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OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.
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Proteínas de Fase Aguda/metabolismo , Aterosclerose/etiologia , Artéria Carótida Primitiva/fisiopatologia , Citocinas/sangue , Inflamação/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Modelos Lineares , Masculino , Estudos Prospectivos , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , UltrassonografiaRESUMO
RATIONALE: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown. OBJECTIVES: To characterize phenotypes of ventilatory control that are associated with the presence of OSA in preterm-born children during early childhood. METHODS: Preterm- and term-born children without comorbid conditions were enrolled. They were categorized into an OSA group and a non-OSA group on the basis of polysomnography. MEASUREMENTS AND MAIN RESULTS: Loop gain, controller gain, and plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and blood gas response to a change in ventilation, respectively, were estimated from spontaneous sighs identified during polysomnography. Cardiorespiratory coupling, a measure of brainstem maturation, was estimated by measuring the interval between inspiration and the preceding electrocardiogram R-wave. Cluster analysis was performed to develop phenotypes based on controller gain, plant gain, cardiorespiratory coupling, and gestational age. The study included 92 children, 63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48% OSA). Three phenotypes of ventilatory control were derived with risks for OSA being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a stepwise decrease in controller gain and an increase in plant gain from clusters 1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling and gestational age than clusters 2 and 3. No difference in loop gain was found between clusters. CONCLUSIONS: The risk for OSA could be stratified according to controller gain, plant gain, cardiorespiratory coupling, and gestational age. These findings could guide personalized care for children at risk for OSA.
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Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Recém-Nascido Prematuro/crescimento & desenvolvimento , Respiração Artificial/efeitos adversos , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de RiscoRESUMO
BackgroundThe baroreflex and central autonomic brain regions together control the cardiovascular system. Baroreflex sensitivity (BRS) decreases with age in adults. Age-related changes in brain regions for cardiovascular control in children are unknown. We studied age-related changes in BRS, cardiac autonomic tone, and gray matter volume (GMV) of brain regions associated with cardiovascular control.MethodsBeat-to-beat blood pressure and heart rate (HR) were recorded in 49 children (6-14 years old). Spontaneous BRS was calculated by the sequence method. Cardiac autonomic tone was measured by spectral analysis of HR variability. GMV was measured using voxel-based morphometryin 112 healthy children (5-18 years old).ResultsAge-related changes in BRS were significantly different in children <10 years and ≥10 years. Age-related changes in GMV in regions of interest (ROI) were also significantly different between children <10 and ≥10 years and between children <11 and ≥11 years. However, age-related changes in cardiac autonomic tone were progressive.ConclusionsSignificant changes in BRS trajectories between <10 and ≥10 years may be associated with similar age-related changes of GMV in brain ROI. This new knowledge will guide future studies examining whether childhood cardiovascular disruption manifests as deviated maturation trajectories of specific brain regions.
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Sistema Nervoso Autônomo/fisiologia , Barorreflexo , Encéfalo/fisiologia , Substância Cinzenta/fisiologia , Adolescente , Fatores Etários , Pressão Sanguínea , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Frequência Cardíaca/fisiologia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Obstructive sleep apnea (OSA) is an airway disease caused by periodic collapse of the airway during sleep. Imaging-based subject-specific computational fluid dynamics (CFD) simulations allow non-invasive assessment of clinically relevant metrics such as total pressure loss (TPL) in patients with OSA. However, most of such studies use static airway geometries, which neglect physiological airway motion. This study aims to quantify how much the airway moves during the respiratory cycle, and to determine how much this motion affects CFD pressure loss predictions. Motion of the airway wall was quantified using cine MRI data captured over a single respiratory cycle in three subjects with OSA. Synchronously-measured respiratory airflow was used as the flow boundary condition for all simulations. Simulations were performed for full respiratory cycles with 5 different wall boundary conditions: (1) a moving airway wall, and static airway walls at (2) peak inhalation, (3) end inhalation, (4) peak exhalation, and (5) end exhalation. Geometric analysis exposed significant local airway cross-sectional area (CSA) variability, with local CSA varying as much as 300%. The comparative CFD simulations revealed the discrepancies between dynamic and static wall simulations are subject-specific, with TPL differing by up to 400% between static and dynamic simulations. There is no consistent pattern to which static wall CFD simulations overestimate or underestimate the airway TPL. This variability underscores the complexity of accurately modeling airway physiology and the importance of considering dynamic anatomical factors to predict realistic respiratory airflow dynamics in patients with OSA.
