Objective adherence to dental device versus positive airway pressure treatment in adults with obstructive sleep apnea.

Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.

Insomnia complaints in lean patients with obstructive sleep apnea negatively affect positive airway pressure treatment adherence.

The objective of this study was to evaluate the determinants of long-term adherence to positive airway pressure treatment among patients with obstructive sleep apnea, with special emphasis on patients who stop positive airway pressure treatment within 1 year. This is a prospective long-term follow-up of subjects in the Icelandic Sleep Apnea Cohort who were diagnosed with obstructive sleep apnea between 2005 and 2009, and started on positive airway pressure treatment. In October 2014, positive airway pressure adherence was obtained by systematically evaluating available clinical files (n = 796; 644 males, 152 females) with moderate to severe obstructive sleep apnea (apnea-hypopnea index ≥15 events per h). The mean follow-up time was 6.7 ± 1.2 years. In total, 123 subjects (15.5%) returned their positive airway pressure device within the first year, 170 (21.4%) returned it later and 503 (63.2%) were still using positive airway pressure. The quitters within the first year had lower body mass index, milder obstructive sleep apnea, less sleepiness, and more often had symptoms of initial and late insomnia compared with long-term positive airway pressure users at baseline. Both initial and late insomnia were after adjustment still significantly associated with being an early quitter among subjects with body mass index <30 kg m-2 , but not among those with body mass index ≥30 kg m-2 . The prevalence of early quitters decreased significantly during the study period (2005-2009). Almost two-thirds of patients with moderate to severe obstructive sleep apnea are positive airway pressure users after 7 years. Obesity level, obstructive sleep apnea severity and daytime sleepiness are important determinants of long-term adherence. Symptoms of initial and late insomnia are associated with early quitting on positive airway pressure among non-obese subjects.

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.

Differences in three-dimensional upper airway anatomy between Asian and European patients with obstructive sleep apnea.

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.

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.

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.

The validity and feasibility of saliva melatonin assessment in the elderly.

Recent work in young and middle-aged subjects suggests that melatonin levels in saliva may represent a viable alternative to serum melatonin measurement. We hypothesized that it may be a valid measure of melatonin levels in older adults as well, but features unique to the elderly may limit its utility. To study this, subjects were admitted to an academic medical center where saliva and serum specimens were collected concurrently in dim light conditions during a 14-hr overnight study period and analyzed for melatonin levels with radioimmunoassays (RIAs). Eighty-five subjects over the age of 65 with a broad range of medical conditions participated in the study. Subjects with dementia, depression and anemia were excluded. We found that saliva volume was inadequate for analysis (<200 microL) in 23.6% of specimens, with the majority of inadequate volume specimens occurring after midnight and inadequate specimens occurring more frequently in females than in males. The correlation coefficient for saliva melatonin and serum melatonin was r = 0.659 (Spearman, P < 0.001), and r = 0.466 for saliva dim light melatonin onset (DLMO) and serum DLMO. Saliva melatonin levels were 30.9% of serum melatonin levels, with a wide range of ratios noted between subjects. Overall melatonin levels influenced both the correlation and ratio of saliva melatonin to serum melatonin; higher correlations and lower ratios were noted when melatonin levels were high. Saliva specimens provide an economical and practical method for melatonin assessment, however, in older adults, issues such as hyposalivation and low melatonin levels limit the feasibility and validity, respectively, of saliva melatonin.

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.