Months Of Continuous Positive Airway Pressure Treatment Research Articles

The Effect of Continuous Positive Airway Pressure (CPAP) Therapy on Serum Caspase-3 Level in Patients with Obstructive Sleep Apnea (OSA).

Intermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level. This study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment. A total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 ± 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024). The results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue.

Obstrüktif Uyku Apnede (OUA) Ortalama Trombosit Hacmi (OTH) ve OUA'da Sürekli Pozitif Hava Yolu Basıncı (CPAP) Tedavisinin OTH Üzerine Etkisi

Aims: In this study, our objective was to evaluate mean platelet volume (MPV), an indirect marker of platelet activation, in patients with obstructive sleep apnea (OSA), and assess the effect of OSA treatment with continuous positive airway pressure (CPAP) on MPV
 Methods: In this study, records of consecutive patients who underwent polysomnographic evaluation for OSA symptoms in the Sleep Disorders Laboratory during a one-year period were reviewed retrospectively. Patients who had both complete blood count and MPV measurements were included in the study.
 Results: A total of 158 patients, including 51 females (32.3%) and 107 males (67.7%), were included in the study. The mean age of the patients was 51±13 (min-18, max-82) years. OSA was detected in 74.1% (117/158) of the patients. It was determined that as the severity of OSA increased, hemoglobin and hematocrit values increased significantly. There was no significant difference in platelet count according to the presence and severity of OSA. The MPV was significantly lower in severe OSA cases compared to those without OSA and mild OSA cases. A negative correlation was observed between MPV and the apnea-hypopnea index, desaturation index, and the amount of oxygen saturation below 90% during sleep. There was no significant difference in median erythrocyte and thrombocyte counts, hematocrit percentage and hemoglobin values before and after treatment in OSA patients who used CPAP therapy. However, a significant decrease in MPV was observed after OSA treatment compared to pre-treatment. (p=0.021).
 Conclusions: The results of the study do not support an increase in MPV and hence platelet activation in severe OSA patients compared with those without OSA. However, the results suggest that one month of CPAP treatment reduces MPV and thus platelet activation in severe OSA patients. Further controlled, prospective studies including treatment outcomes are needed on this subject.

Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Long-term outcomes of CPAP-treated sleep apnea patients: Impact of blood-pressure responses after CPAP initiation and of treatment adherence

Background and objectiveIn randomized controlled trials, continuous positive airway pressure (CPAP) is reported as lowering blood pressure (BP) with a mean systolic blood pressure effect size of 2.5 mmHg. These trials have a median follow-up of less than 6 months. Whether this initial BP response during the first months of CPAP treatment translates into a reduction in long-term cardiovascular events and mortality is unknown. MethodsThis observational study addressed long-term hard cardiovascular outcomes and all-cause mortality in a well-defined population of 241 patients previously included in the AgirSASadom parallel randomized controlled trial (assessing whether fixed-pressure CPAP was superior to auto-adjusted CPAP in reducing BP (baseline evaluations 2010–2012)). Long-term outcomes were analyzed using a Cox survival model, and a logistic regression analysis was performed for long-term CPAP adherence. ResultsSixty-nine cardiovascular events occurred in 61 patients during a median follow-up of 113 months (interquartile range [102 ; 124]) giving an incidence of 26 for 1000 person-years. Twenty-one (8.7%) patients died. BP values at baseline (i.e., office and 24-h BP) was a strong predictor of incident cardiometabolic events and mortality (p < 0.01) whereas initial BP response after the first four months of CPAP was not related to outcomes. Long-term CPAP adherence above 4 h/night was associated with a reduction in all-cause mortality (Log-rank P = 0.02) but not in the occurrence of long-term cardiovascular events. ConclusionIndependently of initial blood pressure response, long-term CPAP adherence is one of the prerequisites for reducing mortality.

Changes in Functional Connectivity of Hippocampal Subregions in Patients with Obstructive Sleep Apnea after Six Months of Continuous Positive Airway Pressure Treatment.

