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Zhu Q, Luo Q, Wang Z, Chen S, Chen G, Huang S. Effects of continuous positive airway pressure therapy on inflammatory markers in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials. Sleep Breath 2025; 29:182. [PMID: 40346316 PMCID: PMC12064446 DOI: 10.1007/s11325-025-03348-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 04/24/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025]
Abstract
OBJECTIVE In this meta-analysis, we provide the findings of randomized controlled trials on the levels of inflammatory markers in patients with obstructive sleep apnea (OSA) receiving continuous positive airway pressure (CPAP). METHODS Literature published in the PubMed, Web of Science, Embase and Cochrane databases up to May 21, 2024, was comprehensively searched, and inclusion and exclusion criteria were developed. Pooled estimates of CPAP therapy were analyzed via the standardized mean difference (SMD). This meta-analysis follows the PRISMA 2020 guidelines and is registered with PROSPERO (ID CRD42024548588). RESULTS A total of 15 studies were included, each reporting data on one or more inflammatory markers, as follows: 10 studies on C-reactive protein (CRP), 12 studies on interleukin-6 (IL-6), 3 studies on interleukin-8 (IL-8), and 9 studies on tumor necrosis factor-α (TNF-α). The results revealed that the SMDs (95% confidence intervals [CIs]) for CRP, IL-6, IL-8 and TNF-α levels before and after CPAP treatment were 0.88 (95% CI 0.28-1.48), 0.58 (95% CI 0.12-1.05), 0.20 (95% CI 0.39-0.80) and 0.17 (95% CI 0.05-0.29), separately. CONCLUSION CPAP therapy used for a certain duration can lower CRP, IL-6 and TNF-α levels in OSA patients, and there are substantial differences observed in the various inflammatory indicators. To confirm the usefulness of these biomarkers in evaluating CPAP therapy for cardiovascular risk reduction among OSA patients, more randomized controlled trials (RCTs) have to be carried out in the future.
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Affiliation(s)
- Qianhong Zhu
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, China
| | - Qiuyi Luo
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Zhichen Wang
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Senlin Chen
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Gengzhao Chen
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Saie Huang
- Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China.
- Fujian University of Traditional Chinese Medicine, Fuzhou, China.
- Fujian Key Laboratory of Cognitive Rehabilitation, Fuzhou, China.
- Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, China.
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Zinchuk AV, Kushida CA, Walker A, Wellman A, Azarbarzin A, Alex RM, Varga AW, Sands SA, Yaggi HK. Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnoea. Eur Respir J 2025; 65:2401183. [PMID: 39572221 DOI: 10.1183/13993003.01183-2024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 10/25/2024] [Indexed: 04/27/2025]
Abstract
BACKGROUND Obstructive sleep apnoea (OSA) is associated with neurocognitive dysfunction. However, randomised trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit. We thus aimed to assess whether arousal threshold (ArTH) modifies the effect of CPAP on neurocognitive function. METHODS We performed a secondary analysis of a randomised, sham-controlled trial (Apnea Positive Pressure Long-term Efficacy Study (APPLES); ClinicalTrials.gov: NCT00051363). ArTH was estimated from polysomnography using a translatable method. Neurocognitive outcomes included the Sustained Working Memory Test-Overall Mid-Day (SWMT-OMD) score (executive function, primary outcome), with the Pathfinder Number Test total time (attention) and Buschke Selective Reminding Test sum recall (learning and memory) as secondary outcomes. Generalised linear modelling assessed whether the effect of CPAP was modified by baseline ArTH (treatment×ArTH interaction). 833 participants with OSA (apnoea-hypopnoea index ≥10 events·h-1), available ArTH and outcomes were analysed (active CPAP n=437 and sham CPAP n=396). RESULTS For executive function, the effect of CPAP treatment was modified by ArTH (pinteraction=0.042). Specifically, for every 1sd increase in ArTH, the SWMT-OMD score improved by 0.091 (95% CI 0.003-0.178) in active compared to sham CPAP at 6 months; at ArTH 1sd above the mean, SWMT-OMD improvements were nearly three times that in those with average ArTH (0.139 (95% CI 0.018-0.261) versus 0.053 (95% CI -0.034-0.140), respectively). No effect modification was observed for attention (p=0.311) or learning and memory (p=0.744). CONCLUSION In OSA, a higher ArTH is associated with greater improvements in executive function following CPAP therapy.
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Affiliation(s)
- Andrey V Zinchuk
- Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Clete A Kushida
- Division of Sleep Medicine, Department of Psychiatry and Behavioral Sciences, Stanford Hospital and Clinics, Stanford, CA, USA
| | - Alexander Walker
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Andrew Wellman
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ali Azarbarzin
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Raichel M Alex
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew W Varga
- Mount Sinai Integrative Sleep Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Scott A Sands
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- S.A. Sands and H.K. Yaggi are joint last authors
| | - H Klar Yaggi
- Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
- Clinical Epidemiology Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
- S.A. Sands and H.K. Yaggi are joint last authors
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Ayoub S, Tanweer H, Javaid HA, Khan MN, Ahmed S, Eljack MMF. Bridging the Gap: The Role of Continuous Positive Airway Pressure Therapy in Diabetic Retinopathy Associated With Obstructive Sleep Apnea-A Perspective. Health Sci Rep 2025; 8:e70502. [PMID: 39995799 PMCID: PMC11847710 DOI: 10.1002/hsr2.70502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
Background Obstructive sleep apnea (OSA) is a highly prevalent, yet under-diagnosed sleep disorder and has a strong association with type 2 diabetes and diabetic retinopathy (DR). Vascular abnormalities, nocturnal glucose dysregulation, impaired blood flow, and hypoxia during OSA induce oxidative stress and promote the inflammatory pathways which increase the VEGF factor levels, leading to the progression of DR. Aims To date, continuous positive airway pressure (CPAP) is the most effective, gold-standard treatment for patients with moderate to severe OSA. However, the implications of CPAP for the treatment of DR due to OSA is still a topic of ongoing debate. Conclusion Evidence suggests that the administration of CPAP therapy led to a reduction in retinal exudates and optical coherence tomography indices for retinal edema and also exhibited improvement in glycemic control, sleepiness, and overall health-related quality of life. Nevertheless, there are limited studies present that have evaluated the impact of CPAP therapy on DR in patients with OSA and well-designed studies are needed to confirm CPAP's therapeutic effect on DR despite these findings. Moreover, concerns regarding its long-term safety, adherence challenges, and inconsistent study designs limit definitive conclusions about CPAP's efficacy in managing DR. This indicates the need for future studies to advocate for enhanced CPAP adherence strategies, refined diagnostic criteria for OSA, and large-scale clinical trials to explore CPAP's therapeutic role in DR. Addressing these challenges could revolutionize clinical practices, optimize patient outcomes, and establish CPAP as a cornerstone in the integrated management of OSA and DR.
