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Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese (NZO) mouse and in a control lean mouse, the New Zealand White (NZW).Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber.Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures, and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI). Dynamic MRI was used to examine the differences in upper airway caliber between inspiration and expiration in NZO versus NZW mice.Measurements and Main Results: The data support the hypothesis that, in obese NZO versus lean NZW mice, airway caliber was significantly smaller (P < 0.03), with greater parapharyngeal fat pad volumes (P < 0.0001) and a greater volume of other upper airway soft tissue structures (tongue, P = 0.003; lateral pharyngeal walls, P = 0.01; soft palate, P = 0.02). Dynamic MRI showed that the airway of the obese NZO mouse dilated during inspiration, whereas in the lean NZW mouse, the upper airway was reduced in size during inspiration.Conclusions: In addition to the increased volume of pharyngeal soft tissue structures, direct fat deposits within the tongue may contribute to airway compromise in obesity. Pharyngeal airway dilation during inspiration in NZO mice compared with narrowing in NZW mice suggests that airway compromise in obese mice may lead to muscle activation to defend upper airway patency during inspiration. [ABSTRACT FROM AUTHOR]

Sleepiness plays an important role in major crashes of commercial vehicles. Because determinants are likely to include inadequate sleep and sleep apnea, we evaluated the role of short sleep durations over 1 wk at home and sleep apnea in subjective sleepiness (Epworth Sleepiness Scale), objective sleepiness (reduced sleep latency as determined by the Multiple Sleep Latency Test), and neurobehavioral functioning (lapses in performance, tracking error in Divided Attention Driving Task) in commercial drivers. Studies were conducted in 247 of 551 drivers at higher risk for apnea and in 159 of 778 drivers at lower risk. A multivariate linear association between the sets of outcomes and risk factors was confirmed (p < 0.0001). Increases in subjective sleepiness were associated with shorter sleep durations but not with increases in severity of apnea. Increases in objective sleepiness and performance lapses, as well as poorer lane tracking, were associated with shorter sleep durations. Associations with sleep apnea severity were not as robust and not strictly monotonic. A significant linear association with sleep apnea was demonstrated only for reduced sleep latency. The effects of severe apnea (apnea-hypopnea index, at least 30 episodes/h), which occurred in 4.7%, and of sleep duration less than 5 h/night, which occurred in 13.5%, were similar in terms of their impact on objective sleepiness. Thus, addressing impairment in commercial drivers requires addressing both insufficient sleep and sleep apnea, the former being more common. [ABSTRACT FROM AUTHOR]

Rationale: Sleep apnea is believed to be a genetic disorder. Thus, we hypothesized that anatomic risk factors for sleep apnea would demonstrate family aggregation.Objectives: We used volumetric magnetic resonance imaging in a sib pair "quad" design to study the family aggregation of the size of upper airway soft tissue structures that are associated with increased risk for obstructive sleep apnea.Methods: We examined 55 sleep apnea probands (apnea-hypopnea index [AHI]: 43.2 +/- 26.3 events/h), 55 proband siblings (AHI: 11.8 +/- 16.6 events/h), 55 control subjects (AHI: 2.1 +/- 1.7 events/h), and 55 control siblings (AHI: 4.2 +/- 4.0 events/h). The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for visceral neck fat and craniofacial dimensions.Measurements and Main Results: The data support our a priori hypothesis that the volume of the important upper airway soft tissue structures is heritable. The volume of the lateral pharyngeal walls (h(2) = 36.8%; p = 0.001), tongue (h(2) = 36.5%; p = 0.0001), and total soft tissue (h(2) = 37.5%; p = 0.0001) demonstrated significant levels of heritability after adjusting for sex, ethnicity, age, visceral neck fat, and craniofacial dimensions. In addition, our data indicate that heritability of the upper airway soft tissue structures is found in normal subjects and patients with apnea. Thus, it is not simply a consequence of the prevalence of apnea.Conclusions: This is the first time family aggregation of size of the upper airway soft tissue structures has been demonstrated. [ABSTRACT FROM AUTHOR]

Since the original clarification of the obstructive nature of obstructive sleep apnea (OSA) in 1965, much has been learned about the disorder. It is a condition with a high prevalence with obesity as a major risk factor. It aggregates in families, a relationship that is not simply explained by obesity. Premenopausal women are relatively protected from the disorder because OSA is uncommon in this group. Its prevalence in women rises after menopause. Although OSA is a risk factor for excessive sleepiness, there is developing evidence that it is also a risk factor for hypertension, acute cardiovascular events, and insulin resistance. The first line of therapy is nasal continuous positive airway pressure. Data as to the efficacy of continuous positive airway pressure in severe OSA have come from randomized, placebo-controlled clinical trials with the endpoints being sleepiness, quality of life, and 24-h ambulatory blood pressure. Data are currently less convincing for treatment outcomes in mild to moderate OSA, and new clinical trials to assess outcomes in this group are underway. Thus, even though this field only began toward the end of the first century of the American Thoracic Society, substantial progress has been made, and OSA has increasingly emerged as a major public health concern. [ABSTRACT FROM AUTHOR]

Unlabelled: We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Methods: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.Results: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Conclusions: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor. [ABSTRACT FROM AUTHOR]

Excluding the presence of obstructive sleep apnea in commercial drivers is valuable, as the syndrome may increase their risk of sleepiness-related accidents. Using polysomnography as the criterion standard, we prospectively compared accuracies of five strategies in excluding the presence of severe sleep apnea and, secondarily, any sleep apnea among 406 commercial drivers. These strategies were as follows: (1) symptoms; (2) body mass index; (3) symptoms plus body mass index; (4) a two-stage approach with symptoms plus body mass index for everyone, followed by oximetry for a subset; and (5) oximetry for all. For excluding severe apnea, the two-stage strategy was highly successful, with 91% sensitivity and specificity, and a negative likelihood ratio of 0.10. This strategy was comparable in accuracy to oximetry, which had a negative likelihood ratio of 0.12, and was 88% sensitive and 95% specific. If we avoided oximetry altogether, then symptoms together with body mass index were 81% sensitive and 73% specific, with a negative likelihood ratio of 0.26. On the other hand, excluding any apnea could not be done with reasonable accuracy unless oximetry was used. We conclude that two-stage screening is likely to be a viable means of excluding severe sleep apnea among commercial drivers. [ABSTRACT FROM AUTHOR]

We used sophisticated volumetric analysis techniques with magnetic resonance imaging in a case-control design to study the upper airway soft tissue structures in 48 control subjects (apnea-hypopnea index, 2.0 +/- 1.6 events/hour) and 48 patients with sleep apnea (apnea-hypopnea index, 43.8 +/- 25.4 events/hour). Our design used exact matching on sex and ethnicity, frequency matching on age, and statistical control for craniofacial size and visceral neck fat. The data support our a priori hypotheses that the volume of the soft tissue structures surrounding the upper airway is enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea. After covariate adjustments the volume of the lateral pharyngeal walls (p < 0.0001), tongue (p < 0.0001), and total soft tissue (p < 0.0001) was significantly larger in subjects with sleep apnea than in normal subjects. These data also demonstrated, after covariate adjustments, significantly increased risk of sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue: (1) total lateral pharyngeal wall (odds ratio [OR], 6.01; 95% confidence interval [CI], 2.62-17.14); (2) total tongue (OR, 4.66; 95% CI, 2.31-10.95); and (3) total soft tissue (OR, 6.95; 95% CI, 3.08-19.11). In a multivariable logistic regression analysis the volume of the tongue and lateral walls was shown to independently increase the risk of sleep apnea. [ABSTRACT FROM AUTHOR]

