Function In Obstructive Sleep Apnea Research Articles

Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in Obstructive Sleep Apnea With Excessive Daytime Sleepiness and Cognitive Impairment

OSA causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS. How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?. Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study (SHARP) was a phase IV, randomized, double-blind, placebo-controlled, crossover trial. Participants (N= 59) were randomized to receive placebo or solriamfetol (75mg/d for 3days, then 150mg/d) for 2weeks, with crossover separated by a 1-week washout period. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and the Epworth Sleepiness Scale (ESS). The primary end point was change from baseline in average postdose DSST RBANS scores. Secondary end points were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours' postdose. Safety was monitored by assessment of treatment-emergent adverse events. Solriamfetol significantly improved postdose average DSST RBANS scores compared with placebo (P= .009; effect size [Cohen's d], 0.37). When evaluated at each 2-hour time point, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all, P< .05). During solriamfetol treatment, there were significant improvements in BC-CCI (P= .002; d= 0.45), PGI-S (P= 0.0mixed; d= 0.29), and ESS (P= .004; d= 0.40) compared with placebo. The most common treatment-emergent adverse events were nausea (7%) and anxiety (3%). SHARP showed that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS. ClinicalTrials.gov; No.: NCT04789174; ;URL: www. gov and EudraCT; No.: 2020-004243-92; URL: https://eudract.ema.europa.eu.

The Success of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in Adult Orthodontics: A Literature Review

This literature review examines the success and effectiveness of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in adult orthodontics. Traditional methods like Surgically Assisted Rapid Palatal Expansion (SARPE) have been commonly used for treating transverse maxillary deficiencies in adults, but they come with significant drawbacks, including higher biological and financial costs. MARPE, which utilizes mini screws to apply controlled forces for palatal expansion, offers a less invasive and more precise alternative. The review analyzes several studies and reports on MARPE's success in expanding skeletal and dental structures, improving respiratory function in obstructive sleep apnea (OSA) patients, and minimizing complications like unwanted tooth movement. Despite some challenges, such as asymmetrical expansion, MARPE has demonstrated a high success rate in adult orthodontics and presents a promising treatment option. Further high-quality, long-term studies are recommended to optimize treatment protocols and evaluate potential risks.

Genes Associated with Altered Brain Structure and Function in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been widely reported to cause abnormalities in brain structure and function, but the genetic mechanisms behind these changes remain largely unexplored. Our research aims to investigate the relationship between sleep characteristics, cognitive impairments, genetic factors, and brain structure and function in OSA. Using structural and resting-state functional magnetic resonance imaging data, we compared cortical morphology and spontaneous brain activity between 28 patients with moderate-to-severe OSA and 34 healthy controls (HCs) utilizing voxel-based morphology (VBM) and the amplitude of low-frequency fluctuations (ALFF) analyses. In conjunction with the Allen Human Brain Atlas, we used transcriptome-neuroimaging spatial correlation analyses to investigate gene expression patterns associated with changes in gray matter volume (GMV) and ALFF in OSA. Compared to the HCs, the OSA group exhibited increased ALFF values in the left hippocampus (t = 5.294), amygdala (t = 4.176), caudate (t = 4.659), cerebellum (t = 5.896), and decreased ALFF values in the left precuneus (t = -4.776). VBM analysis revealed increased GMV in the right inferior parietal lobe (t = 5.158) in OSA. Additionally, functional enrichment analysis revealed that genes associated with both ALFF and GMV cross-sampling were enriched in gated channel activity and synaptic transmission, glutamatergic synapse, and neuron.

Upper airway imaging and function in obstructive sleep apnea in people with and without HIV.