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Hidrodinâmica , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Masculino , Simulação por Computador , Pessoa de Meia-Idade , Adulto , Feminino , Respiração , Imageamento por Ressonância Magnética/métodos , Ventilação Pulmonar/fisiologiaRESUMO
Upper airway neuromuscular response to air pressure during inhalation is an important factor in assessing pediatric subjects with obstructive sleep apnea (OSA). The neuromuscular response's strength, timing, and duration all contribute to the potential for airway collapses and the severity of OSA. This study quantifies these factors at the soft palate, tongue, and epiglottis to assess the relationship between neuromuscular control and OSA severity in 20 pediatric subjects with and without trisomy 21, under dexmedetomidine-induced sedation. The interaction between neuromuscular force and airflow pressure force was assessed based on power transferred between the airway wall and airflow calculated from airway wall motion (from cine magnetic resonance images) and air pressure acting on the airway wall (from computational fluid dynamics simulations). Airway wall motion could be asynchronous with pressure forces due to neuromuscular activation, or synchronous with pressure forces, indicating a passive response to airflow. The obstructive apnea-hypopnea index (oAHI) quantified OSA severity. During inhalation, the normalized work done through asynchronous dilation of the airway at the soft palate, tongue, and epiglottis correlated significantly with oAHI (Spearman's ρ = 0.54, 0.50, 0.64; P = 0.03, 0.03, 0.003). Synchronous collapse at the epiglottis correlated significantly with oAHI (ρ = 0.52; P = 0.02). Temporal order of synchronous and asynchronous epiglottis motion during inhalation predicted the severity of OSA (moderate vs. severe) with 100% sensitivity and 70% specificity. Subjects with severe OSA and/or trisomy 21 have insufficient neuromuscular activation during inhalation, leading to collapse and increased neuromuscular activation. Airflow-driven airway wall motion during late inhalation likely is the main determinant of OSA severity.NEW & NOTEWORTHY This is the first study that combines cine MRI and computational fluid dynamics with in vivo synchronous respiratory flow measurement to quantify the interaction between airway neuromuscular forces, aerodynamic forces, and airway anatomy noninvasively in pediatric patients with obstructive sleep apnea (OSA). The results indicate power transfer predicts OSA severity.
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Síndrome de Down , Apneia Obstrutiva do Sono , Humanos , Criança , Traqueia , Nariz , Movimento (Física)RESUMO
Neuromuscular control of the upper airway contributes to obstructive sleep apnea (OSA). An accurate, non-invasive method to assess neuromuscular function is needed to improve surgical treatment outcomes. Currently, surgical approaches for OSA are based on airway anatomy and are often not curative. When the airway surface moves, the power transferred between air in the airway lumen and the structures of the upper airway may be a measure of airway neuromuscular activity. The aim of this study was to validate power transfer as a measure of externally applied forces, representing neuromuscular activity, through cine computed tomography (CT) imaging and computational fluid dynamics (CFD) analysis in a 3D-printed airway model. A hollow elastic airway model was manufactured. An insufflation/exsufflation device generated airflow within the model lumen. The model was contained in an airtight chamber that could be positively or negatively pressurized to represent muscular forces. These forces were systematically applied to dilate and collapse the model. Cine CT imaging captured airway wall movement during respiratory cycles with and without externally applied forces. Power transfer was calculated from the product of wall movement and internal aerodynamic pressure forces using CFD simulations. Cross-correlation peaks between power transfer and changes in externally applied pressure during exhalation and inhalation were -0.79 and 0.95, respectively. Power transfer calculated via cine CT imaging and CFD was an accurate surrogate measure of externally applied forces representing airway muscular activity. In the future, power transfer may be used in clinical practice to phenotype patients with OSA and select personalized therapies.