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Affiliation(s)
- Sadia Ayoub
- Jinnah Sindh Medical UniversityKarachiPakistan
| | | | | | | | - Shahzaib Ahmed
- Department of MedicineFatima Memorial Hospital College of Medicine and DentistryLahorePakistan
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Mohammadi I, Adibparsa M, Yashooa RK, Sehat MS, Sadeghi M. Effect of continuous positive airway pressure therapy on blood levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in obstructive sleep apnoea adults: A systematic review, meta-analysis and trial sequential analysis. Int Orthod 2024; 22:100917. [PMID: 39213713 DOI: 10.1016/j.ortho.2024.100917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/11/2024] [Accepted: 08/15/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Obstructive sleep apnoea (OSA) is a long-term disorder characterized by frequent blockages in the upper respiratory tract during sleep, often leading to abrupt awakenings, with or without a decrease in oxygen levels. The systematic review and meta-analysis aimed to assess the effect of continuous positive airway pressure therapy (CPAP) on blood interleukin (IL) levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in OSA adults. MATERIALS AND METHODS The published databases from PubMed, Scopus, Web of Science, and Cochrane Library were searched from 2003 to 2024, without any restrictions. The Review Manager software 5.3 was employed to compute effect sizes, which were presented as the standardized mean difference (SMD) along with a 95% confidence interval (CI). RESULTS In total, 320 records were identified through database searching; ultimately, 42 articles were included in the qualitative synthesis and then the meta-analysis. The CPAP therapy significantly reduces IL-6 levels, as indicated SMD=0.64 [95% CI: 0.35, 0.93] and P<0.0001. CPAP therapy significantly reduced IL-18 and IL-1β levels in adults with OSA, but there is no significant difference in IL-10, IL-4, or IL-17 levels. Age, blood sample, body mass index, ethnicity, and treatment duration for IL-6 and apnoea-hypopnea index with IL-10 levels were effective factors in the pooled results. Experimentally, there was an interaction between IL-18 and IL-1β. CONCLUSIONS CPAP therapy has a positive impact on inflammatory markers in OSA adults; remarkably, it reduces IL-6 and IL-1β levels. Nevertheless, more evidence (such as the role of ethnicity) and understanding of interactions are needed.
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Affiliation(s)
- Iman Mohammadi
- Oral and Maxillofacial Surgery Department, School of Dentistry, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran
| | - Mehrdad Adibparsa
- Department of Plastic Surgery, School of Medicine, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran
| | - Raya Kh Yashooa
- Department of Medical Microbiology, College of Science, Knowledge University, Kirkuk Road, 44001 Erbil, Kurdistan Region, Iraq
| | - Mohammad Soroush Sehat
- Oral and Maxillofacial Surgery Department, School of Dentistry, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran
| | - Masoud Sadeghi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, 67144-15185 Kermanshah, Iran.
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Volpentesta M, Condoleo V, Panza A, Severini G, Soraci L, Rotondo C, Armentaro G, Pelaia C, Fiorentino VT, Andreozzi F, Sesti G, Corsonello A, Sciacqua A. Effects of Continuous Positive Airway Pressure Treatment on Vascular Function in a Real-Life Cohort of Elderly Patients with Obstructive Sleep Apnoea Syndrome. Biomedicines 2024; 12:2563. [PMID: 39595129 PMCID: PMC11591960 DOI: 10.3390/biomedicines12112563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 10/29/2024] [Accepted: 11/01/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Obstructive sleep apnoea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality and has a detrimental effect on vascular function, in particular on arterial stiffness and endothelial function. Continuous positive airway pressure (CPAP) is the gold-standard therapy for OSAS and its effects on arterial stiffness and endothelial function have been demonstrated in non-elderly patients. OBJECTIVES The objective of this study was to evaluate the effect of one year of CPAP treatment on arterial stiffness, through assessment of carotid-femoral pulse wave velocity (cf-PWV), and on endothelial function, through the reactive hyperaemia index (RHi), in a real-life cohort of elderly patients with moderate-to-severe OSAS and several comorbidities. METHODS In this nonrandomised prospective study, we enrolled 469 consecutive elderly patients affected by moderate-to-severe OSAS distributed in two groups: CPAP-treated (n = 225) and untreated patients (n = 244). RESULTS At one-year follow-up, in the treated group emerged an important improvement in poligraphics (AHI, ODI, TC90, mean SpO2%), laboratory (HOMA index, eGFR, hs-CRP) and vascular function parameters: cf-PWV. The stepwise multivariate linear regression demonstrated a significant correlation between the delta of the polygraph parameters and the delta of PWV and RHi. CONCLUSIONS Our study confirmed the favourable effects of CPAP therapy in a cohort of elderly patients affected by OSAS and several comorbidities on sleep respiratory parameters and vascular function; early diagnosis and treatment with CPAP might be beneficial to delay or prevent the occurrence of cardiovascular events in these groups of patients.
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Affiliation(s)
- Mara Volpentesta
- Unit of Geriatric Medicine, IRCCS INRCA, 87100 Cosenza, Italy; (M.V.); (L.S.); (A.C.)
| | - Valentino Condoleo
- Geriatrics Division, University Hospital “R. Dulbecco”, 88100 Catanzaro, Italy; (V.C.); (G.A.); (A.S.)
| | - Alberto Panza
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
| | - Giandomenico Severini
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
| | - Luca Soraci
- Unit of Geriatric Medicine, IRCCS INRCA, 87100 Cosenza, Italy; (M.V.); (L.S.); (A.C.)
| | - Cataldo Rotondo
- Coordinamento Medico legale, Istituto Nazionale della Previdenza Sociale, 88100 Catanzaro, Italy;
| | - Giuseppe Armentaro
- Geriatrics Division, University Hospital “R. Dulbecco”, 88100 Catanzaro, Italy; (V.C.); (G.A.); (A.S.)
| | - Corrado Pelaia
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
| | - Vanessa Teresa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00185 Rome, Italy;
| | - Andrea Corsonello
- Unit of Geriatric Medicine, IRCCS INRCA, 87100 Cosenza, Italy; (M.V.); (L.S.); (A.C.)
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87100 Rende, Italy
| | - Angela Sciacqua
- Geriatrics Division, University Hospital “R. Dulbecco”, 88100 Catanzaro, Italy; (V.C.); (G.A.); (A.S.)
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.P.); (C.P.); (V.T.F.); (F.A.)
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Epstein S, Jun D, Deng JC, Zeidler M. Effects of Obstructive Sleep Apnea on Airway Immunity and Susceptibility to Respiratory Infections. Sleep Med Clin 2024; 19:219-228. [PMID: 38692747 DOI: 10.1016/j.jsmc.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
Abstract
Obstructive sleep apnea is a prevalent sleep disorder characterized by recurrent episodes of partial or complete upper airway collapse during sleep, leading to disrupted breathing patterns and intermittent hypoxia. OSA results in systemic inflammation but also directly affects the upper and lower airways leading to upregulation of inflammatory pathways and alterations of the local microbiome. These changes result in increased susceptibility to respiratory infections such as influenza, COVID-19, and bacterial pneumonia. This relationship is more complex and bidirectional in individuals with chronic lung disease such as chronic obstructive lung disease, interstitial lung disease and bronchiectasis.
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Affiliation(s)
- Samuel Epstein
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA
| | - Dale Jun
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA
| | - Jane C Deng
- Pulmonary Medicine, VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA; Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA
| | - Michelle Zeidler
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA.
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He Y, Dong N, Wang X, Lv RJ, Yu Q, Yue HM. Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons. Sleep Breath 2024; 28:1051-1065. [PMID: 38308748 DOI: 10.1007/s11325-024-03001-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 02/05/2024]
Abstract
Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA.
