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Abstract Study Objectives This study evaluated differences in upper airway, soft tissues and craniofacial structures between Asians from China and Europeans from Iceland with OSA using three-dimensional magnetic resonance imaging (MRI). Methods Airway sizes, soft tissue volumes, and craniofacial dimensions were compared between Icelandic (N = 108) and Chinese (N = 57) patients with oxygen desaturation index (ODI) ≥ 10 events/h matched for age, gender, and ODI. Mixed effects models adjusting for height or BMI and residual differences in age and ODI were utilized. Results In our matched sample, compared to Icelandic OSA patients, Chinese patients had smaller BMI (p < 0.0001) and neck circumference (p = 0.011). In covariate adjusted analyses, Chinese showed smaller retropalatal airway size (p ≤ 0.002), and smaller combined soft tissues, tongue, fat pads, and pterygoid (all p ≤ 0.0001), but male Chinese demonstrated a larger soft palate volume (p ≤ 0.001). For craniofacial dimensions, Chinese demonstrated bigger ANB angle (p ≤ 0.0196), differently shaped mandibles, including shorter corpus length (p < 0.0001) but longer ramus length (p < 0.0001), and a wider (p < 0.0001) and shallower (p ≤ 0.0001) maxilla. Conclusions Compared to Icelandic patients of similar age, gender and ODI, Chinese patients had smaller retropalatal airway and combined soft tissue, but bigger soft palate volume (in males), and differently shaped mandible and maxilla with more bony restrictions. Results support an ethnic difference in upper airway anatomy related to OSA, which may inform targeted therapies.

Background A growing proportion of adolescents have poor cardiovascular health behaviors, including low levels of physical activity and high levels of sedentary behavior, thus increasing the likelihood of poor heart health in later years. This study tested the hypothesis that low perceived neighborhood safety would be associated with low levels of physical activity and high levels of recreational sedentary behavior in high-school students. Methods Using cross-sectional, weighted data from the 2015 Pennsylvania (USA) State and Philadelphia city Youth Risk Behavior Survey, multivariable logistic regression modeling was used to examine the association between perceived neighborhood safety, and physical activity levels and recreational screen-based sedentary behavior time respectively, while controlling for potential confounders. Results After adjustment for other significant correlates of physical activity, students with low perceived neighborhood safety had a 21% reduced odds of being physically active on 5 or more days of the last week as compared to those who felt safe ( p  = 0.044). Perceived safety was not related to sedentary behavior; but sports team participation emerged as a strong correlate of low screen-based sedentary behavior (OR = 0.73, p  = .002). Conclusion These data add to a growing body of work demonstrating the importance of perceived safety with physical activity levels in youth. Sports team participation may be a viable target to reduce screen-based sedentary time.

Background Numerous upper airway anatomy characteristics are risk factors for sleep apnea, which affects 26% of older Americans, and more severe sleep apnea is associated with cognitive impairment. This study explores the pathophysiology and links between upper airway anatomy, sleep, and cognition. Methods Participants in the Multi-Ethnic Study of Atherosclerosis underwent an upper airway MRI, polysomnography to assess sleep measures including the apnea-hypopnea index (AHI) and completed the Cognitive Abilities Screening Instrument (CASI). Two model selection techniques selected from among 67 upper airway measures those that are most strongly associated with CASI score. The associations of selected upper airway measures with AHI, AHI with CASI score, and selected upper airway anatomy measures with CASI score, both alone and after adjustment for AHI, were assessed using linear regression. Results Soft palate volume, maxillary divergence, and upper facial height were significantly positively associated with higher CASI score, indicating better cognition. The coefficients were small, with a 1 standard deviation (SD) increase in these variables being associated with a 0.83, 0.75, and 0.70 point higher CASI score, respectively. Additional adjustment for AHI very slightly attenuated these associations. Larger soft palate volume was significantly associated with higher AHI (15% higher AHI (95% CI 2%,28%) per SD). Higher AHI was marginally associated with higher CASI score (0.43 (95% CI 0.01,0.85) per AHI doubling). Conclusions Three upper airway measures were weakly but significantly associated with higher global cognitive test performance. Sleep apnea did not appear to be the mechanism through which these upper airway and cognition associations were acting. Further research on the selected upper airway measures is recommended.

Background An easy-to-use tool to objectively measure intraoral anatomy with meaningful clinical correlations may improve care for patients with Beckwith-Wiedemann syndrome (BWS), who commonly have symptomatic macroglossia. Methods Children aged 2–17 years with BWS were enrolled between 12/2021 and 01/2024. Digital intraoral photographs with a laser ruler were taken, and morphometric measurements were made using ImageJ software. Relationships between morphometrics and outcomes including BWS clinical score, percentage mosaicism, and incidence of tongue reduction surgery were examined using t-tests and multivariate linear models. Results Pharyngeal morphometric measurements were obtained in 49 patients with BWS. Mouth area, width, and height differed significantly across BWS molecular subtypes. Right-to-left tongue width and mouth width were larger in those with loss of methylation at imprinting control region 2 (IC2 LOM) than other BWS variants. Patients with paternal uniparental isodisomy of chromosome 11p15 (pUPD11) had narrower mouths than others. Those with tongue reduction surgery had more tongue ridging than those without surgery. There were correlations between mouth area and BWS clinical score, tongue width and BWS clinical score, and tongue length and percentage mosaicism. Conclusion Intraoral morphometric measurements are associated with phenotypic burden in BWS. Tongue morphology varies across the BWS spectrum, with IC2 LOM having wider tongues and mouths, and pUPD11 having narrower mouths. Tongue ridging is more common in those selected for surgery. Intraoral morphometric measurements may be safely obtained at low costs across centers caring for children with BWS or others at risk of upper airway obstruction.

Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities. Based in the Multi-Ethnic Study of Atherosclerosis, a longitudinal cohort study of community-dwelling adults, a comprehensive sleep study and an MRI of the upper airway and brain were performed on 578 participants. Machine learning models were used to select from 74 upper airway measures those measures most associated with selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between the selected upper airway measures, sleep measures, and brain structure. Maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and gray matter volume. Both coefficients were small (coefficients per standard deviation 0.063 mL, p = 0.04, and − 7.0 mL, p < 0.001 respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume (coefficient 0.164 mL, p = 0.007), and higher percentage of time in the N3 sleep stage was associated with larger total white and gray matter volume (4.8 mL, p = 0.004). Despite associations of two upper airway anatomy measures with brain volume, the evidence did not suggest that these upper airway and brain structure associations were acting primarily through the pathway of sleep disturbance.

Specific fat distributions are risk factors for complex diseases, including coronary heart disease and obstructive sleep apnea. To demonstrate the utility of high-diversity mouse models for elucidating genetic associations, we describe the phenotyping and heritability of fat distributions within the five classical inbred and three wild-derived founder mouse strains of the Collaborative Cross and Diversity Outbred mice. Measurements of subcutaneous and internal fat volumes in the abdomen, thorax and neck, and fat volumes in the tongue and pericardium were obtained using magnetic resonance imaging in male mice from the A/J (n = 12), C57BL/6J (n = 17), 129S1/SvlmJ (n = 12), NOD/LtJ (n = 14), NZO/HILtJ (n = 12), CAST/EiJ (n = 14), PWK/PhJ (n = 12), and WSB/EiJ (n = 15) strains. Phenotypes were compared across strains using analysis of variance and heritability estimated as the proportion of phenotypic variability attributable to strain. Heritability ranged from 44 to 91% across traits, including >70% heritability of tongue fat. A majority of heritability estimates remained significant controlling for body weight, suggesting genetic influences independent of general obesity. Principal components analysis supports genetic influences on overall obesity and specific to increased pericardial and intra-neck fat. Thus, among the founder strains of the Collaborative Cross and Diversity Outbred mice, we observed significant heritability of subcutaneous and internal fat volumes in the neck, thorax and abdomen, pericardial fat volume and tongue fat volume, consistent with genetic architecture playing an important role in explaining trait variability. Findings pave the way for studies utilizing high-diversity mouse models to identify genes affecting fat distributions and, in turn, influencing risk for associated complex disorders.

Abstract Study Objectives Increased neck circumference, a surrogate for the neck fat that can narrow the upper airway in obese individuals, is a risk factor for obstructive sleep apnea syndrome (OSAS) in adults, but the association between neck fat and OSAS in adolescent males and females is unknown. We hypothesized that obese adolescents with OSAS have more neck fat than controls, females more neck fat than males, and that neck fat correlates with obesity and OSAS severity. Methods Obese adolescents with OSAS and obese and normal-weight controls underwent upper airway magnetic resonance imaging, polysomnography, and anthropometrics, including neck circumference measurement. Intra-neck and subcutaneous neck fat measurements were manually segmented and compared among the three groups using ANOVA and between males and females using t-tests. The relationship between polysomnographic parameters and neck fat measurements was assessed in adolescents with OSAS using Pearson correlations. Results One-hundred nineteen adolescents (38 females) were studied: 39 obese with OSAS, 34 obese controls, and 46 normal-weight controls. Neck fat was not greater in adolescents with OSAS compared to obese controls (p=0.35), and neck fat volume was not related to OSAS severity (p = 0.36). However, obese adolescents had more neck fat than normal-weight controls (p < 0.001), and neck fat volume correlated with neck circumference (r = 0.53, p < 0.001). Females had significantly greater cross-sectional neck fat than males (p < 0.001). Conclusions While neck fat is associated with obesity and neck circumference in adolescents and is greater in females versus males, it does not appear to correlate with presence and severity of OSAS.

Obesity is a major risk factor for obstructive sleep apnea. Although greater dimensional changes in the upper airway during wake respiration have been noted in patients with apnea compared with control subjects, whether these differences remain in the presence of obesity is unknown. To evaluate upper airway anatomic characteristics and airway compliance (distensibility) in obese subjects with obstructive sleep apnea compared with obese control subjects. Dynamic magnetic resonance imaging was performed in 157 obese subjects with apnea and 46 obese control subjects during wakefulness in the midsagittal and three axial upper airway regions (retropalatal, retroglossal, epiglottal). Differences in measurements between subjects with apnea and control subjects, and correlations with apnea-hypopnea index among subjects with apnea, were examined. Measurements included airway areas and linear dimensions. Subject-specific coefficients of variation were calculated to examine variability in airway size. Controlling for covariates, the retropalatal area during respiration was significantly smaller in subjects with apnea than control subjects, based on the average (P = 0.003), maximum (P = 0.004), and minimum (P = 0.001) airway area. Airway narrowing was observed in anteroposterior and lateral dimensions (adjusted P < 0.05). Results were similar in an age, sex, and body mass index-matched subsample. There were significant correlations between apnea-hypopnea index and dynamic measures of airway caliber in the retropalatal and retroglossal regions among subjects with apnea. Upper airway caliber during respiration was significantly narrower in obese subjects with apnea than obese control subjects in the retropalatal region. These findings provide further evidence that retropalatal airway narrowing plays an important role in the pathogenesis of obstructive sleep apnea in obese subjects.

Abstract Study Objectives Tongue fat is associated with obstructive sleep apnea (OSA). Magnetic resonance imaging (MRI) is the standard for quantifying tongue fat. Ultrasound echo intensity has been shown to correlate to the fat content in skeletal muscles but has yet to be studied in the tongue. The objective of this study is to evaluate the relationship between ultrasound echo intensity and tongue fat. Methods Ultrasound coronal cross-sections of ex-vivo cow tongues were recorded at baseline and following three 1 mL serial injections of fat into the tongue. In humans, adults with and without OSA had submental ultrasound coronal cross-sections of their posterior tongue. The average echo intensity of the tongues (cow/human) was calculated in ImageJ software. Head and neck MRIs were obtained on human subjects to quantify tongue fat volume. Echo intensity was compared to injected fat volume or MRI-derived tongue fat percentage. Results Echo intensity in cow tongues showed a positive correlation to injected fat volume (rho = 0.93, p < .001). In human subjects, echo intensity of the tongue base strongly correlated with MRI-calculated fat percentage for both the posterior tongue (rho = 0.95, p < .001) and entire tongue (rho = 0.62, p < .001). Larger tongue fat percentages (rho = 0.38, p = .001) and higher echo intensity (rho = 0.27, p = .024) were associated with more severe apnea-hypopnea index, adjusted for age, body mass index, sex, and race. Conclusions Ultrasound echo intensity is a viable surrogate measure for tongue fat volume and may provide a convenient modality to characterize tongue fat in OSA.

Introduction This study aimed to evaluate upper airway soft tissues and craniofacial structures differences between Chinese and Caucasian patients with obstructive sleep apnea (OSA). Methods Airway sizes, soft tissue volumes and craniofacial dimensions quantified using three-dimensional magnetic resonance imaging (MRI) were compared between Caucasians (N=134) and Chinese (N=67) patients with moderate-severe OSA (AHI≥15 events/hour) matched for age and gender. Analyses were performed using mixed effects models. Results When compared to Caucasian patients, Chinese OSA patients had similar age (49.61±9.78 vs. 49.62±9.72 years, p=0.8702), lower BMI (28.0±3.5 vs. 33.46±5.67 kg/m2, p<0.0001) and no significant difference in AHI (45.68±21.54 vs. 41.3±15.78 events/hour, p=0.0959) ; smaller RP airway mean cross-sectional area (80.78±37.82 vs 147.3±62.8 mm2, p<0.0001) which may be contributed by bigger soft palate (11240±3422 vs 9801±2267 mm3, p<0.0001), but smaller combined soft tissues (176849±27366 vs 205000±33818 mm3, p<0.0001); bigger ANB angle (5.26±3.13 vs 2.93±2.66°, p<0.0001), different shaped mandibular including shorter mandibular corpus length (78.56±4.82 vs 94.41±6.60 mm, p<0.0001) but longer mandibular ramus length (66.40±5.75 vs 45.36±6.51mm, p<0.0001), and wider (width first molar 48.7±2.79vs 45.21±3.02 mm, p<0.0001) and shallower (unit depth 44.47±4.11 vs 47.57±3.96 mm, p<0.0001) maxillary. These findings remained after controlling age, AHI, height or age, AHI, BMI. Conclusion When compared to Caucasian patients, Chinese patients had bigger soft palates which likely contributes to the smaller airway in the retropalatal region, smaller combined soft tissue, and different shaped mandibular and maxillary bones. The anatomical basis of OSA is different in Caucasians and Chinese in several ways. Support (If Any) LX was supported by Young Elite Scientists Sponsorship Program of China Association for Science and Technology. Funds were also provided by NIH grant P01 HL094307.