Prevalence, Severity, and Treatment of Obstructive Sleep Apnea in Children with Down Syndrome in Qatar.

INTRODUCTION: Patients with Down syndrome (DS) are at risk for sleep disorder breathing (SDB) due to their abnormal craniofacial anatomy, hypotonia, and propensity for obesity. The prevalence and severity of SDB in this population vary between different cohorts due to the multifactorial nature of these patients and the different diagnostic criteria used. We aim to report the prevalence and severity of SDB in the DS population in Qatar. METHODS: This study is a retrospective review of all patients with genetically confirmed DS who completed a diagnostic polysomnography (PSG) study at Sidra Medicine in Doha, Qatar, which is the only pediatric sleep center in the country, between September 2019 and July 2022. Clinical and PSG data were collected from the patients' electronic medical records. Central and obstructive events were scored according to the American Academy of Sleep Medicine (AASM) criteria. Obstructive sleep apnea (OSA) diagnosis was made based on apnea-hypopnea index (AHI) and defined as AHI >1.5 events/hour. OSA was considered mild if AHI was ≥ 1.5 but < 5, moderate if AHI was ≥ 5 but < 10, and severe if AHI was ≥ 10 events/hour. Diagnosis with central apnea was considered if the central apnea index was > 5 events/hour. Hypoventilation was considered present if end-tidal/transcutaneous carbon dioxide gas was more than 50 mmHg for more than 25% of total sleep time. Multiple regression analysis was performed to evaluate predictors of high AHI and rapid eye movement (REM)-AHI. RESULTS: A total of 80 patients (49 males and 31 females) were included. Median (range) age was 7.3 years (0.9, 21). The mean (range) BMI z-score was 1.7 (-1.3, 4.3). Sixty-five patients were diagnosed with OSA, with a prevalence rate of 81%. OSA was mild in 25 (38.5%) patients, moderate in 15 (23.1%) patients, and severe in 25 (38.5%) patients. Only one patient was diagnosed with central apnea and five patients (6.9%) with alveolar hypoventilation. Multiple regression analysis showed BMI (P = 0.007) and snoring/apnea symptoms (P=0.023) to be predictive of high AHI. No correlation was found between the same variables and REM-AHI. Treatments used for OSA included anti-inflammatory medications in 37 (46%) patients, tonsillectomy/adenoidectomy in 13 (16.5%) patients, and positive airway pressure support in 10 (15%) patients. CONCLUSION: Our patient population with DS had a high prevalence of OSA comparable to other reported cohorts. High BMI and symptoms of snoring are predictive of OSA.

Sleep Respiratory Disorders in Children and Adolescents with Cystic Fibrosis and Primary Ciliary Dyskinesia.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.

Mouth puffing phenomena of patients with obstructive sleep apnea when mouth-taped: device's efficacy confirmed with physical video observation.

PURPOSE: This study aimed to design a device to monitor mouth puffing phenomena of patients with obstructive sleep apnea when mouth-taped and to employ video recording and computing algorithms to double-check and verify the efficacy of the device. METHODS: A mouth puffing detector (MPD) was developed, and a video camera was set to record the patients' mouth puffing phenomena in order to make ensure the data obtained from the device was appropriate and valid. Ten patients were recruited and had polysomnography. A program written in Python was used to investigate the efficacy of the program's algorithms and the relationship between variables in polysomnography (sleep stage, apnea-hypopnea index or AHI, oxygen-related variables) and mouth puffing signals (MPSs). The video recording was used to validate the program. Bland-Altman plot, correlations, independent sample t-test, and ANOVA were analyzed by SPSS 24.0. RESULTS: Patients were found to mouth puff when they sleep with their mouths taped. An MPD was able to detect the signals of mouth puffing. Mouth puffing signals were noted and categorized into four types of MPSs by our algorithms. MPSs were found to be significantly related to relative OSA indices. When all participants' data were divided into minutes, intermittent mouth puffing (IMP) was found to be significantly different from non-mouth puffing in AHI, oxygen desaturation index (ODI), and time of oxygen saturation under 90% (T90) (AHI: 0.75 vs. 0.31; ODI: 0.75 vs. 0.30; T90: 5.52 vs. 1.25; p < 0.001). Participants with severe OSA showed a higher IMP percentage compared to participants with mild to moderate OSA and the control group (severe: 38%, mild-to-moderate: 65%, control: 95%; p < 0.001). CONCLUSIONS: This study established a simple way to detect mouth puffing phenomena when patients were mouth-taped during sleep, and the signals were classified into four types of MPSs. We propose that MPSs obtained from patients wearing the MPD can be used as a complement for clinicians to evaluate OSA.

