue. DESIGN: A questionnaire survey was conducted. SETTING: National survey. SUBJECTS: Certified Israeli pediatric anesthesiologists from all 24 general hospitals in Israel. MEASUREMENT: Twenty-one questions regarding the approach to preoperative management of asthmatic children including 6 case scenarios with a variety of clinical situations and treatments of asthmatic children. The results were compared with the attitude of pediatric pulmonologists recently published using a similar methodology. MAIN RESULTS: Forty-four pediatric anesthesiologists from all 24 general hospitals in Israel responded. Twenty-five percent of pediatric anesthesiologists answered that, in addition to pediatric anesthesiologists, the primary pediatrician should be consulted, and 70% believed that a pediatric pulmonologists should also be consulted. Overall, results showed a wide variability between responders especially for preschool children and unstable school-aged asthmatic children for both disciplines. The variability referred to the use of any treatment, bronchodilators, inhaled corticosteroids and their combination, addition of systemic corticosteroids, and the length of preoperative treatment. Compared with pediatric pulmonologists, a better within-discipline agreement was observed by the pediatric anesthesiologists for stable school-aged asthmatic children with a lower inclination to augment preoperative treatment (P< .001). No difference was observed for the preschool children with asthma and for the unstable school-aged asthmatic child. CONCLUSIONS: A wide variability exists in pediatric anesthesiologists' approach to the preoperative management of asthmatic children for most common case scenarios. This is probably explained by the heterogeneity of asthma, the type of surgery, the lack of guidelines, and the paucity of data. Similarities as well as differences exist between pediatric anesthesiologists and pulmonologists. Further studies and implementation of consensus guidelines are needed.

Adenoidectomy for Obstructive Sleep Apnea in Children.

STUDY OBJECTIVE: Adenotonsillectomy is the recommended treatment for children with obstructive sleep apnea (OSA). Since adenoidectomy alone may be associated with significantly lower morbidity, mortality, and cost, we aimed to investigate whether adenoidectomy alone is a reasonable and appropriate treatment for children with OSA. METHODS: Five-hundred fifteen consecutive children diagnosed with moderate-to-severe OSA (apnea-hypopnea index > 5) based on polysomnography and who underwent adenoidectomy or adenotonsillectomy were reevaluated after 17-73 months (mean 41) for residual or recurrent OSA using a validated questionnaire (Pediatric Sleep Questionnaire, PSQ). Failure of OSA resolution was defined as a positive mean PSQ score ≥ 0.33. Contribution of age, obesity, tonsil size, and OSA severity at baseline to adenoidectomy or adenotonsillectomy failure was examined. RESULTS: Positive PSQ score occurred in 15% of the entire sample and was not influenced by age or gender. No difference in failure rate was observed between adenoidectomy and adenotonsillectomy for children who were not obese with apnea-hypopnea index < 10 and had small tonsils (< 3). Children with apnea-hypopnea index ≥ 10 and/or tonsil size ≥ 3 showed a higher failure rate after adenoidectomy compared to adenotonsillectomy (20% versus 9.8%, p = 0.028). CONCLUSIONS: We suggest that subjective, long term outcomes of adenoidectomy are comparable to those of adenotonsillectomy in non-obese children under 7 years old with moderately OSA and small tonsils. Hence, adenoidectomy alone is a reasonable option in some children. Future prospective randomized studies are warranted to define children who may benefit from adenoidectomy alone and those children in whom adenoidectomy alone is unlikely to succeed.

Alveolar ventilation in children during flexible bronchoscopy.

