Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood.

Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.

Vitamin D as a biomarker of health in snoring children: a familial aggregation study.

BACKGROUND: Hypovitaminosis D is a common health problem. The purpose of this study was to investigate the inter-relationship between serum 25(OH)D levels and paternal and maternal vitamin D status in a sample of snoring children. METHODS: We selected 137 participants for whom serum 25(OH)D had been measured and underwent overnight polysomnography evaluation. Serum glucose, lipids, liver enzymes, parathyroid hormone, insulin, and glycated hemoglobin were also measured. Glucose and insulin levels were used to estimate insulin resistance with the homeostasis model assessment (HOMA-IR). RESULTS: Vitamin D insufficiency (<30 ng/mL) and deficiency (<20 ng/mL) were found in 40.9 and 17.5% of children, respectively. After adjustments for age, BMI z-score and seasonality, the odds ratio for risk of vitamin D insufficiency according to the vitamin D status of parents were: OR (95% CI): paternal insufficiency 15.1 (2.7-35.7), p = 0.002; maternal insufficiency 7.2 (2.4-22), p = 0.001. When children with vitamin D deficiency were analyzed separately, serum 25(OH)D concentration was found to be associated with the apnea-hypopnea index (r = -0.647, p = 0.009) and respiratory arousal index (r = -0.669, p = 0.034). CONCLUSIONS: Family patterns of vitamin D could be helpful for the early identification of children at risk of metabolic and/or sleep disturbances and when considering strategies to improve vitamin D status. IMPACT: Family patterns of vitamin D could be helpful for the early identification of snoring children at risk of metabolic and/or sleep disturbances. Significant associations were found between serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and their parents. An inverse association between 25(OH)D levels and OSA severity was detected in deficient vitamin D children. Children with insufficient and deficient vitamin D status tended to have a worse metabolic profile, so strategies are needed to improve vitamin D status.

Surfactant protein D concentration in a pediatric population with suspected sleep disorder.

Obstructive sleep apnea (OSA) affects between 2% and 4% in children and there is a search for new biomarkers that can be useful both in the diagnosis and in the evolution of the disease. The surfactant protein D (SP-D) is a collection that is part of the innate immune system exerting an anti-inflammatory and antimicrobial effect. Thus, the objective of this study was to evaluate the concentration of SP-D in the suspect OSA pediatric population. A total of 178 children were recruited in this prospective study. Blood samples, sleep parameters, feeding habits, anthropometric, sociodemographic, and family data were collected. Specific biochemical determinations were made, and the plasmatic concentrations of SP-D were measured by enzyme-linked immunosorbent assay. We found no statistical correlation between the SP-D concentration and the apnea-hypopnea index (AHI) from the data. Nevertheless, the changes in SP-D levels could be correlated to a large extent by the arousals that often go along with hypopneas (r = -0.258, p = 0.011 unadjusted; r = -0.258, p = 0.014 adjusted by age and body mass inded [BMI] Z-score). Intermittent hypoxia was correlated with C-reactive protein levels (r = 0.547, p < 0.001 unadjusted; r = 0.542, p < 0.001 adjusted by age and BMI Z-score). Although AHI and SP-D did not appear to correlate, a secondary analysis suggests that sleep fragmentation, which is produced by arousals, may do, and further research is needed to determine the mechanisms by which changes in SP-D occur in OSA.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.

Utility of fiberoptic bronchoscopy for difficult airway in neonates.

BACKGROUND: Newborns diagnosed with craniofacial malformations or laryngeal and tracheal alterations may often need advanced airway-management for airway stabilization. Although fiberoptic bronchoscopy (FB) is currently the gold standard for difficult airway management, there is a scarcity of published data on the application of FB in newborns for intubation and controlled extubation (CE). OBJECTIVES: This study describes a case series where FB is used for intubation and/or extubation to manage newborns with difficult airway in either urgent procedures or scheduled ones. METHODS: All FB were carried out on newborns with difficult airway in the neonatal unit over the period January 2005 to December 2018. Patient characteristics were collected from clinical reports, description of the technique from the procedure report. RESULTS: 66 FBs were performed from a total of 40 newborns, a median age of 25 days and a weight of 3217 g. Eighteen were ex-premature babies (45%). Six (15%) had craniocervical malformations. 17 (25.7%) FBs were performed for tracheal intubation (TI), 6 in emergency situations, 34 (51.5%) for CE, and 15 (22.7%) for precise tube placement. Clearing of the airway was achieved in all cases and thus there were no failed TIs. In 32 cases (94.1%), CE was successfully performed. In 6 cases, withdrawal of the ET midprocedure was decided to postpone as 4 of these required extra treatment prior to renewed extubation attempt and 2 needed a tracheostomy. 2 patients required subsequent FB reintubation due to airway pathology. Complications during the procedure were mild desaturations (3%) and deep desaturations (7.5%). CONCLUSIONS: FB is very safe and highly useful when performing intubation in neonates with difficult airway but is essential during extubation to avoid any risk of failure with a potentially fatal outcome. Neonatal units of tertiary hospitals should provide equipment and training to manage these neonates. WHAT IS ALREADY KNOWN?: A failed intubation or extubation can lead to cardiac arrest and anoxic brain damage and/or to death in a neonate. Fiberoptic bronchoscopy is recommended as the safest tool for neonates with difficult airway. However, there is little concrete data published in the current literature to support the recommendations. WHAT IS NEW: Fiberoptic bronchoscopy is an essential tool to avoid the risk of a failed extubation in neonates with difficult airway.