Impact of sleep-disordered breathing on ventricular tachyarrhythmias after left ventricular assist device implantation.

Sleep-disordered breathing (SDB) is associated with an increased risk of adverse events in patients with heart failure (HF); however, its impact in patients implanted with a left ventricular assist device (LVAD) remains unclear. We aimed to investigate the prevalence of SDB in patients with LVAD and its impact on their clinical outcomes. Fifty consecutive patients with LVAD who underwent portable sleep monitoring between September 2017 and April 2018 were prospectively enrolled, and they were followed up for 170 ± 36 days. According to their respiratory disturbance indexes (RDIs), they were categorized into the SDB group (RDI ≥ 15, n = 12) and the non-SDB group (RDI < 15, n = 38). The incidence of adverse events during the follow-up period was investigated after enrollment. Multivariate logistic regression analysis revealed significant differences in SDB in LVAD-implanted patients in terms of the logarithmic transformation brain natriuretic peptide (BNP) values (p = 0.005). The optimal BNP cut-off value for SDB prediction in LVAD-implanted patients was 300 pg/mL (sensitivity: 58.3%, specificity: 94.7%). During follow-up, ventricular tachyarrhythmias (VTas) occurred significantly more frequently in the SDB group (4 [33%] vs. 2 [5%] patients, p = 0.02); Atrial tachyarrhythmia (ATa) also tended to occur more frequently in the SDB group (2 [25%] vs. 2 [2%] patients, p = 0.07). SBD was prevalent in 24% of the LVAD-implanted patients with advanced HF. Furthermore, SDB was significantly associated with high BNP levels and was also potentially associated with subsequent incidence of VTa in patients with LVAD.

Undiagnosed sleep disorder breathing as a risk factor for critical COVID-19 and pulmonary consequences at the midterm follow-up.

INTRODUCTION: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB). OBJECTIVES: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis. METHODS: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed. RESULTS: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT. CONCLUSION: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm. STUDY REGISTER: ISRCTN16865246.

Outcomes of adenoidectomy with and without tonsillectomy in patients younger than 2 years with moderate to severe upper airway obstruction.

OBJECTIVES: The effectiveness of adenotonsillectomy for obstructive sleep disorder breathing (OSDB) in children under age 2 years is unclear. The present study aimed to identify the perioperative symptoms and clinical outcomes of adenoidectomy and tonsillectomy in very young children. PATIENTS AND METHODS: The present, single-center, retrospective cohort study, conducted from January 2010 to April 2020, enrolled patients under age 2 years with moderate to severe upper airway obstruction who underwent an adenoidectomy or tonsillectomy. The patients were divided according to The Brodsky grading scale into group 1 (Grade 0 to 1 tonsils) or group 2 (Grade 2 or higher tonsils), who received only an adenoidectomy. Group 3 comprised patients with a concomitant adenoidectomy and tonsillectomy. Perioperative symptoms among the groups and the cumulative revision-free status and recurrence-free status rates in groups 1 and 2 were analyzed. RESULTS: Fifty-three patients were enrolled. The median standard deviation score (SDS) for height and weight was -0.79 and -0.31, respectively. No postoperative complications, such as bleeding, were observed. However, two patients underwent intubation preoperatively due to severe obstruction. Seven patients underwent revision surgery. The cumulative revision-free and recurrence-free rates at week 60 were 81% and 100% for Group 1 and 42% and 48.5% for Group 2, respectively. The cumulative revision-free rate and cumulative recurrence-free rate were significantly higher in Group 1 (P < 0.0001; HR: 47.9; 95% CI: 1.12-2050 and P < 0.007; HR: 4.62; 95% CI: 1.37-15.6, respectively). None of the patients in Group 3 had revision surgery or symptom recurrence. CONCLUSION: Simple adenoidectomy in children with large tonsils carries a high risk of revision surgery. However, given the high risk of severe obstruction in very young children with OSDB, timely surgery is recommended. LEVEL OF EVIDENCE: 3.

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature.

BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA. OBJECTIVE: To examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity. DATA SOURCES: A systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case-control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep. STUDY ELIGIBILITY CRITERIA: The inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added - English articles published in the last 15 years. Studies that were not included were reviews and case reports. STUDY APPRAISAL AND SYNTHESIS METHODS: In order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list. RESULTS: The search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT) - variable number of tandem repeats (VNTR) and linked polymorphic region (LPR) - are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long (L/L) allele genotype were associated with a higher prevalence of OSA and the L allele with a higher apnea-hypopnea index and a longer time during sleep with oxygen desaturation. LIMITATIONS: The main limitation of the present study consists of heterogeneity of the information. Being a less studied subject, randomized trials are not widely available and most data were obtained from case-control trials. Moreover, the included material indirectly approached the subject by demonstrating the effects of serotoninergic system over the metabolism, the connection between serotonin and obesity, factors which are implied in the pathogenesis of OSA. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: The two polymorphisms of serotonin gene can be considered important factors in the diagnosis and management of OSA.

Characterization of cyclic alternating pattern during sleep in older men and women using large population studies.

STUDY OBJECTIVES: To assess the microstructural architecture of non-rapid eye movement (NREM) sleep known as cyclic alternating pattern (CAP) in relation to the age, gender, self-reported sleep quality, and the degree of sleep disruption in large community-based cohort studies of older people. METHODS: We applied a high-performance automated CAP detection system to characterize CAP in 2,811 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 426 women from the Study of Osteoporotic Fractures (SOF). CAP was assessed with respect to age and gender and correlated to obstructive apnea-hypopnea index, arousal index (AI-NREM), and periodic limb movements in sleep index. Further, we evaluated CAP across levels of self-reported sleep quality measures using analysis of covariance. RESULTS: Age was significantly associated with the number of CAP sequences during NREM sleep (MrOS: p = 0.013, SOF = 0.051). CAP correlated significantly with AI-NREM (MrOS: ρ = 0.30, SOF: ρ = 0.29). CAP rate, especially the A2+A3 index, was inversely related to self-reported quality of sleep, independent of age and sleep disturbance measures. Women experienced significantly fewer A1-phases compared to men, in particular, in slow-wave sleep (N3). CONCLUSIONS: We demonstrate that automated CAP analysis of large-scale databases can lead to new findings on CAP and its subcomponents. We show that sleep disturbance indices are associated with the CAP rate. Further, the CAP rate is significantly linked to subjectively reported sleep quality, independent from traditionally scored markers of sleep fragmentation. Finally, men and women show differences in the microarchitecture of sleep as identified by CAP, despite similar macro-architecture.

Preschoolers with recurrent wheezing have a high prevalence of sleep disordered breathing.

Objective: Sleep-disordered breathing (SDB) is highly prevalent in school children with poorly-controlled asthma. However, this association has not been assessed in preschoolers with recurrent wheeze, nor in those at risk for asthma. We hypothesized that preschoolers with asthma risk (positive asthma predictive index [API]) have a higher prevalence of SDB and higher inflammatory biomarkers (blood-hsCRP and urinary-LTE4) levels than those with negative API.Method: Children 2 to 5 years of age with recurrent wheezing were classified as positive or negative API. SDB was determined by the pediatric sleep questionnaire (PSQ) and its subscale (PSQSub6). Demographic characteristics, spirometry, blood hsCRP and urinary LTE4 were assessed.Results: We enrolled 101 preschoolers: 70 completed all measurements, 55.4% were males, mean age 4.07 ± 0.87 years, 45% overweight or obese, 70% had positive API, 87.5% had rhinitis. The prevalence of SDB measured by PSQ was 40.8% and by PSQSub6 was 29.6%. However, the proportion of SDB was similar between positive and negative API groups. The hsCRP (mean ± SD) was higher in the positive than in negative API (3.58 ± 0.58 and 1.32 ± 0.36 mg/L, p = 0.69, respectively); moreover, no differences in urinary LTE4 were found between groups. No correlation of PSQ (+) or PSQSub6 (+) with hsCRP and uLTE4 was found. However, preschoolers with positive API had significantly more post-bronchodilator percentage change in FEF25-75 than negative API (24.14 ± 28.1 vs. 4.13 ± 21.8, respectively, p = 0.01).Conclusions: In preschoolers with recurrent wheezing, we should be investigating for the coexistence of SDB, using early screening methods for detecting those conditions.