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Affiliation(s)
- Yao He
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Na Dong
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Xiao Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Ren-Jun Lv
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Qin Yu
- Department of Respiratory and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, China
| | - Hong-Mei Yue
- Department of Respiratory and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, China.
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Dong M, Liang X, Zhu T, Xu T, Xie L, Feng Y. Reoxygenation Mitigates Intermittent Hypoxia-Induced Systemic Inflammation and Gut Microbiota Dysbiosis in High-Fat Diet-Induced Obese Rats. Nat Sci Sleep 2024; 16:517-530. [PMID: 38812701 PMCID: PMC11135559 DOI: 10.2147/nss.s454297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 05/12/2024] [Indexed: 05/31/2024] Open
Abstract
Background Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations. Methods Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O2, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing. Results DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p<0.0167), and significant alterations in the microbial structure (p=0.014), notably the order Clostridiales, accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with Ruminococcaceae (p=0.0008) and Clostridiales (p=0.0019), while body weight was linked to Blautia producta (p=0.0377). Additionally, the abundance of Lactobacillus was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339). Conclusion IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.
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Affiliation(s)
- Menglu Dong
- Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Xili Liang
- Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Tian Zhu
- Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Ting Xu
- Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Liwei Xie
- Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, People’s Republic of China
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Yuan Feng
- Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
- Institute of Brain Disease, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China
- Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Science, Southern Medical University, Guangzhou, People’s Republic of China
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Liu J, Xu J, Guan S, Wang W. Effects of different treatments on metabolic syndrome in patients with obstructive sleep apnea: a meta-analysis. Front Med (Lausanne) 2024; 11:1354489. [PMID: 38515989 PMCID: PMC10955063 DOI: 10.3389/fmed.2024.1354489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/22/2024] [Indexed: 03/23/2024] Open
Abstract
Background Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) often coexist, and the causal relationship between them is not yet clear; treatments for OSA include continuous positive airway pressure (CPAP), mandibular advancement device (MAD), surgery, and lifestyle intervention and so on. However, the effects of different treatments on metabolic syndrome in OSA patients are still under debate. Objectives Review the effects of different treatments on metabolic syndrome in OSA patients by meta-analysis. Methods we searched articles in PubMed, Embase, Cochrane Library, CNKI, CBM, and Wanfang data from database construction to Feb. 2024.RevMan5.4 and Stata software were used to conduct a meta-analysis of 22 articles. Results A total of 22 articles were finally included. The results showed that CPAP treatment could reduce the prevalence of metabolic syndrome in OSA patients in randomized controlled trials (RCTs) (RR = 0.82 [95% CI, 0.75 to 0.90]; p < 0.01) and single-arm studies (RR = 0.73 [95% CI, 0.63 to 0.84]; p < 0.01). As for metabolic syndrome components, CPAP treatment reduces blood pressure, fasting glucose (FG), triglycerides (TG), and waist circumference (WC) but can't affect high-density lipoprotein cholesterol (HDL-C) levels. Lifestyle intervention could significantly reduce the prevalence of metabolic syndrome in OSA patients (RR = 0.60 [95% CI, 0.48 to 0.74]; p < 0.01) and can lower blood pressure, fasting glucose, and waist circumference but can't affect the lipid metabolism of OSA patients. Upper airway surgery can only reduce TG levels in OSA patients (MD = -0.74 [95% CI, -1.35 to -0.13]; p = 0.02) and does not affect other components of metabolic syndrome. There is currently no report on the impact of upper airway surgery on the prevalence of metabolic syndrome. No study has reported the effect of MAD on metabolic syndrome in OSA patients. Conclusion We confirmed that both CPAP and lifestyle intervention can reduce the prevalence of MetS in OSA patients. CPAP treatment can lower blood pressure, fasting glucose, waist circumference, and triglyceride levels in OSA patients. Lifestyle intervention can lower blood pressure, fasting glucose, and waist circumference in OSA patients. Upper airway surgery can only reduce TG levels in OSA patients. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022326857.
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Affiliation(s)
| | | | | | - Wei Wang
- Institute of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Swami SS, Aye SL, Trivedi Y, Bolgarina Z, Desai HN, Senaratne M, Mohammed L. From Snoring to Soaring: Unveiling the Positive Effects of Continuous Positive Airway Pressure Ventilation on Cardiovascular Health in Patients With Obstructive Sleep Apnoea Through a Systematic Review. Cureus 2023; 15:e45076. [PMID: 37711271 PMCID: PMC10497801 DOI: 10.7759/cureus.45076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 09/11/2023] [Indexed: 09/16/2023] Open
Abstract
Increased cardiovascular (CV) morbidity and death are linked to obstructive sleep apnoea (OSA). The primary method of treating OSA is continuous positive airway pressure (CPAP). CPAP has some debatable outcomes on CV events in people suffering from OSA. The current study investigates how CPAP affects CV outcomes. The goal is to evaluate CPAP's effectiveness in lowering CV outcomes in OSA patients. We used a computer to search the PubMed, PubMed Central Library, Science Direct, and Google Scholar databases for studies comparing the effects of CPAP and a control group on CV outcomes in OSA patients. These included randomised control trials (RCT), narrative reviews, systematic reviews, case-control studies, observational studies and meta-analyses. A total of 52,937 patients were included in the final analysis of six RCTs, four observational studies, 10 meta-analyses, one case-control study, two systematic reviews and one narrative review. The weighted mean follow-up lasted for a period of between three months and nine years. The risk of major cardiovascular adverse events (MACE) was the same for both the CPAP and control groups. According to subgroup analysis, patients with lower MACE adherence rates (four hours per night) were more likely to use CPAP. The risk of all-cause mortality, CV-related complications causing mortality, acute myocardial infarction acute stroke, or hospitalisations for angina was the same in the CPAP and control groups. The primary outcome was that in patients with therapy with CPAP in addition to usual care and usual care alone did not prevent CV events in patients with moderate-to-severe OSA and existing CV illness. Patients with OSA who utilise CPAP may not experience fewer CV events. Patients who use CPAP consistently (four hours per night) could benefit from improved CV results. Future research must assess how well-adherent patients with severe OSA and low CV event rates respond to CPAP therapy. In patients who use CPAP for more than four hours each night, CPAP therapy may minimise the risk of MACE and stroke. Additional randomised trials requiring adequate CPAP time adherence are needed to support this perception. Despite the fact that there is no evidence to support the claim that CPAP therapy improves CV outcomes, bias difficulties, CPAP adherence problems, and the patient groups included in each RCT may have made it more difficult to generalise the findings to all patients. Future research is therefore needed to look at these relevant results.
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Affiliation(s)
- Shivling S Swami
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Soe Lwin Aye
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Yash Trivedi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Zoryana Bolgarina
- Obstetrics and Gynecology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Heet N Desai
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mithum Senaratne
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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11
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Sheng W, Ji G, Zhang L. Management of non-alcoholic fatty liver disease patients with sleep apnea syndrome. World J Gastroenterol 2022; 28:6099-6108. [PMID: 36483151 PMCID: PMC9724487 DOI: 10.3748/wjg.v28.i43.6099] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/20/2022] [Accepted: 11/06/2022] [Indexed: 11/16/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with sleep apnea syndrome (SAS). Many NAFLD patients have SAS, and obstructive sleep apnea hypopnea syndrome is also considered to be an independent risk factor for NAFLD, as it contributes to the progression of NAFLD via oxidative stress, lipid peroxidation, inflammation, and insulin resistance. This review aims to provide some recommendations for the management of NAFLD patients with SAS, including diet, exercise, weight loss, and continuous positive airway pressure. This review also highlights the importance of effective strategies in NAFLD prevention and treatment.