Obstructive sleep apnea (OSA) is common in people living with human immunodeficiency virus (HIV) (PLWH), but the underlying mechanisms are unclear. With improved long-term survival among PLWH, aging and obesity are increasingly prevalent in this population. These are also strong risk factors for the development of obstructive sleep apnea. We used magnetic resonance imaging (MRI) to measure upper airway (UA) anatomy and tongue fat content in PLWH with OSA (PLWH + OSA, n = 9) and in age-, sex-, and body mass index (BMI)-matched OSA controls (OSA, n = 11). We also quantified change in UA dimension during tidal breathing (during wakefulness and natural sleep) at four anatomical levels from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal flow measurements. All participants underwent on a separate night a baseline polysomnogram to assess OSA severity and an additional overnight physiological sleep study to measure OSA traits. We found no difference between the PLWH + OSA and the OSA control group in UA volume [PLWH + OSA: 12.8 mL (10.1-17.0), OSA: 14.0 mL (13.3-17.9), median (IQR)] or tongue volume [PLWH + OSA: 140.2 mL (125.1-156.9), OSA: 132.4 mL (126.8-154.7)] and a smaller tongue fat content in PLWH + OSA [11.2% (10.2-12.4)] than in the OSA controls [14.8% (13.2-15.5), P = 0.046]. There was no difference in the dynamic behavior of the UA between the two groups. When pooled together, both static and dynamic imaging metrics could be correlated with measures of UA mechanical properties. Our data suggest similar underlying UA physiology in OSA in subjects with and without HIV.NEW & NOTEWORTHY Obstructive sleep apnea is common in people living with human immunodeficiency virus (HIV), but the underlying mechanisms are unclear. We did not find differences in upper airway morphology using magnetic resonance imaging (MRI) during wake and natural sleep between people living with HIV (PLWH) with obstructive sleep apnea (OSA) and age, gender, and body mass index (BMI)-matched people with OSA but without HIV. Nor were there differences in tongue volume or changes in airway size during inspiration and expiration. MRI-derived anatomy was correlated with measures of airway collapse.

Impact of CPAP Therapy on the Autonomic Nervous System.

Obstructive sleep apnea (OSA) is a significant risk factor for cardiovascular disease (CVD) with increasing prevalence. An important mechanism of CVD development is a dysregulation of the autonomic nervous system (ANS). This prospective and controlled cohort study aimed to investigate ANS function in OSA including the response to long-term continuous positive airway pressure (CPAP) therapy by analyzing 24 h Holter electrocardiogram and 24 h Holter ambulatory blood pressure recording parameters. The study enrolled 57 patients who were newly diagnosed with severe OSA. After 6 months of CPAP therapy, 37 patients had a good therapy adherence (usage of CPAP device >4 h per night), and their data were analyzed. The difference in nocturnal diastolic blood pressure values before and after CPAP therapy reached statistical significance (76 (68-84) vs. 74 (63-80) mmHg, p = 0.0439). Lower nocturnal values after CPAP therapy of SDNN (101.5 vs. 95 ms, p = 0.0492) and RMSSD (29.5 vs. 26 ms, p = 0.0193) were found. An increase in diurnal spectral power (1742 vs. 2112 ms2, p = 0.0282) and a decrease in nocturnal spectral power (3256 vs. 2124 ms2, p = 0.0097), nocturnal VLF band (2493 vs. 1485.4 ms2, p = 0.0176), nocturnal LF band (638.7 vs. 473 ms2, p = 0.0097), and nocturnal HF band (234.9 vs. 135.7 ms2, p = 0.0319) was found. The results showed an imbalance of the ANS with a sympathetic predominance, especially during the night hours and in those with arterial hypertension. The impact of CPAP therapy on the improvement in ANS parameters was more pronounced at night, in men, and those with arterial hypertension.

Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea

BackgroundIt has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA. MethodsFifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis. ResultsCompared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = −0.449, FDR-corrected P = 0.0025; r = −0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643–0.836, P < 0.0001). ConclusionsStructural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.