Efficacy and tolerability of a custom-made Narval mandibular repositioning device for the treatment of obstructive sleep apnea: ORCADES study 2-year follow-up data.

OBJECTIVE/BACKGROUND: Mandibular repositioning device (MRD) therapy is an alternative to continuous positive airway pressure (CPAP). The Orkney Complex Disease Study-ORCADES study is assessing the long-term efficacy and tolerability of MRD therapy in obstructive sleep apnoea syndrome (OSAS); two-year follow-up data are presented. PATIENTS/METHODS: OSAS patients who refused or were noncompliant with CPAP were fitted with a custom-made computer-aided design/computer-aided manufacturing (CAD/CAM) bi-block MRD (ResMed, Narval CC™); mandibular advancement was individually titrated. Sleep and respiratory parameters were determined at baseline, 3-6 months, and two years. The primary endpoint was treatment success (percentage of patients achieving a ≥50% reduction in the apnoea-hypopnoea index [AHI]). RESULTS: Of 315 enrolled patients, 237 remained on MRD treatment at two years, and 197 had follow-up data. The treatment success rate at two years was 67%; AHI <5/h, <10/h and <15/h was achieved in 30%, 56% and 72% of patients, respectively. On multivariate analysis, ≥50% decrease in AHI at 3-6 months and absence of nocturia at 3-6 months were significant predictors of MRD treatment continuation. Adverse events were generally mild, and the majority occurred in the first year of treatment. CONCLUSIONS: Two years' treatment with an MRD was effective and well tolerated in patients with mild to severe OSAS who refused or were intolerant of CPAP.

Central Sleep Apnoea and Arrhythmogenesis After Myocardial Infarction-The CESAAR Study.

The prevalence of sleep disordered breathing (SDB) after acute myocardial infarction (AMI) is high. However, little is known about predominant SDB type and the impact of SDB severity on arrhythmogenesis. We conducted a prospective single-center observational study and performed an unattended sleep study and Holter monitoring within 10 days after AMI, and an unattended sleep study 11.3 months after AMI. All patients were included from the Department of Cardiology at the University Hospital Schleswig-Holstein, Lübeck, Germany. A total of 202 subjects with AMI (73.8% with ST-elevation; 59.8 years; 73.8% male) were included. The mean BMI was 27.8 kg/m2 and the mean neck/waist circumference was 41.7/103.3 cm. The mean left ventricular ejection fraction was 56.6%. The SDB prevalence defined as apnoea-hypopnea-index (AHI) ≥ 5/h was 66.7% with 44.9% having central (CSA), and 21.8% obstructive sleep apnoea (OSA). The mean AHI was 13.8 1/h. In 10.2% nsVT was detected in the Holter monitoring. AI >23/h was independently associated with higher risk of nsVT in the subacute AMI period. SDB is highly prevalent and CSA a predominant type of SDB in the subacute phase after uncomplicated AMI treated with modern revascularization procedures and evidence-based pharmacological therapy. Severe SDB is independently associated with higher risk for nsVT in the subacute AMI period and its course should be monitored as it can potentially have a negative impact on relevant outcomes of AMI patients. Further prospective studies are needed to assess long-term follow up of SDB after AMI and its impact on mortality and morbidity.

Leucotrienos urinarios en pacientes pediátricos con trastorno respiratorio del sueño secundario a hiperplasia adenoamigdalina / Urinary leukotrienes in pediatric patients with sleep disordered breathing secondary to adenotonsillar hypertrophy

RESUMEN Introducción: El trastorno respiratorio del sueño (TRS) afecta al 2% a 3% de la población pediátrica, siendo la hiperplasia adenoamigdalina (HAA) su principal causa. Se ha observado un aumento en los niveles de leucotrienos excretados en orina (LTU) en estos pacientes, los cuales se correlacionarían con la severidad de la enfermedad. Objetivo: Determinar el nivel de LTU en niños con TRS e HAA antes y después de adenoamigdalectomía (AA), y en controles sanos. Correlacionar los niveles de LTU con los síntomas de TRS. Material y método: Estudio prospectivo. Se incluyeron pacientes con TRS e HAA (n =12) y controles sanos (n =12). Se determinó la concentración de LTU en ambos grupos de forma basal y un mes después de cirugía en el grupo con TRS. Resultados: No hubo diferencias en los niveles de LTU antes y después de AA. Tampoco existieron diferencias entre el grupo control y grupo TRS previo a la cirugía. No se encontró asociación entre LTU y la severidad de síntomas respiratorios. Conclusión: Los LTU no se encuentran elevados en pacientes con TRS e HAA, no disminuyen luego de AA y no se correlacionan con la severidad de los síntomas. La medición de LTU no sería una herramienta útil en la evaluación de pacientes con TRS. Nuevos estudios son necesarios para evaluar el rol de los leucotrienos en esta enfermedad.