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Laringe , Apneia Obstrutiva do Sono , Humanos , Hidrodinâmica , Traqueia , Tomografia Computadorizada por Raios XRESUMO
Surgical treatment of obstructive sleep apnea (OSA) in children requires knowledge of upper airway dynamics, including the closing pressure (Pcrit), a measure of airway collapsibility. We applied a flow-structure interaction (FSI) computational model to estimate Pcrit in patient-specific upper airway models obtained from magnetic resonance imaging (MRI) scans. We sought to examine the agreement between measured and estimated Pcrit from FSI models in children with Down syndrome. We hypothesized that the estimated Pcrit would accurately reflect measured Pcrit during sleep and therefore reflect the severity of OSA as measured by the obstructive apnea-hypopnea index (AHI). All participants (n = 41) underwent polysomnography and sedated sleep MRI scans. We used Bland-Altman plots to examine the agreement between measured and estimated Pcrit. We determined associations between estimated Pcrit and OSA severity, as measured by AHI, using regression models. The agreement between passive and estimated Pcrit showed a fixed bias of -1.31 [confidence interval (CI) = -2.78, 0.15] and a nonsignificant proportional bias. A weaker agreement with active Pcrit was observed. A model including AHI, gender, an interaction term for AHI, and gender and neck circumference explained the largest variation (R2 = 0.61) in the relationship between AHI and estimated Pcrit (P < 0.0001). Overlap between the areas of the airway with the lowest stiffness, and areas of collapse on dynamic MRI, was 77.4 ± 30% for the nasopharyngeal region and 78.6 ± 33% for the retroglossal region. The agreement between measured and estimated Pcrit and the significant association with AHI supports the validity of Pcrit estimates from the FSI model.NEW & NOTEWORTHY We present a noninvasive method for estimating critical closing pressure (Pcrit) using fluid-structure interaction (FSI) simulations and magnetic resonance imaging (MRI) scans in patients with obstructive sleep apnea (OSA). We used patient-specific stiffness measures in our FSI model to account for any individual variability in the elasticity of soft tissues surrounding the upper airway. We validated this model by measuring the degree of agreement between measured and estimated Pcrit.
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Faringe , Apneia Obstrutiva do Sono , Criança , Humanos , Imageamento por Ressonância Magnética , Faringe/diagnóstico por imagem , Polissonografia , SonoRESUMO
RATIONALE: We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage. OBJECTIVES: Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea. METHODS: A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (+/-2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains. MEASUREMENTS AND MAIN RESULTS: Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index. CONCLUSIONS: Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.
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Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Estudos de Casos e Controles , Criança , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Masculino , PolissonografiaRESUMO
OBJECTIVE: Respiratory compromise in congenital muscular dystrophy (CMD) occurs, in part, from chest wall contractures. Passive stretch with hyperinsufflation therapy could reduce related costo-vertebral joint contractures. We sought to examine the impact of hyperinsufflation use on lung function and quality of life in children with CMD. STUDY DESIGN: We conducted a randomized controlled trial on hyperinsufflation therapy in children with CMD at two centers. An individualized hyperinsufflation regimen of 15 minutes twice daily using a cough assist device over a 12 months period was prescribed. We measured lung function, quality of life, and adherence. To demonstrate reproducibility, pulmonary function was measured twice on the same day. A mixed-effects regression model adjusting for confounders was used to assess the effects of hyperinsufflation. RESULTS: We enrolled 34 participants in the study; 31 completed the trial (n = 17 treatment group and n = 14 controls). Participants in the treatment group demonstrated a relative gain in lung volume measured at 4 and 8 months, but not at 12 months. The control group required increases in the maximum insufflation pressures to achieve maximum lung volumes while the treatment group did not. Adherence was best early in the study, peaking at the first visit and decreasing at subsequent visits. Caregiver-reported quality of life was higher in the treatment group. CONCLUSION: Hyperinsufflation therapy is effective in increasing and sustaining lung volume over time. Adherence, however, was inconsistent and difficult to maintain. Further research should determine if improved adherence leads to sustained benefits of hyperinsufflation.