BACKGROUND: Hypoxia and hypercarbia complicate flexible bronchoscopy (FB). Unlike oxygenation by pulse-oximetry, alveolar ventilation is not routinely monitored during FB. The aim of this study was to investigate ventilation in children undergoing FB by measuring carbon-dioxide (CO2 ) levels using the transcutaneous technique. METHODS: Children admitted for FB were recruited. In addition to routine monitoring, transcutaneous CO2 (TcCO2 ) levels were recorded. All were sedated using the same protocol. RESULTS: Ninety-five children were studied. There was no association between peak TcCO2 or rise in TcCO2 and age, weight percentile, bronchoscope size, or diagnosis. Median baseline TcCO2 was 36 mmHg (IQR 32,40), median peak TcCO2 was 51 mmHg (IQR 43,62) with median TcCO2 rise of 17 mmHg (IQR 6.5,23.7). A rise of 15 mmHg or higher was recorded in 55% (n = 52) patients. Children requiring total propofol dose over 3.5 mg/kg had a significantly higher TcCO2 peak of 57.6 mmHg (IQR 47.8,66.7) compared to 47.1 mmHg (IQR 40,57) (P = 0.004) and a higher rise in TcCO2 22.5 mmHg (IQR 17,33.9) compared to 13.6 mmHg (6,22) (P = 0.001). Results were not affected by intranasal midazolam and broncho-alveolar lavage. No complications were reported. Non clinically significant (i.e., not lower than 90%) brief drops in oxygen saturation were observed. CONCLUSIONS: A large proportion of children undergoing FB have significant alveolar hypoventilation indicated by a rise in TcCO2 . Monitoring ventilation with TcCO2 is feasible and should be added during FB particularly in cases that are expected to require large amounts of sedation and patients susceptible to complications from respiratory acidosis. Pediatr Pulmonol. 2016;51:1177-1182. © 2016 Wiley Periodicals, Inc.

Low parental tolerance for infant crying: an underlying factor in infant sleep problems?

Parenting behaviours play a major role in the evolution of infant sleep. Sleep problems in infancy have been associated with excessive parental involvement at night-time, and with shorter delays in response to infant night wakings and signalling. Infant crying and sleep problems are linked, yet little is known about the impact of parental responses to crying on infant sleep patterns. This study examined the hypothesis that lower parental tolerance for crying is associated with infant sleep problems. We studied 144 married couples divided into three groups: parents of infants suffering from night-waking problems (i.e. the clinical group), parents of infants without sleep problems and childless couples. Crying tolerance was assessed using questionnaires, audio recordings of crying infants and using a novel paradigm, in which participants were shown a video of a crying infant and asked when they would intervene. Parents in the clinical group demonstrated shorter intervention delays in the crying infant clip (group effect: P < 0.0001), and tended to attribute more distress to the crying infants compared to parents in both control groups (P < 0.05). Additionally, women demonstrated lower tolerance for infant crying on most measures compared to men. Our results suggest that parents of sleep-disturbed infants appear to have lower tolerance for infant crying, which may be a predisposition underlying their excessive involvement in soothing their infants to sleep which may lead to the development of sleep problems. These preliminary findings should be explored further to assess their clinical validity and utility.

Pulmonary functions in children with inflammatory bowel disease.

OBJECTIVE: To investigate fractional exhaled nitric-oxide (FeNO) levels in children with Crohn's disease (CD) and ulcerative colitis (UC) and their correlation to disease activity. MATERIALS AND METHODS: Children with CD and UC (aged 8-18 years) and age-matched healthy controls without respiratory symptoms were recruited. Disease activity was assessed using validated scores. All children performed spirometry and FeNO tests and the association between intestinal disease parameters and pulmonary functions was studied. RESULTS: Thirty-five children with CD, nine with UC, and 24 healthy controls were enrolled. The mean FeNO level was higher in children with CD compared with the controls. Increased FeNO levels (>23 parts per billion) were more common among CD and UC compared with healthy children (46, 33, and 0%, respectively, P<0.05). Nevertheless, FeNO levels did not correlate with disease activity. There were no significant differences between CD, UC patients, and healthy controls in any of the spirometric variables. CONCLUSION: FeNO level, a marker of airway inflammation, is elevated in children with inflammatory bowel diseases irrespective of their intestinal disease activity. Increased FeNO levels are not associated with respiratory symptoms, suggesting a latent pulmonary involvement in the systemic disease.

The history of primary snoring in children: the effect of adenotonsillectomy.