ABSTRACT Introduction: Sleep disorder breathing (SDB) affects 2%-3% of the pediatric population, being adenotonsillar hyperplasia (ATH) its main cause. An increase in the levels of urinary leukotrienes (ULT) has been measured in these patients, which could be correlated with the severity of the disease. Aim: To determine the level of ULT in children with SDB and ATH before and after adenotonsillectomy, and healthy controls. To correlate the levels of ULT with symptoms of SDB. Material and method: prospective study. SDB and ATH patients (n =12) and healthy controls (n =12) were included. The concentration of ULT in both groups was determined, before surgery and after a month of surgery. Results: There were no differences in the levels of ULT before and after tonsillectomy in the studied group. There were also no differences between the control group and the SDB group. No association was observed between the level of ULT and the severity of respiratory symptoms. Conclusions: ULT are not elevated in patients with SDB and ATH and they do not decrease after adenotonsillectomy. ULT are not correlated with the severity of the symptoms of SDB. The measurement of ULT would not be a useful tool in the evaluation of patients with SDB. New studies are needed to assess the role of the role of leukotrienes in this disease.

Anesthesia in a pediatric patient with ROHADD syndrome. / Anestesia en paciente pediátrico con síndrome de Rohhad.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare entity that is characterised by its onset in healthy children at 2-4 years of age. It is a complex syndrome that includes, among other symptoms, rapid weight gain with hyperphagia, hypothalamic dysfunction, central hypoventilation, and autonomic dysregulation. The case is presented of a 10-year-old boy with a diagnosis of ROHHAD syndrome undergoing insertion of a port-a-cath under general anaesthesia, who developed complications during the anaesthetic procedure related to his illness. The peri-operative management of these patients represents a challenge for the anaesthetist, given the involvement of multiple systems and the frequent respiratory comorbidities associated with them. A summary is presented of some of the implications and anaesthetic considerations that must be taken into account in the management of these patients.

Sleep apnea and pesticide exposure in a study of US farmers.

INTRODUCTION: Carbamate and organophosphate pesticides inhibit acetylcholinesterase, and poisoning leads to respiratory depression. Thus, involvement in sleep apnea is plausible, but no data exist at lower levels of exposure. Other pesticides could impact sleep apnea by different mechanisms but have not been studied. Our study examines the associations between pesticide exposure and sleep apnea among pesticide applicators from a US farming population. PARTICIPANTS AND METHODS: We analyzed data from 1569 male pesticide applicators, mostly farmers, from an asthma case-control study nested within the prospective Agricultural Health Study. On questionnaires, participants reported use of specific pesticides and physician diagnosis plus prescribed treatments for sleep apnea. We used multivariable logistic regression to estimate associations between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases). RESULTS: The most notable association was for carbofuran, a carbamate (100 exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P=.0002). Carbofuran use began before reported onset of sleep apnea in all cases. DISCUSSION: This study adds to the known adverse health outcomes of exposure to carbofuran, a pesticide canceled in the United States in 2009 for most agricultural purposes but persists in the environment and remains in use in some other countries. CONCLUSIONS: We conducted the first epidemiological study investigating the association of pesticide exposure and sleep apnea. Our results in a male agricultural population suggests that exposure to carbofuran is positively associated with sleep apnea.

Glycated hemoglobin and sleep apnea syndrome in children: beyond the apnea-hypopnea index.