Long-term outcomes of necrotizing pneumonia.

INTRODUCTION: Necrotizing pneumonia (NP) is a serious complication of community-acquired pneumonia characterised by the destruction of normal lung parenchyma. No study has evaluated the repercussions of the lung damage in the years following the episode. The aim of this study was to assess the long-term impact on lung function and respiratory symptoms in children hospitalised due to NP. METHODS: We analysed outcomes in children given a diagnosis of NP between January 2003 and April 2016. We selected patients aged more than 4 years capable of undergoing a lung function test, that had been followed up for at least 2 years. The patients completed a respiratory questionnaire and underwent a lung function test. RESULTS: We included a total of 24 patients (12 male). The median age at the time of diagnosis was 28 months, the median length of stay was 15 days, and 18 patients required pleural drainage. The mean duration of follow-up after NP was 8.75 years. During the evaluation, none of the patients exhibited asthma, cough, or exercise-induced symptoms. Three children had a second episode of pneumonia that did not require hospital admission. The spirometry results were the following (given as mean±standard deviation): FEV1 Z-score, -0.47±0.65; FVC Z-score, -0.56±0.73; and FEV1/FVC Z-score, 0.19±0.98. We found no evidence of obstructive pulmonary disease or restrictive patterns. CONCLUSIONS: The long-term outcomes of paediatric NP are good. However, patients exhibited mildly impaired lung function several years after the episode. We recommend follow-up of these patients due to potential impairments in lung function in adulthood.

Diagnosis and management of aspiration using fiberoptic endoscopic evaluation of swallowing in a Pediatric Pulmonology Unit.

BACKGROUND AND OBJECTIVES: Swallowing disorders lead to chronic lung aspiration. Early detection and treatment of aspiration in children with dysphagia are important to prevent lung damage. Diagnosis of aspiration, which may be silent, requires an instrumental study such as fiberoptic endoscopic evaluation of swallowing (FEES). Despite its usefulness, it is rarely practiced by pediatric pulmonologists. This study aimed to evaluate the feasibility and utility of FEES performed in the pediatric respiratory unit of a tertiary hospital, analyze the clinical characteristics, endoscopic findings and proposed treatments, and identify the factors associated with penetration or aspiration. METHODS: Medical records of 373 children with suspected aspiration who were referred to the pediatric respiratory unit for FEES were reviewed retrospectively. Clinical characteristics, FEES findings, and the proposed treatments were analyzed. RESULTS: Laryngeal penetration/aspiration was seen in 47.9% of the patients. The most common associated conditions were neurological disease and prematurity. The most frequently observed endoscopic finding was altered laryngeal sensitivity (36.5%). Intervention was recommended in 54.2% of the patients. Complications were not seen during any of the procedures. The multivariate logistic regression model revealed an independent association between aspiration and alterations in laryngeal sensitivity (odds ratio [OR], 5.68), pharyngeal pooling (OR, 11.47), and post-swallowing food residues (OR, 8.08). CONCLUSIONS: The FEES procedure performed by pediatric pulmonologists is a reliable method for diagnosing aspiration in children. It can be safely executed by trained pulmonologists, and significant endoscopic signs other than aspiration can guide in the diagnosis and management recommendations.

Polysomnographic Characteristics of Snoring Children: A Familial Study of Obstructive Sleep Apnea Syndrome.

BACKGROUND AND OBJECTIVES: Available evidence suggests a familial basis for OSA. The aim of the present study was to assess the potential influences of parental OSA in predicting the diagnosis and severity of OSA in snoring children. METHODS: Observational study, we prospectively enrolled 84 children and their parents. A complete nocturnal polysomnography was performed. Children were categorized into 3 severity groups according to the apnea-hypopnea index (AHI<1h-1, AHI≥1h-1 to AHI<5h-1, and AHI≥5h-1). Adults were grouped according two criteria (AHI≥5h-1 and ≥10h-1). RESULTS: There were no significant differences in age, gender, BMI and BMI z-score among groups. Among the children, 54.7% had an AHI≥1h-1 and 21.4% had an AHI≥5h-1. Overall, we observed that 60.7% of fathers and 23.8% of mothers of our population had OSA (AHI≥5h-1). The prevalence of fathers with OSA increases with the children's severity (83% in the group of children with moderate-severe OSA, p=0.035). The odds of having moderate-severe pediatric OSA (AHI≥5h-1) were more than 4 times higher among children with a father with AHI≥5h-1 (OR: 4.92, 95% CI: 1.27-19.06; p=0.021). There was no evidence of any maternal influence on OSA severity among the children studied. CONCLUSIONS: Our findings suggest a high prevalence of OSA among the family members studied with an increased association of childhood OSA with paternal OSA. Prediction of OSA risk among children can be significantly improved by adding data on paternal OSA status.