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Affiliation(s)
- Wei Sheng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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12
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Mo J, Zeng C, Li W, Song W, Xu P. Manuscript Title: A 4-miRNAs Serum Panel for Obstructive Sleep Apnea Syndrome Screening. Nat Sci Sleep 2022; 14:2055-2064. [PMID: 36394070 PMCID: PMC9656345 DOI: 10.2147/nss.s382765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 11/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea syndrome (OSAS) is a common chronic sleep disorder. OSAS is closely related to cardiovascular disease, metabolic disorders, cancer risk, and sudden death. This association has special significance in young people. Although it is known that OSAS has a great impact on physical health, it is estimated that 70-80% of patients with moderate-to-severe OSAS remain undiagnosed. Therefore, a new method for early diagnosis of the disease, the therapeutic effect of OSAS and prevention of complications to important. METHODS A total of 110 patients with moderate-to-severe OSAS diagnosed in the Sleep Disorders Diagnosis and Treatment Center of Peking University Shenzhen Hospital were selected. After excluding other diseases, 59 patients were finally selected as the OSAS group. In addition, 60 healthy people were selected as the control group. Serum RNA was then extracted. Eight RNA samples were randomly selected from the two groups for high-throughput miRNA sequencing. The 10 miRNAs with the greatest differences were selected as preselected markers from the results. Then, qRT-PCR was performed on the remaining RNA samples of the two groups to extract and verify the 10 miRNAs, and statistical analysis was performed between groups. RESULTS A diagnostic panel was constructed by a stepwise logistic regression model combined with the expression data of miRNAs in the validation phase. A four-miRNA panel was identified to better predict OSAS, and the model was calculated using the following formula: Logit (P)= 0.77-1.65 × miR-486-5p - 4.56 × miR-148a-3p + 1.79 × miR-744-5p + 1.13 × let-7d-3p. The AUC for the four-miRNA panel was 0.955 (95% CI: 0.899 to 0.985; sensitivity = 91.38%, specificity = 91.38%). Gene Ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was included in bioinformatic analysis. CONCLUSION A 4-miRNAs panel as a diagnostic biomarker for OSAS screening is feasible.
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Affiliation(s)
- Jianming Mo
- Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People's Republic of China
| | - Chao Zeng
- Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People's Republic of China
| | - Wei Li
- Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People's Republic of China
| | - Weidong Song
- Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People's Republic of China
| | - Ping Xu
- Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People's Republic of China
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13
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Liu PK, Chiu TY, Wang NK, Levi SR, Tsai MJ. Ocular Complications of Obstructive Sleep Apnea. J Clin Med 2021; 10:jcm10153422. [PMID: 34362205 PMCID: PMC8348497 DOI: 10.3390/jcm10153422] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 07/20/2021] [Accepted: 07/28/2021] [Indexed: 12/13/2022] Open
Abstract
Obstructive sleep apnea (OSA), the most common form of sleep-disordered breathing, is characterized by repetitive episodes of paused breathing during sleep, which in turn induces transient nocturnal hypoxia and hypercapnia. The high prevalence of OSA and its associated health consequences place a heavy burden on the healthcare system. In particular, the consequent episodic oxygenic desaturation/reoxygenation series and arousals from sleep in patients with OSA have the potential to trigger oxidative stress, elevated systemic inflammatory responses, and autonomic dysfunction with sympathetic activation. Given these adverse side-effects, OSA is highly correlated to many eye diseases that are common in everyday ophthalmic practices. Some of these ocular consequences are reversible, but they may permanently threaten a patient’s vision if not treated appropriately. Here, this article seeks to review the ocular consequences and potential pathophysiologic associations in patients with OSA. Understanding these OSA-related eye diseases may help clinicians provide comprehensive care to their patients.
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Affiliation(s)
- Pei-Kang Liu
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (P.-K.L.); (T.-Y.C.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032, USA; (N.-K.W.); (S.R.L.)
| | - Tzu-Yu Chiu
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (P.-K.L.); (T.-Y.C.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Nan-Kai Wang
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032, USA; (N.-K.W.); (S.R.L.)
| | - Sarah R. Levi
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032, USA; (N.-K.W.); (S.R.L.)
| | - Ming-Ju Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Sleep Disorders Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7-3121101 (ext. 5601)
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14
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Fernández-Torres R, Ruiz-Muñoz M, Pérez-Belloso AJ, García-Romero J, Gónzalez-Sánchez M. Is There an Association between Sleep Disorders and Diabetic Foot? A Scoping Review. J Clin Med 2021; 10:2530. [PMID: 34200453 PMCID: PMC8201034 DOI: 10.3390/jcm10112530] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/26/2021] [Accepted: 06/03/2021] [Indexed: 12/04/2022] Open
Abstract
Diabetic foot is associated with a low quality of life since physical disabilities, mood disturbances and psychological disorders are frequent. One of the most important biological processes to ensure quality of life is sleep. Sleep disorders can impair glycemic control in patients with diabetes mellitus or even cause long-term type 2 diabetes mellitus. The aim of this study is to carry out a scoping review about the association between sleep cycle disorders and diabetic foot. PubMed, Scopus, CINAHL, PEDro, Cochrane Library, SCIELO and EMBASE databases were chosen for the search and the following terms were used: "diabetic foot","sleep*","rest-activity","mood" and"behavior". All the studies should include outcome variables about sleep and diabetic foot. Finally, 12 articles were selected, all of whichwere observational. The most frequent variables were those regarding diabetic foot ulcer aspects and diabetic neuropathy on one side, and obstructive sleep apnea, sleep duration and sleep quality on the other side. The results suggest that there is a possible association between obstructive sleep apnea and the presence or history of diabetic foot ulcers. No direct associations between sleep quality or sleep duration and diabetic foot or diabetic foot ulcer variables have been found.
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Affiliation(s)
- Raúl Fernández-Torres
- Department of Nursing and Podiatry, University of Málaga, Arquitecto Francisco Peñalosa, s/n, Ampliación Campus de Teatinos, 29071 Málaga, Spain;
| | - María Ruiz-Muñoz
- Department of Nursing and Podiatry, University of Málaga, Arquitecto Francisco Peñalosa, s/n, Ampliación Campus de Teatinos, 29071 Málaga, Spain;
| | - Ana J. Pérez-Belloso
- Department of Podiatry, Faculty of Nursing, Physiotherapy and Podiatry, University of Sevilla, 41009 Sevilla, Spain;
| | - Jerónimo García-Romero
- Medical School of Physical Education and Sports, University of Málaga, C/Jiménez Fraud 10, Edificio López de Peñalver, 29010 Málaga, Spain;
| | - Manuel Gónzalez-Sánchez
- Department of Physiotherapy, University of Málaga, Arquitecto Francisco Peñalosa, s/n, Ampliación Campus de Teatinos, 29071 Málaga, Spain;
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15
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Zeng QC, Sun Q, Zhang M, Tang Y, Long HC. Relation between IL-8 level and obstructive sleep apnea syndrome. Open Med (Wars) 2021. [DOI: 10.1515/med-2020-0240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Objective
This meta-analysis was conducted to explore the relationship between serum level of IL-8 and obstructive sleep apnea syndrome (OSAS).
