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Objectives: Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short‐ versus long‐term exposure to intermittent hypoxia (IH) on pro‐inflammatory mediators within vulnerable organs impacted by OSA. Study Design: Experimental animal study. Methods: A total of 8–10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short‐term) or 6 weeks (long‐term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro‐inflammatory mediators from peripheral tissues. Results: We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short‐term exposure to IH. Although there were tissue‐specific alterations in the gene expression of pro‐inflammatory mediators, with down‐regulation in the lung and up‐regulation in the heart, we also observed reduced protein levels of pro‐inflammatory mediators in the serum, lung, and heart following short‐term exposure to IH. Long‐term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart. Conclusions: We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs. Level of Evidence: NA Laryngoscope, 134:S1–S11, 2024 [ABSTRACT FROM AUTHOR]

Objective: To develop an expert consensus statement regarding persistent pediatric obstructive sleep apnea (OSA) focused on quality improvement and clarification of controversies. Persistent OSA was defined as OSA after adenotonsillectomy or OSA after tonsillectomy when adenoids are not enlarged. Methods: An expert panel of clinicians, nominated by stakeholder organizations, used the published consensus statement methodology from the American Academy of Otolaryngology‐Head and Neck Surgery to develop statements for a target population of children aged 2‐18 years. A medical librarian systematically searched the literature used as a basis for the clinical statements. A modified Delphi method was used to distill expert opinion and compose statements that met a standardized definition of consensus. Duplicate statements were combined prior to the final Delphi survey. Results: After 3 iterative Delphi surveys, 34 statements met the criteria for consensus, while 18 statements did not. The clinical statements were grouped into 7 categories: general, patient assessment, management of patients with obesity, medical management, drug‐induced sleep endoscopy, surgical management, and postoperative care. Conclusion: The panel reached a consensus for 34 statements related to the assessment, management and postoperative care of children with persistent OSA. These statements can be used to establish care algorithms, improve clinical care, and identify areas that would benefit from future research. [ABSTRACT FROM AUTHOR]

Objective: To characterize polysomnographic sleep architecture in children with Down syndrome and compare findings in those with and without obstructive sleep apnea.Study Design: Case series with retrospective review.Setting: Single tertiary pediatric hospital (2005-2018).Methods: We reviewed the electronic health records of patients undergoing polysomnography who were referred from a specialized center for children with Down syndrome (age, ≥12 months). Continuous positive airway pressure titration, oxygen titration, and split-night studies were excluded.Results: A total of 397 children were included (52.4% male, 81.6% Caucasian). Mean age at the time of polysomnography was 4.7 years (range, 1.4-14.7); 79.4% had obstructive sleep apnea. Sleep variables were reported as mean (SD) values: sleep efficiency, 85% (11%); sleep latency, 29.8 minutes (35.6); total sleep time, 426 minutes (74.6); rapid eye movement (REM) latency, 126.8 minutes (66.3); time spent in REM sleep, 22% (7%); arousal index, 13.3 (5); and time spent supine, 44% (28%). There were no significant differences between those with obstructive sleep apnea and those without. Sleep efficiency <80% was seen in 32.5%; 34.3% had a sleep latency >30 minutes; 15.9% had total sleep time <360 minutes; and 75.6% had an arousal index >10/h. Overall, 69.2% had ≥2 metrics of poor sleep architecture. REM sleep time <20% was seen in 35.3%. REM sleep time decreased with age.Conclusion: In children with Down syndrome, 32.5% had sleep efficiency <80%; 75.6% had an elevated arousal index; and 15.9% had total sleep time <360 minutes. More than a third of the patients had ≥3 markers of poor sleep architecture. There was no difference in children with or without obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

Objectives: To compare the demographic and clinical characteristics of children with Down syndrome who did and did not receive polysomnography to evaluate for obstructive sleep apnea after publication of the American Academy of Pediatrics' guidelines recommending universal screening by age 4 years.Study Design: Retrospective cohort study.Setting: Single tertiary pediatric hospital.Methods: Review was conducted of children with Down syndrome born between 2007 and 2012. Children who obtained polysomnography were compared with children who did not, regarding demographic data, socioeconomic status, and comorbidities.Results: We included 460 children with Down syndrome; 273 (59.3%) received at least 1 polysomnogram, with a median age of 3.6 years (range, 0.1-8.9 years). There was no difference in the distribution of sex, insurance status, or socioeconomic status between children who received polysomnography and those who did not. There was a significant difference in race distribution (P = .0004) and distance from home to the medical center (P < .0001) between groups. Among multiple medical comorbidities, only children with a history of hypothyroidism (P = .003) or pulmonary aspiration (P = .01) were significantly more likely to have obtained polysomnography.Conclusions: Overall, 60% of children with Down syndrome obtained a polysomnogram. There was no difference between groups by payer status or socioeconomic status. A significant difference in race distribution was noted. Proximity to the medical center and increased medical need appear to be associated with increased likelihood of obtaining a polysomnogram. This study illustrates the need for improvement initiatives to increase the proportion of patients receiving guideline-based screening. [ABSTRACT FROM AUTHOR]