UNLABELLED: Primary snoring (PS) is considered as the most benign form of sleep-disordered breathing (SDB), and treatment is usually not prescribed. Studies suggest that PS may not be as benign as had formerly been considered. We aimed to investigate the natural history of PS in children with adenotonsillar hypertrophy, and compare those who underwent adenotonsillectomy (AT) with those who did not. MATERIAL AND METHODS: Children diagnosed with PS based on polysomnographic findings were included in the study. Information retrieved from their medical records, including medical history, physical examination, anthropometric measures, and polysomnography (PSG) results, was reviewed. A telephone interview was conducted 4-6 years following the PSG evaluation. The interview included the Pediatric Sleep Questionnaire Sleep-related Breathing Disorder (PSQ-SRBD) scale, demographics, anthropometric measures, and history of AT. RESULTS: A total of 248 children (56% males) were studied (mean age: 5.4 ± 3.4 years). Telephone interviews were conducted 5.3 ± 1.1 years following PSG. Sixty-four children (26%) underwent AT/adenoidectomy (A) following PSG. Of the 184 children who did not undergo surgery, 62 (34%) had positive PSQ-SRBD scores five years after diagnosis. Children with PS who underwent AT had better PSQ-SRBD scores at five years post diagnosis than the nonoperated children. CONCLUSIONS: A significant proportion of children with PS persist with SDB symptoms even five years following the diagnosis. In our cohort, a considerable percentage of children with a PSG diagnosis of PS underwent AT despite non-supportive sleep study results. Surgical intervention may have beneficial effects on some children with PS. Further studies using objective measures of sleep and incorporating the effect of SDB duration are required.

Nasal nitric oxide in sleep-disordered breathing in children.

BACKGROUND: Inflammation plays a role in the pathogenesis and consequences of sleep-disordered breathing (SDB). The nasal mucosa and paranasal sinuses produce high levels of nitric oxide (NO). In asthma, exhaled NO is a marker of airway inflammation. There is only limited information whether nasal NO (nNO) accompanies also chronic upper airway obstruction, specifically, SDB. The objective of this study was to investigate nNO levels in children with SDB in comparison to healthy non-snoring children. METHODS: Nasal NO was measured in children who underwent overnight polysomnographic studies due to habitual snoring and suspected SDB and in healthy non-snoring controls. RESULTS: One hundred and eleven children participated in the study: 28 with obstructive sleep apnea (OSA), 60 with primary snoring (PS), and 23 controls. Nasal NO levels were significantly higher in children with OSA and PS compared to controls (867.4 ± 371.5, 902.0 ± 330.9, 644.1 ± 166.5 ppb, respectively, p = 0.047). No difference was observed between children with OSA and PS. No correlations were found between nNO levels and any of the PSG variables, nor with age, BMI percentile or tonsils size. CONCLUSIONS: Compared to healthy controls, nNO is increased in children with SDB, but it is not correlated with disease severity. This is probably due to the local mechanical processes and snoring.

Surgical treatment for cervicomedullary compression among infants with achondroplasia.

PURPOSE: Achondroplasia is the most common form of dwarfism. Respiratory failure is responsible for most deaths among these children and is often related to cervicomedullary compression (CMC). We present our experience with early cervicomedullary decompression in infants with achondroplasia. METHODS: Data was retrospectively collected for infants with achondroplasia who underwent CMC decompression between 1998 and 2013. Data included presurgical and postsurgical neurological examinations, MRI scans, and sleep study results. RESULTS: Ten infants were included. Ages at surgery were 4 to 23 months (12.5 ± 6.88 months). All infants displayed neurological findings prior to surgery, although often subtle. All infants underwent a foramen magnum opening with a wide C1 laminectomy. Following surgery, seven patients (70 %) demonstrated improved neurological status, and one displayed neurological deterioration. Seven patients demonstrated improved sleep quality 1 year after surgery. These patients had a good or improved neurological status following surgery. Preoperative radiological findings included abnormal hyperintense T2 changes in all children (improved following surgery in six children), brainstem distortion in four children (improved in all), and diminished cerebrospinal fluid (CSF) spaces at the level of the foramen magnum in eight children (improved in seven). One child with extensive preoperative T2 changes accompanied by neurological and respiratory decline, deteriorated following surgery, and remains chronically ventilated. CONCLUSIONS: Infants with achondroplasia are prone to neurological and respiratory symptoms. We believe that early diagnosis and early surgery for decompression of the foramen magnum and C1 lamina can alleviate respiratory symptoms, improve neurological status, and perhaps prevent sudden infant death in this population.

The effect of maternal sleep-disordered breathing on the infant's neurodevelopment.

OBJECTIVE: We sought to examine the effect of maternal sleep-disordered breathing (SDB) on infant general movements (GMs) and neurodevelopment. STUDY DESIGN: Pregnant women with uncomplicated full-term pregnancies and their offspring were prospectively recruited from a community and hospital low-risk obstetric surveillance. All participants completed a sleep questionnaire on second trimester and underwent ambulatory sleep evaluation (WatchPAT; Itamar Medical, Caesarea, Israel). They were categorized as SDB (apnea hypopnea index>5) and controls. Infant GMs were assessed in the first 48 hours and at 8-11 and 14-16 weeks of age. At 12 months of age the Infant Developmental Inventory and the Brief Infant Sleep Questionnaire were administered. RESULTS: In all, 74 women and their full-term infants were studied. Eighteen (24%) women had SDB. Mean birthweight was 3347.1±423.9 g. Median Apgar score at 5 minutes was 10 (range, 8-10). In adjusted comparisons, no differences were found between infants born to mothers with SDB and controls in GM scores in all 3 evaluations. Low social developmental score was detected at 12 months in 64% of infants born to SDB mothers compared to 25% of infants born to controls (adjusted P=.036; odds ratio, 16.7). Infant snoring was reported by 41.7% of mothers with SDB compared to 7.5% of controls (P=.004). CONCLUSION: Our preliminary results suggest that maternal SDB during pregnancy has no adverse effect on neonatal and infant neuromotor development but may affect social development at 1 year.

Pediatric pulmonologists approach to the pre-operative management of the asthmatic child.

OBJECTIVE: No consensus guidelines exist for the respiratory treatment of asthmatic children referred for elective surgery. The aim of this study was to evaluate the attitude of pediatric pulmonologists regarding the pre-operative management of these children. METHODS: A survey of pre-operative management of asthmatic children was conducted. All 48 certified pediatric pulmonologists in Israel completed a questionnaire that comprised 20 questions regarding their approach to pre-operative management including six case scenarios with a variety of clinical situations and treatments of children with asthma. RESULTS: Response rate was 100%. All believed that pre-operative treatment should be considered in all asthmatic children. Almost 50% suggested that a pediatric pulmonologist should be consulted in all pre-operative assessments. 50% recommended consultation only in individual cases. Overall, results showed a very wide variability between responders especially in pre-school and poorly controlled school children. The variability referred to the use of bronchodilators, inhaled corticosteroids and their combination during the pre-operative days, the addition of systemic CS and the length of pre-operative treatment. Almost all participants suggested either the initiation or augmentation of pre-operative treatment in high risk situations. CONCLUSIONS: This data demonstrate an important variability among pediatric pulmonologists in Israel regarding the practice of pre-operative treatment of infants and children with asthma especially for the less controlled and high risk children. This is most probably explained by the paucity of evidence-based data and the lack of established guidelines. Consensus guidelines for the pre-operative management of asthmatic children are needed.

Oxidative stress in children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with cardiovascular consequences, including accelerated atherosclerosis and endothelial dysfunction. Increased lipid peroxidation, a marker of oxidative stress, has been identified in adults with OSA in a severity-dependent manner, with attenuation following treatment with continuous positive airway pressure therapy. Studies on oxidative stress in children with OSA are sparse and results are inconclusive. The objective of this study was to compare lipid peroxidation in children with OSA to non-OSA children. METHODS: A prospective cross-sectional study of 26 children with polysomnography-confirmed OSA (oAHI ≥ 5/h TST) was conducted. Thirty age- and body mass index z-score-matched children with primary snoring (PS) served as a comparison group (oAHI ≤ 1/h TST). Fasting blood samples were obtained on the morning following the sleep study. Plasma oxidized low-density lipoprotein (oxLDL) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: There were no group differences in patient characteristics and their lipid profiles. The mean oxLDL levels of the OSA group were significantly higher than those of the comparison group (53.1 ± 13.0 vs. 45.7 ± 10.0 U/L, respectively, p = 0.02). There was a significant positive correlation between plasma oxLDL and the apnea hypopnea index (r = 0.29, p = 0.03) and between oxLDL and the oxygen desaturation index (r = 0.51, p = 0.003), and a significant negative correlation between SpO2 nadir and oxLDL (r = -0.29, p = 0.03). CONCLUSIONS: OSA in children is associated with increased lipid peroxidation in a severity-dependent manner. Lipid peroxidation levels correlate with the degree of intermittent hypoxia.