PURPOSE: Snoring and obstructive sleep apnea syndrome (OSA) are frequent conditions in pediatrics. Glycated hemoglobin (HbA1C) is a useful homeostatic biomarker of glycemia and may reflect alterations deriving from sleep breathing disorders. The aim of this study was to relate the severity of OSA with blood HbA1C levels in children. METHODS: A descriptive observational study in snoring patients was performed. All patients underwent a sleep study and classified either as simple snorers (apnea-hypopnea index; AHI ≤ 1 episodies/h) or as OSA patients (AHI > 1 episodes/h). In the following morning, a blood glycemic profile (fasting glucose, insulin, HbA1C, and the HOMA index) was performed to every individual. RESULTS: A total of 48 patients were included. HbA1C levels were shown to be increased in the moderate OSA (AHI > 5 episodes/h) group (5.05 ± 0.25 vs. 5.24 ± 0.29%; p = 0.019). Significant correlations were found between HbA1C values and AHI (r = 0.345; p = 0.016) and also with oxygen desaturation index (r = 0.40; p = 0.005). Correlations remained significant after adjusting by age and body mass index. The AHI-associated change in HbA1C was 13.4% (p = 0.011). CONCLUSIONS: In the pediatric population, HbA1C is a biomarker associated with OSA severity, and this relationship is age- and obesity-independent. The fact that this association was observed in snoring patients could help the physician in the distinction between those patients affected with OSA and those with simple snoring. Therefore, HbA1C measurement could play a major role in the diagnosis and the management of the syndrome.

Characterization of the microvascular cerebral blood flow response to obstructive apneic events during night sleep.

Obstructive apnea causes periodic changes in cerebral and systemic hemodynamics, which may contribute to the increased risk of cerebrovascular disease of patients with obstructive sleep apnea (OSA) syndrome. The improved understanding of the consequences of an apneic event on the brain perfusion may improve our knowledge of these consequences and then allow for the development of preventive strategies. Our aim was to characterize the typical microvascular, cortical cerebral blood flow (CBF) changes in an OSA population during an apneic event. Sixteen patients (age 58 ± 8 years , 75% male) with a high risk of severe OSA were measured with a polysomnography device and with diffuse correlation spectroscopy (DCS) during one night of sleep with 1365 obstructive apneic events detected. All patients were later confirmed to suffer from severe OSA syndrome with a mean of 83 ± 15 apneas and hypopneas per hour. DCS has been shown to be able to characterize the microvascular CBF response to each event with a sufficient contrast-to-noise ratio to reveal its dynamics. It has also revealed that an apnea causes a peak increase of microvascular CBF ( 30 ± 17 % ) at the end of the event followed by a drop ( - 20 ± 12 % ) similar to what was observed in macrovascular CBF velocity of the middle cerebral artery. This study paves the way for the utilization of DCS for further studies on these populations.

Poligrafía en menores de 3 meses hospitalizados / Polygraphy in hospitalized children under 3 months

La apnea y eventos aparentemente letales poseen una gran diversidad etiológica por tanto exámenes complementarios podrían contribuir a su diagnóstico. El objetivo del presente estudio fue describir los resultados de estudios poligráficos de niños menores de 3 meses hospitalizados con sospecha de apnea. PACIENTES Y MÉTODO: Serie retrospectiva de casos. Se consideraron niños menores de 3 meses con sospecha de apnea y en quienes se realizó una poligrafía (PG) durante su hospitalización. Se registraron datos generales, así como también, el índice de apnea/hipopnea (IAH), índice de apnea central, índice de apnea obstructiva, saturación promedio y mínima. Como criterios de trastornos respiratorios del sueño (TRS) fueron considerados: índice de desaturaciones (ID) por debajo de 80% mayor 1 por hora; uno o más eventos de desaturaciones por debajo de 80% por más de 20 segundos; o un IAH mayor o igual 1. Se realizó estadística descriptiva y se determinó la posible asociación entre el IAH y parámetros de saturación. RESULTADOS: Ingresaron 51 pacientes, 32 varones. 8 (15,6%) presento PG alteradas, de ellos, en 5 coexistió más de un criterio diagnóstico. En el 15,6% se observó un IAH mayor o igual a 1, en el 7,8% se observó un índice de desaturación bajo 80% y en el 11,8% un índice de desaturación bajo 80% por más de 20 segundos. El IAH se asoció con los parámetros de saturación. CONCLUSIÓN: La mayoría de los pacientes presentó PG normales y entre los pacientes con TRS predominó un patrón poligráfico sugerente de inmadurez respiratoria, lo cual, es característico de esta edad.