Oral appliance influence on jaw function in obstructive sleep apnea

Oral appliance (OA) therapy in obstructive sleep apnea (OSA) could be a risk factor for normal jaw function, given the prolonged effect of an OA in keeping the mandible in a protruded position away from a normal position. This study aimed to assess changes in symptoms and clinical findings related to jaw function after 1 year of treating OSA with an OA. In this follow-up clinical trial, 302 patients with OSA were assigned to treatment with either monobloc or bibloc OA. Baseline and 1-year follow-up assessment included using the Jaw Functional Limitation Scale, self-reported symptoms and signs related to jaw function. The clinical examination of jaw function included mandibular mobility, dental occlusion, and tenderness in the temporomandibular joints and masticatory muscles. Descriptive analyses of variables are presented for the per-protocol population. To evaluate differences between the baseline and the 1-year follow-up, paired Student t tests and the McNemar change test was used. One-hundred and ninety-two patients completed the 1-year follow-up (male 73%, mean aged 55 ± 11 years). There was no change in the Jaw Functional Limitation Scale score at the follow-up (nonsignificant). The patients described no change in symptoms at the follow-up, except for improvements in morning headache (P<0.001) and increased frequency of difficulties in opening the mouth or chewing on awakening (P= 0.002). Subjectively reported changes in dental occlusion during biting/chewing increased significantly at the follow-up (P= 0.009). No changes in measurements of jaw mobility, dental occlusion, or pain on palpation of the temporomandibular joints or masticatory muscles were seen at the follow-up. Thus, using an OA in treating OSA had limited influence on jaw functions and related symptoms. Moreover, the risk of developing pain and functional impairment in the masticatory system was infrequent, indicating that this treatment is safe and can be recommended.

WITHDRAWN: Mitochondrial replication, transcription, and function in obstructive sleep apnea

We assessed mitochondrial replication, transcription, and function in the upper airways of obstructive sleep apnea (OSA) patients and the effects of uvulopalatopharyngoplasty. Twenty subjects with mild and 40 with moderate to severe OSA requiring uvulopalatopharyngoplasty were included. Mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in uvula specimens were assessed by immunohistochemical staining, and their mRNA and protein expression was examined using reverse-transcription polymerase chain reaction and western blotting, respectively. The mitochondrial to nuclear DNA (Mt/N) ratio in the blood, exhaled breath condensate (EBC), and uvula was measured using quantitative reverse-transcription polymerase chain reaction. TFAM and PGC-1α protein concentrations in the plasma and EBC were determined using enzyme-linked immunosorbent assay. All tested parameters were higher in the OSA group than in the control. Three months later, 21 uvulopalatopharyngoplasty-responsive patients with OSA showed decreased TFAM and PGC-1α concentrations and EBC Mt/N ratio while these remained high in 19 uvulopalatopharyngoplasty-unresponsive patients. The OSA group showed severe inflammation, increased mitochondrial replication and transcription-related signaling, and mitochondrial dysfunction in the uvula. Successful OSA treatment using uvulopalatopharyngoplasty restored the TFAM and PGC-1α levels and EBC Mt/N ratio.

Sleep electroencephalography biomarkers of cognition in obstructive sleep apnea.

Obstructive sleep apnea has been associated with cognitive impairment and may be linked to disorders of cognitive function. These associations may be a result of intermittent hypoxaemia, sleep fragmentation and changes in sleep microstructure in obstructive sleep apnea. Current clinical metrics of obstructive sleep apnea, such as the apnea-hypopnea index, are poor predictors of cognitive outcomes in obstructive sleep apnea. Sleep microstructure features, which can be identified on sleep electroencephalography of traditional overnight polysomnography, are increasingly being characterized in obstructive sleep apnea and may better predict cognitive outcomes. Here, we summarize the literature on several major sleep electroencephalography features (slow-wave activity, sleep spindles, K-complexes, cyclic alternating patterns, rapid eye movement sleep quantitative electroencephalography, odds ratio product) identified in obstructive sleep apnea. We will review the associations between these sleep electroencephalography features and cognition in obstructive sleep apnea, and examine how treatment of obstructive sleep apnea affects these associations. Lastly, evolving technologies in sleep electroencephalography analyses will also be discussed (e.g. high-density electroencephalography, machine learning) as potential predictors of cognitive function in obstructive sleep apnea.

