Sanghun Sin

Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study.

RATIONALE The overall efficacy of adenotonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children is unknown. Although success rates are likely lower than previously estimated, factors that promote incomplete resolution of OSAS after AT remain undefined. OBJECTIVES To quantify the effect of demographic and clinical confounders known to impact the success of AT in treating OSAS. METHODS A multicenter collaborative retrospective review of all nocturnal polysomnograms performed both preoperatively and postoperatively on otherwise healthy children undergoing AT for the diagnosis of OSAS was conducted at six pediatric sleep centers in the United States and two in Europe. Multivariate generalized linear modeling was used to assess contributions of specific demographic factors on the post-AT obstructive apnea-hypopnea index (AHI). MEASUREMENTS AND MAIN RESULTS Data from 578 children (mean age, 6.9 +/- 3.8 yr) were analyzed, of which approximately 50% of included children were obese. AT resulted in a significant AHI reduction from 18.2 +/- 21.4 to 4.1 +/- 6.4/hour total sleep time (P < 0.001). Of the 578 children, only 157 (27.2%) had complete resolution of OSAS (i.e., post-AT AHI <1/h total sleep time). Age and body mass index z-score emerged as the two principal factors contributing to post-AT AHI (P < 0.001), with modest contributions by the presence of asthma and magnitude of pre-AT AHI (P < 0.05) among nonobese children. CONCLUSIONS AT leads to significant improvements in indices of sleep-disordered breathing in children. However, residual disease is present in a large proportion of children after AT, particularly among older (>7 yr) or obese children. In addition, the presence of severe OSAS in nonobese children or of chronic asthma warrants post-AT nocturnal polysomnography, in view of the higher risk for residual OSAS.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.

Effect of Lateral Positioning on Upper Airway Size and Morphology in Sedated Children

Background:Lateral positioning decreases upper airway obstruction in paralyzed, anesthetized adults and in individuals with sleep apnea during sleep. The authors hypothesized that lateral positioning increases upper airway cross-sectional area and total upper airway volume when compared with the supine position in sedated, spontaneously breathing children. Methods:Children aged 2–12 yr requiring magnetic resonance imaging examination of the head or neck region using deep sedation with propofol were studied. Exclusion criteria included any type of anatomical or neurologic entity that could influence upper airway shape or size. T1 axial scans of the upper airway were obtained in the supine and lateral positions, with the head and neck axes maintained neutral. Using software based on fuzzy connectedness segmentation (3D-VIEWNIX; Medical Imaging Processing Group, University of Pennsylvania, Philadelphia, PA), the magnetic resonance images were processed and segmented to render a three-dimensional reconstruction of the upper airway. Total airway volumes and cross-sectional areas were computed between the nasal vomer and the vocal cords. Two-way paired t tests were used to compare airway sizes between supine and lateral positions. Results:Sixteen of 17 children analyzed had increases in upper airway total volume. The total airway volume (mean ± SD) was 6.0 ± 2.9 ml3 in the supine position and 8.7 ± 2.5 ml3 in the lateral position (P < 0.001). All noncartilaginous areas of the upper airway increased in area in the lateral compared with the supine position. The region between the tip of the epiglottis and vocal cords demonstrated the greatest relative percent change. Conclusions:The upper airway of a sedated, spontaneously breathing child widens in the lateral position. The region between the tip of the epiglottis and the vocal cords demonstrates the greatest relative percent increase in size.

Changes in heart rate variability after adenotonsillectomy in children with obstructive sleep apnea.

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality, and increased sympathetic activity is considered to be a causative link in this association. Higher levels of sympathetic activity have been reported in children with OSAS. Sympathetic predominance is indicated on heart rate variability (HRV) analysis by increased heart rate (HR) and a higher ratio of low-frequency to high-frequency band power (LF/HF). Improvement in OSAS after adenotonsillectomy (AT) in children with OSAS could, therefore, be associated with reduced HR and reduced LF/HF. METHODS Changes in HR and time and frequency components of HRV were retrospectively analyzed in 2-min epochs free of respiratory events during light, deep, and rapid-eye-movement (REM) sleep in children with OSAS who underwent polysomnography before and after AT. RESULTS Eighteen children with OSAS, aged 4.9 ± 2.4 years (mean ± SD) were studied. After AT, the apnea-hypopnea index decreased from 31.9 ± 24.8 events/h to 4.1 ± 3.7 events/h. The HR decreased after AT in all stages of sleep (99.8 ± 16.9 beats/min to 80.7 ± 12.9 beats/min [light sleep]; 100.2 ± 15.4 beats/min to 80.5 ± 12.4 beats/min [deep sleep)]; and 106.9 ± 16.4 beats/min to 87.0 ± 12.1 beats/min [REM sleep]), as did the LF/HF (1.6 ± 2.7 to 0.6 ± 0.5 [light sleep]; 1.2 ± 1.6 to 0.5 ± 0.6 [deep sleep]; and 3.0 ± 5.4 to 1.4 ± 1.7 [REM sleep]). CONCLUSIONS The proportion of sympathetic activity of the autonomic nervous system declines in children with OSAS after AT in association with improvement in sleep-disordered breathing.

Body-Wide Hierarchical Fuzzy Modeling, Recognition, and Delineation of Anatomy in Medical Images

To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and testing data sets are divided into equal size in all cases except for the neck. Overall the AAR method achieves a mean accuracy of about 2 voxels in localizing non-sparse blob-like objects and most sparse tubular objects. The delineation accuracy in terms of mean false positive and negative volume fractions is 2% and 8%, respectively, for non-sparse objects, and 5% and 15%, respectively, for sparse objects. The two object groups achieve mean boundary distance relative to ground truth of 0.9 and 1.5 voxels, respectively. Some sparse objects - venous system (in the thorax on CT), inferior vena cava (in the abdomen on CT), and mandible and naso-pharynx (in neck on MRI, but not on CT) - pose challenges at all levels, leading to poor recognition and/or delineation results. The AAR method fares quite favorably when compared with methods from the recent literature for liver, kidneys, and spleen on CT images. We conclude that separation of modality-independent from dependent aspects, organization of objects in a hierarchy, encoding of object relationship information explicitly into the hierarchy, optimal threshold-based recognition learning, and fuzzy model-based IRFC are effective concepts which allowed us to demonstrate the feasibility of a general AAR system that works in different body regions on a variety of organs and on different modalities.

Noninvasive estimation of pharyngeal airway resistance and compliance in children based on volume-gated dynamic MRI and computational fluid dynamics

Computational fluid dynamics (CFD) analysis was used to model the effect of collapsing airway geometry on internal pressure and velocity in the pharyngeal airway of three sedated children with obstructive sleep apnea syndrome (OSAS) and three control subjects. Model geometry was reconstructed from volume-gated magnetic resonance images during normal tidal breathing at 10 increments of tidal volume through the respiratory cycle. Each geometry was meshed with an unstructured grid and solved using a low-Reynolds number k-ω turbulence model driven by flow data averaged over 12 consecutive breathing cycles. Combining gated imaging with CFD modeling created a dynamic three-dimensional view of airway anatomy and mechanics, including the evolution of airway collapse and flow resistance and estimates of the local effective compliance. The upper airways of subjects with OSAS were generally much more compliant during tidal breathing. Compliance curves (pressure vs. cross-section area), derived for different locations along the airway, quantified local differences along the pharynx and between OSAS subjects. In one subject, the distal oropharynx was more compliant than the nasopharynx (1.028 vs. 0.450 mm(2)/Pa) and had a lower theoretical limiting flow rate, confirming the distal oropharynx as the flow-limiting segment of the airway in this subject. Another subject had a more compliant nasopharynx (0.053 mm(2)/Pa) during inspiration and apparent stiffening of the distal oropharynx (C = 0.0058 mm(2)/Pa), and the theoretical limiting flow rate indicated the nasopharynx as the flow-limiting segment. This new method may help to differentiate anatomical and functional factors in airway collapse.

Adenotonsillectomy in Obese Children with Obstructive Sleep Apnea Syndrome: Magnetic Resonance Imaging Findings and Considerations

OBJECTIVE The reasons why adenotonsillectomy (AT) is less effective treating obese children with obstructive sleep apnea syndrome (OSAS) are not understood. Thus, the aim of the study was to evaluate how anatomical factors contributing to airway obstruction are affected by AT in these children. METHODS Twenty-seven obese children with OSAS (age 13.0 ± 2.3 y, body mass index Z-score 2.5 ± 0.3) underwent polysomnography and magnetic resonance imaging of the head during wakefulness before and after AT. Volumetric analysis of the upper airway and surrounding tissues was performed using commercial software (AMIRA®). RESULTS Patients were followed for 6.1 ± 3.6 mo after AT. AT improved mean obstructive apnea-hypopnea index (AHI) from 23.7 ± 21.4 to 5.6 ± 8.7 (P < 0.001). Resolution of OSAS was noted in 44% (12 of 27), but only in 22% (4 of 18) of those with severe OSAS (AHI > 10). AT increased the volume of the nasopharynx and oropharynx (2.9 ± 1.3 versus 4.4 ± 0.9 cm(3), P < 0.001, and 3.2 ± 1.2 versus 4.3 ± 2.0 cm(3), P < 0.01, respectively), reduced tonsils (11.3 ± 4.3 versus 1.3 ± 1.4 cm(3), P < 0.001), but had no effect on the adenoid, lingual tonsil, or retropharyngeal nodes. A small significant increase in the volume of the soft palate and tongue was also noted (7.3 ± 2.5 versus 8.0 ± 1.9 cm(3), P = 0.02, and 88.2 ± 18.3 versus 89.3 ± 24.4 cm(3), P = 0.005, respectively). CONCLUSIONS This is the first report to quantify volumetric changes in the upper airway in obese children with OSAS after adenotonsillectomy showing significant residual adenoid tissue and an increase in the volume of the tongue and soft palate. These findings could explain the low success rate of AT reported in obese children with OSAS and are important considerations for clinicians treating these children.

Upper airway lymphoid tissue size in children with sickle cell disease.

BACKGROUND The prevalence of obstructive sleep apnea syndrome (OSAS) is higher in children with sickle cell disease (SCD) as compared with the general pediatric population. It has been speculated that overgrowth of the adenoid and tonsils is an important contributor. METHODS The current study used MRI to evaluate such an association. We studied 36 subjects with SCD (aged 6.9 ± 4.3 years) and 36 control subjects (aged 6.6 ± 3.4 years). RESULTS Compared with control subjects, children with SCD had a significantly smaller upper airway (2.8 ± 1.2 cm(3) vs 3.7 ± 1.6 cm(3), P < .01), and significantly larger adenoid (8.4 ± 4.1 cm(3) vs 6.0 ± 2.2 cm(3), P < .01), tonsils (7.0 ± 4.3 cm(3) vs 5.1 ± 1.9 cm(3), P < .01), retropharyngeal nodes (3.0 ± 1.9 cm(3) vs 2.2 ± 0.9 cm(3), P < .05), and deep cervical nodes (15.7 ± 5.7 cm(3) vs 12.7 ± 4.0 cm(3), P < .05). Polysomnography showed that 19.4% (seven of 36) of children with SCD had OSAS compared with 0% (zero of 20) of control subjects (P < .05) and that in children with SCD the apnea-hypopnea index correlated positively with upper airway lymphoid tissues size (r = 0.57, P < 001). In addition, children with SCD had lower arterial oxygen saturation nadir (84.3% ± 12.3% vs 91.2% ± 4.2%, P < .05), increased peak end-tidal CO(2) (53.4 ± 8.5 mm Hg vs 42.3 ± 5.3 mm Hg, P < .001), and increased arousals (13.7 ± 4.7 events/h vs 10.8 ± 3.8 events/h, P < .05). CONCLUSIONS Children with SCD have reduced upper airway size due to overgrowth of the surrounding lymphoid tissues, which may explain their predisposition to OSAS.

Computational fluid dynamics endpoints to characterize obstructive sleep apnea syndrome in children

Computational fluid dynamics (CFD) analysis may quantify the severity of anatomical airway restriction in obstructive sleep apnea syndrome (OSAS) better than anatomical measurements alone. However, optimal CFD model endpoints to characterize or assess OSAS have not been determined. To model upper airway fluid dynamics using CFD and investigate the strength of correlation between various CFD endpoints, anatomical endpoints, and OSAS severity, in obese children with OSAS and controls. CFD models derived from magnetic resonance images were solved at subject-specific peak tidal inspiratory flow; pressure at the choanae was set by nasal resistance. Model endpoints included airway wall minimum pressure (Pmin), flow resistance in the pharynx (Rpharynx), and pressure drop from choanae to a minimum cross section where tonsils and adenoids constrict the pharynx (dPTAmax). Significance of endpoints was analyzed using paired comparisons (t-test or Wilcoxon signed rank test) and Spearman correlation. Fifteen subject pairs were analyzed. Rpharynx and dPTAmax were higher in OSAS than control and most significantly correlated to obstructive apnea-hypopnea index (oAHI), r = 0.48 and r = 0.49, respectively (P < 0.01). Airway minimum cross-sectional correlation to oAHI was weaker (r = -0.39); Pmin was not significantly correlated. CFD model endpoints based on pressure drops in the pharynx were more closely associated with the presence and severity of OSAS than pressures including nasal resistance, or anatomical endpoints. This study supports the usefulness of CFD to characterize anatomical restriction of the pharynx and as an additional tool to evaluate subjects with OSAS.

Sleep and cardiometabolic function in obese adolescent girls with polycystic ovary syndrome.

OBJECTIVE To compare the polysomnography findings and cardiometabolic function among adolescent girls with polycystic ovary syndrome (PCOS) and matched female and male controls. METHOD Retrospective chart review of electronic medical records of 28 girls with PCOS (age: 16.8±1.9 years, body mass index (BMI) Z-score 2.4±0.4), 28 control females (age: 17.1±1.8, BMI Z-score 2.4±0.3) and 28 control males (age: 16.6±1.6, BMI Z-score 2.5±0.5) in a tertiary care centre. RESULTS The prevalence of obstructive sleep apnoea (OSA) was higher in girls with PCOS compared to control females (16/28 (57%) vs. 4/28(14.3%), p<0.01); however, it was comparable to that of the control males (16/28(57%) vs. 21/28(75%), p=0.4). Girls with PCOS had a significantly higher prevalence of insulin resistance compared to control females and control males (20/28 (71.4%) vs. 9/22 (41.0%) (p=0.04) vs. 8/23 (34.8%) (p=0.01). Among girls with PCOS, those with OSA had significantly higher proportions of metabolic syndrome (MetS) (9/16 (56.3%) vs. 1/12 (8.3%) p=0.03), higher insulin resistance (14/16 (87.5%) vs. 6/12 (50%), p=0.04), elevated daytime systolic blood pressure (128.4±12.8 vs. 115.6±11.4, p<0.01), lower high-density lipoprotein (HDL) (38.6±8.7 vs. 49±10.9, p=0.01) and elevated triglycerides (TG) (149.7±87.7 vs. 93.3±25.8, p=0.03) compared to those without OSA. CONCLUSIONS We report a higher prevalence of OSA and metabolic dysfunction in a selected group of obese girls with PCOS referred with sleep-related complaints compared to BMI-matched control girls without PCOS. We also report higher prevalence of cardiometabolic dysfunction in girls with PCOS and OSA compared to girls with PCOS without OSA.