Detailed analysis of the upper airway has not been performed in children with obstructive sleep apnea. We used magnetic resonance imaging and automatic segmentation to delineate the upper airway in 20 children with obstructive sleep apnea and in 20 control subjects (age, 3.7 +/- 1.4 versus 3.9 +/- 1.7 years, respectively). We measured mean and minimal cross-sectional area, length, and volume of: (1) the total airway; (2) regions along the adenoid, tonsils, and where adenoid and tonsils overlap; and (3) 10 segments at 10% increments along the airway. The mean cross-sectional area of the total airway of the obstructive sleep apnea group was significantly smaller in comparison with the control group, 28.1 +/- 12.6 versus 47.1 +/- 18.2 mm2, respectively (p < 0.0005). Minimal cross-sectional area and airway volume were smaller in this group, 4.6 +/- 3.3 versus 15.7 +/- 12.7 mm2 (p < 0.0005), and 1,129 +/- 515 versus 1,794 +/- 846 mm3 (p < 0.005), respectively. Regional analysis suggested that the upper airway in children with obstructive sleep apnea is most restricted where adenoid and tonsils overlap. Segmental analysis demonstrated that the upper airway is restricted throughout the initial two-thirds of its length and that the narrowing is not in a discrete region adjacent to either the adenoid or tonsils, but rather in a continuous fashion along both. [ABSTRACT FROM AUTHOR]

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 β [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P  < 0.001), mandibular width (standardized β [95% CI] = 0.15 [0.10-0.20]; P  < 0.001), and tongue thickness (standardized β [95% CI] = 0.06 [0.02-0.10]; P  = 0.001) and smaller airway width (standardized β [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.

Rationale: Obesity is the primary risk factor for obstructive sleep apnea (OSA). Tongue fat is increased in obese persons with OSA, and may explain the relationship between obesity and OSA. Weight loss improves OSA, but the mechanism is unknown. Objectives: To determine the effect of weight loss on upper airway anatomy in subjects with obesity and OSA. We hypothesized that weight loss would decrease soft tissue volumes and tongue fat, and that these changes would correlate with reductions in apnea-hypopnea index (AHI). Methods: A total of 67 individuals with obesity and OSA (AHI ≥ 10 events/h) underwent a sleep study and upper airway and abdominal magnetic resonance imaging before and after a weight loss intervention (intensive lifestyle modification or bariatric surgery). Airway sizes and soft tissue, tongue fat, and abdominal fat volumes were quantified. Associations between weight loss and changes in these structures, and relationships to AHI changes, were examined. Measurements and Main Results: Weight loss was significantly associated with reductions in tongue fat and pterygoid and total lateral wall volumes. Reductions in tongue fat were strongly correlated with reductions in AHI (Pearson's rho = 0.62, P  < 0.0001); results remained after controlling for weight loss (Pearson's rho = 0.36, P  = 0.014). Reduction in tongue fat volume was the primary upper airway mediator of the relationship between weight loss and AHI improvement. Conclusions: Weight loss reduced volumes of several upper airway soft tissues in subjects with obesity and OSA. Improved AHI with weight loss was mediated by reductions in tongue fat. New treatments that reduce tongue fat should be considered for patients with OSA.

Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences. Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study. Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality. Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease ( P  < 0.001), coronary heart disease ( P  = 0.015), and heart failure ( P  = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype. Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

Rationale: 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., Objectives: To evaluate upper airway anatomic characteristics and airway compliance (distensibility) in obese subjects with obstructive sleep apnea compared with obese control subjects., Methods: 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 and Main Results: 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., Conclusions: 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.

Dr. Leroy Hood promotes a paradigm to advance medical care that he calls P4 medicine. The four Ps are: personalized, predictive, preventative, and participatory. P4 medicine encourages a convergence of systems medicine, the digital revolution, and consumer-driven healthcare. Might P4 medicine be applicable to obstructive sleep apnea (OSA)? OSA should be personalized in that there are different structural and physiological pathways to disease. Obesity is a major risk factor. The link between obesity and OSA is likely to be fat deposits in the tongue compromising the upper airway. Clinical features at presentation also vary between patients. There are three distinct subgroups: (1) patients with a primary complaint of insomnia, (2) relatively asymptomatic patients with a high prevalence of cardiovascular comorbidities, and (3) excessively sleepy patients. Currently, there have been limited efforts to identify subgroups of patients on the basis of measures obtained by polysomnography. Yet, these diagnostic studies likely contain considerable predictive information. Likewise, there has currently been limited application of -omic approaches. Determining the relative role of obesity and OSA for particular consequences is challenging, because they both affect the same molecular pathways. There is evidence that the effects of OSA are modified by the level of obesity. These insights may lead to improvements in predicting outcomes to personalized therapies. The final P-participatory-is ideally suited to OSA, with technology to obtain extensive data remotely from continuous positive airway pressure machines. Providing adherence data directly to patients increases their use of continuous positive airway pressure. Thus, the concept of P4 medicine is very applicable to obstructive sleep apnea and can be the basis for future research efforts.

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.

Obstructive sleep apnea may lead to complications if not identified and treated. Polysomnography is the diagnostic standard, but is often inaccessible due to bed shortages. A system that facilitates prioritization of patients requiring sleep studies would thus be useful. We retrospectively compared the accuracy of a two-stage risk-stratification algorithm for sleep apnea using questionnaire plus nocturnal pulse oximetry against using polysomnography to identify patients without apnea (Objective 1) and those with severe apnea (Objective 2). Patients were those referred to a university-based sleep disorders clinic due to suspicion of sleep apnea. Subjects completed a sleep apnea symptom questionnaire, and underwent oximetry and two-night polysomnography. We used bootstrap methodology to maximize sensitivity of our model for Objective 1 and specificity for Objective 2. We calculated sensitivity, specificity, positive and negative predictive values, and rate of misclassification error of the two-stage risk-stratification algorithm for each of our two objectives. The model identified cases of sleep apnea with 95% sensitivity and severe apnea with 97% specificity. It excluded only 8% of patients from sleep studies, but prioritized up to 23% of subjects to receive in-laboratory studies. Among sleep disorders clinic referrals, a two-stage risk-stratification algorithm using questionnaire and nocturnal pulse oximetry excluded few patients from sleep studies, but identified a larger proportion of patients who should receive early testing because of their likelihood of having severe disease.

Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of modafinil for the treatment of residual daytime sleepiness in such patients. Patients received modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p < 0.001) and in multiple sleep latency times (MSLT) at Week 4 (p < 0.05). The percentage of patients with normalized daytime sleepiness (Epworth score < 10) was significantly higher with modafinil (51%) than with placebo (27%) (p < 0.01), but not for MSLT (> 10 min; 29% versus 25%). Headache (modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (modafinil, 12%; placebo, 3%; p = 0.024) were the most common adverse events. During modafinil or placebo treatment, the mean duration of nCPAP use was 6.2 h/night, with no significant change from baseline observed between groups. Modafinil may be a useful adjunct treatment for the management of residual daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome who are regular users of nasal continuous positive airway pressure therapy.

The anatomical relationships between lymphoid, bony, and other tissues affecting the shape of the upper airway in children with obstructive sleep apnea syndrome (OSAS) have not been established. We therefore compared the upper airway structure in 18 young children with OSAS (age 4.8 +/- 2.1 yr; 12 males and 6 females) and an apnea index of 4.3 +/- 3.9, with 18 matched control subjects (age, 4.9 +/- 2.0 yr; 12 males and 6 females). All subjects underwent magnetic resonance imaging under sedation. Axial and sagittal T1- and T2-weighted sequences were obtained. Images were analyzed with image-processing software to obtain linear, area, and volumetric measurements of the upper airway and the tissues comprising the airway. The volume of the upper airway was smaller in subjects with OSAS in comparison with control subjects (1.5 +/- 0.8 versus 2.5 +/- 1.2 cm(3); p < 0.005) and the adenoid and tonsils were larger (9.9 +/- 3.9 and 9.1 +/- 2.9 cm(3) versus 6.4 +/- 2.3 and 5.8 +/- 2.2 cm(3); p < 0.005 and p < 0.0005, respectively). Volumes of the mandible and tongue were similar in both groups; however, the soft palate was larger in subjects with OSAS (3.5 +/- 1.1 versus 2.7 +/- 1.2 cm(3); p < 0.05). We conclude that in children with moderate OSAS, the upper airway is restricted both by the adenoid and tonsils; however, the soft palate is also larger in this group, adding further restriction.

As compared with control subjects, children with Down syndrome have different size and shape relationships among tissues composing the upper airway, which may predispose them to obstructive sleep apnea (OSA). We hypothesized that Down syndrome children without OSA have similar subclinical differences. We used magnetic resonance imaging to study the upper airway in 11 Down syndrome children without OSA (age, 3.2 +/- 1.4 yr) and in 14 control subjects (age, 3.3 +/- 1.1 yr). Sequential T1- and T2-weighted spin-echo axial and sagittal images were obtained. We found a smaller airway volume in subjects with Down syndrome (1.4 +/- 0.4 versus 2.3 +/- 0.8 cm(3) in controls, p < 0.005). Subjects with Down syndrome had a smaller mid- and lower face skeleton. They had a shorter mental spine-clivus distance (5.7 +/- 0.6 versus 6.2 +/- 0.4 cm, p < 0.05), hard palate length (3.2 +/- 0.4 versus 3.7 +/- 0.2 cm, p < 0.005), and mandible volume (11.5 +/- 3.7 versus 16.9 +/- 2.9 cm3, p < 0.0005). Adenoid and tonsil volume was significantly smaller in the subjects with Down syndrome. However, the tongue, soft-palate, pterygoid, and parapharyngeal fat pads were similar to those of control subjects. This study shows that Down syndrome children without OSA do not have increased adenoid or tonsillar volume; reduced upper airway size is caused by soft tissue crowding within a smaller mid- and lower face skeleton.

Unlabelled: Little is known about sleep/wake abnormalities in intensive care and less is known about the mechanisms responsible for these abnormalities. We studied 22 (20 mechanically ventilated) medical intensive care unit (ICU) patients with continuous polysomnography (PSG) and environmental noise measurements for 24-48 h to characterize sleep-wake patterns and objectively determine the effect of environmental noise on sleep disruption. All 22 patients demonstrated sleep-wake cycle abnormalities. There were large variations in total sleep time (TST) with the mean total sleep time per 24-h study period of 8.8 +/- 5.0 h. Sleep-wake cycles were fragmented and nonconsolidated with a mean of 57 +/- 18% and 43 +/- 18% of the TST occurring during the day and night, respectively. Environmental noise was responsible for 11.5 and 17% of the overall arousals and awakenings from sleep, respectively. The mean noise arousal index was 1.9 +/- 2.1 arousals/h sleep., Conclusions: (1) ICU patients are qualitatively, but not necessarily quantitatively, sleep deprived; and (2) although environmental noise is in part responsible for sleep-wake abnormalities, it is not responsible for the majority of the sleep fragmentation and may therefore not be as disruptive to sleep as the previous literature suggests.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a prevalent disorder, for which there are no universally effective pharmacotherapeutics. We hypothesized that in OSAHS, excitatory serotoninergic influences are important for maintaining patency of the upper airway in waking, and that in sleep, reduced serotoninergic drive plays a significant role in upper airway collapse and OSAHS. The previously reported small responses in humans with OSAHS to serotoninergics may relate, in part, to study design and the drugs/doses selected. We therefore performed multitrials/dose, multidose, randomized sleep studies testing the effectiveness of a combination of serotoninergics, trazodone, and L-tryptophan, in our animal model of OSAHS, the English bulldog. Trazodone/L-tryptophan caused dose-dependent reductions in respiratory events in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS). During NREMS, the respiratory disturbance index (RDI) +/- standard error was 6.3 +/- 1.4 events/h (placebo) and 0.9 +/- 0.3 (highest dose), p < 0.01. During REMS, the RDI was 31.4 +/- 6.1 events/h (placebo) and 11.5 +/- 4.3 (highest dose), p = 0.002. Trazodone/ L-tryptophan dose-dependently reduced sleep fragmentation, p = 0.03, increased sleep efficiency, p = 0.005, enhanced slow-wave sleep, p = 0.0004, and minimized sleep-related suppression of upper airway dilator activity, p < 0.02. Trazodone with L-tryptophan can treat sleep-disordered breathing (SDB) in an animal model of OSAHS; the effectiveness of this therapy may be related to increased upper airway dilator activity in sleep and/or enhanced slow-wave sleep.

Several features of obstructive sleep apnea (OSA) suggest that it may be an appropriate disease for screening programs for general populations and more specific high-risk groups. Preliminary data suggest that OSA represents an important health problem in terms of high prevalence, increased levels of morbidity and mortality, and increased public safety risk. Furthermore, the chronicity of the disease and the relatively low levels of recognition of the disorder in the medical community suggest a potential for lead-time gains for screening programs. Specific groups that might be considered for screening programs include commercial vehicle operators, hazardous duty personnel, and certain groups of medical patients. The purpose of this clinical commentary is to consider the issues of population and specific group screening for OSA by reviewing the general principles of screening for chronic disease and then applying these principles specifically in the case of OSA. More extensive outcomes data relating levels of severity of the disorder to its potential adverse outcomes are needed and will assist in tailoring appropriate screening programs and determining the cost-effectiveness of screening various populations.

Nasal continuous positive airway pressure (CPAP) is the treatment of choice for adults with obstructive sleep apnea. CPAP is known to increase upper airway size; however, the direct effects of CPAP on soft tissue structures surrounding the upper airway are less well understood. Magnetic resonance imaging was used to study the effect of incremental levels (0, 5, 10, and 15 cm H2O) of CPAP on the upper airway and surrounding soft tissue structures in 10 normal subjects. Progressive increases in CPAP resulted in the following major findings: (1) airway volume and airway area (measured at several different locations [midregion, minimal, maximal]) within the retropalatal and retroglossal regions increased; (2) lateral airway dimensional changes were greater than anterior-posterior changes; (3) lateral upper airway soft tissue structural changes were significantly greater than anterior-posterior changes; (4) lateral pharyngeal wall thickness decreased and the distance between the lateral parapharyngeal fat pads increased. An inverse relationship was demonstrated between CPAP level and pharyngeal wall thickness; (5) minimal changes were noted in the soft palate and tongue. These data suggest that the lateral pharyngeal walls are more "compliant" than the soft palate and tongue. This investigation provides further evidence that the lateral pharyngeal walls play an important role in mediating upper airway caliber.

Recent studies have shown excitatory effects of serotonin on upper airway motoneurons. This excitatory effect is normally present and arises from cells in the caudal raphe nuclei. The firing of these serotonergic neurons is reduced during sleep. To determine the importance of serotonin in the maintenance of patient airways and normal respiration in waking in obstructive sleep apnea, we studied the effects of two serotonin antagonists on upper airway dilator muscle activity, diaphragm activity, Sao2, and upper airway cross-sectional area in an animal model of sleep-disordered breathing, the English bulldog. Systemic administration of both antagonists resulted in significant reductions in the peak amplitudes of upper airway muscle respiratory bursts (range, 39 to 62% suppression; p < 0.05). Lesser reductions in diaphragm activity were noted (range, 10 to 33% suppression; p < 0.05). Oxyhemoglobin saturations also fell (p < 0.05), coinciding with suppressions in upper airway muscle activity. With reductions in dilator muscle activity, upper airway cross-sectional areas, as measured with cine CT, showed significant inspiratory collapse. These results support the hypothesis that serotonin is important in the maintenance of patent upper airways in obstructive sleep apnea.

The geometry and caliber of the upper airway in apneic patients differs from those in normal subjects. The apneic airway is smaller and is narrowed laterally. Examination of the soft tissue structures surrounding the upper airway can lead to an understanding of these apneic airway dimensional changes. Magnetic resonance imaging was utilized to study the upper airway and surrounding soft tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26 patients with obstructive sleep apnea. The major findings of this investigation in the 68 subjects were as follows: (1) minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region; (2) airway narrowing in apneic patients was predominantly in the lateral dimension; there was no significant difference in the anterior-posterior (AP) airway dimension between subject groups; and (3) distance between the rami of the mandible was equal between subject groups, and thus the narrowing of the lateral dimension was not explained by differences in bony structure; (4) lateral airway narrowing was explained predominantly by larger pharyngeal walls in apneic patients (the parapharyngeal fat pads were not closer together as one would expect if the airway walls were compressed by fat); and (5) fat pad size at the level of the minimum airway was not greater in apneic than normal subjects. At the minimum airway area, thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pads was the predominant anatomic factor causing airway narrowing in apneic subjects.