The role of 3D speckle tracking echocardiography in the diagnosis of obstructive sleep apnea and its severity

There is a consistent relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. It is already recognized that OSA may influence the geometry and function of the right ventricle (RV). This has encouraged the development of echocardiographic evaluation for screening of OSA and its severity. Three-dimensional speckle tracking echocardiography (3D STE) is in assumption better, compared with 2D STE, because it overcomes the standard 2D echo limitations. Thus, the purpose of our study is to evaluate whether 3D STE measurements, could predict the positive diagnosis and severity of OSA. We enrolled 69 patients with OSA and 37 healthy volunteers who underwent a cardiorespiratory sleep study. 2DE was performed in all patients. RVEF and 3D RVGLS were measured by 3DSTE. NT pro BNP plasma level was also assessed in all participants. 3D RV GLS (− 13.5% vs. − 22.3%, p < 0.001) and 3D RVEF (31.9% vs. 50%, p < 0.001) were reduced in patients with OSA, compared with normal individuals. 3D Strain parameters showed better correlation to standard 2D variables, than 3D RVEF. Except for NT pro BNP (p = 0.059), all parameters served to distinguish between severe and mild-moderate cases of OSA. 3D STE may be a reliable and accurate method for predicting OSA. Consequently, 3D RV GLS is a good tool of assessing the RV global function in OSA, because it correlates well with other established measurements of RV systolic function. Furthermore, 3D RV GLS was a precise parameter in identifying severe cases of OSA, while NT pro BNP showed no association.

Abnormal dynamic functional network connectivity in male obstructive sleep apnea with mild cognitive impairment: A data-driven functional magnetic resonance imaging study.

The purpose of this study was to investigate the dynamic functional network connectivity (FNC) and its relationship with cognitive function in obstructive sleep apnea (OSA) patients from normal cognition (OSA-NC) to mild cognitive impairment (OSA-MCI). Eighty-two male OSA patients and 48 male healthy controls (HC) were included in this study. OSA patients were classified to OSA-MCI (n = 41) and OSA-NC (n = 41) based on cognitive assessments. The independent component analysis was used to determine resting-state functional networks. Then, a sliding-window approach was used to construct the dynamic FNC, and differences in temporal properties of dynamic FNC and functional connectivity strength were compared between OSA patients and the HC. Furthermore, the relationship between temporal properties and clinical assessments were analyzed in OSA patients. Two different connectivity states were identified, namely, State I with stronger connectivity and lower frequency, and State II with lower connectivity and relatively higher frequency. Compared to HC, OSA patients had a longer mean dwell time and higher fractional window in stronger connectivity State I, and opposite result were found in State II, which was mainly reflected in OSA-MCI patients. The number of transitions was an increasing trend and positively correlated with cognitive assessment in OSA-MCI patients. Compared with HC, OSA patients showed extensive abnormal functional connectivity in stronger connected State I and less reduced functional connectivity in lower connected State II, which were mainly located in the salience network, default mode network, and executive control network. Our study found that OSA patients showed abnormal dynamic FNC properties, which was a continuous trend from HC, and OSA-NC to OSA-MCI, and OSA patients showed abnormal dynamic functional connectivity strength. The number of transformations was associated with cognitive impairment in OSA-MCI patients, which may provide new insights into the neural mechanisms in OSA patients.

Heart rate variability changes in patients with obstructive sleep apnea: A systematic review and meta-analysis.

Obstructive sleep apnea is a common sleep breathing disorder related to autonomic nervous function disturbances. Heart rate variability is an important non-invasive indicator of autonomic nervous system function. The PubMed, Embase, Medline and Web of Science databases were systematically searched for English literature comparing patients with obstructive sleep apnea with controls up to May 2021. Heart rate variability outcomes, including integrated indices (parasympathetic function and total variability), time domain indices (the standard deviation of NN intervals and the root mean square of the successive differences between normal heartbeats) and frequency domain indices (high-frequency, low-frequency, very-low-frequency and the ratio of low-frequency to high-frequency) were derived from the studies. Twenty-two studies that included 2565 patients with obstructive sleep apnea and 1089 healthy controls were included. Compared with controls, patients with obstructive sleep apnea exhibited significantly reduced parasympathetic function. For the obstructive sleep apnea severity subgroup meta-analysis, patients with severe obstructive sleep apnea had significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and higher low-frequency and ratios of low-frequency to high-frequency. However, only the ratio of low-frequency to high-frequency was significantly higher in patients with moderate obstructive sleep apnea than in controls. Finally, for the collection time analysis, patients with obstructive sleep apnea had significantly higher low-frequency and ratio of low-frequency to high-frequency at night, significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and a higher ratio of low-frequency to high-frequency during the day than controls. Autonomic function impairment was more serious in patients with severe obstructive sleep apnea. During sleep, low-frequency can well reflect the impairment of autonomic function in obstructive sleep apnea, and the ratio of low-frequency to high-frequency may play an important role in obstructive sleep apnea diagnosis.