Are frequency and severity of sleep-disordered breathing in obese children and youth with and without type 2 diabetes mellitus different?

Obstructive sleep apnea (OSA) is a risk factor for insulin resistance and type 2 diabetes mellitus (T2DM) in adults. Data in children are limited. The aim was to study the frequency and severity of OSA and its association with cardiometabolic risk factors in obese children and adolescents with and without T2DM. In this prospective cross-sectional study, obese children and adolescents with and without T2DM underwent polysomnography and blood tests for fasting lipids, insulin, glucose, liver functions, and C-reactive protein. All participants completed a questionnaire on past and present sleep-disordered breathing (SDB). Results were compared between T2DM and obese non-diabetic controls matched for body mass index-standard deviation score (BMI-SDS) and also according to the glycemic status: T2DM, impaired glucose tolerance (IGT), and normal glycemic control. Eleven patients with T2DM (age 15.9 ± 3.6 years) and 30 BMI-SDS matched non-diabetic subjects (age 12.7 ± 3.0 years) were studied. Among the entire cohort, 45 % had a history of snoring, 26 % reported apneic episodes during sleep, and 65 % had daytime fatigue. There were no significant between-group differences in SDB history or abnormal polysomnographic results [apnea-hypopnea index (AHI) >5/h]. The percentage of subjects with AHI >5/h was 45.5 % in T2DM patients, 25 % in obese patients with IGT, and 18.2 % in obese patients without IGT, although the difference was not statistically significant (p = 0.25). Plasma C-reactive protein levels were related to both glycemic status and OSA severity. The severity of OSA in obese children and adolescents is unrelated to the presence of diabetes. OSA may play a minor role in the development and progression of T2DM in children and adolescents. Further studies in larger cohorts are required.

The effect of seasonality on sleep-disordered breathing severity in children.

OBJECTIVE: Sleep-disordered breathing (SDB) is a common disorder associated with substantial morbidity that occurs in otherwise healthy children. Atopy, asthma, and viral upper respiratory tract infections are known risk factors for pediatric SDB that exhibit seasonal variability. The aim of our study was to investigate the effect of seasonality on SDB severity in children and adolescents referred for polysomnographic evaluation for suspected SDB and to examine the effect of atopy/asthma on this variability. METHODS: The medical records of all children and adolescents referred for a polysomnography (PSG) for suspected SDB between 2008 and 2010 were retrospectively assessed for seasonal patterns. The effect of atopy/asthma, age, and obesity on seasonal variability was investigated. RESULTS: A total of 2178 children and adolescents (65% boys) were included. The mean age of the cohort was 4.9±3.5 years (range, 3 months-18 years). Eighteen percent of patients had a history of asthma/atopy. The mean obstructive apnea-hypopnea index (OAHI) in the winter was significantly higher compared to the summer (9.1±9.6 vs. 7.5±7.0; P=.01; Cohen d=0.19), particularly in children younger than the age of 5 years (10.2±10.5 vs. 7.9±7.3; P=.008; Cohen d=0.25). Asthma/atopy had no significant effect on seasonal variability. CONCLUSIONS: SDB severity alters in a season-dependent manner in children and adolescents referred for polysomnographic evaluation for suspected SDB. These alterations are more prominent in children younger than the age of 5 years. The presence of asthma/atopy does not contribute to this seasonal variability. These findings suggest that viral respiratory infections are most likely the major contributor for the seasonal variability observed in pediatric SDB; additionally, the time of the year when a child is evaluated for suspected SDB may affect the clinical management and outcome in borderline cases.