Methods
Electronic databases were retrieved according to the inclusion and exclusion criteria, relevant studies exploring the relationship between serum level of IL-8 and OSAS were enrolled. Statistical analysis was performed using STATA 12.0.
Results
Totally 199 studies were retrieved, among which 10 were qualified for the inclusion criteria and were finally included in the meta-analysis with 367 cases of OSAS patients and 335 control cases. Serum level of IL-8 was higher in patients than healthy controls (Standard mean difference (SMD) = 2.16, 95% CI = 1.17–3.15, P < 0.001). The subgroup analysis based on ethnicity revealed that average serum level of IL-8 were higher in Asian and Caucasian OSAS patients than healthy controls (Asian: SMD = 2.50, 95% CI = 1.13–3.87, P < 0.001; Caucasian: SMD = 1.59, 95% CI = 0.11–3.06, P = 0.035). Further subgroup analysis based on age indicated a statistical difference in serum level of IL-8 between adult OSAS patients and healthy counterparts (SMD = 2.73, 95% CI = 1.49–3.98, P < 0.001).
Conclusion
The level of IL-8 was related to OSAS in adult patients, and increased serum IL-8 level may increase the risk of OSAS.
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Affiliation(s)
- Qing-Cui Zeng
- Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu , China
- Department of Geriatrics, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital , Chengdu 610072 , China
| | - Qin Sun
- Center of Diabetes Mellitus, School of Medicine, University of Electronic Science and Technology of China, Chengdu , Sichuan 610000 , People’s Republic of China
| | - Min Zhang
- Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu , China
- Department of Geriatrics, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital , Chengdu 610072 , China
| | - Yi Tang
- Department of Endocrinology, The Fifth People’s Hospital of Chengdu , Chengdu 611130 , People’s Republic of China
| | - Huai-Cong Long
- Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu , China
- Department of Geriatrics, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital , Chengdu 610072 , China
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16
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Ee JS, Pham CK, Shaha DP, Rogers MC, Cacace GS, Mounts CW. Soldiers' Perception of a Behavioral Intervention for Positive Airway Pressure Therapy Adherence in a Military Treatment Facility. Mil Med 2021; 186:239-245. [PMID: 33499498 DOI: 10.1093/milmed/usaa306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 07/14/2020] [Accepted: 09/02/2020] [Indexed: 11/12/2022] Open
Abstract
INTRODUCTION The incidence of obstructive sleep apnea in military personnel has increased over 500% since the early 2000s. Adherence to continuous positive airway pressure (PAP), an efficacious treatment, has been suboptimal. This article presents a behavioral intervention model for enhancing PAP therapy adherence and describes how the model was received by military personnel. MATERIALS AND METHODS The study population comprised 254 out of 280 military personnel (93% men, mean age 39 years) who attended a 90-minute behavioral intervention class within the first 8 weeks of PAP use. They were coached on the Knowledge, Skills, Attitudes (KSA) model of PAP therapy success: Knowledge about obstructive sleep apnea and PAP treatment; Skills to develop a habitual loop for nightly PAP use; and Attitudes that address readiness, barriers, and solutions for sustaining PAP use. Participants completed a voluntary, anonymous postclass survey that inquired of their perception of various elements of the class. Data were analyzed using descriptive statistics and a paired sample t-test. RESULTS In participants' self-rating of how much they know about PAP treatment before and after the class, their ratings indicated that they experienced a significant increase in knowledge (P < 0.0001). On the postclass survey, 77% of the participants (N = 195/254) "agree a lot" or "strongly agree" that the class gave them tools to have a successful treatment and 78% (N = 198/254) noted that it was a valuable educational experience. The Knowledge portion was rated by 79% (N = 201/254) of the participants as "quite a lot" or "extremely" beneficial. The Skills segment was rated as "quite a lot" or "extremely" beneficial by 72% (N = 183/254) of the participants. The Attitudes discussion was perceived as "quite a lot" or "extremely" beneficial by 70% (N = 178/254) of the participants. Participants' free-text responses to "what was most helpful" were generally positive. CONCLUSIONS A KSA model of behavioral intervention for enhancing PAP therapy adherence was well received by participants. Future research will assess the impact of this intervention on adherence as measured by objective indicators.
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Affiliation(s)
- Juliana S Ee
- Department of Family Medicine, Womack Army Medical Center, NC, 28310, USA
| | | | - David P Shaha
- Department of Medicine, Womack Army Medical Center, NC, 28310, USA
| | - Mary C Rogers
- Department of Medicine, Womack Army Medical Center, NC, 28310, USA
| | - Gregory S Cacace
- Department of Medicine, Womack Army Medical Center, NC, 28310, USA
| | - Charles W Mounts
- Department of Family Medicine, Womack Army Medical Center, NC, 28310, USA
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17
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Oxidative Stress and Inflammation Biomarker Expression in Obstructive Sleep Apnea Patients. J Clin Med 2021; 10:jcm10020277. [PMID: 33451164 PMCID: PMC7828672 DOI: 10.3390/jcm10020277] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/06/2021] [Accepted: 01/08/2021] [Indexed: 02/08/2023] Open
Abstract
Obstructive Sleep Apnea Syndrome (OSAS) is a respiratory sleep disorder characterised by repeated episodes of partial or complete obstruction of the upper airway during the night. This obstruction usually occurs with a reduction (hypopnea) or complete cessation (apnea) of the airflow in the upper airways with the persistence of thoracic-diaphragmatic respiratory movements. During the hypopnea/apnea events, poor alveolar ventilation reduces the oxygen saturation in the arterial blood (SaO2) and a gradual increase in the partial arterial pressure of carbon dioxide (PaCO2). The direct consequence of the intermittent hypoxia is an oxidative imbalance, with reactive oxygen species production and the inflammatory cascade’s activation with pro and anti-inflammatory cytokines growth. Tumour necrosis factors, inflammatory cytokines (IL2, IL4, IL6), lipid peroxidation, and cell-free DNA have been found to increase in OSAS patients. However, even though different risk-related markers have been described and analysed in the literature, it has not yet been clarified whether specified inflammatory bio-markers better correlates with OSAS diagnosis and its clinical evolution/comorbidities. We perform a scientific literature review to discuss inflammatory and oxidative stress biomarkers currently tested in OSAS patients and their correlation with the disease’s severity and treatment.
