Changes In Obstructive Sleep Apnea Research Articles

Altered cervical proprioception and biomechanics in obstructive sleep apnea: a case-control study.

This study aimed to compare cervical proprioception and related biomechanical factors among patients with Obstructive Sleep Apnea (OSA) and asymptomatic controls. In this case-control study, polysomnography scores (apnea-hypopnea index-AHI) were examined to determine the disease severity of the OSA group. Also, we evaluated cervical proprioception by using a laser pointer to detect joint repositioning error sense in cervical rotational movements. Comparison statistics were also conducted for the cervical musculoskeletal variables such as range of motion (ROM) with bubble inclinometer, cranio-cervical (CVA), and thoracic posture (TKA) through photometric analysis, neck flexor muscle endurance test, and pain pressure thresholds of trapezius (PPT). This case-control study included 59 male participants: patients with OSA (n = 29; mean age = 49.10 years; mean BMI = 28.41kg/m2) and asymptomatic controls (n = 30; mean age = 49.73 years; mean BMI = 26.89 ± 3.60kg/m2). The mean AHI score was 26.06 events/hour, categorizing the severity of OSA as mild (31.03%), moderate (31.03%), and severe (37.94%). Patients with OSA demonstrated significantly poorer cervical proprioception compared to controls for both sides of cervical rotation with larger effect sizes (d:1.36-1.45; p < 0.05). Also, cervical ROM, CVA, TKA, neck flexor muscle endurance test, and PPT values were altered in the OSA group compared to the control group (p < 0.05). Impaired cervical proprioception may be a previously unrecognized factor associated with OSA. This finding has implications for understanding the mechanisms underlying cervical musculoskeletal changes in OSA and for developing potential new interventions or exercise designs targeting postural control.

Machine-learning-based classification of obstructive sleep apnea using 19-channel sleep EEG data

ObjectiveThis study aimed to investigate the neurophysiological effects of obstructive sleep apnea (OSA) using multi-channel sleep electroencephalography (EEG) through machine learning methods encompassing various analysis methodologies including power spectral analysis, network analysis, and microstate analysis. MethodsTwenty participants with apnea-hypopnea index (AHI) ≥ 15 and 18 participants with AHI <15 were recruited. Overnight polysomnography was conducted concurrently with 19-channel EEG. Preprocessed EEG data underwent computation of relative spectral power. A weighted network based on graph theory was generated; and indices of strength, path length, eigenvector centrality, and clustering coefficient were calculated. Microstate analysis was conducted to derive four topographic maps. Machine learning techniques were employed to assess EEG features capable of differentiating two groups. ResultsAmong 71 features that showed significant differences between the two groups, seven exhibited good classification performance, achieving 88.3 % accuracy, 92 % sensitivity, and 84 % specificity. These features were power at C4 theta, P3 theta, P4 theta, and F8 gamma during NREM1 sleep and at Pz gamma during REM sleep from power spectral analysis; eigenvector centrality at F7 gamma during REM sleep from network analysis; and duration of microstate 4 during NREM2 sleep from microstate analysis. These seven EEG features were significantly correlated with polysomnographic parameters reflecting the severity of OSA. ConclusionsThe application of machine learning techniques and various EEG analytical methods resulted in a model that showed good performance in classifying moderate to severe OSA and highlights the potential of EEG to serve as a biomarker of functional changes in OSA.

The effect of hypoxia on interoception in patient with obstructive sleep apnea.

