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Background: Obstructive sleep apnea syndrome (OSAS) is a chronic syndrome, affecting about 1%-5% of children. OSAS is characterized by increased resistance and collapse of the upper airways, with different degrees of severity requiring interventions ranging from lifestyle modifications to surgery. Sympathetic activity is increased in OSAS, and the reduction of disease symptoms, occurring after adenotonsillectomy, correlates with biomarkers indicating a reduced sympathetic response. The aim of this study is to explore the potential role of single nucleotide polymorphisms (SNPs) in the gene encoding β2-adrenergic receptors (ADRB2) as a biomarker for the early identification of pediatric OSAS patients at high risk of developing severe symptoms., Materials and Methods: In this exploratory genetic study, the frequencies of functional SNPs in ADRB2 within a cohort of pediatric patients were evaluated by using reverse transcription-polymerase chain reaction with TaqMan probes. The severity of OSAS was assayed by the apnea-hypopnea index (AHI)., Results: The rs1042713 SNP (GG genotype) in ADRB2 was more frequent in patients with severe OSAS compared to patients with mild/moderate OSAS., Conclusions: The availability of genetic biomarkers for the early identification of patients at high risk of severe OSAS will help clinicians start personalized treatments, thus reducing morbidity associated with OSAS., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Insubria Ethics Committee issued approval 14/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ferrari et al.)

Background/objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts normal breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, patient age at the time of PSG, and PSG outcomes in children., Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records regarding the patients' age at the time of a referral for PSG and their age at the time of its execution. Information on the waiting times for PSG, a diagnosis (primary snoring, mild, moderate, and severe OSA), and a history of snoring and apnoea were also collected. Additional data included medications, surgical interventions, passive smoke exposure, and allergies. The records also included the Paediatric Sleep Questionnaire (PSQ)., Results: The patient age at the time of a PSG prescription was lower for patients with a short history of sleep apnoeas (≤12 months; 4.6 (SD 2.6) years) compared to those with a long history (>12 months; 5.5 (SD 2.7) years; p = 0.027). The waiting time from prescription to PSG execution was shorter for patients with a short history of sleep apnoea (4.1 (SD 3.8) months) compared to those with a longer history (5.9 (SD 3.8) months; p = 0.001). A higher frequency of having an adenotonsillectomies before a PSG prescription was observed in the long-history group compared to the short-history group (13.3% vs. 6.9%). Conversely, a higher frequency of adenoidectomies before a PSG prescription was noted in the short-history group compared to the long-history group (9.7% vs. 1.3%)., Conclusions: This study found that younger children with a shorter history of OSA are diagnosed and evaluated earlier than older children with a longer history of the condition, suggesting that prolonged symptoms may delay a diagnosis. ENT surgeries also vary among patients, with less invasive procedures (adenoidectomy) being more common in younger children with shorter histories of OSA. The increasing awareness of OSA highlights the need for improved access to diagnostic and treatment resources.

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20-40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Background: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying., Methods: We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis., Results: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH ( p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) ( p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH ( p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH., Conclusions: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

(1) Background: Sleep-disordered breathing represents a growing public health concern, especially among children and adolescents. The main risk factors for pediatric sleep-disordered breathing in school-age children are tonsillar and adenoid hypertrophy. Adenoidectomy, often in combination with tonsillectomy, is the primary treatment modality for pediatric sleep-disordered breathing. This study aims to comprehensively investigate various risk and protective factors in children with sleep-disordered breathing undergoing adenotonsillar or adenoidal surgeries. We also aim to explore the differences in neuropsychological profiles. (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy in children referred to our center. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. The Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) screen sleep-disordered breathing and quality of life, respectively. The data were statistically analyzed using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL, USA). (3) Results: The study involved 138 patients, but only 100 children participated. A higher percentage of patients with sleep-disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep-disordered breathing habitually used a pacifier. A rise in physical score was associated with a reduced PSQ at follow-up ( p = 0.051). An increase in the overall academic score was related to a decrease in the PSQ at follow-up ( p < 0.001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth. (4) This comprehensive study delves into the intricate interplay of risk and protective factors impacting children with sleep-disordered breathing undergoing adenotonsillectomy and adenoidectomy.

Background: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically <1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children. This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUEs before the COVID-19 pandemic and after the spread of SARS-CoV-2., Methods: We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUEs., Results: The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2 this number was 268 (59%). The risk of infection at birth for children developing BRUEs was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUEs during the pandemic (coefficient B = 0.783; p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = -0.465, p = 0.046)., Conclusions: These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

Background: Obstructive Sleep Apnea Syndrome (OSAS) affects approximately 1-5% of children and is linked to cardiovascular, metabolic, and neurobehavioral complications. Dysregulation of inflammatory process and sympathetic nervous system overstimulation leading to increased catecholamine production may contribute to OSAS pathogenesis. Polymorphonuclear Neutrophils (PMN), key cells in the inflammatory process, express adrenergic receptors, including β2-adrenergic receptor (ADRB2), which modulate their functions through an autocrine/paracrine loop. In this pilot study, we aimed to investigate the relationship between OSAS severity, ADRB2 expression in PMN and patient's inflammatory profile before and after adenotonsillectomy., Patients/methods: In this pilot study we enrolled OSAS pediatric patients in which ADRB2, IL-6 and IL-8 mRNA expression levels were evaluated in circulating PMN by RT-PCR., Results: 9 OSAS pediatric patients, ranged from 3 to 8 years of age, were enrolled in the study. We found that adenotonsillectomy significantly reduced ADRB2 as well as IL-6, IL-8 mRNA expression levels in PMN., Conclusions: These findings offer valuable insights into the underlying immune and inflammatory mechanisms of OSAS and open the way for the development of novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obstructive sleep apnea (OSA) affects neurobehavioral, cognitive, and cardiovascular aspects, particularly in children, by obstructing the upper airways during sleep. While its impact in adult ocular health is recognized, there is ongoing debate about OSA's relevance in pediatrics. This review explores the relationship between OSA and ocular health in children, focusing on the effects and potential improvements through treatment. A systematic search found 287 articles through PubMeD/MEDLINE, Scopus, Web of Science, and ScienceDirect; 94.4% were excluded. After careful selection, six English articles were included, addressing the effects of OSA on children's eyes. Three studies examined choroidal alterations, three explored retinal and optic nerve changes, and two analyzed ocular changes following otorhinolaryngological intervention. The immediate correlation in children is inconclusive, but age may be a contributing factor. Pediatric OSA patients exhibit corneal anomalies and increased optic nerve thickness, possibly due to intermittent hypoxia. OSA influences retinal vascular density in children, with increased density after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. This review emphasized OSA's significant impact on children's ocular health, revealing alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve is not always evident, OSA raises intraocular pressure and induces structural changes. Treatment holds promise, highlighting the need for regular monitoring to promptly address childhood OSA.

Sleep-disordered breathing is a significant problem affecting the pediatric population. These conditions can affect sleep quality and children's overall health and well-being. Difficulties in social interaction, communication, and repetitive behavioral patterns characterize autism spectrum disorder. Sleep disturbances are common in children with ASD. This literature review aims to gather and analyze available studies on the relationship between SDB and children with autism spectrum disorder. We comprehensively searched the literature using major search engines (PubMed, Scopus, and Web of Science). After removing duplicates, we extracted a total of 96 records. We selected 19 studies for inclusion after a thorough title and abstract screening process. Seven articles were ultimately incorporated into this analysis. The research findings presented herein emphasize the substantial influence of sleep-disordered breathing on pediatric individuals diagnosed with autism spectrum disorder (ASD). These findings reveal a high incidence of SDB in children with ASD, emphasizing the importance of early diagnosis and specialized treatment. Obesity in this population further complicates matters, requiring focused weight management strategies. Surgical interventions, such as adenotonsillectomy, have shown promise in improving behavioral issues in children with ASD affected by OSA, regardless of their obesity status. However, more comprehensive studies are necessary to investigate the benefits of A&T treatment, specifically in children with ASD and OSA. The complex relationship between ASD, SDB, and other factors, such as joint hypermobility and muscle hypotonia, suggests a need for multidisciplinary treatment approaches. Physiotherapy can play a critical role in addressing these intricate health issues. Early sleep assessments and tailored weight management strategies are essential for timely diagnosis and intervention in children with ASD. Policy initiatives should support these efforts to enhance the overall well-being of this population. Further research is crucial to understand the complex causes of sleep disturbances in children with ASD and to develop effective interventions considering the multifaceted nature of these conditions.

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the "gracilization theory" and the "gravitational hypothesis" have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals' well-being and quality of life.

Background: An apparent life-threatening event (ALTE) describes an acute, unexpected change in an infant's breathing, aspect, or behavior frightening to the parent or caretaker. According to the new recent terminology, clinicians should use the term brief resolved unexplained event (BRUE) to describe an event occurring in an infant <1 year of age when the observer reports a sudden, brief, and now resolved episode. The aims of the present study in infants were to investigate sleep disturbances in both ALTE event and after their classification according the new BRUE criteria., Methods: We enrolled (from April to May 2016) 32 consecutive infants referred to our ambulatory for sleep disorders for follow-up after an ALTE episode and 32 pair healthy controls. We administered to parents the adapted questionnaire "Sleep Disturbance Scale for Children - SDSC.", Results: Among enrolled infants with ALTE, there were 26 infants in line with the new BRUE definition, of which 10 at low risk and 16 at the high-risk event., Conclusions: Infants with ALTE and BRUE had more referred-by-parents' sleep symptoms than controls. In particular, sleep disordered breathing wa prevalent in both, requiring a longer follow-up for this disturbance.

Background: Obstructive sleep apnea can have a negative impact on children's and adolescents' neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored., Methods: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject's parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings., Results: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up., Conclusions: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status.