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18
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Fadaei R, Koushki M, Sharafkhaneh A, Moradi N, Ahmadi R, Rostampour M, Khazaie H. The impact of continuous positive airway pressure therapy on circulating levels of malondialdehyde: a systematic review and meta-analysis. Sleep Med 2020; 75:27-36. [PMID: 32853915 DOI: 10.1016/j.sleep.2020.02.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/28/2020] [Accepted: 02/14/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder which associated with increased oxidative stress and cardiovascular diseases. Malondialdehyde (MDA) is a reliable marker of lipid peroxidation and is elevated in patients with OSA. Studies reported inconsistent findings on the effect of continuous positive airway pressure (CPAP) therapy on MDA levels. As the study power maybe a reason for the inconsistent findings, we aimed to use meta-analysis to assess effect of CPAP therapy on MDA in patients with OSA. METHOD Electronic search was performed to find out studies on the effect of CAPA on MDA levels in OSA patients. Search carried out in databases of PubMed, EMBASE, Scopus, Cochrane library and web of science. RESULTS Search resulted in 161 records of which 83 remained after removing duplicated records. Further, 51 articles were removed by title and abstract and 22 records evaluated by full text. Finally 13 articles were included in the intended meta-analysis. Pooled analysis demonstrated that CPAP therapy reduced MDA levels significantly [SMD (-1.51) (95% CI, -2.06 to -0.97) p < 0.05]. Subgroup analyses showed that CPAP therapy was effective in categories of age (≤50 and > 50 years), BMI (≤30 and > 30 kg/m2) and therapy duration (≤12 week and >12 week). CONCLUSION the results of the present study demonstrated considerable effect of CPAP therapy on MDA as independent risk factor for cardiovascular diseases and robust marker of lipid peroxidation.
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Affiliation(s)
- Reza Fadaei
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehdi Koushki
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Sharafkhaneh
- Department of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Nariman Moradi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Reza Ahmadi
- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Masoumeh Rostampour
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Habibolah Khazaie
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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19
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Wang Y, Meagher RB, Ambati S, Ma P, Phillips BG. Patients with obstructive sleep apnea have suppressed levels of soluble cytokine receptors involved in neurodegenerative disease, but normal levels with airways therapy. Sleep Breath 2020; 25:1641-1653. [PMID: 33037528 PMCID: PMC8376707 DOI: 10.1007/s11325-020-02205-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 08/13/2020] [Accepted: 09/26/2020] [Indexed: 12/14/2022]
Abstract
Purpose Obstructive sleep apnea (OSA) results in systemic intermittent hypoxia. By one model, hypoxic stress signaling in OSA patients alters the levels of inflammatory soluble cytokines TNF and IL6, damages the blood brain barrier, and activates microglial targeting of neuronal cell death to increase the risk of neurodegenerative disorders and other diseases. However, it is not yet clear if OSA significantly alters the levels of the soluble isoforms of TNF receptors TNFR1 and TNFR2 and IL6 receptor (IL6R) and co-receptor gp130, which have the potential to modulate TNF and IL6 signaling. Methods Picogram per milliliter levels of the soluble isoforms of these four cytokine receptors were estimated in OSA patients, in OSA patients receiving airways therapy, and in healthy control subjects. Triplicate samples were examined using Bio-Plex fluorescent bead microfluidic technology. The statistical significance of cytokine data was estimated using the nonparametric Wilcoxon rank-sum test. The clustering of these high-dimensional data was visualized using t-distributed stochastic neighbor embedding (t-SNE). Results OSA patients had significant twofold to sevenfold reductions in the soluble serum isoforms of all four cytokine receptors, gp130, IL6R, TNFR1, and TNFR2, as compared with control individuals (p = 1.8 × 10−13 to 4 × 10−8). Relative to untreated OSA patients, airways therapy of OSA patients had significantly higher levels of gp130 (p = 2.8 × 10−13), IL6R (p = 1.1 × 10−9), TNFR1 (p = 2.5 × 10−10), and TNFR2 (p = 5.7 × 10−9), levels indistinguishable from controls (p = 0.29 to 0.95). The data for most airway-treated patients clustered with healthy controls, but the data for a few airway-treated patients clustered with apneic patients. Conclusions Patients with OSA have aberrantly low levels of four soluble cytokine receptors associated with neurodegenerative disease, gp130, IL6R, TNFR1, and TNFR2. Most OSA patients receiving airways therapy have receptor levels indistinguishable from healthy controls, suggesting a chronic intermittent hypoxia may be one of the factors contributing to low receptor levels in untreated OSA patients. Electronic supplementary material The online version of this article (10.1007/s11325-020-02205-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ye Wang
- Department of Statistics, University of Georgia, Athens, GA, 30602, USA
| | - Richard B Meagher
- Department of Genetics, University of Georgia, Athens, GA, 30602, USA.
| | - Suresh Ambati
- Department of Genetics, University of Georgia, Athens, GA, 30602, USA
| | - Ping Ma
- Department of Statistics, University of Georgia, Athens, GA, 30602, USA
| | - Bradley G Phillips
- Clinical and Administrative Pharmacy, University of Georgia, Athens, GA, 30602, USA.,Clinical and Translational Research Unit, University of Georgia, Athens, GA, 30602, USA
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20
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Phillips BG, Wang Y, Ambati S, Ma P, Meagher RB. Airways therapy of obstructive sleep apnea dramatically improves aberrant levels of soluble cytokines involved in autoimmune disease. Clin Immunol 2020; 221:108601. [PMID: 33017651 DOI: 10.1016/j.clim.2020.108601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/21/2020] [Accepted: 09/25/2020] [Indexed: 12/17/2022]
Abstract
Obstructive Sleep Apnea (OSA) damages the health of 35% of adult Americans. Disordered sleep results in increased risk of several autoimmune disorders, but the molecular links to autoimmunity are poorly understood. Herein, we identified four cytokines associated with autoimmune disease, whose median serum levels were significantly different for OSA patients receiving airways therapy, from the levels in untreated OSA patients, APRIL (5.2-fold lower, p = 3.5 × 10-11), CD30 (1.6-fold higher, p = 7.7 × 10-5), IFN-Alpha-2 (2.9-fold higher, p = 9.6 × 10-14) and IL-2 (1.9-fold higher, p = 0.0003). Cytokine levels in airways treated patients were similar to the levels in control subjects. t-SNE and UMAP analysis of these high dimensional patient cytokine data identified only two groups, suggesting a similar global response for all four cytokines to airways therapy. Our findings suggest the levels of these four cytokines may be altered by disordered sleep and perhaps by chronic hypoxia. Therapeutic options are discussed.
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Affiliation(s)
- Bradley G Phillips
- Clinical and Administrative Pharmacy, University of Georgia, Athens, GA 30602, USA; Clinical and Translational Research Unit, University of Georgia, Athens, GA 30602, USA
| | - Ye Wang
- Department of Statistics, University of Georgia, Athens, GA 30602, USA
| | - Suresh Ambati
- Department of Genetics, University of Georgia, Athens, GA 30602, USA
| | - Ping Ma
- Department of Statistics, University of Georgia, Athens, GA 30602, USA
| | - Richard B Meagher
- Department of Genetics, University of Georgia, Athens, GA 30602, USA.
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Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. Int J Mol Sci 2019; 20:ijms20030459. [PMID: 30678164 PMCID: PMC6387387 DOI: 10.3390/ijms20030459] [Citation(s) in RCA: 207] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/12/2019] [Accepted: 01/15/2019] [Indexed: 12/19/2022] Open
Abstract
Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.