The Impact of the SARS-CoV-2 Pandemic on the Emergency Department and Management of the Pediatric Asthmatic Patient.

INTRODUCTION: Asthma exacerbation is among the commonest causes for pediatric emergency room visits, and respiratory viruses are frequent triggers of such exacerbations. Few studies have evaluated the consequences of the novel human coronavirus that causes the illness currently known as COVID-19, in the pediatric population. PURPOSE: The objective of this study was to analyze the impact of the COVID-19 pandemic and lockdown measures on the emergency department in the pediatric asthmatic patient. PATIENTS AND METHODS: This retrospective observational study evaluated pediatric patients treated at the Pediatric Emergency Service for wheezing episodes. Changes in the number and characteristics of these patients over the same period of 2019 as compared to 2020 during the month following the alarm declaration (March 14 to April 15) were evaluated. RESULTS: In total, data of 30 asthma patients managed in the period after the declaration of the coronavirus pandemic and of 158 asthma patients managed in the pre-COVID-19 period were included. In 2020, patient visits decreased by 82% in 2019. No statistically significant differences among age, sex, oxygen saturation, fever status, or number of severe bronchospasm episodes were found. Nebulized medication usage was reduced significantly since the alarm declaration. No significant increase in requests for complementary testing in the COVID-19 period was found. No patient requiring hospital admission was found to be PCR SARS-CoV-2 positive. Median time spent in the emergency department decreased from 180 minutes in 2019 to 85 minutes in the COVID-19 era. CONCLUSION: The COVID-19 pandemic and ensuing lockdown measures have led to an extraordinary reduction in emergency visits to the pediatric service. The ongoing pandemic has also led to improvements in the approach to asthma exacerbations and wheezing, to reduce the risk of exposure to the virus, such as increased use of pressurized metered dose inhaler and decreased time in the Emergency Department.

High flow nasal cannula versus standard low flow nasal oxygen during flexible bronchoscopy in children: A randomized controlled trial.

BACKGROUND: Hypoxemia is the most frequent complication of fiberoptic bronchoscopy (FB) in children. Guidelines recommend oxygen supplementation and conventional nasal prongs (NC) are used for this purpose. The aim of this study was to evaluate if the use of high-flow nasal cannula therapy (HFNC) in children undergoing FB result in a lower incidence of hypoxemia than standard oxygen administration. METHODS: Patients aged 1 month-16 years undergoing elective FB were included in a prospective randomized controlled, nonblinded, single-center clinical trial and randomly assigned to receive oxygen via NC or HFNC. Patients' baseline characteristics were recorded pre-bronchoscopy. The primary outcome was oxygen desaturation during the procedure defined as saturation less than 94%. RESULTS: An intention to treat analysis for 53 patients receiving NC and 51 receiving HFNC, showed HFNC patients were less likely to have hypoxemia than were NC patients (p = .011), with an absolute risk reduction of 0.27 (95% confidence interval [CI]: 0.08-0.45) and a number needed to treat of 3.75 (95% CI: 2.22-12.04). Moderate hypoxemia (SpO2 ≥ 90% and <94%, and <60 s) was observed significantly less often with HFNC than with NC (p = .012). Severe hypoxemia (SpO2 < 90% and >30 s) was not different between groups. Patients undergoing bronchoalveolar lavage (BAL) presented fewer desaturations with HFNC (p = .0003). CONCLUSIONS: HFNC offers optimized oxygenation during elective FB with a significant reduction in desaturations and can be considered for oxygen administration, especially when BAL is performed.

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy.

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy. Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea-hypopnea index (AHI) of ≥ 5 h-1. Plasma cytokines levels (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) were determined by multiple immunoassays. Results: We included 11 patients with OSA and 22 women with AHI < 5 h-1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1ß, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1ß (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1ß (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = -0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = -0.48). Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.

[Long-term outcomes of necrotizing pneumonia]. / Resultados a largo plazo de la neumonía necrotizante.