Apnea and apparently lethal events have great etiological diversity thus complementary tests may help diagnosis. The aim of this study was to describe the results of polygraph studies of children under 3 months hospitalized with suspected apnea. PATIENTS AND METHODS: Retrospective case series. Children under 3 months with suspected apnea were considered and in whom a polygraphy (PG) was performed during hospitalization. General data, the apnea/hypopnea index (AHI), index of central. apnea, obstructive apnea index, average and minimum saturation were recorded. Desaturation index (ID) below 80% higher 1 per hour, one or more events of desaturation below 80% for more than 20 seconds or an AHI greater than or equal 1 were considered as criteria of sleep disorder breathing (SLB). Descriptive analysis was performed and the associations between AHI and saturation parameters were determined. RESULTS: 51 patients, 32 males, entered the study. 15,6% had altered PG. In 5 of them coexisted more than one diagnostic criterion. Iin 15,6% of the patients was observed an IAH greater 1, in 7.8% a desaturation index below 80% and in 11,8% a desaturation index under 80% for 20 seconds greater than 1. The AHI was associated with the parameters of saturation. CONCLUSION: Most of the patients had normal PG and among patients with a suggestive SLB a pattern of respiratory immaturity prevailed, which is characteristic of this age.

Advances and New Approaches to Managing Sleep-Disordered Breathing Related to Chronic Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common disease affecting about 20 million US adults. Sleep-disordered breathing (SDB) problems are frequent and poorly characterized for patients with COPD. Both the well-known success of noninvasive ventilation (NIV) in the acute COPD exacerbation in the hospital setting and that NIV is the cornerstone of chronic therapy for SDBs have urged the attention of the medical community to determine the impact of NIV on chronic COPD management with and without coexisting SDBs. Early observational studies showed decreased long-term survival rates on patients with COPD with concomitant chronic hypercapnia when compared with normocapnic patients.

Endothelial dysfunction and oxidative stress in children with sleep disordered breathing: role of NADPH oxidase.

OBJECTIVE: Oxidative stress plays a crucial role in impairing endothelial function in sleep disordered breathing (SDB) but the underlying mechanism is still undefined. The objective of this study was to evaluate the interplay between oxidative stress, assessed by serum isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function, assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls (HC). METHODS: One-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post adeno-tonsillectomy (AT). RESULTS: Compared with HC, OSA and PS children had significantly higher sNOX2-dp and serum 8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p<0.001) and with serum 8-iso-PGF2α (p<0.001). In multiple linear regression analysis, sNOX2-dp (p<0.001) and serum 8-iso-PGF2α (p<0.001) were the only independent predictive variables associated with FMD. AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2±8.8 to 22.4±11.1 pg/ml, p<0.001, and from 281.4±69.7 to 226.0±66.4 pg/ml, p<0.001, respectively); conversely, FMD significantly increased after AT in OSA children (from 3.0±1.5 to 8.0±2.8%, p<0.001). CONCLUSION: This study suggests that NOX2-derived oxidative stress is involved in artery dysfunction in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally with oxidative stress lowering. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.

Prevalence of central sleep apnea during continous positive airway pressure (CPAP) titration in subjects with obstructive sleep apnea syndrome at an altitude of 2640 m.

BACKGROUND: The occurrence of central apneas when applying positive pressure (CPAP) to patients with obstructive sleep apnea syndrome (OSAS) is called complex sleep apnea (CompSA). This causes poor adherence to CPAP and persistence of symptoms. In Bogota, a city located at an altitude of 2640 m above sea level, chronic hypoxemia can generate certain instability of the respiratory system during sleep which could increase the presence of central apnea. The aim was to establish the prevalence of central apnea (central apnea index >5/h) in adults with moderate or severe OSAS during CPAP titration, and the factors associated with this. METHOD: Patients over 18 years old with OSAS were referred to the Fundacion Neumologica Colombiana Sleep Center, from January 2008 to June 2010. Polysomnogram (PSG) for CPAP titration was performed according to the American Academy of Sleep Medicine criteria. The prevalence was calculated and the clinical and baseline PSG factors associated with the CompSA were analyzed. RESULTS: We included 988 patients, 58% men. CompSA prevalence was 11.6%. Factors associated with CompSA were: central apneas in the baseline PSG (OR: 5.34 [3.49-8.16]), history of heart failure (OR: 2.53 [1.58-4.07]), and male sex (OR: 1.68 [1.06-2.69]). CONCLUSION: The prevalence of complex sleep apnea in Bogota (11.6%) was intermediate compared to the reported in lower altitudes. The factors associated with the development of CompSA were male sex, heart failure, and the presence of central apnea in the baseline PSG.