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Insuflação , Distrofias Musculares/terapia , Terapia Respiratória , Adolescente , Criança , Pré-Escolar , Tosse , Feminino , Humanos , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Qualidade de Vida , Reprodutibilidade dos TestesRESUMO
RATIONALE: Adenotonsillectomy, the first line of treatment of sleep-disordered breathing (SDB), is the most commonly performed pediatric surgery. Predictors of the recurrence of SDB after adenotonsillectomy and its impact on cardiovascular risk factors have not been identified. OBJECTIVES: Demonstrate that gain velocity in body mass index (BMI) defined as unit increase in BMI/year confers an independent risk for the recurrence of SDB 1 year after adenotonsillectomy. METHODS: Children with SDB and hypertrophy of the tonsils and a comparison group of healthy children were followed prospectively for 1 year. MEASUREMENTS AND MAIN RESULTS: Serial polysomnographies, BMI, and blood pressure were obtained before adenotonsillectomy and 6 weeks, 6 months, and 1 year postoperatively. Gain velocity in BMI, BMI and being African American (odds ratios, 4-6/unit change/yr; 1.4/unit and 15, respectively) provided equal amounts of predictive power to the risk of recurrence of SDB. In the group that experienced recurrence, systolic blood pressure at 1 year was higher than at baseline and higher than in children who did not experience recurrence. CONCLUSIONS: Three clinical parameters confer independent increased risk for high recurrence of SDB after adenotonsillectomy: gain velocity in BMI, obesity, and being African American. A long-term follow-up of children with SDB and monitoring of gain velocity in BMI are essential to identifying children at risk for recurrence of SDB and in turn at risk for hypertension.
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Adenoidectomia , Negro ou Afro-Americano , Índice de Massa Corporal , Obesidade , Síndromes da Apneia do Sono/cirurgia , Tonsilectomia , Adolescente , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Polissonografia , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Fatores de Risco , População BrancaRESUMO
RATIONALE: An association between neurocognitive deficits and pediatric sleep-disordered breathing has been suggested; however, weak correlations between disease severity and functional outcomes underscore the lack of knowledge regarding factors modulating cognitive morbidity of sleep-disordered breathing. OBJECTIVES: To identify the parameters affected by sleep-disordered breathing that modulate cerebral oxygenation, an important determinant of cognition. A further objective was to use these parameters with demographic data to develop a predictive statistical model of pediatric cerebral oxygenation. METHODS: Ninety-two children (14 control subjects, 32 with primary snoring, and 46 with obstructive sleep apnea) underwent polysomnography with continuous monitoring of cerebral oxygenation and blood pressure. Analysis of covariance was used to relate the blood pressure, sleep diagnostic parameters, and demographic characteristics to regional cerebral oxygenation. MEASUREMENTS AND MAIN RESULTS: To account for anatomic variability, an index of cerebral oxygenation during sleep was derived by referencing the measurement obtained during sleep to that obtained during wakefulness. In a repeated measures model predicting the index of cerebral oxygenation, mean arterial pressure, rapid eye movement (REM) sleep, female sex, age, and oxygen saturation had a positive effect on cerebral oxygenation levels, whereas arousal index and non-REM (NREM) sleep had a negative effect. CONCLUSIONS: Increasing mean arterial pressure, age, oxygen saturation, and REM sleep augment cerebral oxygenation, while sleep-disordered breathing, male sex, arousal index, and NREM sleep diminish it. The proposed model may explain the sources of variability in cognitive function of children with sleep-disordered breathing.
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Circulação Cerebrovascular/fisiologia , Consumo de Oxigênio/fisiologia , Síndromes da Apneia do Sono/metabolismo , Adolescente , Pressão Sanguínea , Criança , Feminino , Seguimentos , Humanos , Masculino , Oximetria , Polissonografia , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/fisiopatologia , Sono REM/fisiologiaRESUMO
STUDY OBJECTIVES: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in children and the effect of adenotonsillectomy are unknown. We aimed to examine the difference in ventilatory control between children with OSA and those without OSA. We also examined the effect of adenotonsillectomy on parameters of ventilatory control. METHODS: Healthy children with OSA and matched controls were recruited. Polysomnography was performed before adenotonsillectomy in the OSA group and 6 months postoperatively. Controls underwent the same assessment at the two time points. Loop gain (LG), controller gain (CG), and plant gain (PG), which reflect the stability of ventilatory control, chemoreceptor sensitivity and the pulmonary control of blood gas in response to a change in ventilation, respectively, were estimated from polysomnographic tracings which included spontaneous sighs and tracings with tidal breathing. A linear mixed model was used to examine the changes of the ventilatory control parameters from baseline to 6 months. RESULTS: Ninety-nine children aged 7-13 were recruited to the study. Fifty-three with OSA and 46 controls. At baseline, compared with controls, children with OSA had higher PG and lower CG. LG did not differ between groups. Six months following adenotonsillectomy, there was a significant decrease in PG in the OSA group, while no change observed in the control group. CONCLUSIONS: The study demonstrates that the pulmonary control of blood gas homeostasis is disturbed in children with OSA and it normalizes following adenotonsillectomy.