INTRODUCTION: Necrotizing pneumonia (NP) is a serious complication of community-acquired pneumonia characterised by the destruction of normal lung parenchyma. No study has evaluated the repercussions of the lung damage in the years following the episode. The aim of this study was to assess the long-term impact on lung function and respiratory symptoms in children hospitalised due to NP. METHODS: We analysed outcomes in children given a diagnosis of NP between January 2003 and April 2016. We selected patients aged more than 4 years capable of undergoing a lung function test, that had been followed up for at least 2 years. The patients completed a respiratory questionnaire and underwent a lung function test. RESULTS: We included a total of 24 patients (12 male). The median age at the time of diagnosis was 28 months, the median length of stay was 15 days, and 18 patients required pleural drainage. The mean duration of follow-up after NP was 8.75 years. During the evaluation, none of the patients exhibited asthma, cough, or exercise-induced symptoms. Three children had a second episode of pneumonia that did not require hospital admission. The spirometry results were the following (given as mean ± standard deviation): FEV1 z-score, -0.47±0.65; FVC z-score, -0.56±0.73; and FEV1/FVC z-score, 0.19±0.98. We found no evidence of obstructive pulmonary disease or restrictive patterns. CONCLUSIONS: The long-term outcomes of paediatric NP are good. However, patients exhibited mildly impaired lung function several years after the episode. We recommend follow-up of these patients due to potential impairments in lung function in adulthood.

Red cell distribution width: a new tool for the severity prediction of sleep apnoea syndrome in children.

INTRODUCTION: Red cell distribution width (RDW) is a parameter included in the complete blood count which informs about the size of the circulating red blood cell population and its distribution. In adults, an increase in RDW was shown to be associated both with obstructive sleep apnoea (OSA) and with an increase in cardiovascular mortality. The aim of this study was to determine whether RDW is a potential biomarker for screening children with moderate-severe OSA. METHODS: An observational study in snoring patients was performed. All patients underwent a sleep study and were classified either as simple snorers (apnoea-hypopnoea index (AHI) <1 event·h-1) or as patients with OSA (mild AHI ≥1 to <5 events·h-1; moderate-severe AHI ≥5 events·h-1). Blood analyses (complete blood count and C-reactive protein) were performed for every individual. RESULTS: A total of 175 individuals were recruited. The mean age was 8.3±3.6 years. Correlation studies between RDW and several sleep-related parameters showed negative significant associations with minimum oxygen saturation, and positive significant associations with oxygen desaturation index (≥3% and ≥4%), AHI and the arousal index. A predictive model for paediatric severe OSA (AHI ≥5 events·h-1) was found based on mean corpuscular haemoglobin concentration (MCHC) <34.9 g·dL-1 and RDW >13.1% values, adjusting for body mass index z-score and age (area under the curve 0.657; p=0.004). In addition, differences were found in eosinophil count and C-reactive protein concentrations among the three subgroups. CONCLUSIONS: In children, RDW stands out as a biomarker associated with the severity of OSA. The use of RDW and MCHC could be a simple but useful tool for the severity prediction of paediatric OSA in snoring patients.

Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children.

Recurrent respiratory papillomatosis can be a devastating condition for a child, with severe consequences. Currently, there is no proven successful medical treatment. We describe the use of systemic bevacizumab to treat two children affected by aggressive recurrent respiratory papillomatosis. Respiratory symptoms and quality of life improved dramatically in both patients, without observing any toxicity. The only complication was mild proteinuria. Systemic bevacizumab is a promising adjuvant treatment in aggressive recurrent respiratory papillomatosis in children. It is effective and well tolerated. Further studies are needed to establish the optimal dosing frequency and duration of therapy. Laryngoscope, 129:1001-1004, 2019.

Prothrombotic state in children with obstructive sleep apnea.

OBJECTIVE: Increased blood coagulation might be one important mechanism linking obstructive sleep apnea (OSA) with cardiovascular diseases. We tested the association between several hemostatic parameters and sleep breathing-related variables in a representative pediatric population with a clinical suspicion of OSA. METHODS: Polysomnography was performed in 152 snoring children to diagnose OSA. Anthropometric and clinical data were registered and venous blood samples were collected for the measurement of platelet count, plateletcrit, platelet distribution width (PDW), mean platelet volume (MPV), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and C-reactive protein. RESULTS: Children with OSA had significantly higher platelet count, plateletcrit and PDW compared with those without OSA. After controlling for the anthropometric characteristics (age, gender, body mass index (BMI) z-score), platelet count negatively correlated with minimum SaO2 while the plateletcrit correlated with time with SaO2 <90% and MPV correlated with apnea-hypopnea index. PT and PT international normalized ratio correlated with mean SaO2 and aPTT correlated with the oxygen desaturation index. CONCLUSION: Our findings suggest that different OSA-related effects may be factors contributing to an enhanced coagulability in pediatric OSA. Measures reflecting apnea severity and disrupted sleep were associated with clotting factor changes independent of covariates affecting hemostatic function.