Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome
ABSTRACT Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis. CD40-CD40 ligand interaction promotes several proinflammatory mediators and plays a pivotal role in the various stages of atherosclerotic diseases. The present study examines whether CD40 ligation contributes to outcomes in patients with OSAS.
The study population comprised OSAS patients with an apnea hypopnea index (AHI) > or = 30 (n = 35) and control subjects (AHI < 5; n = 16). We measured serum levels of soluble CD40 ligand (sCD40L), tumor necrosis factor (TNF)-alpha, and hypersensitive C-reactive protein (hsCRP) before and after nasal continuous positive airway pressure (nCPAP) therapy for 3 months.
Baseline levels of sCD40L were significantly higher in patients with OSAS (6.93 +/- 4.64 ng/mL) [mean +/- SD] than in control subjects (3.43 +/- 2.11 ng/mL, p < 0.01). Baseline levels of sCD40L positively correlated with TNF-alpha but not with hsCRP. The elevation of sCD40L was improved for 1 night after nCPAP therapy (3.83 +/- 2.78 ng/mL, p < 0.001). Even though patients with severe OSAS did not receive any other medication to control atherosclerotic risk factors for 3 months, nCPAP was continued to reduce the levels of sCD40L.
The present study suggested that sCD40L is a key factor that links OSAS and atherosclerotic progression.
SourceAvailable from: Peter J. Van der Spek[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exhibits oxidative stress and inflammation in patients who have a congenital, craniofacial anomaly.This prospective, cross-sectional cohort study included ambulant sleep study data to asses OSAS in patients with syndromic craniosynostosis and Treacher Collins syndrome. Laboratory analyses were performed including malondialdehyde, tumor necrosis factor α (TNF-α), interleukin 6, and high-sensitivity C-reactive protein.Forty-eight patients were included; 11 were adults; 37 were children. The patients' body mass indexes were normal, with a median (SD) of 0.7 (-1.82 to 2.48) in children and 20.5 (15.2-29.4) in adults. Obstructive sleep apnea syndrome was diagnosed in 23 of 48 patients. It was mild (median obstructive apnea-hypopnea index [oAHI], 2.3; oxygenation-desaturation index [ODI], 0.9) in 16 patients and moderate/severe in 7 patients (median oAHI, 10.8; ODI, 5.0). Neither oxidative stress nor inflammation had a correlation with the oAHI and ODI. Only TNF-α was found significantly higher in both the OSAS and non-OSAS groups compared with the reference values (median, 15.1 pg/mL and 12.3 pg/mL versus 4.05 [0.0-8.1 pg/mL], P < 0.001 and P < 0.001, respectively).Based on our findings we conclude that (mainly mild) OSAS, oxidative stress, as well as high-sensitivity C-reactive protein and interleukin 6 levels are not abnormal in the day time in a population of nonobese patients with a craniofacial anomaly. The increased level of TNF-α cannot be explained by OSAS. Future research should focus on mapping chronobiologic changes for further interpretation of the results.The Journal of craniofacial surgery 11/2013; 24(6):1908-13. DOI:10.1097/SCS.0b013e3182a41c05 · 0.68 Impact Factor
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ABSTRACT: Obstructive sleep apnea (OSA) occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow-derived endothelial progenitor cells (EPCs) within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has emerged. The possible mechanisms underlying the decrease in the number or function of EPCs include prolonged inflammation response, oxidative stress, increased sympathetic activation, physiological adaptive responses of tissue to hypoxia, reduced EPC mobilization, EPC apoptosis, and functional impairment in untreated OSA. Continuous positive airway pressure (CPAP) therapy for OSA affects the mobilization, apoptosis, and function of EPCs through preventing intermittent hypoxia episodes, improving sleep quality, and reducing systemic inflammation, oxidative stress levels, and sympathetic overactivation. To improve CPAP adherence, the medical staff should pay attention to making the titration trial a comfortable first CPAP experience for the patients; for example, using the most appropriate ventilators or proper humidification. It is also important to give the patients education and support about CPAP use in the follow-up, especially in the early stage of the treatment.Patient Preference and Adherence 10/2013; 7:1077-1090. DOI:10.2147/PPA.S51562 · 1.49 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: Obstructive sleep apnea (OSA) has been linked to and is associated with increased cardiovascular and cerebrovascular morbidity. Ongoing inflammatory responses play an important role in this association. Multiple small size studies addressing the profile of the inflammatory markers in OSA are available therefore we performed a meta-analysis. Systematic review of medical literature was conducted using PubMed, Cochrane, and EMBASE databases from 1968 to 2011 by utilizing the key words obstructive sleep apnea, C-Reactive protein, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and Selectins. Inclusion criteria were: full text English articles; studies with adult population; reported values for at least one of the markers of interest; with at least two separate groups (subjects with OSA and control group); OSA was defined as AHI of ≥ 5/h. Five hundred and twelve studies were reviewed for inclusion with 51 studies pooled for analysis (30 studies for CRP, 19 studies for TNF-α, 8 studies for ICAM, 18 studies for IL-6, six studies for VCAM and 5 studies for Selectins). The levels of inflammatory markers were higher in patients with OSA compared to control group. Standardized pooled Mean differences were calculated to be 1.77 for CRP, 1.03 for TNF-α, 2.16 for IL-6, 4.22 for IL-8, 2.93 for ICAM, 1.45 for Selectins and 2.08 for VCAM. In this meta-analysis, the levels of systemic inflammatory markers were found to be higher in OSA patients compared to control subjects. Nadeem R; Molnar J; Madbouly EM; Nida M; Aggarwal S; Sajid H; Naseem J; Loomba R. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med 2013;9(10):1003-1012.Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2013; 9(10):1003-1012. DOI:10.5664/jcsm.3070 · 2.93 Impact Factor