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Gu X, Luo X, Wang X, Tang J, Yang W, Cai Z. The correlation between obstructive sleep apnea and diabetic neuropathy: A meta-analysis. Prim Care Diabetes 2018; 12:460-466. [PMID: 29728306 DOI: 10.1016/j.pcd.2018.03.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 03/13/2018] [Accepted: 03/24/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND The aim of this study was to explore the correlation between obstructive sleep apnea (OSA) and diabetic neuropathy. MATERIALS AND METHODS After working out searching strategy, literatures were screened from the electronic databases: PubMed, Embase, and the Cochrane library. R 3.12 was utilized to perform meta-analysis, and odds ratio (OR) and its 95% confidence interval (CI) were used to present effect size. Heterogeneity was assessed by χ2-based Q test and I2 statistics. Publication bias was estimated by Egger's test and sensitivity was evaluated by leave one out methods. RESULTS According to the criteria, a total of 11 studies with 1842 patients were enrolled in this study. With a significant heterogeneity (Q=31.83, I2=68.60%), the random effects model was utilized to assess the effect size of pooled data. A remarkable correlation was identified OSA and diabetic neuropathy (OR=1.84, 95% CI: 1.18-2.87) without publication bias (t=1.68, P=0.13). Meanwhile, the result of leave one out performed a well sensitivity. Moreover, the subgroup analyses presented that OSA was significantly correlated with type 1 diabetic neuropathy (OR=1.97, 95% CI: 1.19-3.25), but no remarkable correlation was identified between OSA and type 1 (OR=1.84, 95% CI: 0.86-3.93) or 1+2 (OR=1.30, 95% CI: 0.43-3.92) diabetic neuropathy. CONCLUSION OSA was significantly correlated with neuropathy in type 1 diabetes, but not in type 2 and type 1+2 diabetes.
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Affiliation(s)
- Xiandong Gu
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Xuming Luo
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Xiongbiao Wang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Jihong Tang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Wei Yang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Zhuying Cai
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
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Gabryelska A, Łukasik ZM, Makowska JS, Białasiewicz P. Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets. Front Neurol 2018; 9:635. [PMID: 30123179 PMCID: PMC6085466 DOI: 10.3389/fneur.2018.00635] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 07/16/2018] [Indexed: 12/31/2022] Open
Abstract
Obstructive sleep apnea is a chronic condition characterized by recurrent episodes of apneas or hypopneas during sleep leading to intermittent hypoxemia and arousals. The prevalence of the sleep disordered breathing is estimated that almost 50% of men and 24% of women suffer from moderate to severe form of the disorder. Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates. Platelets participate in the process of transcellular production of bioactive lipids by delivering both specific enzymes and substrate molecules. Despite their lack of nucleus, platelets synthetize proteins in a stimuli-dependent manner. Atherosclerosis and consequent cardiovascular complications result from disruption in homeostasis of both of the platelet roles: blood coagulation and inflammatory processes modulation. Platelet parameters, routinely evaluated as a part of complete blood count test, were proposed as markers of cardiovascular comorbidity in patients with obstructive sleep apnea. Platelets were found to be excessively activated in this group of patients, especially in obese subjects. Persistent activation results in enhanced spontaneous aggregability and change in cytokine production. Platelet-lymphocyte ratio was suggested as an independent marker for cardiovascular disease in obstructive sleep apnea syndrome and continuous positive air pressure therapy was found to have an impact on platelet parameters and phenotype. In this literature review we summarize the current knowledge on the subject of platelets involvement in obstructive sleep apnea syndrome and consider the possible pathways in which they contribute to cardiovascular comorbidity.
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Affiliation(s)
- Agata Gabryelska
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, Lodz, Poland
| | - Zuzanna M Łukasik
- Department of Rheumatology, Medical University of Lodz, Lodz, Poland
| | - Joanna S Makowska
- Department of Rheumatology, Medical University of Lodz, Lodz, Poland
| | - Piotr Białasiewicz
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, Lodz, Poland
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Mieno Y, Hayashi M, Sakakibara H, Takahashi H, Fujita S, Isogai S, Goto Y, Uozu S, Okazawa M, Imaizumi K. Gender Differences in the Clinical Features of Sleep Apnea Syndrome. Intern Med 2018; 57:2157-2163. [PMID: 29607972 PMCID: PMC6120817 DOI: 10.2169/internalmedicine.7570-16] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Objective Sleep apnea syndrome is more prevalent among men than women and is frequently accompanied by metabolic syndrome (MetS). However, gender differences in the effect of sleep-disordered breathing (SDB) leading to the risk of MetS remain unclear. The aim of our study was to investigate the clinical characteristics of SDB in women and the differential influence of SDB on MetS between genders. Methods In a single-center retrospective study, we compared the data of 1,809 consecutive SDB patients by gender to clarify the characteristics of sleep disorders in women. We also compared the prevalence of MetS and its related abnormalities by gender. A logistic regression analysis was used to determine the contributory factors for MetS. Results The mean age and proportion of patients over 50 years of age were higher in women than in men. SDB was milder in women than in men according to polysomnography findings. Elevated Hemoglobin A1c levels and hyperlipidemia were less frequent in women than in men. The MetS prevalence was similar in women and men (30.0% vs. 35.2%). A logistic regression analysis showed that the apnea-hypopnea index (AHI) was an independent risk factor for MetS in both genders, but that female gender was independently associated with a decreased prevalence of MetS and its related abnormalities. Conclusion Female SDB patients tend to be older with milder apnea and sleepiness than male SDB patients. A higher AHI is a significant risk factor for MetS in both genders, although female gender is an independent inhibitory factor for developing MetS in SDB patients.
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Affiliation(s)
- Yuki Mieno
- Department of Respiratory Medicine, Fujita Health University, Japan
| | | | | | | | - Shiho Fujita
- Department of Laboratory Medicine, Fujita Health University, Japan
| | - Sumito Isogai
- Department of Respiratory Medicine, Fujita Health University, Japan
| | - Yasuhiro Goto
- Department of Respiratory Medicine, Fujita Health University, Japan
| | - Sakurako Uozu
- Department of Respiratory Medicine, Fujita Health University, Japan
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Becatti M, Taddei N, Fiorillo C. Oxidative stress management during non-invasive ventilation in acute respiratory failure. Intern Emerg Med 2018; 13:141-142. [PMID: 29270832 DOI: 10.1007/s11739-017-1779-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 12/14/2017] [Indexed: 11/29/2022]
Affiliation(s)
- Matteo Becatti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
| | - Niccolò Taddei
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Claudia Fiorillo
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
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Garramone A, Cangemi R, Bresciani E, Carnevale R, Bartimoccia S, Fante E, Corinti M, Brunori M, Violi F, Bertazzoni G, Pignatelli P. Early decrease of oxidative stress by non-invasive ventilation in patients with acute respiratory failure. Intern Emerg Med 2018; 13:183-190. [PMID: 28914417 DOI: 10.1007/s11739-017-1750-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 09/05/2017] [Indexed: 01/07/2023]
Abstract
Oxidative stress plays an important role in chronic respiratory diseases where the use of non-invasive ventilation seems to reduce the oxidative damage. Data on acute respiratory failure are still lacking. The aim of the study is to investigate the interplay between oxidative stress and acute respiratory failure, and the role of non-invasive ventilation in this setting. We enrolled 60 patients suffering from acute respiratory failure (PaO2/FiO2 ratio <300): 30 consecutive patients treated with non-invasive ventilation and 30 consecutive patients treated with conventional oxygen therapy. Serum levels of soluble Nox2-derived peptide (sNOX2-dp), a marker of NADPH-oxidase activation, and 8-iso-PGF2α and H2O2, markers of oxidative stress, were evaluated at baseline and after 3 h of treatment. At baseline, higher values of sNOX2-dp, 8-iso-PGF2α and H2O2 are associated with lower values of PaO2/FiO2 ratio (p < 0.001). After 3 h, serum levels of sNOX2-dp, H2O2, and 8-iso-PGF2α significantly decrease in patients treated with non-invasive ventilation, but not in patients treated with conventional oxygen therapy. Delta changes of oxidative stress parameters correlate inversely with the delta changes of PaO2/FiO2 (R = -0.623, p < 0.001 for sNOX2-dp; R = -0.428, p < 0.001 for H2O2; R = -0.548, p < 0.001 for 8-iso-PGF2α). In the acute respiratory failure setting, treatment with non-invasive ventilation reduces the levels of oxidative stress in the first hours. This reduction is associated with an improvement of PaO2/FiO2 ratio as well as in a reduction of NADPH-oxidase activity.