Obstructive Sleep Apnea (OSA) is the most common sleep-related disorder. Interoception is the collection of sensory and cognitive processes that involve receiving and interpreting physiological signals from internal body structures and conveying the perception of inner sensations. In this study, it was hypothesized that the impairment in cognitive functions associated with chronic hypoxemia and the insular effects due to OSA would negatively affect interoceptive functions. The aim of this study was to evaluate whether interoception in OSA changes consistent with the hypothesis. A total of 102 patients diagnosed with OSA were included in this study. All participants were divided into groups based on their T90 values: desaturated OSA (T90 ≥ 20%) and non-desaturated OSA (T90 < 20%). The Heartbeat Counting Task was used to assess interoceptive accuracy, while the Interoceptive Sense Questionnaire (ISQ) was employed to identify subjective challenges in evaluating interoception. Interoceptive accuracy was lower in the desaturated OSA group than in the non-desaturated OSA group (Z = -2.463; p = 0.014). Interoceptive accuracy was negatively correlated with the body mass index (r = -0.228; p = 0.021), T90 (r = -0.269; p = 0.006), and positively correlated with the average SaO2 (r = 0.377; p < 0.001) and SaO2 nadir (r = 0.243; p = 0.014). This study examined interoceptive functions in patients with OSA. It was concluded that interoceptive accuracy is affected by the severity of hypoxia as hypothesized.

Correlation of diffusion tensor tractography with obstructive sleep apnea severity.

Using correlation tractography, this study aimed to find statistically significant correlations between white matter (WM) tracts in participants with obstructive sleep apnea (OSA) and OSA severity. We hypothesized that changes in certain WM tracts could be related to OSA severity. We enrolled 40 participants with OSA who underwent diffusion tensor imaging (DTI) using a 3.0 Tesla MRI scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and quantitative anisotropy (QA)-values were used in the connectometry analysis. The apnea-hypopnea index (AHI) is a representative measure of the severity of OSA. Diffusion MRI connectometry that was used to derive correlational tractography revealed changes in the values of FA, MD, AD, RD, and QA when correlated with the AHI. A false-discovery rate threshold of 0.05 was used to select tracts to conduct multiple corrections. Connectometry analysis revealed that the AHI in participants with OSA was negatively correlated with FA values in WM tracts that included the cingulum, corpus callosum, cerebellum, inferior longitudinal fasciculus, fornices, thalamic radiations, inferior fronto-occipital fasciculus, superior and posterior corticostriatal tracts, medial lemnisci, and arcuate fasciculus. However, there were no statistically significant results in the WM tracts, in which FA values were positively correlated with the AHI. In addition, connectometry analysis did not reveal statistically significant results in WM tracts, in which MD, AD, RD, and QA values were positively or negatively correlated with the AHI. Several WM tract changes were correlated with OSA severity. However, WM changes in OSA likely involve tissue edema and not neuronal changes, such as axonal loss. Connectometry analyses are valuable tools for detecting WM changes in sleep disorders.

Recent progresses in gut microbiome mediates obstructive sleep apnea-induced cardiovascular diseases.

Obstructive sleep apnea (OSA) is a multifactorial sleep disorder with a high prevalence in the general population. OSA is associated with an increased risk of developing cardiovascular diseases (CVDs), particularly hypertension, and is linked to worse outcomes. Although the correlation between OSA and CVDs is firmly established, the mechanisms are poorly understood. Continuous positive airway pressure is primary treatment for OSA reducing cardiovascular risk effectively, while is limited by inadequate compliance. Moreover, alternative treatments for cardiovascular complications in OSA are currently not available. Recently, there has been considerable attention on the significant correlation between gut microbiome and pathophysiological changes in OSA. Furthermore, gut microbiome has a significant impact on the cardiovascular complications that arise from OSA. Nevertheless, a detailed understanding of this association is lacking. This review examines recent advancements to clarify the link between the gut microbiome, OSA, and OSA-related CVDs, with a specific focus on hypertension, and also explores potential health advantages of adjuvant therapy that targets the gut microbiome in OSA.

Systematic review of miRNA expression changes in Obstructive Sleep Apnea: insights into associated pathways and contribution to disease

Systematic review of miRNA expression changes in Obstructive Sleep Apnea: insights into associated pathways and contribution to disease

Acute Effect of Positive Airway Pressure on Heart Rate Variability in Obstructive Sleep Apnea.