Frequency‑Specific Regional Homogeneity Alterations and Cognitive Function in Obstructive Sleep Apnea Before and After Short-Term Continuous Positive Airway Pressure Treatment

PurposePrevious studies have demonstrated abnormal local spontaneous brain activity in the conventional frequency bands (0.01–0.08 Hz) in obstructive sleep apnea (OSA). However, it is not clear whether these abnormalities are associated with the specific frequency band of low-frequency oscillations or whether it can be improved with a continuous positive airway pressure (CPAP) treatment. This study aimed to investigate the regional homogeneity (ReHo) in specific frequency at baseline (pre-CPAP) and after one month of CPAP adherence treatment (post-CPAP) in OSA patients.MethodsTwenty-one patients with moderate-to-severe OSA and 21 age- and sex-matched healthy controls (HCs) were included in the final analysis. ReHo was calculated in three different frequency bands (typical frequency band: 0.01–0.1 Hz; slow-5 band: 0.01–0.027 Hz; slow-4 band: 0.027–0.073 Hz), respectively. A partial correlational analysis was performed to assess the relationship between altered ReHo and clinical evaluation.ResultsOSA patients revealed increased ReHo in the brainstem, bilateral inferior temporal gyrus (ITG)/fusiform, and right-cerebellum posterior lobe (CPL), and decreased ReHo in the bilateral inferior parietal lobule (IPL), right superior temporal gyrus (STG), and left precentral gyrus (PG) compared to HC groups in different frequency bands. Significantly changed ReHo in the bilateral middle temporal gyrus (MTG), PG, medial frontal gyrus (MFG), supplementary motor area (SMA), CPL, IPL, left superior frontal gyrus (SFG), ITG, MTG, and right STG were observed between post-CPAP and pre-CPAP OSA patients, which was associated with specific frequency bands. The altered ReHo in specific frequency bands was correlated with Montreal cognitive assessment score, Epworth sleepiness scale, and apnea hypopnea index in pre-CPAP OSA patients.ConclusionThese findings indicate that OSA has frequency-related abnormalities of spontaneous neural activity before and after short-term CPAP treatment, which might contribute to a better understanding of local neural psychopathology and may serve as potential biomarkers for clinical CPAP treatment.

The Impact of Glycolipid Metabolic Disorders on Severity Stage-Specific Variation of Cardiac Autonomic Function in Obstructive Sleep Apnea: A Data-Driven Clinical Study.

BackgroundCardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood.MethodsIn total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose–response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA.ResultsThe RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function.ConclusionThese results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.

Insular functional organization during handgrip in females and males with obstructive sleep apnea.

Brain regulation of autonomic function in obstructive sleep apnea (OSA) is disrupted in a sex-specific manner, including in the insula, which may contribute to several comorbidities. The insular gyri have anatomically distinct functions with respect to autonomic nervous system regulation; yet, OSA exerts little effect on the organization of insular gyral responses to sympathetic components of an autonomic challenge, the Valsalva. We further assessed neural responses of insular gyri in people with OSA to a static handgrip task, which principally involves parasympathetic withdrawal. We measured insular function with blood oxygen level dependent functional MRI. We studied 48 newly-diagnosed OSA (age mean±std:46.5±9 years; AHI±std:32.6±21.1 events/hour; 36 male) and 63 healthy (47.2±8.8 years;40 male) participants. Subjects performed four 16s handgrips (1 min intervals, 80% subjective maximum strength) during scanning. fMRI time trends from five insular gyri-anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)-were assessed for within-group responses and between-group differences with repeated measures ANOVA (p<0.05) in combined and separate female-male models; age and resting heart-rate (HR) influences were also assessed. Females showed greater right anterior dominance at the ASG, but no differences emerged between OSA and controls in relation to functional organization of the insula in response to handgrip. Males showed greater left anterior dominance at the ASG, but there were also no differences between OSA and controls. The males showed a group difference between OSA and controls only in the ALG. OSA males had lower left activation at the ALG compared to control males. Responses were mostly influenced by HR and age; however, age did not impact the response for right anterior dominance in females. Insular gyri functional responses to handgrip differ in OSA vs controls in a sex-based manner, but only in laterality of one gyrus, suggesting anterior and right-side insular dominance during sympathetic activation but parasympathetic withdrawal is largely intact, despite morphologic injury to the overall structure.