Objective: Mild obstructive sleep apnea (OSA), particularly in young children, is often treated with observation. However, there is little evidence regarding the outcomes with this approach. Our aim was to assess the impact of observation on sleep for children aged <3 years with mild OSA. Study Design: Case-control study. Setting: Pediatric tertiary care center. Methods: We reviewed cases of children (<3 years old) diagnosed with mild OSA (obstructive apnea-hypopnea index, 1-5 events/h) who were treated with observation between 2012 and 2017 and had at least 2 polysomnograms performed 3 to 12 months apart. Demographic data and comorbid diagnoses were collected. Results: Twenty-six children met inclusion criteria; their median age was 7.2 months (95% CI, 1.2-22.8). Nine (35%) were female and 24 (92%) were White. Their median body mass index percentile was 39 (95% CI, 1-76). Comorbidities included cardiac disease (42.3%), laryngomalacia (42.3%), allergies (34.6%), reactive airway disease (23.1%), and prematurity (7.7%). The obstructive apnea-hypopnea index significantly decreased from 2.7 events/h (95% CI, 1-4.5) to 1.3 (95% CI, 0-4.5; P =.013). There was no significant improvement in median saturation nadir (baseline, 86%; P =.76) or median time with end-tidal carbon dioxide >50 mm Hg (baseline, 0 minutes; P =.34). OSA resolved in 8 patients (31%) and worsened in 1 (3.8%). Only race was a significant predictor of resolution per regression analysis; however, only 2 non-White children were included. Conclusion: In our cohort, resolution of mild OSA occurred in 31% of patients treated with 3 to 12 months of observation. The presence of laryngomalacia, asthma, and allergies did not affect resolution. Larger studies are needed to better identify factors (including race) associated with persistent OSA and optimal timing of intervention for these children. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Objectives: Nasal steroids, oral anti-leukotrienes and supplemental oxygen are effective in the treatment of mild obstructive sleep apnea (OSA) in otherwise healthy children. However, their efficacy is unknown in children with Down syndrome (DS). Here we examine the effect of single medication therapy versus observation versus oxygen on polysomnographic outcomes in these children.Methods: We reviewed children (<18 years) diagnosed with DS and mild OSA (obstructive apnea-hypopnea index [oAHI] ≥1 to <5 events/hour) treated non-surgically (with supplemental oxygen, one medication, or observation) between 2012 and 2017. Demographic data, comorbid diagnoses, and pre- and posttreatment polysomnograms were analyzed. We assessed pre- and posttreatment oAHI, oxyhemoglobin saturation nadir, percent total sleep time (%TST) in rapid eye movement (REM), and end-tidal carbon dioxide (ETCO2 ) >50 mmHg.Results: Twenty-four children met inclusion criteria; 10 treated with medication, one with oxygen, and 13 with observation (baseline oAHI was 3.5, 3.3, and 2.9 events/hour, respectively). There was no significant change in oAHI, oxyhemoglobin saturation nadir, ETCO2 , or percent TST in REM after treatment for any treatment group (P = .21-.94). There was no association between reported symptoms and AHI severity or change in AHI. OSA resolved in one patient treated with observation and two treated with medication, but worsened in two each in the medication and observation groups. Resolution of OSA occurred in 20% treated with medication, 7.7% with observation, and 0% with oxygen (P = .82).Conclusion: In our cohort, resolution of mild OSA was low. This suggests that consideration should be given to multimodality treatments in children with DS and mild OSA. Prospective studies will help establish effectiveness in this cohort.Level Of Evidence: 4 Laryngoscope, 130:1828-1835, 2020. [ABSTRACT FROM AUTHOR]

The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transcriptional response to acute hypoxia is tissue-specific and time-of-day-dependent. In particular, clock components differentially responded at the transcriptional and posttranscriptional level, and these responses depended on an intact circadian clock. Importantly, exposure to hypoxia phase-shifted clocks in a tissue-dependent manner led to intertissue circadian clock misalignment. This differential response relied on the intrinsic properties of each tissue and could be recapitulated ex vivo. Notably, circadian misalignment was also elicited by intermittent hypoxia, a widely used model for OSA. Given that phase coherence between circadian clocks is considered favorable, we propose that hypoxia leads to circadian misalignment, contributing to the pathophysiology of OSA and potentially other diseases that involve hypoxia. [ABSTRACT FROM AUTHOR]

Objectives: To compare the percentage and mean age of children with Down syndrome (DS) who underwent polysomnography (PSG) to evaluate for obstructive sleep apnea (OSA) before and after the introduction of the American Academy of Pediatrics guidelines recommending universal screening by age 4 years.Study Design: Retrospective cohort study.Setting: Single tertiary pediatric hospital.Methods: This study is a review of patients with DS seen in a subspecialty clinic. Children born preguidelines (2000-2006) were compared with children born postguidelines (2007-2012) regarding percentage receiving PSG, age at first PSG, and rate of OSA.Results: We included 766 children with DS; 306 (40%) were born preguidelines. Overall, 61% (n = 467) underwent PSG, with a mean ± SD age of 4.2 ± 2.9 years at first PSG; 341 (44.5%) underwent first PSG by age 4 years. The rate of OSA (obstructive index ≥1 event/hour) among children undergoing first PSG was 78.2%. No difference was seen in the percentage receiving PSG preguidelines (63.4%) versus postguidelines (59.4%, P = .26). The mean age at the time of first PSG was 5.3 ± 3.5 years preguidelines versus 3.4 ± 2.0 years postguidelines (P < .0001). Children in the postguidelines cohort were more likely to undergo first PSG during the ages of 1 through 4 years (67.4% vs 52.1%, P < .0001). There was no difference in rates of OSA between the pre- and postguidelines cohorts (79.8% vs 75.9%, P = .32).Conclusions: Nearly two-thirds of children with DS (61%) underwent PSG overall, with a significant shift toward completion of PSG at an earlier age after the introduction of the American Academy of Pediatrics guidelines for universal screening for OSA. [ABSTRACT FROM AUTHOR]

Objective: To review the effects of the circadian clock on homeostasis, the functional interaction between the circadian clock and hypoxia-inducible factors, and the role of circadian dysregulation in the progression of cardiopulmonary disease in obstructive sleep apnea (OSA).Data Sources: The MEDLINE database was accessed through PubMed.Review Methods: A general review is presented on molecular pathways disrupted in OSA, circadian rhythms and the role of the circadian clock, hypoxia signaling, crosstalk between the circadian and hypoxia systems, the role of the circadian clock in cardiovascular disease, and implications for practice. Studies included in this State of the Art Review demonstrate the potential contribution of the circadian clock and hypoxia in animal models or human disease.Conclusions: Molecular crosstalk between the circadian clock and hypoxia-inducible factors has not been evaluated in disease models of OSA.Implications For Practice: Pediatric OSA is highly prevalent and, if left untreated, may lead to cardiopulmonary sequelae. Changes in inflammatory markers that normally demonstrate circadian rhythmicity are also seen among patients with OSA. Hypoxia-inducible transcription factors interact with core circadian clock transcription factors; however, the interplay between these pathways has not been elucidated in the cardiopulmonary system. This gap in knowledge hinders our ability to identify potential biomarkers of OSA and develop alternative therapeutic strategies. A deeper understanding of the mechanisms by which OSA impinges on clock function and the impact of clock dysregulation on the cardiopulmonary system may lead to future advancements for the care of patients with OSA. The aim of this review is to shed light on this important clinical topic. [ABSTRACT FROM AUTHOR]

Objectives To determine the effectiveness of pediatric drug-induced sleep endoscopy (DISE)-directed surgery for children with infant obstructive sleep apnea (OSA) or OSA after adenotonsillectomy. Study Design Case series with chart review. Setting Tertiary care pediatric hospital. Subjects and Methods We included 56 children undergoing DISE from October 2013 to September 2015 who underwent subsequent surgery to address OSA. The primary outcome was successful response to DISE-directed surgery based on the postoperative obstructive Apnea-Hypopnea Index (oAHI). Wilcoxon matched-pairs signed-ranks tests were used to compare polysomnography variables before and after surgery, and regression was used to model response to surgery. Results We evaluated 56 patients with a mean age of 5.9 ± 5.5 years (range, 0.1-17.4) and mean body mass index of 21.2 ± 7.9 kg/m2 (percentile, 77 ± 30). The most commonly performed surgical procedures were adenoidectomy (48%, n = 27), supraglottoplasty (38%, n = 21), tonsillectomy (27%, n = 15), lingual tonsillectomy (13%, n = 7), nasal surgery (11%, n = 6), pharyngoplasty (7%, n = 4), and partial midline glossectomy (7%, n = 4). Mean oAHI improved from 14.9 ± 13.5 to 10.3 ± 16.2 events/hour, with 54% (30 of 56) of children with oAHI <5 and 16.1% (9 of 56) with oAHI <1. There was a significant improvement in oAHI ( P = .001) and saturation nadir ( P < .001) but not in time with end tidal carbon dioxide >50 mm Hg ( P = .14). Multivariable modeling, controlling for age, race, body mass index, sex, and baseline polysomnography variables, revealed that white race predicted success of DISE-directed surgery. Conclusion Fifty-four percent of children with infant OSA or persistent OSA after adenotonsillectomy had oAHI <5 events per hour after DISE-directed surgery. Only white race was predictive of oAHI <5 events per hour. [ABSTRACT FROM AUTHOR]

Objective Home oximetry is commonly used to screen for obstructive sleep apnea (OSA) in children; however, normal oxygen desaturation levels by disease severity are not well known. It was our objective to determine if oxygen saturation levels differed by OSA severity category in children and if these differences were similar for preteen children and adolescents. Study Design Retrospective case series of children undergoing polysomnography from September 2011 to July 2015. Setting Tertiary pediatric hospital. Subjects and Methods Six- to 18-year-olds (preteen, 6-12 years old; adolescent, 13-18 years old). Chi-square, Wilcoxon rank sum test, and Kruskal-Wallis testing were used to compare variables between age groups. Results The study included 342 children with a mean age of 11.3 ± 2.4 years (range, 6.5-17.5) and a mean body mass index of 25.6 ± 9.2 kg/m2 (78 ± 29 percentile); 61% were white, 35% were black, and 4% were other or unknown. Of the children, 48% were female, and this was not a significant difference between age groups ( P = .81). Overall, 50% of the children had no OSA, 32% mild, 10% moderate, and 8% severe. When compared with the younger children, the adolescents had a longer sleep time ( P = .014) and a higher mean obstructive apnea-hypopnea index (3.53 ± 5.1 vs 3.03 ± 6.1 events per hour, P = .02). The 3% and 4% oxygen desaturation indices were not significantly different between age groups when accounting for OSA severity. Conclusion Adolescents have longer sleep times and higher obstructive apnea-hypopnea indexes than preteens, but oxygen saturations and desaturation indices were similar. This supports current triage algorithms for children with OSA, as we found no significant age-based differences. [ABSTRACT FROM AUTHOR]

Objective To determine common polysomnographic (PSG) diagnoses for children referred by otolaryngologists. Study Design Retrospective case series with chart review. Setting Single tertiary pediatric hospital (2010-2015). Subjects and Methods Review of the medical records of 1258 patients undergoing PSG by otolaryngology referral. Patients who underwent previous otolaryngologic surgery were excluded. Data distributions were evaluated using means with standard deviations for continuous variables and frequencies with percentages for categorical variables. Results A total of 1258 patients were included; 55.9% were male, 64.5% were Caucasian, 16.6% had Down syndrome, and 48% had public insurance. The median age at the time of PSG was 5.2 years (range = 0.2-18.94). Indications for PSG were sleep-disordered breathing (SDB; 69.4%), restless sleep (12.7%), airway anomalies (7.5%), and laryngomalacia (7.2%). SDB was seen in 73.4%, obstructive sleep apnea (OSA) in 53.2%, OSA + central sleep apnea (CSA) in 4.5%, CSA in 0.9%, and non-OSA snoring in 15%. Other diagnoses included periodic limb movements of sleep (PLMS; 7.4%), hypoventilation (6.8%), and nonapneic hypoxemia (2.6%). SDB was more common in younger children and seen in 91.4% of children <12 months and in 69.2% of children ≥24 months, while non-OSA snoring was more common with increasing age (3.7% in children <12 months, 17.7% of children ≥24 months). PLMS were seen in 8.9% of children ≥24 months and in no children <12 months. Conclusion While OSA and snoring were the most common diagnoses reported, PLMS, alveolar hypoventilation, and CSA occurred in 7.4%, 6.8%, and 5.4%, respectively. These findings indicate that additional diagnoses other than OSA should be considered for children seen in an otolaryngology clinic setting who undergo PSG for sleep disturbances. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: We sought to characterize changes in the patterns of inpatient surgical sleep care over time and ascertain if these changes were consistent with previously reported trends in adult surgical sleep care.Study Design: Repeated cross-sectional study.Methods: Discharge data from the U.S. Nationwide Inpatient Sample for 125,691 nasal, palatal, or hypopharyngeal procedures in children for sleep-disordered breathing or obstructive sleep apnea (OSA) from 1993 to 2010 were analyzed using cross-tabulations and multivariate regression modeling.Results: Inpatient surgical sleep procedures increased from 45,671 performed in 1993 to 2000 (study period 1) to 80,020 in 2001 to 2010 (study period 2). Overall, patients were commonly male (61.3%), privately insured (46.8%), 2 to 6 years old (39.4%), and white (36.4%). Obesity was reported in 4.6% and 6.7% of children during study periods 1 and 2, respectively (P < .0001). Tonsillectomy (with and without adenoidectomy) was the most commonly performed procedure in both study periods. With the exception of uvulopalatopharyngoplasty and tracheostomy, all sleep procedures increased over time; however, multilevel surgery did not significantly increase (P = .28). Children who underwent sleep surgery during study period 2 were more likely to receive a supraglottoplasty (P = .0125) and to undergo procedures at high-volume hospitals (P = .0311), and less likely to undergo a tracheostomy (P < .0001).Conclusions: These data reflect changing trends in the surgical management of pediatric OSA, with significant increases in nasal and hypopharyngeal procedures, particularly lingual tonsillectomy and supraglottoplasty. Unlike the trend in adults, multilevel surgery in children with sleep disordered breathing or OSA has not yet been integrated into routine clinical practice.Level Of Evidence: 2C Laryngoscope, 127:1235-1241, 2017. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Obstructive sleep apnea (OSA) is increasingly recognized as a significant factor in perioperative and inpatient health. Because of this, hospitalized OSA patients are encouraged to utilize continuous positive airway pressure (CPAP) therapy while inpatients. We investigated the cost difference of patient-owned versus hospital-provided CPAP machine use by admitted adult patients with OSA. Study Design Prospective cohort study at a tertiary academic center. Methods All new-patient admissions >18 years of age who were prescribed CPAP while inpatients over a 2-month period were included. Demographic information was collected, and cost analysis was performed. Results CPAP was used for 162 (1.2%) admissions. Mean patient age was 59 ± 13 years; the majority were white (56.8%) and male (64.2%). Average CPAP utilization was 5.3 ± 5.5 nights. The differential cost per day for patients using hospital-provided CPAP was $416.10 more than for patients using home CPAP machines. This cost included direct costs of an extended respiratory therapy (RT) initial visit, machine rental fee ($27.50), and additional RT evaluation time (mean, 85-145 relative value units). The base initial visit was the same for all patients. Over the 2-month study period, the total cost difference in charges was $195,912; this extrapolates to $1,175,471 yearly. Conclusions This is the first study to characterize the magnitude of cost savings from utilization of home versus hospital-provided CPAP machines in patients requiring inpatient CPAP machine use. The use of patient-owned CPAP machines may reflect an opportunity to provide cheaper care while maintaining high patient safety and quality care. The actual economic impact to an individual hospital would vary based on the insurance payer mix. Level of Evidence 4 Laryngoscope, 124:2200-2204, 2014 [ABSTRACT FROM AUTHOR]

Background: We evaluated the prevalence of sleep-disordered breathing (SDB) and sleepiness in children with allergy and compared sleep-specific quality of life measures to those of children without allergy. Methods: A prospective case-control study was done at a tertiary care academic center. The parents of 21 pediatric patients with positive environmental allergy testing completed questionnaires including the Obstructive Sleep Apnea-18 (OSA18), the Pediatric Sleep Questionnaire (PSQ), and the Pediatric Daytime Sleepiness Scale (PDSS). Comparisons were made to 113 children without allergy who had undergone cochlear implantation (CI) who served as controls. Results: SDB was suggested in 19% of children with allergy using the OSA18 and in 29% using the PSQ vs 6% and 7% of controls ( p = 0.029; p = 0.003), respectively. In addition, daytime sleepiness was suggested in 45% to 48% of children with allergy using the PSQ and PDSS vs 17% to 25% of controls ( p = 0.015; p = 0.025), respectively. Patients with allergy had SDB and sleepiness scores higher than population normal values: OSA-18 of 41.7 vs 34.0, PSQ-SDB of 0.25 vs 0.14, PSQ-Sleepy of 0.34 vs 0.15, and PDSS of 14.2 vs 11.4. The difference between cases and controls was significant for all measures of sleepiness and SDB. Conclusion: Children with allergy have higher SDB and sleepiness scores than controls. This suggests that children with allergic rhinitis are at increased risk for SDB and screening should be considered in this population. In addition, studies with a larger sample size are important to fully understand this relationship. © 2011 ARS-AAOA, LLC. [ABSTRACT FROM AUTHOR]

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients. [ABSTRACT FROM AUTHOR]