Does weight influence the course of RSV bronchiolitis in hospitalized infants?

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease.  Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study.

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

Foreign body aspiration in Israeli children during the COVID-19 pandemic.

BACKGROUND: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been a decline in pediatric emergency department visits. Our aim was to assess the pattern of pediatric foreign body aspiration (FBA) during the first year of the COVID-19 pandemic, in comparison to the prior years. METHODS: In this retrospective multicenter study, we compared the number of children who presented with FBA during the COVID-19 year (March 1, 2020 to February 28, 2021) to the annual average of the years 2016-2019. We also compared the lockdown periods to the postlockdown periods, and the percentage of missed FBA, proven FBA, and flexible bronchoscopy as the removal procedure. RESULTS: A total of 345 children with FBA from six centers were included, 276 in the pre-COVID-19 years (average 69 per year) and 69 in the COVID-19 year. There was no difference in the prevalence of FBA between the COVID-19 year and any of the prior 4 years. Examining the lockdown effect, the monthly incidence of FBA dropped from a pre-COVID-19 average of 5.75 cases to 5.1 cases during lockdown periods and increased to 6.3 cases in postlockdown periods. No difference in the percentage of missed FB or proven FB was observed. There was a significant rise in the usage of flexible bronchoscopy as the removal procedure (average of 15.4% vs. 30.4%, p = 0.001). CONCLUSION: There were fewer cases of pediatric FBA during lockdown periods, compared to post-lockdown periods, presumably related to better parental supervision, with no difference in the prevalence of FBA during the COVID-19 year.

Obstructive sleep apnea and metabolic disorders in morbidly obese adolescents.

BACKGROUND: Little known about the prevalence of obstructive sleep apnea (OSA) in morbid obese adolescents and the association between OSA and comorbid factors. AIM: To examine the association between apnea-hypopnea index (AHI, a measure for OSA severity) and metabolic morbidity among morbidly obese adolescents. METHODS: We performed a population-based retrospective cohort study by reviewing sleep study, metabolic indices, and comorbidity-related data of a cohort (n = 106) of adolescents referred to a bariatric surgery clinic. We compared subjects with moderate/severe OSA (AHI ≥ 5) versus no/mild OSA (AHI < 5) OSA and three groups of subjects with increasing body mass index (BMI) concerning sleep-study and metabolic indices using univariate analyses. To assess the link between AHI and ferritin levels a multivariate linear regression (adjusted for BMI and mean cell volume) was preformed. RESULTS: A total of 71 patients met the inclusion criteria. Subjects with moderate/severe OSA (n = 32, 45%) had higher BMI, cholesterol, cholesterol/high-density lipoprotein (HDL) ratio, hemoglobin A1c, and serum ferritin levels (p < .05). AHI significantly increased across BMI strata (p = .02). Multivariate linear regression indicated that moderate/severe OSA was associated with higher levels of ferritin, unstandardized ß = 49.1 (nIU/ml) (p = .025). CONCLUSIONS: Morbidly obese adolescents with moderate/severe OSA versus no/mild OSA have a higher risk for metabolic complications. Therefore, OSA management should be considered in adolescents with morbid obesity, in addition to weight loss.

Nuclear factor kappa B activation in cardiomyocytes by serum of children with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSA) is associated with cardiovascular morbidity in adults and children. NFκB activity is enhanced in circulating monocytes of adults with OSA, that decreases following positive pressure therapy. OSA children's serum activates NFκB in a cell line. We hypothesized that OSA children's serum can activate NFκB in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NFκB in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls. Increased expression of NFκB classical subunits p65/p50 as well as major morphological changes occurred in cardiomyocytes following OSA's serum exposure. OSA children's serum induced NFκB activity as measured by p65 nuclear translocation in immortalized human CM and rat cardiomyocytes as well as dense immunostaining of the nucleus. Trypan blue and XTT assays showed that OSA sera induced CM apoptosis. We conclude that NFκB is systemically activated in cardiomyocytes, who also demonstrate decreased viability and contractility following exposure to OSA serum. It supports the hypothesis NFκB plays a role in the evolution of cardiovascular morbidity in OSA. It may support the search for new therapeutic interventions controlling NFκB activation in OSA.

Obesity and sleep disorders: A nationwide study of 1.3 million Israeli adolescents.

OBJECTIVES: To assess the association between sleep disorders prevalence and obesity in Israeli adolescents. METHODS: A nationwide, population-based, cross-sectional study of 1,348,817 Israeli adolescents (57% males) who were medically examined prior to military service between 1997 and 2015; height and weight were measured along with assessment of medical status at age 17.3⬰±â¬°0.4 years. The diagnosis of a sleep disorder was made based on objective diagnostic criteria. The prevalence and odds ratio (OR) for a sleep disorder were computed across BMI subgroups and were adjusted for socio-demographic confounders. RESULTS: Overall sleep disorders prevalence was 1.8:1000 (males) and 0.45:1000 (females), with a total of 1601 cases. There was a gradual increase in the odds ratio for sleep disorders with increasing BMI. Multivariable-adjusted ORs for sleep disorders were 1.29 (95% CI 1.10⬜1.52), 1.44 (1.18⬜1.75), 3.03 (2.32⬜3.96) and 3.38 (1.98⬜5.75) for overweight, obese class I, II and III, respectively (5th⬜49th BMI percentile was the reference). Results persisted in extensive sensitivity analyses including limiting the study sample to participants with unimpaired health. CONCLUSIONS: We found a higher prevalence of sleep disorders in males and a dose-dependent association between sleep disorders and adolescent BMI in both sexes. Our findings warrant clinical awareness among healthcare providers, given the rise in obesity in teenagers, and particularly in light of the obesity epidemic that we are experiencing in this era. Sleep related complaints should be actively screened in adolescents who suffer obesity.

Altered slow-wave sleep activity in children with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation syndrome.

STUDY OBJECTIVES: Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition. Little is known about sleep/wake and slow-wave activity in this condition, although the central hypothalamic dysfunction associated with autonomic dysregulation would make the occurrence of SWA deregulation most likely. METHODS: Two children with clinical presentation of ROHHAD syndrome were evaluated, diagnosed, and treated. Their polysomnographic studies were compared with 4 matched children with obstructive sleep apnea and 6 controls. RESULTS: Children that were clinically diagnosed with ROHHAD exhibited significantly weaker slow-wave activity power and shallower slow-wave activity slopes during the first 2 sleep cycles compared with children with obstructive sleep apnea or controls. CONCLUSIONS: This study shows that children with ROHHAD have suppressed slow-wave activity, possibly because of hypothalamic dysregulation that may contribute to their rapid-onset obesity and excessive daytime sleepiness.

Nitric oxide inhalations in bronchiolitis: A pilot, randomized, double-blinded, controlled trial.

AIM: The aims of this pilot study were to determine safety, tolerability (primary outcome) and efficacy (secondary outcome) of high-dose inhaled nitric oxide for the treatment of infants with moderately severe bronchiolitis. METHODS: This was a pilot, double-blinded, randomized controlled study (phase IIa). Intermittent inhalations of nitric oxide 160 ppm for 30 min or oxygen/air (control) were given 5 times/day to hospitalized infants (2-11 months) with acute bronchiolitis. Oxygen saturation, methemoglobin, and nitric dioxide (NO2 ) levels and vital signs were monitored. RESULTS: Forty-three infants were enrolled. Baseline characteristics were comparable in both study groups. Mean clinical score, comprised of four components: respiratory rate, use of accessory muscles, wheezes and crackles, and % room-air oxygen saturation, was 7.86 (±1.1) and 8.09 (±1.2) in the NO and control groups, respectively, consistent with moderate severity. The overall frequency of adverse events was similar between the groups. Repeated nitric oxide inhalations did not result in increased inhaled NO2 levels or cumulative effect on methemoglobin levels. Secondary outcomes of efficacy were measured by length of hospitalization (LOS) in hours: LOS did not differ between groups. However, in a post-hoc analysis of a subgroup of infants hospitalized for >24 h (n = 24), the median LOS was shorter in the nitric oxide (41.9 h) than in the control group (62.5 h) (P = 0.014). CONCLUSION: Our study was unable to detect a difference in side effects using intermittent high-dose nitric-oxide inhalation or supportive treatment alone, in infants with moderate bronchiolitis. Preliminary efficacy outcomes are encouraging.

Sleep medicine.

PURPOSE OF REVIEW: To reflect the recent advances in the field of pediatric sleep medicine. The pediatrician will be able to define which children to refer for a sleep study and what to expect from the sleep specialist in 2015. RECENT FINDINGS: In the first study that compared adeno tonsillectomy (TA) to watchful waiting, TA reduced symptoms and improved children's behavior, quality of life, and polysomnographic results. Anti-inflammatory therapy for mild obstructive sleep apnea was effective and well tolerated according to a double-blind study. A retrospective study showed that it is beneficial for 80% of the patients. TA is associated with a decrease in asthma symptoms and medication utilization. SUMMARY: Pediatricians need to be aware of the clear benefits of tonsillectomy (including better asthma control), although anti-inflammatory therapy may improve symptoms and polysomnographic findings in children with nonsevere obstructive sleep apnea.

Detection of common respiratory viruses in tonsillar tissue of children with obstructive sleep apnea.

BACKGROUND: Early life viral infection is associated with neurogenic inflammation that is present in lymphoid tissues of the upper airway in children with obstructive sleep apnea (OSA). We hypothesized that viral genomic material is present in tonsils of children with OSA. Therefore, we examined tonsils for the presence of respiratory viruses' nucleic acids in children with OSA, and in children without OSA (undergoing surgery for recurrent throat infections (RI)). METHODS: Tonsillar tissue from patients with OSA and RI was subjected to multiplex quantitative real time reverse transcription PCR (mqRTPCR), analyzed for the presence of common respiratory viruses' genetic material. RESULTS: Fifty-six patients were included, of whom 34 had OSA (age (years ± S.D), 4.22 ± 1.14) and 22 with RI (4.35 ± 1.36). Respiratory viruses nucleic acids (24 detections) were observed in 17 (50%) OSA samples. In contrast, no virus was detected in RI samples (relative frequency P<0.0001). Viruses detected, based on frequency were Rhinovirus, Adenovirus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), and corona virus. CONCLUSIONS: Respiratory viruses are detected in OSA hypertrophic tonsils, suggestive of their role in the evolution of tonsillar inflammation and hypertrophy. Early life viral infections may contribute to the pathogenesis of pediatric OSA.

Inflammation and growth in young children with obstructive sleep apnea syndrome before and after adenotonsillectomy.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with growth impairment that usually improves following effective treatment. In this study we investigated the mechanisms underlying the growth processes in young children diagnosed with OSA, before and after adenotonsillectomy (T&A). METHODS: Young children (6-36 months old) were enrolled and evaluated before and several months after T&A surgery for height, weight, circulating high sensitive C-reactive protein (CRP), and insulin-like growth factor 1 (IGF-1) levels. Caloric intake was assessed by a validated Short Food Frequency Questionnaire (SFFQ). RESULTS: Following T&A, children added 4.81 cm and 1.88 kg to their height and weight, respectively (P < 0.001 for both) and had a significant increase in BMI Z score (P = 0.002). Increased caloric intake of 377 kcal/day was noted (P < 0.001), with increased protein and decreased fat intake. The decrease in CRP levels correlated with the increase in body weight in boys (P < 0.05, adjusted for caloric intake). CONCLUSIONS: Adenotonsillectomy results in enhanced somatic growth in young children that correlates with a decrease in systemic inflammation and caloric intake increment. Our findings imply that systemic inflammation may have an important role in this OSA-related morbidity.

A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS. DESIGN: Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1ß, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein). SETTING: Sleep research laboratory. PATIENTS OR PARTICIPANTS: Twenty-five children with OSAS and 24 without OSAS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1ß showed increased epithelial expression in OSAS tissues. CONCLUSIONS: Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.

Novel pharmacological approaches for treatment of obstructive sleep apnea in children.

INTRODUCTION: The lymphadenoid tissues in the upper airway are sparse and organized lympho-epithelial structures playing an important role against foreign pathogens, with the palatine tonsils being the major components of the lymphoid tissues contained in the Waldeyer's ring. Obstructive sleep apnea (OSA) has emerged as a very frequent condition in the pediatric age range that is associated with substantial neurobehavioral, cardiovascular and metabolic morbidities. Adenotonsillar hypertrophy is the major pathophysiological contributor to OSA occurrence in children. AREAS COVERED: Here, the authors provide a systematic review and summary of some of the known histological and pathological features of human lymphadenoid tissues and their fundamental immunological functions, provide insights into the pathophysiology of pediatric OSA, particularly focusing on inflammatory pathways and the available outcomes associated with targeting such pathways with compounds such as corticosteroids and leukotriene modifiers. Furthermore, they present findings from an unbiased approach to discovery of therapeutic targets and formulate constructs toward putative future interventional approaches for this highly prevalent condition. EXPERT OPINION: Surgical approaches for pediatric OSA may not be as effective as previously anticipated. Accordingly, expanded use of existing systemic or topical anti-inflammatory agents or development of novel compounds targeting selected immune cell populations underlying pathophysiological determinants of OSA is needed.

Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study.

OBJECTIVES: Children with nonsevere obstructive sleep apnea (OSA) benefit from alternative therapeutic interventions such as leukotriene modifiers. We hypothesized that montelukast might improve OSA in children. We tested this hypothesis in a double-blind, randomized, placebo-controlled fashion. METHODS: Of 50 possible candidates, we recruited 46 children with polysomnographically diagnosed OSA. In this prospective, double-blind, randomized trial, children received daily oral montelukast at 4 or 5 mg (<6 or >6 years of age, respectively) or placebo for 12 weeks. Polysomnographic assessments, parent questionnaires, and radiographs to assess adenoid size were performed before and after therapy. RESULTS: Compared with the 23 children that received placebo, the 23 children that received montelukast showed significant improvements in polysomnographic measures of respiratory disturbance (obstructive apnea index), children's symptoms, and adenoid size. The obstructive apnea index decreased by >50% in 65.2% of treated children. No attrition or side effects occurred. CONCLUSIONS: A 12-week treatment with daily, oral montelukast effectively reduced the severity of OSA and the magnitude of the underlying adenoidal hypertrophy in children with nonsevere OSA.

Impaired behavioral and neurocognitive function in preschool children with obstructive sleep apnea.

OBJECTIVE: We aimed to examine the hypothesis that behavioral and neurocognitive functions of preschool children with Obstructive Sleep Apnea Syndrome (OSAS) are impaired compared to healthy children, and improve after adenotonsillectomy (TA). METHODS: A comprehensive assessment battery was used to assess cognitive and behavioral functions, and quality of life in children with OSAS compared to matched controls. RESULTS: 45 children (mean age 45.5 ± 9 months, 73% boys, BMI 15.7 ± 2) with OSAS were compared to 26 healthy children (mean age 48.6 ± 8 months, 46% boys, BMI 16.4 ± 2). Mean AHI in the OSAS group was 13.2 ± 10.7 (ranging from 1.2 to 57). Significantly impaired planning and fluency (executive function) were found in children with OSAS, as well as impaired attention and receptive vocabulary. Parents and teachers described the OSAS group as having significantly more behavior problems. Quality of life questionnaire in children with OSAS (mean 2.3, range 0.7-4.3) was significantly worse compared to controls (mean 0, range: 0-4), P < 0.004. One year following TA, 23 children with OSAS and 18 controls were re-evaluated. Significant improvement was documented in verbal and motor fluency, sustained attention, and vocabulary. After TA, fewer behavioral problems were seen. CONCLUSIONS: Preschool children with OSAS present significantly impaired executive functions, impaired attention and receptive vocabulary, and more behavior problems. One year after TA, the prominent improvements were in behavior and quality of life. These findings suggest that the impact of OSAS on behavioral and cognitive functions begins in early childhood.

Sleep-disordered breathing is a risk factor for community-acquired alveolar pneumonia in early childhood.

BACKGROUND: Data are scarce with regard to risk factors for acute community-acquired alveolar pneumonia (CAAP) in children, but it is known that children with sleep-disordered breathing (SDB) experience more respiratory infections. We aimed to assess whether SDB is a risk factor for CAAP in early childhood. METHODS: We conducted a prospective, nested, case-control study assessing children < 5 years old who had been given a diagnosis of CAAP based on World Health Organization radiographic criteria. Demographic and clinical data were collected. SDB symptoms were documented using a structured questionnaire. CAAP study and retrospective sleep laboratory databases were compared. SDB presence and severity were determined by questionnaire and polysomnography (PSG). RESULTS: A total of 14,913 children underwent chest radiography during the study period; 1,546 children with radiographically proven CAAP (58% boys) and 441 control subjects (54% boys) were prospectively enrolled. Frequent snoring was reported in 18.6% vs 2.9% subjects with CAAP and control subjects, respectively (P < .001). The respective figures for subjects with CAAP and control subjects for restless sleep, nocturnal breathing problems, abnormal behavior, and chronic rhinorrhea were 21.6% vs 5.3%, 5% vs 1.4%, 6.4% vs 0.2%, and 12.9% vs 1.8%, (P < .001 for each). Fifty children (3.3%) with CAAP vs three control subjects (0.7%) underwent adenoidectomy (P < .001). PSG diagnosis of obstructive sleep apnea had been established previously in 79 patients (5%) with CAAP vs six (1.3%) of the control subjects (OR, 3.7 [95% CI, 1.6-10.0]; P < .001), with higher severity in patients with CAAP than in control subjects. CONCLUSIONS: SDB is common in children with CAAP and is possibly a predisposing risk factor for CAAP in children < 5 years old. We recommend considering SDB in young children who are given a diagnosis of CAAP.

Endobronchial echinococcosis presenting as non-resolving pneumonia.

Hydatid disease of the lungs is caused by larval cysts of the Echinococcus tapeworm. Pulmonary cysts may occasionally invade bronchi or pleura as a result of coughing, trauma, or elevated intra-abdominal pressure. We present the case of a patient evaluated for non-resolving pneumonia whose radiographic and bronchoscopic findings were strikingly similar to those seen in pulmonary tuberculosis with endobronchial invasion; he was ultimately diagnosed with pulmonary echinococcosis. This case underscores the importance of considering unusual diagnoses even when typical features of more common conditions are present.

B-type natriuretic peptide and cardiovascular function in young children with obstructive sleep apnea.

OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular strain, and C-reactive protein (CRP), a marker of inflammation, are reportedly elevated in school-aged children with obstructive sleep apnea (OSA). We hypothesized that cardiovascular morbidity affects circulating markers and their echocardiographic and polysomnographic (PSG) correlates in young children with OSA. METHODS: We assessed young children undergoing adenotonsillectomy (TA) for OSA by polysomnography, echocardiography, and serum CRP and NT-proBNP levels. RESULTS: A total of 90 children with OSA (mean age 19 +/- 7 months; 71.2% male; BMI, z = 0.62 +/- 1.04) and 45 age- and sex-matched controls were included. Three months following TA, 72 children were reassessed for NT-proBNP and CRP. NT-proBNP level (pg/mL) was higher in subjects with OSA (189.1 +/- 112.7) vs control subjects (104.8 +/- 49.5; P = .006). Both NT-proBNP (187.8 +/- 114 vs 86 +/- 32.6; P = .002) and CRP levels (mg %) (0.49 +/- 0.41 vs 0.1 +/- 0.17; P < .05) decreased following TA. Doppler pulse wave measuring tricuspid regurgitation (TR), a reflection of pulmonary hypertension, correlated with CRP (r = 0.61, P < .01) but not NT-proBNP (r = -0.14, P = .53) levels. Left ventricle end-diastolic diameter (LVEDD) was at the maximal normal range (0.91 +/- 0.11), but did not correlate with CRP or NT-proBNP levels. Both CRP level and TR correlated with PSG variables reflecting nocturnal hypoxemia, whereas NT-proBNP level and LVEDD did not. Echocardiography in 40 children (out of 90) showed a decline in TR that was abnormal before TA and correlated with the decrease in CRP following TA. CONCLUSIONS: NT-proBNP levels are increased in children with OSA and decrease following TA. Echocardiographic parameters suggesting increased pulmonary pressure in young children with OSA are related to nocturnal hypoxemia and systemic inflammation, which also decrease following therapy.

Physical activity attenuates intermittent hypoxia-induced spatial learning deficits and oxidative stress.

RATIONALE: Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying learning and memory in rats. Physical activity (PA) is now recognized as neuroprotective in models of neuronal injury and degeneration. OBJECTIVES: To examine whether PA will ameliorate IH-induced deficits. METHODS: Young adult Sprague-Dawley rats were randomly assigned to one of four treatment groups including normal activity (NA) or PA for 3 months and then subjected to either normoxia (RA) or exposure to IH during the light phase during the last 14 days. MEASUREMENTS AND MAIN RESULTS: Significant impairments in IH-exposed rats emerged on both latency and pathlength to locate the hidden platform in a water maze and decreased spatial bias during the probe trials. These impairments were not observed in PA-IH rats. In addition, the PA-IH group, relative to NA-IH, conferred greater resistance to both lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (DNA damage) in both the cortex and hippocampus. In support of a neuroprotective effect from PA, PA-IH versus NA-IH rats showed greater AKT activation and neuronal insulin growth factor-1 in these regions. CONCLUSIONS: Behavioral modifications such as increased physical activity are associated with decreased susceptibility to IH-induced spatial task deficits and lead to reduced oxidative stress, possibly through improved preservation of insulin growth factor-1-Akt neuronal signaling. Considering the many advantages of PA, interventional strategies targeting behavioral modifications leading to increased PA should be pursued in patients with sleep-disordered breathing.