1042 Assessment of left ventricular systolic function in obstructive sleep apnea with automatic function imaging and its relation relation with hypoxia

Abstract Funding Acknowledgements OSA &amp; Subclinical myocardial impairment Background Early detection of left ventricular (LV) systolic dysfunction is crucial for patients with obstructive sleep apnea (OSA) . LV longitudinal strain (GLS), derived from automated function imaging (AFI) based on 2D echocardiography, provides a new tool to detect subclinical impairment of both global and regional myocardium. Its value in OSA remains unclear compared to traditional parameters since obesity is not uncommon in OSA, which may compromise the accuracy of AFI. We aimed to investigate the feasibility of AFI in OSA and further to explore the impact of OSA severity and degree of hypoxia on LV function. Methods Comprehensive transthoracic echocardiography was done in those receiving polysomnography (PSG) suspected as OSA consecutively (n = 322). All subjects were divided into 3 groups by apnea-hyponea index (AHI) by PSG (Control: AHI＜5; mild-to-moderate AHI 5-30; severe: AHI≥30) and GLS and mitral annular plane systolic excursion (MAPSE) were compared among the 3 groups. Results 322 patients with normal LVEF (≥50%) were finally analyzed. Though more segments were measured, inter- and intra- observer variability of GLS were comparable with MAPSE in a Bland-Altman analysis. For group comparison, GLS was reduced compared to the other 2 groups in the severe OSA category (p ≤ 0.001) while MAPSE showed no differences. Further analysis showed the feasibility of AFI was acceptable even in obese patients. In multivariable analysis of GLS, only maximum desaturation was an independent associated factor (p = 0.027). Conclusions Even in OSA patients with obesity, AFI-derived GLS is feasible. GLS is more sensitive than MAPSE or TDI for detection of reduced LV systolic function in OSA. Control(n = 27) Mild-Mod OSA(n = 145) Severe OSA(n = 160) P-value Age(years) 43 ± 13 47 ± 12 46 ± 11 0.218 Males, n(%) 17(63.0%) 118(81.4%) 154(96.3%) ＜0.001 BSA(m2) 1.82 ± 0.18 1.88 ± 0.18 1.97 ± 0.17*† ＜0.001 BMI(kg/ m2) 24.7 ± 4.4 26.8 ± 3.7* 28.6 ± 4.2*† ＜0.001 LVEF(%) 66.5 ± 6.4 67.0 ± 5.0 66.7 ± 4.6 0.813 Sep S’(cm/s) 8.3 ± 1.7 8.4 ± 1.5 8.7 ± 1.9 0.256 Sep E’(cm/s) 9.5 ± 3.0 9.0 ± 2.4 8.2 ± 2.0*† 0.003 E/ E’ 9.2 ± 2.9 9.1 ± 2.9 9.8 ± 2.9 0.145 GLS(%) 19.1 ± 2.7 19.0 ± 2.5 17.9 ± 2.4*† ＜0.001 MAPSE(mm) 15.1 ± 2.5 14.7 ± 2.3 14.3 ± 2.2 0.302 *p＜0.05 compared with mild OSA patients, †p＜0.05 compared with moderate OSA patients Echo Comparison between 3 OSA Groups

Association between Upper-airway Surgery and Ameliorative Risk Markers of Endothelial Function in Obstructive Sleep Apnea