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Adenoidectomia/tendências , Ventilação Pulmonar/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/tendências , Adolescente , Gasometria/tendências , Criança , Feminino , Humanos , Masculino , Polissonografia/tendências , Apneia Obstrutiva do Sono/sangueRESUMO
BACKGROUND: Computational fluid dynamics simulations of respiratory airflow in the upper airway reveal clinically relevant information, including sites of local resistance, inhaled particle deposition, and the effect of pathological constrictions. Unlike previous simulations, which have been performed on rigid anatomical models from static medical imaging, this work utilises ciné imaging during respiration to create dynamic models and more closely represent airway physiology. METHODS: Airway movement maps were obtained from non-rigid image registration of fast-cine MRI and applied to high-spatial-resolution airway surface models. Breathing flowrates were recorded simultaneously with imaging. These data formed the boundary conditions for large eddy simulation computations of the airflow from exterior mask to bronchi. Simulations with rigid geometries were performed to demonstrate the resulting airflow differences between airflow simulations in rigid and dynamic airways. FINDINGS: In the analysed rapid breathing manoeuvre, incorporating airway movement significantly changed the findings of the CFD simulations. Peak resistance increased by 19.8% and occurred earlier in the breath. Overall pressure loss decreased by 19.2%, and the proportion of flow in the mouth increased by 13.0%. Airway wall motion was out-of-phase with the air pressure force, demonstrating the presence of neuromuscular motion. In total, the anatomy did 25.2% more work on the air than vice versa. INTERPRETATIONS: Realistic movement of the airway is incorporated into CFD simulations of airflow in the upper airway for the first time. This motion is vital to producing clinically relevant computational models of respiratory airflow and will allow novel analysis of dynamic conditions, such as sleep apnoea.
Assuntos
Hidrodinâmica , Pulmão/fisiopatologia , Movimento , Respiração , Traqueia/fisiopatologia , Adulto , Simulação por Computador , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Modelos Biológicos , Movimento (Física)RESUMO
STUDY OBJECTIVES: To examine the role of ventilatory control in asthmatic children with obstructive sleep apnea (OSA) and the relationships between measures of ventilatory control, OSA severity, and pulmonary function. METHODS: Five- to 18-year-old children with persistent asthma and nightly snoring were enrolled in the study. Children had physical examination, pulmonary function test, and polysomnography. Loop and controller gains were derived from 5 min segments which included a sigh during nonrapid eye movement sleep by applying a mathematical model that quantifies ventilatory control from the ensuing responses to the sighs. Plant gain was derived from 5 min segments of spontaneous breathing (i.e. without sighs). Nonparametric statistical tests were used for group comparisons. Cluster analysis was performed using Bayesian profile regression. RESULTS: One hundred thirty-four children were included in the study, 77 with and 57 without OSA. Plant gain was higher in children with OSA than in those without OSA (p = 0.002). A negative correlation was observed between plant gain and forced expiratory volume in 1 second (p = 0.048) and the ratio of f forced expiratory volume to forced vital capacity (p = 0.02). Plant gain correlated positively with severity of OSA. Cluster analysis demonstrated that children with more severe OSA and abnormal lung function had higher plant gain and a lower controller gain compared with the rest of the population. CONCLUSIONS: Children with OSA and persistent asthma with abnormal lung function have phenotypic characteristics which consist of diminished capacity of the lungs to maintain blood gas homeostasis reflected by an increase in plant gain and decreased chemoreceptor sensitivity.