Previous studies have shown that the structural and functional impairments of hippocampal subregions in patients with obstructive sleep apnea (OSA) are related to cognitive impairment. Continuous positive airway pressure (CPAP) treatment can improve the clinical symptoms of OSA. Therefore, this study aimed to investigate functional connectivity (FC) changes in hippocampal subregions of patients with OSA after six months of CPAP treatment (post-CPAP) and its relationship with neurocognitive function. We collected and analyzed baseline (pre-CPAP) and post-CPAP data from 20 patients with OSA, including sleep monitoring, clinical evaluation, and resting-state functional magnetic resonance imaging. The results showed that compared with pre-CPAP OSA patients, the FC between the right anterior hippocampal gyrus and multiple brain regions, and between the left anterior hippocampal gyrus and posterior central gyrus were reduced in post-CPAP OSA patients. By contrast, the FC between the left middle hippocampus and the left precentral gyrus was increased. The changes in FC in these brain regions were closely related to cognitive dysfunction. Therefore, our findings suggest that CPAP treatment can effectively change the FC patterns of hippocampal subregions in patients with OSA, facilitating a better understanding of the neural mechanisms of cognitive function improvement, and emphasizing the importance of early diagnosis and timely treatment of OSA.

Defining the impact of continuous positive airway pressure therapy on diastolic function in adults with moderate-to-severe obstructive sleep apnea.

Although studies have shown that continuous positive airway pressure (CPAP) therapy to treat obstructive sleep apnea improves left ventricular diastolic function, modifiers of improvement are unknown. We explored race and pre-treatment 24-h non-dipping blood pressure status as modifiers of improved diastolic function. Participants (N=220) with obstructive sleep apnea (apnea-hypopnea index ≥15 events/h) and hypertension were recruited to a cohort study that examined effects of 3-month CPAP therapy on 24-h blood pressure. Those who completed echocardiogram at baseline and follow-up were included in this analysis. Diastolic function parameters (E, A, e', E/A, E/e') were assessed. Race was categorised to African American versus others. Participants were categorised as nocturnal dippers (night-time blood pressure decrease by ≥10%) versus non-dippers. We compared changes in parameters of diastolic function by race and nocturnal dipping status. A total of 92 participants were included. They were men (86%), African American (67.4%), and current smoker (29.5%). Mean apnea-hypopnea index was 32.9 events/h. Mean CPAP usage was 3.15 h/day. After 3 months of CPAP treatment, there were significant improvements in measures of diastolic function: a median (interquartile range [IQR]) increase in E velocity by 4.00(-5.75 to 13.75)cm/s, an increase in e' by 2.00(0-4.00)cm/s, and a decrease in the E/e' ratio by 1.74(-4.27 to 0.00) at follow-up (p < 0.05). These changes did not differ by race or nocturnal dipping status. Improvements in diastolic function after CPAP therapy did not differ by race or nocturnal dipping status. Further studies are needed to understand predictors of CPAP effects on diastolic function.

Functional Connectivity Changes in the Insular Subregions of Patients with Obstructive Sleep Apnea after 6 Months of Continuous Positive Airway Pressure Treatment.

This study was aimed at investigating the functional connectivity (FC) changes between the insular subregions and whole brain in patients with obstructive sleep apnea (OSA) after 6 months of continuous positive airway pressure (CPAP) treatment and at exploring the relationship between resting-state FC changes and cognitive impairment in OSA patients. Data from 15 patients with OSA before and after 6 months of CPAP treatment were included in this study. The FC between the insular subregions and whole brain was compared between baseline and after 6 months of CPAP treatment in OSA. After 6 months of treatment, OSA patients had increased FC from the right ventral anterior insula to the bilateral superior frontal gyrus and bilateral middle frontal gyrus and increased FC from the left posterior insula to the left middle temporal gyrus and left inferior temporal gyrus. Hyperconnectivity was found from the right posterior insula to the right middle temporal gyrus, bilateral precuneus, and bilateral posterior cingulate cortex, which mainly involved the default mode network. There are changes in functional connectivity patterns between the insular subregions and whole brain in OSA patients after 6 months of CPAP treatment. These changes provide a better understanding of the neuroimaging mechanisms underlying the improvement in cognitive function and emotional impairment in OSA patients and can be used as potential biomarkers for clinical CPAP treatment.

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) &gt; 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p &lt; 0.001). Conventional RV longitudinal and global function parameters (S', fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p &lt; 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process-increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.

The effect of continuous positive airway pressure treatment on inflammatory parameters and periostin levels in patients with obstructive sleep apnea syndrome.

The purpose of the study was to examine the effects of continuous positive airway pressure (CPAP) treatment on inflammation parameters in patients with obstructive sleep apnea syndrome (OSAS). Patients aged 18to65years who underwent polysomnography (PSG) in the sleep clinic between January 1, 2019, and December 31, 2019, were included in the study. Patients with severe OSAS initiated treatment with CPAP.Patients and control subjectswere assessed for levels of periostin, TNF-alpha, TGF-beta, and IL-6. Patients were re-evaluated 3months later. Comparisons for the serum markers were made between controls and patients of different severity of OSAS. Comparisons of serum markers were also made between baseline and 3 month follow-up. RESULTS: A total of 92 patients were enrolled in the study, including 25 controls (apnea-hypopnea index or AHI < 5/h), 39 patents with mild to moderate OSAS who did not receive CPAP, and 28 patients with severe OSAS receiving CPAP treatment. When all three groups were compared, levels of periostin, TNF-alpha, TGF-beta, and IL-6, as inflammatory markers, were higher in the OSAS group,though not at a statistically significant level. In patients with severe OSAS, there were statistically significant decreases in the TGF-beta 1, TNF-alpha, and IL-6 values between baseline values and the same measures taken after 3months of CPAP treatment. Periostin values alsodecreased after treatment, butthis decrease was not at a significant level. Inflammatory parameters of patients with OSAS were significantlyhigher compared with healthy participants. Regression of inflammation was detected after CPAP treatment.

The Effects of CPAP Treatment on Resting-State Network Centrality in Obstructive Sleep Apnea Patients.

Background and ObjectivesObstructive sleep apnea (OSA) is the most common sleep disorder and previous studies have shown that OSA patients suffer from brain network impairments associated with cognitive deficits, and continuous positive airway pressure (CPAP) treatment can improve clinical symptoms. However, the relationship between CPAP treatment and brain network changes remains unclear. This study explored the characteristics of brain network changes in OSA patients before (pre-CPAP) and after one month of CPAP treatment (post-CPAP).MethodsWe collected data, including sleep monitoring, clinical assessment, and magnetic resonance imaging scans, from 21 OSA patients and 21 age-matched healthy controls (HCs). Voxel-level degree centrality (DC) was used to assess whole-brain network connectivity characteristics, a two-sample t-test was used to compare network differences between pre-CPAP OSA patients and HCs, and a paired sample t-test was used to compare the characteristics of brain network changes in OSA patients before and after treatment. The correlations between the DC value and each of the clinical variables were analyzed in the OSA patients.ResultsCompared with HCs, pre-CPAP OSA patients showed increased DC values in the bilateral cerebellar posterior lobes (CPLs) and decreased DC values in the right superior temporal gyrus, left superior frontal gyrus and right middle frontal gyrus. Compared with pre-CPAP OSA patients, post-CPAP OSA patients showed reduced DC values in the bilateral CPL and increased DC values in several brain regions in the frontal, temporal, and insular lobes after CPAP treatment. The Montreal Cognitive Assessment MoCA (MoCA) scores were positively correlated with the DC value of the bilateral cerebellum posterior lobe, right middle temporal gyrus, left superior temporal gyrus, left paracentral lobule and left paracentral lobule. Also, Pittsburgh Sleep Quality Index (PSQI) scores were negatively correlated with the DC value of the right middle temporal gyrus in post-CPAP OSA patients.ConclusionCPAP treatment can effectively reverse the compensatory response of the bilateral CPL and functional network damage brought about by OSA, which may provide potential neuroimaging biomarkers for CPAP treatment evaluation.

Factors Associated With the Improvement of Left Ventricular Systolic Function by Continuous Positive Airway Pressure Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Obstructive Sleep Apnea

BackgroundObstructive sleep apnea (OSA) is a potential risk factor in cardiovascular diseases, including arrhythmia, coronary artery disease, and heart failure (HF). Continuous positive airway pressure (CPAP) therapy is an effective therapy for OSA and the underlying HF, partly through a 5–9% increase in the left ventricular ejection fraction (LVEF). However, the data on the factors associated with the efficacy of CPAP on LVEF in patients with HF complicated by OSA are scarce. This study aimed to investigate whether LVEF improves in patients with OSA and HF after 1 month of CPAP therapy, and to clarify which factors are associated with the degree of LVEF improvement.MethodThis was a prospective, single-arm, open-label study. We enrolled moderate-to-severe patients with OSA and HF who were being followed up at the cardiovascular center of Toranomon Hospital (Tokyo, Japan). The parameters of sleep study and LVEF were assessed at the baseline and after 1 month of CPAP. The multivariate regression analyses, with changes in LVEF as a dependent variable, were performed to determine the factors that were associated with the degree of LVEF improvement.ResultsWe analyzed 55 consecutive patients with OSA and HF (mean age: 60.7 ± 12.2 years, mean LVEF value: 37.2 ± 9.8%). One month of CPAP treatment decreased the apnea-hypopnea index (AHI) from 45.3 ± 16.1 to 5.4 ± 4.1 per hour, and the LVEF improved from 37.2 ± 9.8 to 43.2 ± 11.7%. The multivariate regression analyses demonstrated that age and body mass index (BMI) were significant determinants of LVEF improvement.ConclusionThe LVEF improved significantly after 1 month of CPAP therapy in Japanese patients with OSA and HF. Multivariate regression analyses indicated that an improvement in LVEF was likely to be observed in young patients with obesity.

Change in quality of life with nasal CPAP in patients with OSA

Background: Obstructive sleep apnea (OSA) is a major global problem, associated with increased morbidity mortality and decreased quality of life. There are many possible treatment options, but noninvasive ventilation (NIV) nasal continuous positive airway pressure (CPAP) is most commonly used and most effective modality. In this study, we evaluated and assessed 30 cases of patients with OSA. Patients and methods: A prospective study was performed by using Short Form 36 (SF-36) questionnaire; OSA was assessed pre- and post-NIV therapies for 1 month. Results and conclusion: This study demonstrated a marked impairment of the quality of life in patients with even mild OSA. One month of CPAP treatment improved the quality of life in the all domains of SF-36 health questionnaire. We concluded that health-related quality of life of patients with OSA improved remarkably with CPAP therapy.

Continuous positive airway pressure affects mitochondrial function and exhaled PGC1-α levels in obstructive sleep apnea

Purpose: Subjects with obstructive sleep apnea (OSA) exhibit systemic and upper airway oxidative stress and inflammation, which cause mitochondrial dysfunction. The intend of this study is to estimate mitochondrial function (mitochondrial DNA/nuclear DNA [Mt/N] ratio) and protein levels of peroxisome proliferator-coactivated receptor gamma co-activator 1-alpha (PGC1-α) in the exhaled breath condensate (EBC) and plasma before and after continuous positive airway pressure (CPAP) treatment. Materials and methods: Twenty healthy individuals (control) and 40 subjects with severe or moderate OSA were recruited to undergo CPAP treatment and evaluation in a sleep study. The Mt/N ratio in the EBC and blood were assayed by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the protein concentration of PGC1-α in the EBC and plasma. All experiments were performed after 3 months of CPAP treatment in subjects with OSA. Results: We observed no noteworthy differences between the control and treatment groups. Moreover, there were no differences in the Mt/N ratio in the blood and plasma levels of PGC1-α in subjects with OSA before and after treatment. However, the Mt/N ratio and protein levels of PGC1-α in the EBC of OSA subjects were higher than those in the control group and returned to normal levels after CPAP treatment. Conclusions: We successfully treated subjects with OSA by CPAP, which restored the Mt/N ratio and levels of PGC1-α in the EBC.

Facilitators and barriers to getting obstructive sleep apnea diagnosed: perspectives from patients and their partners.

Obstructive sleep apnea (OSA) is a prevalent and debilitating condition that is significantly underdiagnosed. The majority of adults sleep with someone-a partner. Partners can play a significant role in the patient's OSA diagnosis. The goal of this work is to describe facilitators and barriers to OSA diagnosis as discussed by patients with OSA and their partners. This was a qualitative secondary analysis with results drawn from 20 dyadic interviews, conducted 1 couple at a time, in 20 newly diagnosed adult patients with OSA and their partners. Qualitative interview data were analyzed using conventional content analysis. Facilitators of OSA diagnosis were partners pushing patients to seek care, patients actively seeking care, and care providers identifying the patient's risk of OSA. Barriers to OSA diagnosis were patients' lack of serious attention to symptoms, patients' negative perceptual framing of diagnosis and treatment of OSA, and poor coordination of health care services. We recommend engaging partners in the OSA diagnosis and developing educational and behavioral interventions to raise public awareness about OSA. It is important to educate clinicians on atypical presentations of OSA. Further investigation is needed to evaluate the impact of health care services on OSA diagnosis. Ye L, Li W, Willis DG. Facilitators and barriers to getting obstructive sleep apnea diagnosed: perspectives from patients and their partners. J Clin Sleep Med. 2022;18(3):835-841.

Effets de la ventilation en pression positive continue sur la dépression, l’anxiété et la qualité de vie au cours du syndrome des apnées-hypopnées obstructives du sommeil

IntroductionThe obstructive sleep apnea hypopnea syndrome (OSAHS) is a chronic stressor that may alter the emotional state and quality of life (QOL) of patients suffering from it. In this work, we proposed to estimate the prevalence of depression and anxiety, to assess the QOL in a Tunisian population of apneic patients, and to assess their evolution under continuous positive airway pressure (CPAP). MethodsWe conducted a prospective study, involving 33 apneic patients followed for SAHOS with moderate or severe class disease in the pneumology department at Hedi Chaker university hospital in Sfax, Tunisia. They received CPAP treatment for three months. We used an epidemiological record. Two scales, the Hospital Anxiety and Depression Scale (HADS) and the 36-item Short-Form Health Survey (SF-36), were completed before and after treatment to evaluate the effect of three months of treatment with CPAP. ResultsThe prevalence of depression in the study's patients, according to the HADS, was 45.5% and that of anxiety was 21.2%. After 3months of CPAP, the prevalence of depression and anxiety had become 18.2% and 6.1%, respectively. QOL was impaired in 81.8% of cases before treatment, according to the SF-36. This figure had decreased to 69.7% after 3months of treatment with CPAP. Apart from the third dimension (physical pain), all other dimensions were significantly improved after 3months of CPAP treatment. The treatment with CPAP induced a significant improvement in the average scores of depression (P<0.001), anxiety (P=0.002) and QOL (P<0.001). ConclusionsThese results attest to the importance of the frequency of anxio-depressive disorders as well as an altered QOL in patients with OSAHS. CPAP treatment was shown to be effective in improving these parameters, but this efficacy was partial. Specialized care may be needed in cases of residual anxio-depressive symptoms.

Whole blood gene expression signature in patients with obstructive sleep apnea and effect of continuous positive airway pressure treatment

The molecular mechanisms of obstructive sleep apnea (OSA), in particular the gene expression patterns in whole blood of patients with OSA, can shed more light on the underlying pathophysiology of OSA and suggest potential biomarkers. In the current study, we have enrolled thirty patients with untreated moderate-severe OSA together with 20 BMI, age, and sex-matched controls and 15 normal-weight controls. RNA-sequencing of whole blood and home sleep apnea testing were performed in the untreated state and after three and twelve months of continuous positive airway pressure (CPAP) treatment. Analysis of the whole blood transcriptome of the patients with OSA revealed a unique pattern of differential expression with a significant number of downregulated immune-related genes including many heavy and light chain immunoglobulins and interferon-inducible genes. This was confirmed by the gene ontology analysis demonstrating enrichment with the biological processes associated with various immune functions. Expression of these genes was recovered after three months of CPAP treatment. After 12 months of CPAP treatment, the overall gene expression profile returns to the initial, untreated level. In addition, we have confirmed the importance of choosing BMI-matched controls as a reference group as opposed to normal-weight healthy individuals based on the significantly different gene expression signatures between these two groups.

454 Obesity does not modify the effect of 4 months of CPAP on leptin or adiponectin

Abstract Introduction Leptin and adiponectin are cytokines produced by adipocytes. Leptin is involved in the pathogenesis of obesity and adiponectin is cardioprotective. Previous studies in adults with obstructive sleep apnea (OSA) assessing the effect of continuous positive airway pressure (CPAP) on these cytokines are conflicting, and whether obesity modifies the effect remains unknown. We examined the baseline and follow up levels of changes in plasma leptin and adiponectin following 4 months of CPAP treatment among obese (BMI&amp;gt;30) and non-obese (BMI≤30) participants. Methods We evaluated 221 adults (84.6% males) in the Penn Icelandic Sleep Apnea (PISA) Study, with mean (±SD) body mass index (BMI) 31.7±4.9 kg/m2 and apnea-hypopnea index (AHI) 35.7±15.6 events/hour. Associations between changes in natural log of the biomarkers in obese and non-obese participants were evaluated, controlling for a priori baseline covariates of age, baseline BMI, race, sex, site, and current smoking status. Results The mean proportional change (from baseline to follow-up) in log-transformed adiponectin and leptin in CPAP adherent participants was not significantly different between BMI groups. The baseline to follow up change in leptin post-CPAP was 1.01 (95% CI 0.95–1.08) in obese participants and 1.05 (95% CI 0.96–1.14) in non-obese participants. For adiponectin, the change post-CPAP was 1.04 (95% CI 0.95–1.15) in obese participants and 1.08 (95% CI 0.96–1.22) in non-obese participants. Conclusion CPAP treatment did not have an impact on leptin or adiponectin levels. We also find no evidence for obesity modifying the effect of four months of CPAP on leptin or adiponectin. Support (if any) 1P01-1HL094307

Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study.

Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations via oxidative stress. Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidant t-butyl hydroperoxide (TBHP). In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength. IH and OSA per se do not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.

Changes in sleepiness and 24-h blood pressure following 4 months of CPAP treatment are not mediated by ICAM-1.

Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment. The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use. Among 140 adults (83% men),mean (± SD) body mass index (BMI) was 31.5± 4.2 kg/m2, and apnea-hyopnea index (AHI) was 36.8± 15.3 events/h.Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures. Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or notother biomarkers may have a role in mediating these treatment outcomes in adults with OSA.

0053 Effect of Changes in Intracellular Adhesion Molecule-1 on Measures of Sleepiness and 24-hour Ambulatory Blood Pressure After 4 Months of Continuous Positive Airway Pressure

Abstract Introduction Previous studies have shown that continuous positive airway pressure (CPAP) therapy of adults with obstructive sleep apnea (OSA) reduces circulating levels of intercellular adhesion molecule 1 (ICAM-1). ICAM-1 levels may affect daytime sleepiness and elevated blood pressure associated with OSA. Our goals were to explore associations between changes in ICAM-1 and objective and subjective measures of sleepiness, as well as 24-hour ambulatory blood pressure monitor (ABPM) parameters in adults with OSA following 4 months of CPAP treatment. Methods We identified 140 adults with newly diagnosed OSA in the Penn Icelandic Sleep Apnea (PISA) Study, with a mean (±SD) body mass index (BMI) of 31.5±4.2 kg/m2 and apnea-hypopnea index (AHI) of 36.8±15.3 events/hour; 83.3% were males. Plasma ICAM-1 levels, 24-hour ABPM, Epworth Sleepiness Scale (ESS), and Psychomotor Vigilance Task (PVT) measures were obtained at baseline and after 4 months of CPAP treatment. Associations between changes in natural log ICAM-1 and both sleepiness and 24-hour mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, use of anti-hypertensive medications, AHI and hours/night of CPAP usage. Results Overall, there was no significant change in ICAM-1 from baseline to follow-up among all participants after 4 months (0.027 ng/ml, p=0.52). There were no statistically significant associations between the change in ICAM-1 and change in sleepiness measures (all p&amp;gt;0.05) or 24-hour MAP (1.124 mm Hg, p=0.07). A nominal association between increased ICAM-1 and increased daytime MAP after 4 months was observed (1.39 mm Hg, p=0.033), although this result was not significant after correction for multiple comparisons. Conclusion Our results do not support changes in ICAM-1 as the biological pathway linking changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Support P01-HL094307 (NHLBI, PI: Pack AI)