The objective of our study was to evaluate the effects of upper-airway surgery on improvement of endothelial function-related markers in patients with obstructive sleep apnea (OSA). Subjects with moderate to severe OSA who underwent upper-airway surgery, with a follow-up duration of at least 6 months, were included. Pre- and postoperative polysomnographic variables and endothelial function-related markers were compared. Subgroup and correlation analyses were conducted to find possible indicators for better endothelial function-related markers after upper-airway surgery. In total, 44 patients with OSA were included. The mean follow-up duration was 1.72 ± 0.92 years. Serum VEGFA [−20.29 (CI: −35.27, −5.31), p < 0.05], Ang2 [−0.06 (CI: −0.16, 0.03), p < 0.05], E-selectin [−7.21 (CI: −11.01, −3.41), p < 0.001], VWF [−58.83 (CI: −103.93, −13.73), p < 0.05], VWFCP [−33.52 (CI: −66.34, −0.70), p < 0.05], and TM [−0.06 (CI: −0.09, −0.03), p < 0.05] were significantly lower after upper-airway surgery. However, other risk markers of endothelial function, such as Ang1, ICAM1, VEGFR1, and VCAM, did not change significantly. Correlations between improved endothelial function-related markers and ameliorated oxyhemoglobin saturation and glucolipid metabolism were established. Upper-airway surgery might be associated with an improvement in endothelial function in patients with OSA. These changes may be associated with improved oxygen saturation after upper-airway surgery.

Metallothionein induction attenuates the progression of lung injury in mice exposed to long-term intermittent hypoxia.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is prevalent in older adults and associated with inflammation. We previously showed that IH induces renal fibrosis and cardiomyopathy and hypothesized that lung inflammatory changes may underlie deficits in pulmonary function in OSA. Pulmonary inflammatory and oxidative markers were assessed in metallothionein KO (MT-KO) mice and WT 129S1 controls exposed to IH or to normoxia for 8weeks. MT expression increased at 3days in WT, falling back at 1week. Pro-fibrotic markers CTGF and PAI-1 were unchanged in WT, but increased at 3 or 8weeks, with enhanced Sirius Red staining at 8weeks, in IH-exposed MT-KO. Cellular infiltration, TNF-α and IL-6 increased earlier in IH-exposed MT-KO than in WT. Oxidative markers, 3-nitrotyrosine and 4-hydroxynonenal increased in both but persisted in MT-KO. Antioxidant Nrf2, HO-1 and NQO1, increased at 3days in WT mice and at 8weeks IH in MT-KO. While early Nrf2 induction required MT, its later increase at 8weeks in MT-KO was independent from MT. We conclude that early MT and antioxidant gene response protects from fibrotic changes in long-term IH-exposed mouse lung. Without this response, pulmonary fibrosis may develop with longer IH exposure.

N-terminalpro-brainnatriuretic peptide: a potential follow-up biomarker of mandibular advancement device efficacy on cardiac function in obstructive sleep apnea.

Interrelationships between obstructive sleep apnea (OSA) and cardiovascular diseases are now recognized, but some underlying pathophysiological mechanisms remain controversial. Circulating cardiac biomarkers are diagnostic tools that can help understand them, in particular the N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of myocardial stretch, and a potential indicator of subclinical cardiac stress in OSA. Continuous positive airway pressure (CPAP), the first-line treatment of moderate to severe OSA, may be considered as uncomfortable, resulting in poor adherence, and reduced effectiveness. In this case, mandibular advancement devices (MAD) are an effective alternative therapy, more comfortable, and generally well accepted, with higher compliance. To date, few studies have compared the cardiovascular effects of CPAP and MAD. From recent literature reviews, it emerges that both therapies are effective in blood pressure reduction. However, the effects of MAD on other cardiovascular outcomes are conflicting, in particular as regards to its impact on circulating cardiac biomarkers. In a recent ancillary study from a randomized controlled trial, Recoquillon et al concluded that two months of MAD treatment had no effect on NT-proBNP plasma levels in patients with severe OSA. The present discussion analyses this result from a biological, statistical, and analytical standpoint, in light of results from other studies evaluating natriuretic peptides in MAD-treated OSA, with the aim to support further longitudinal studies designed with a high methodological quality.

Dose-dependent effects of mandibular advancement on upper airway collapsibility and muscle function in obstructive sleep apnea.

Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy. Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome. Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O; p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement. Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy.