Facial and Intraoral Photographic Traits Related to Sleep Apnea in a Clinical Sample with Genetic Ancestry Analysis.

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included (N = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized ß [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P < 0.001), mandibular width (standardized ß [95% CI] = 0.15 [0.10-0.20]; P < 0.001), and tongue thickness (standardized ß [95% CI] = 0.06 [0.02-0.10]; P = 0.001) and smaller airway width (standardized ß [95% CI] = -0.08 [-0.15 to -0.002]; P = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/ß-TCP)-Collagen Matrix as an Alternative to Autograft.

BACKGROUND: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (ß-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/ß-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/ß-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/ß-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/ß-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/ß-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE: Level I, prospective randomized study.

Mandibular dimensions in children with obstructive sleep apnea syndrome.

OBJECTIVE: We hypothesized that mandibular size may play a role in the etiology of obstructive sleep apnea syndrome (OSAS) in children, since a smaller mandible may reduce airway size. We used magnetic resonance imaging to determine the mandible dimensions of children with OSAS. DESIGN: Case control study. SETTING: Tertiary-care pediatric hospital. PARTICIPANTS: Twenty-four subjects (mean age 4.9 +/- 1.7 years) with mild to moderate OSAS (Apnea Index 3.5 +/- 5.1), and 24 matched controls (mean age 4.9 +/- 1.8 years). INTERVENTION: Magnetic resonance imaging of the upper airway under sedation. MEASUREMENTS: Eight measurements were obtained from a 3-dimensional segmentation of the mandible using 3DVIEWNIX software. Measurements included length, height, width, midsymphysis menti angle, angle of mandible, enclosure area, surface area, and volume. Descriptive comparisons using Student t test and multivariate analyses of variance were performed. RESULTS: Individual measurement comparisons revealed no significant differences between groups. Multivariate analysis showed a lower bound of a 95% confidence interval for an effect size measure for "general mandibular size," including all 6 linear, the area, and the volume measurements, to be -0.25. CONCLUSION: Our study shows that a smaller mandible is not a feature in children with OSAS who do not have apparent craniofacial abnormalities.

Heritability of craniofacial structures in normal subjects and patients with sleep apnea.

OBJECTIVES: Accumulating evidence has shown that there is a genetic contribution to obstructive sleep apnea (OSA).The objectives were to use magnetic resonance imaging (MRI) cephalometry to (1) confirm heritability of craniofacial risk factors for OSA previously shown by cephalometrics; and (2) examine the heritability of new craniofacial structures that are measurable with MRI. DESIGN: A sib pair "quad" design examining apneics, apneic siblings, controls, and control siblings. The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for differences in age, sex, ethnicity, height, and weight. SETTING: Academic medical center. PATIENTS: We examined 55 apneic probands (apnea-hypopnea index [AHI]: 46.8 ± 33.5 events/h), 55 proband siblings (AHI: 11.1 ± 15.9 events/h), 55 controls (AHI: 2.2 ± 1.7 events/h), and 55 control siblings (AHI: 4.1 ± 4.0 events/h). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Five independent domains reflecting different aspects of the craniofacial structure were examined. We confirmed heritability of sella-nasion-subspinale (38%, P = 0.002), saddle angle (55%, P < 0.0001), mandibular length (24%, P = 0.02) and lower facial height (33%, P = 0.006) previously measured by cephalometry. In addition, the current study added new insights by demonstrating significant heritability of mandibular width (30%, P = 0.005), maxillary width (47%, P < 0.0001), distance from the hyoid bone to the retropogonion (36%, P = 0.0018) and size of the oropharyngeal space (31%, P = 0.004). Finally, our data indicate that heritability of the craniofacial structures is similar in normal patients and those with apnea. CONCLUSIONS: The data support our a priori hypothesis that the craniofacial structures that have been associated with obstructive sleep apnea (OSA) are heritable. We have demonstrated heritability for several intermediate craniofacial phenotypes for OSA. Thus, we believe that future studies should be able to identify genes associated with these intermediate craniofacial phenotypes.

Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in Icelandic sleep apnea patients.

STUDY OBJECTIVES: (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity. DESIGN: Cross-sectional cohort. SETTING: Landspitali, The National University Hospital, Iceland. PARTICIPANTS: One hundred forty patients (87.1% male) from the Icelandic Sleep Apnea Cohort who had both calibrated frontal and profile craniofacial photographs and upper airway MRI. Mean ± standard deviation age 56.1 ± 10.4 y, body mass index 33.5 ± 5.05 kg/m(2), with on-average severe OSA (apnea-hypopnea index 45.4 ± 19.7 h(-1)). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Relationships between surface facial dimensions (photos) and facial bony dimensions and upper airway soft-tissue volumes (MRI) was assessed using canonical correlation analysis. Photo and MRI craniofacial datasets related in four significant canonical correlations, primarily driven by measurements of (1) maxillary-mandibular relationship (r = 0.8, P < 0.0001), (2) lower face height (r = 0.76, P < 0.0001), (3) mandibular length (r = 0.67, P < 0.0001), and (4) tongue volume (r = 0.52, P = 0.01). Correlations 1, 2, and 3 were unchanged when controlled for weight and neck and waist circumference. However, tongue volume was no longer significant, suggesting facial dimensions relate to tongue volume as a result of obesity. CONCLUSIONS: Significant associations were found between craniofacial variable sets from facial photography and MRI. This study confirms that facial photographic phenotype reflects underlying aspects of craniofacial skeletal abnormalities associated with OSA. Therefore, facial photographic phenotyping may be a useful tool to assess intermediate phenotypes for OSA, particularly in large-scale studies.

Linear dimensions of the upper airway structure during development: assessment by magnetic resonance imaging.

The upper airway undergoes progressive changes during childhood. Using magnetic resonance imaging (MRI), we studied the growth relationships of the tissues surrounding the upper airway (bone and soft tissues) in 92 normal children (47% males; range, 1 to 11 yr) who underwent brain MRI. None had symptoms of sleep-disordered breathing or conditions that impacted on their upper airway. MRI was performed under sedation. Sequential T1-weighted spin echo sagittal and axial sections were obtained and analyzed on a computer. We measured lower face skeletal growth along the midsagittal and axial oropharyngeal planes. In the midsagittal plane the mental spine-clivus distance related linearly to age (r = 0.86, p < 0.001). Along this axis, the dimensions of tongue, soft palate, nasopharyngeal airway, and adenoid increased with age and maintained constant proportion to the mental spine-clivus distance. Similarly, a linear relationship was noted for mandibular growth measured along the intermandibular line on the axial plane and age (r = 0.78, p < 0.001). In addition, the intertonsillar, tonsils, parapharyngeal fat pads, and pterygoids widths maintained constant proportion to intermandibular width with age. We conclude that the lower face skeleton grows linearly along the sagittal and axial planes from the first to the eleventh year. Our data indicate that soft tissues, including tonsils and adenoid, surrounding the upper airway grow proportionally to the skeletal structures during the same time period.