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Asma/patologia , Gasometria/métodos , Apneia Obstrutiva do Sono/fisiopatologia , Sono de Ondas Lentas/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Adolescente , Teorema de Bayes , Criança , Pré-Escolar , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/fisiologia , Masculino , Fenótipo , Polissonografia , Testes de Função Respiratória , Ronco/fisiopatologiaRESUMO
Computational fluid dynamics (CFD) simulations of airflow in the human airways have the potential to provide a great deal of information that can aid clinicians in case management and surgical decision making, such as airway resistance, energy expenditure, airflow distribution, heat and moisture transfer, and particle deposition, as well as the change in each of these due to surgical interventions. However, the clinical relevance of CFD simulations has been limited to date, as previous models either did not incorporate neuromuscular motion or any motion at all. Many common airway pathologies, such as obstructive sleep apnea (OSA) and tracheomalacia, involve large movements of the structures surrounding the airway, such as the tongue and soft palate. Airway wall motion may be due to many factors including neuromuscular motion, internal aerodynamic forces, and external forces such as gravity. Therefore, to realistically model these airway diseases, a method is required to derive the airway wall motion, whatever the cause, and apply it as a boundary condition to CFD simulations. This paper presents and validates a novel method of capturing in vivo motion of airway walls from magnetic resonance images with high spatiotemporal resolution, through a novel combination of non-rigid image, surface, and surface-normal-vector registration. Coupled with image-synchronous pneumotachography, this technique provides the necessary boundary conditions for dynamic CFD simulations of breathing, allowing the effect of the airway's complex motion to be calculated for the first time, in both normal subjects and those with conditions such as OSA.
Assuntos
Simulação por Computador , Imageamento por Ressonância Magnética , Modelos Biológicos , Movimento , Sistema Respiratório , Apneia Obstrutiva do Sono , Adulto , Criança , Humanos , Masculino , Mecânica Respiratória , Sistema Respiratório/diagnóstico por imagem , Sistema Respiratório/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
Objective Home oximetry is commonly used to screen for obstructive sleep apnea (OSA) in children; however, normal oxygen desaturation levels by disease severity are not well known. It was our objective to determine if oxygen saturation levels differed by OSA severity category in children and if these differences were similar for preteen children and adolescents. Study Design Retrospective case series of children undergoing polysomnography from September 2011 to July 2015. Setting Tertiary pediatric hospital. Subjects and Methods Six- to 18-year-olds (preteen, 6-12 years old; adolescent, 13-18 years old). Chi-square, Wilcoxon rank sum test, and Kruskal-Wallis testing were used to compare variables between age groups. Results The study included 342 children with a mean age of 11.3 ± 2.4 years (range, 6.5-17.5) and a mean body mass index of 25.6 ± 9.2 kg/m2 (78 ± 29 percentile); 61% were white, 35% were black, and 4% were other or unknown. Of the children, 48% were female, and this was not a significant difference between age groups ( P = .81). Overall, 50% of the children had no OSA, 32% mild, 10% moderate, and 8% severe. When compared with the younger children, the adolescents had a longer sleep time ( P = .014) and a higher mean obstructive apnea-hypopnea index (3.53 ± 5.1 vs 3.03 ± 6.1 events per hour, P = .02). The 3% and 4% oxygen desaturation indices were not significantly different between age groups when accounting for OSA severity. Conclusion Adolescents have longer sleep times and higher obstructive apnea-hypopnea indexes than preteens, but oxygen saturations and desaturation indices were similar. This supports current triage algorithms for children with OSA, as we found no significant age-based differences.
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Oxigênio/metabolismo , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Introduction: Biomarkers of atherosclerosis (pro-inflammatory cytokines and acute phase reactants) are elevated in children with obstructive sleep apnea (OSA). However, their association with cardiovascular endpoints in children are not understood. We hypothesized that biomarkers of atherosclerosis in children with OSA correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT. Methods: Children with OSA and matched controls were recruited to the study. Pro-inflammatory cytokines and acute phase reactants were measured at 6:00 pm and 6:00 am. Polysomnography with beat-to-beat blood pressure was performed. PTT during wakefulness and stage 2 sleep was calculated. Diurnal variation of biomarkers and their associations with PTT was estimated. Factor analysis was used to determine the effect of groups of cytokines on PTT. Results: One hundred fifty-five children participated in the study; 90 were healthy controls and 65 had OSA. Children with OSA exhibited a different diurnal variation of biomarkers than healthy controls, with pro-inflammatory cytokines peaking in the morning and acute phase reactants peaking in the afternoon. Structural equation modeling demonstrated that interleukins 6 and 8, tumor necrosis factor-α, and sCD40L had a shortening effect, while serum amyloid A, C-reactive protein, and adiponectin had a prolonging effect on PTT. As a result, there was no difference in PTT between the two groups. Conclusion: The differential relationships of acute phase reactants and pro-inflammatory cytokines with PTT suggest that in children with OSA, these mediators may have opposing actions to maintain cardiovascular homeostasis.
Assuntos
Citocinas/sangue , Homeostase , Inflamação/sangue , Inflamação/complicações , Análise de Onda de Pulso , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Adiponectina/sangue , Adolescente , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Proteína C-Reativa/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/fisiopatologia , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Polissonografia , Proteína Amiloide A Sérica/análise , Sono , Apneia Obstrutiva do Sono/sangue , Fator de Necrose Tumoral alfa/sangue , Vigília/fisiologiaRESUMO
BACKGROUND: Congenital muscular dystrophy (CMD) is a rare, inherited neuromuscular disease characterized by progressive muscle weakness, thoracic insufficiency, and ultimately respiratory failure. Adherence to respiratory therapies in children with neuromuscular disorders is unknown. This study examined the multimodal assessment of adherence and barriers to 15 min, twice daily hyperinsufflation in children with CMD. Adherence was hypothesized to be greater than 50% and discomfort, embarrassment, and difficulty finding time were hypothesized to be barriers. METHODS: Participants included 18 children with CMD. Personalized hyperinsufflation settings were determined based on pressure-volume measurements at each study visit. Adherence was measured by a daily phone diary (DPD) and by electronic data download from the hyperinsufflation device. The DPD was conducted twice over a 48-hr period to capture a weekend and weekday, with the goal being 60 min of hyperinsufflation over the 48 hr (100% adherence). The hyperinsufflation objective electronic data reflected daily use of hyperinsufflation for the same 48-hr period. Data from DPD and the corresponding hyperinsufflation device data were used for analyses. RESULTS: Adherence to hyperinsufflation was 40% via DPD and 44% for electronic data, with strong convergence between methods (r = 0.75, P < 0.001). Surprisingly, 53% of participants reported no barriers despite low adherence. Social distractions and family obligations were identified as barriers. There were no differences in adherence between those who did and did not endorse barriers to hyperinsufflation (DPD: t(13) = 0.44, P = n.s.; hyperinsufflation device: t(13) = -0.23, P = n.s.). CONCLUSION: Adherence to hyperinsufflation is a significant problem in children with CMD and families have difficulty identifying adherence barriers. An important next step is to encourage open dialog around adherence barriers and promote adherence behaviors via intervention. Pediatr Pulmonol. 2017; 52:939-945. © 2016 Wiley Periodicals, Inc.
Assuntos
Distrofias Musculares/terapia , Cooperação do Paciente , Insuficiência Respiratória/terapia , Terapia Respiratória , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
STUDY OBJECTIVES: To describe a dynamic three-dimensional (3D) computed tomography (CT) technique for the upper airway and compare the required radiation dose to that used for common clinical studies of a similar anatomical area, such as for subjects undergoing routine clinical facial CT. METHODS: Dynamic upper-airway CT was performed on eight subjects with persistent obstructive sleep apnea, four of whom were undergoing magnetic resonance imaging and an additional four subjects who had a contraindication to magnetic resonance imaging. This Health Insurance Portability and Accountability Act-compliant study was approved by our institutional review board, and informed consent was obtained. The control subjects (n = 41) for comparison of radiation dose were obtained from a retrospective review of the clinical picture-archiving computer system to identify 10 age-matched patients per age-based control group undergoing facial CT. RESULTS: Dynamic 3D CT can be performed with an effective radiation dose of less than 0.38 mSv, a dose that is less than or comparable to that used for clinical facial CT. The resulting data- set is a uniquely complete, dynamic 3D volume of the upper airway through a full respiratory cycle that can be processed for clinical and modeling analyses. CONCLUSIONS: A dynamic 3D CT technique of the upper airway is described that can be performed with a clinically reasonable radiation dose and sets a benchmark for future use.