Autonomic dysregulation is associated with cardiovascular consequences in obstructive sleep apnea (OSA). This study aimed to investigate the effect of acute continuous positive airway pressure (CPAP) treatment on autonomic activity and to identify factors contributing to heart rate variability (HRV) changes in OSA. Frequency domain HRV parameters were calculated and compared between the baseline polysomnography and during the CPAP titration in 402 patients with moderate to severe OSA. There were significant reductions in total power, very low-frequency band power, low-frequency band power, and high-frequency band power during the CPAP titration as compared to the baseline polysomnography. This tendency was pronounced in male patients with severe OSA. Multivariate analysis found that changes in the apnea-hypopnea index and oxygen saturation were significantly associated with changes in sympathetic and parasympathetic activity, respectively. This study demonstrated that HRV parameters significantly changed during the CPAP titration, indicating a beneficial effect of CPAP in the restoration of sympathetic and parasympathetic hyperactivity in OSA. Prospective longitudinal studies should determine whether long-term CPAP treatment aids in maintaining the long-lasting improvement of the autonomic functions, thereby contributing to the prevention of cardiovascular and cerebrovascular diseases in patients with OSA.

Retrospective Analysis of the Polysomnographic and Airway Changes in Obstructive Sleep Apnea (OSA) Subjects Who Underwent Maxillomandibular Advancement (MMA) Surgery

Retrospective Analysis of the Polysomnographic and Airway Changes in Obstructive Sleep Apnea (OSA) Subjects Who Underwent Maxillomandibular Advancement (MMA) Surgery

Developmental changes in obstructive sleep apnea and sleep architecture in Down syndrome.

Down syndrome (DS, also known as Trisomy 21) is a condition associated with abnormal neurodevelopment and a higher risk for sleep apnea. Our study sought to better understand and characterize the age-related developmental differences in sleep architecture and obstructive sleep apnea (OSA) severity in children with DS compared to euploid individuals. Retrospective review of polysomnograms in over 4151 infants, children, and adolescents in the pediatric sleep center at Children's National Hospital in Washington D.C. (0-18 years) including 218 individuals with DS. The primary findings of our study are that: (1) severe OSA (obstructive apnea-hypopnea index ≥ 10/h) was more prevalent in the DS group (euploid 18% vs. DS 34%, p < 0.001) with the highest OSA severity being present in young children (<3 years old) and adolescents (>10 years old), (2) abnormalities in sleep architecture in children with DS were characterized by a prolonged rapid-eye movement (REM) sleep onset latency (SOL) (euploid 119 min vs. DS 144 min, p < 0.001) and greater arousal indexes (euploid 10.7/h vs. DS 12.2/h, p < 0.001), (3) developmental changes in the amount of REM sleep or slow wave sleep were not different in DS individuals relative to euploid children, (4) multivariate analyses showed that OSA and REM sleep latency differences between DS and euploid individuals were still present after adjusting by age, biological sex, and body mass index. Severe OSA is highly prevalent in children with DS and follows an age-dependent "U" distribution with peaks in newborns/infants and children >10 years of age. Children with DS also have disturbances in sleep architecture characterized by a longer REM SOL and elevated arousal indexes. As sleep cycle generation and continuity play crucial roles in neuroplasticity and cognitive development, these findings offer clinically relevant insights to guide anticipatory guidance for infants, children, and adolescents with DS.

The complex interplay of hypoxia and sleep disturbance in gray matter structure alterations in obstructive sleep apnea patients.

Obstructive Sleep Apnea (OSA) characteristically leads to nocturnal hypoxia and sleep disturbance. Despite clear evidence of OSA-induced cognitive impairments, the literature offers no consensus on the relationship between these pathophysiological processes and brain structure alterations in patients. This study leverages the robust technique of structural equation modeling to investigate how hypoxia and sleep disturbance exert differential effects on gray matter structures. Seventy-four Male participants were recruited to undergo overnight polysomnography and T1-weighted Magnetic Resonance Imaging. Four structural outcome parameters were extracted, namely, gray matter volume, cortical thickness, sulcal depth, and fractal dimension. Structural equation models were constructed with two latent variables (hypoxia, and sleep disturbance) and three covariates (age, body mass index, and education) to examine the association between gray matter structural changes in OSA and the two latent variables, hypoxia and sleep disturbance. The structural equation models revealed hypoxia-associated changes in diverse regions, most significantly in increased gray matter volume, cortical thickness and sulcal depth. In contrast, sleep disturbance. Was shown to be largely associated with reduce gray matter volume and sulcal depth. This study provides new evidence showing significant effects of OSA-induced hypoxia and sleep disturbance on gray matter volume and morphology in male patients with obstructive sleep apnea. It also demonstrates the utility of robust structural equation models in examining obstructive sleep apnea pathophysiology.

The Impact of Mouth-Taping in Mouth-Breathers with Mild Obstructive Sleep Apnea: A Preliminary Study.

Background: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. Method: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A “responder” was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. Results: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = −0.52, p = 0.02), oxygen desaturation index (ODI) (r = −0.54, p = 0.01), and SI (r = −0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = −0.77, p = 0.001). Conclusions: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.

The Role of Inflammation, Hypoxia, and Opioid Receptor Expression in Pain Modulation in Patients Suffering from Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a relatively common disease in the general population. Besides its interaction with many comorbidities, it can also interact with potentially painful conditions and modulate its course. The association between OSA and pain modulation has recently been a topic of concern for many scientists. The mechanism underlying OSA-related pain connection has been linked with different pathophysiological changes in OSA and various pain mechanisms. Furthermore, it may cause both chronic and acute pain aggravation as well as potentially influencing the antinociceptive mechanism. Characteristic changes in OSA such as nocturnal hypoxemia, sleep fragmentation, and systemic inflammation are considered to have a curtailing impact on pain perception. Hypoxemia in OSA has been proven to have a significant impact on increased expression of proinflammatory cytokines influencing the hyperalgesic priming of nociceptors. Moreover, hypoxia markers by themselves are hypothesized to modulate intracellular signal transduction in neurons and have an impact on nociceptive sensitization. Pain management in patients with OSA may create problems arousing from alterations in neuropeptide systems and overexpression of opioid receptors in hypoxia conditions, leading to intensification of side effects, e.g., respiratory depression and increased opioid sensitivity for analgesic effects. In this paper, we summarize the current knowledge regarding pain and pain treatment in OSA with a focus on molecular mechanisms leading to nociceptive modulation.

Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging.

Patients with obstructive sleep apnea (OSA) show brain injury in sites responsible for autonomic, cognitive, and respiratory functions. Brain changes in OSA may vary with disease severity as assessed by the apnea-hypopnea index (AHI), which does not provide information about the apnea depth and length in contrast to oxygen desaturation. Although significant associations with brain injury and AHI are known in OSA, it is unclear whether AHI or the extent of oxygen desaturations better correlate with brain damage. We evaluated associations between brain changes, AHI, and oxygen desaturation using diffusion tensor imaging-based measures. We acquired diffusion tensor imaging data from 19 patients with OSA using a 3.0-Tesla MRI scanner and calculated, normalized, and smoothed mean, axial, and radial diffusivity maps that were used for correlations between brain changes, oxygen desaturation, and AHI values. Positive correlations with extent of injury (mean, axial, and radial diffusivity values) and AHI appeared in the frontal areas, cingulate and insula, amygdala, hippocampus, and basal pons, and negative associations emerged in the putamen, internal-capsule, globus-pallidus, and cerebellar cortices. Regional diffusivity values and oxygen desaturation showed positive correlations in the cingulate, frontal, putamen, and cerebellar sites, and negative relationships in several areas, including the occipital cortex. Patients with OSA show negative and positive correlations, indicated by increased and decreased diffusivity values, resulting from chronic and acute changes in those areas. The extent of injury in OSA partially depends on the extent of AHI and oxygen desaturation, with the effects representing continued development from acute to chronic processes. Sahib A, Roy B, Kang D, Aysola RS, Wen E, Kumar R. Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging. J Clin Sleep Med. 2022;18(12):2713-2721.

The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study.

Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men. Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11-16 Hz), slow density (11-13 Hz), and fast density (13-16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics. In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = -0.003, p = 0.032; TST90, B = -0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = -1.27, p = 0.030) and fast density (B = -4.36, p = 0.028) during N3 sleep. Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.

The positional characteristics of patients with obstructive sleep apnea: a single institute retrospective study in Japan.

Obstructive sleep apnea (OSA) causes sleep-disordered breathing (SDB) due to upper airway obstruction. The severity of OSA changes with position during sleep. Patients with marked significant improvement in apnea-hypopnea index (AHI) level by sleep position change are defined as ''positional patients'' (PP), while those without improvement are defined as ''non-positional patients'' (NPP). We aimed to verify their clinical characteristics. Between May 2008 and May 2020, 237 patients with OSA were registered retrospectively and classified into two groups: PP (n = 158) and NPP (n = 79). The differences in clinical background and full-night polysomnography (PSG) between the two groups were observed. A logistic regression analysis was conducted to identify the risk factors for severe AHI (≥ 30 events/h) in the PP group. Moreover, confounding factor-adjusted sub-analysis by a propensity score matching method was performed, and the PSG results were compared between the two groups. The PP group was older than the NPP group. Furthermore, the PP group had lower body mass index (BMI) and AHI levels compared with the NPP group. The independent risk factors for severe AHI in the PP group were BMI and being in the supine position during sleep. The PP group had a significantly milder nocturnal hypoxemia despite having no significant difference in AHI levels between the two groups. The characteristics of PP were old age, low BMI, and low AHI associated with milder nocturnal hypoxemia. Moreover, they were less likely to worsen with nocturnal hypoxemia compared with NPP having similar severity.

Impact of bariatric surgery on obstructive sleep apnea severity and continuous positive airway pressure therapy compliance\u2014prospective observational study

To evaluate association between bariatric surgery and changes in obstructive sleep apnea (OSA) severity and sleep architecture was as well as to asses continuous positive airway pressure (CPAP) effectiveness and compliance. We enrolled patients undergoing bariatric surgery. Polysomnography was performed in each patient preoperatively and 12 months after the procedure in a subgroup of patients diagnosed with OSA. STOP-BANG, Epworth Sleepiness Scale (ESS) and Berlin questionnaire scores were obtained pre- and postoperatively. CPAP compliance data was recorded during follow-up hospitalization. Among 44 patients with median age of 49.5 years, predominantly women (68.2%) pre- and postoperative polysomnography was performed. We observed significant improvement in STOP-BANG (6.0 vs. 3.0, p < 0.001) and ESS (12.0 vs. 5.0, p < 0.001) scores, apnea–hypopnea index (44.9 vs. 29.2, p < 0.001), oxygen desaturation index (43.6 vs. 18.3, p < 0.001) and sleep architecture parameters. CPAP compliance was poor with a median percentage of days with CPAP use accounting to 49.3%. Bariatric surgery is associated with a significant decrease in the number of sleep-related respiratory disturbances, as well as improvement of sleep efficiency. Postoperative CPAP therapy compliance was poor despite low rate of OSA resolution. This study suggests that patients with OSA undergoing bariatric surgery require postoperative reassessment.

The impact of continuous positive airway pressure treatment on retinal vascular changes in obstructive sleep apnea

Obstructive sleep apnea (OSA) was recently shown to be associated with quantifiable retinal vascular changes, which correlate with disease severity. This follow-up study examines the response of retinal vascular changes in patients with OSA receiving continuous positive airway pressure (CPAP) treatment. This prospective cohort study recruited adult patients undergoing diagnostic polysomnography at a tertiary sleep clinic in Sydney, Australia, stratified into 4 groups by the apnea-hypopnea index; control patients and patients with mild, moderate, and severe OSA. At baseline and follow-up approximately 24 months later, static retinal vascular calibers were derived from fundus photographs, and dynamic vascular pulsation amplitudes were measured on video fundoscopy. A proportion of patients started CPAP therapy after baseline assessment. Seventy-nine patients participated in this follow-up study: 9 control patients and 18 patients with mild OSA, 21 patients with moderate OSA, and 31 patients with severe OSA. Twenty-five patients started CPAP after baseline. In the severe group, patients not on treatment showed progressive narrowing of retinal arteries from baseline, whereas those on CPAP showed a slight improvement (mean, 171.3-165.1 and 171.2-174.0 μm, respectively; P = .012). Arterio-venous ratio was also significantly reduced in the nontreatment group compared to the treatment group in those with severe OSA (0.836-0.821 and 0.837-0.855, respectively; P = .031). CPAP did not seem to have a significant impact on venous caliber or vascular pulsatility. This study shows that patients with severe untreated OSA demonstrate progressive retinal arterial narrowing, whereas CPAP treatment may be protective.

Does craniofacial morphology relate to sleep apnea severity reduction following weight loss intervention? A patient-level meta-analysis.

Obesity is a common and reversible risk factor for obstructive sleep apnea (OSA). However, there is substantial unexplained variability in the amount of OSA improvement for any given amount of weight loss. Facial photography is a simple, inexpensive, and radiation-free method for craniofacial assessment. Our aims were (1) to determine whether facial measurements can explain OSA changes, beyond weight loss magnitude and (2) whether facial morphology relates to how effective weight loss will be for OSA improvement. We combined data from three weight loss intervention trials in which participants had standardized pre-intervention facial photography (N = 91; 70.3% male, mean ± SD weight loss 10.4 ± 9.6% with 20.5 ± 51.2% apnea-hypopnea index [AHI] reduction). Three skeletal-type craniofacial measurements (mandibular length, lower face height, and maxilla-mandible relationship angle) were assessed for relationship to AHI change following weight loss intervention. Weight and AHI changes were moderately correlated (rho = 0.3, p = 0.002). In linear regression, an increased maxilla-mandible relationship angle related to AHI improvement (β [95% CI] -1.7 [-2.9, -0.5], p = 0.004). Maxilla-mandible relationship angle explained 10% in the variance in AHI over the amount predicted by weight loss amount (20%). The relationship between weight change and AHI was unaffected by the maxilla-mandible relationship angle (interaction term p > 0.05). Regardless of facial morphology, weight loss is similarly moderately predictive of OSA improvement. Increased maxilla-mandible relationship angle, suggestive of retrognathia, was weakly predictive of OSA response to weight loss. Although this is unlikely to be clinically useful, exploration in other ethnic groups may be warranted.

Obstructive sleep apnea and fatigue in patients with inflammatory arthritis taking TNF-inhibitors

p>Background: Fatigue is common in inflammatory arthritis (IA). Obstructive sleep apnea (OSA) causes fatigue and is common in IA. OSA and IA are associated with systemic inflammation, including elevated levels of tumor necrosis factor alpha (TNFα). Tumor necrosis factor inhibitors (TNFi) reduce musculoskeletal symptoms and fatigue in IA. The effects of TNFi on OSA are unknown. Our goal was to explore the relationships between TNFi, fatigue, and OSA in IA. Methods: Consecutive patients starting TNFi for IA and high risk for OSA were enrolled. OSA was assessed with the Apnea Hypopnea Index (AHI) and percent time below 90% oxygen saturation (%time < 90%). Fatigue was assessed with the Functional Severity Scale (FSS). Sleep was assessed with the Functional Outcome of Sleep Questionnaire (FOSQ). IA was assessed with the patient global assessment of arthritis (PGA). Parameters were compared before and after TNFi. Changes in OSA, sleep, and fatigue outcomes were adjusted for changes in the PGA. Findings: Eighteen participants completed the study between September 2011 and February of 2014. The mean age was 54 years. 72% were male. Before and after TNFi: mean AHIs were 12.5 and 13.1, respectively (p=0.97); mean %times < 90% were 29.5 and 35.4, respectively (p=0.18); and mean FSS scores were 43.1 and 41.3, respectively (p=0.08); mean FOSQ scores were 11.4 and 11.8, respectively (p=0.09). Conclusions: OSA parameters did not improve with TNFi, but there were statistically non-significant trends toward improvement in fatigue and sleepiness with TNFi.

Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea.

Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.