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Affiliation(s)
- Alessia Garramone
- UOC Emergency Medicine, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Roberto Cangemi
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Emanuela Bresciani
- UOC Emergency Medicine, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Roberto Carnevale
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Simona Bartimoccia
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Elisa Fante
- Department of Emergency, M.G. Vannini Hospital, Rome, Italy
| | - Marco Corinti
- UOC Emergency Medicine, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Marco Brunori
- Respiratory Pathophysiology and Rehabilitation Unit, Policlinico Umberto I, Rome, Italy
| | - Francesco Violi
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Giuliano Bertazzoni
- UOC Emergency Medicine, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
| | - Pasquale Pignatelli
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
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Serum Romo1 is significantly associated with disease severity in patients with obstructive sleep apnea syndrome. Sleep Breath 2018; 22:743-748. [PMID: 29302924 DOI: 10.1007/s11325-017-1606-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 11/23/2017] [Accepted: 12/12/2017] [Indexed: 01/11/2023]
Abstract
PURPOSE We aim to evaluate reactive oxygen species modulator 1 (Romo1) levels in obstructive sleep apnea syndrome (OSAS) and analyze its possible relationships to OSAS severity, reactive oxygen species (ROS), and C-reactive protein (CRP). Additionally, we also investigated the effects of nasal continuous positive airway pressure (nCPAP) on serum Romo1. METHODS One hundred and five patients diagnosed with OSAS were classified into the OSAS group, and 41 subjects without OSAS were recruited for the control group. The OSAS group was further divided into mild, moderate, and severe OSAS subgroups. Fifteen patients with moderate and severe OSAS were treated with nCPAP. Serum levels of Romo1, ROS, and CRP were also measured. RESULTS Serum Romo1, ROS, and CRP were the lowest in normal subjects and increased across OSAS severities (P < 0.05). Univariate analysis showed that serum Romo1 was positively correlated with apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time spent below 90% oxygen saturation (Ts90%), arousal index, ROS, and CRP, and was negatively correlated with minimal oxygen saturation (miniSaO2) (all P < 0.05). Multiple linear regression analysis showed that serum Romo1 level was significantly associated with AHI and ODI, after adjusting for age, gender, BMI, and CRP. After 6 months of nCPAP therapy, serum Romo1, ROS, and CRP were significantly decreased (P < 0.05). CONCLUSIONS The increase of serum Romo1 in OSAS patients was positively correlated with disease severity. Serum Romo1 may be an important parameter for monitoring the severity of OSAS and treatment efficiency.
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Roubille F, Fischer K, Guensch DP, Tardif JC, Friedrich MG. Impact of hyperventilation and apnea on myocardial oxygenation in patients with obstructive sleep apnea – An oxygenation-sensitive CMR study. J Cardiol 2017; 69:489-494. [DOI: 10.1016/j.jjcc.2016.03.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Revised: 03/06/2016] [Accepted: 03/22/2016] [Indexed: 11/30/2022]
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Dinc ME, Ozdemir C, Ayan NN, Bozan N, Ulusoy S, Koca C, Erel O. Thiol/disulfide homeostasis as a novel indicator of oxidative stress in obstructive sleep apnea patients. Laryngoscope 2016; 127:E244-E250. [DOI: 10.1002/lary.26444] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 10/20/2016] [Accepted: 11/10/2016] [Indexed: 11/10/2022]
Affiliation(s)
| | - Cengiz Ozdemir
- Department of Sleep Laboratory; Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital; Istanbul
| | - Nilhan Nurlu Ayan
- Department of Medical Biochemistry; Istanbul Gaziosmanpasa Taksim Research and Training Hospital
| | - Nazım Bozan
- Medical Faculty, Department of Otolaryngology, Head and Neck Surgery, Yuzuncu Yıl University; Van
| | | | | | - Ozcan Erel
- Department of Medical Biochemistry; Dışkapı Yıldırım Bayezit Training and Research Hospital; Ankara Turkey
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Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:9626831. [PMID: 27774119 PMCID: PMC5059616 DOI: 10.1155/2016/9626831] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Accepted: 09/01/2016] [Indexed: 01/28/2023]
Abstract
Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.
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Lu W, Kang J, Hu K, Tang S, Zhou X, Yu S, Li Y, Xu L. Angiotensin-(1-7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats. ACTA ACUST UNITED AC 2016; 49:e5431. [PMID: 27599201 PMCID: PMC5018691 DOI: 10.1590/1414-431x20165431] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 07/20/2016] [Indexed: 02/03/2023]
Abstract
Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1-7 [Ang-(1-7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180-200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1-7)-treated normoxia control (N-A), and Ang-(1-7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1-7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.
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Affiliation(s)
- W Lu
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - J Kang
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - K Hu
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - S Tang
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - X Zhou
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - S Yu
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Y Li
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - L Xu
- Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China
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Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment. Sleep Breath 2016; 21:181-189. [PMID: 27502205 DOI: 10.1007/s11325-016-1393-1] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 07/10/2016] [Accepted: 07/25/2016] [Indexed: 12/11/2022]
Abstract
PURPOSE The associations between obstructive sleep apnea (OSA) and all-cause and cardiovascular mortality are well established but are not entirely consistent. To accurately evaluate these associations as well as the therapeutic effects of continuous positive airway pressure (CPAP), we conducted a comprehensive meta-analysis of all eligible cohort studies. METHODS Electronic literature databases (i.e., PubMed and Embase) were searched for relevant studies published before January 2016 that evaluated the associations between OSA and all-cause or cardiovascular mortality. Random-effect models were used to calculate the pooled hazard ratio (HR) and corresponding 95 % confidence intervals (CIs) for categorical risk estimates. The therapeutic effects of CPAP treatment for all-cause and cardiovascular mortality in OSA were examined through the meta-analysis. RESULTS The 27 cohort studies included in the meta-analysis included 3,162,083 participants. Compared to the control group, the pooled HR of all-cause mortality was 1.19 (95 % CI, 0.86-1.65) for mild OSA, 1.28 (0.96-1.69) for moderate OSA, and 2.13 (1.68-2.68) for severe OSA. The pooled HR of cardiovascular mortality was 1.24 (0.53-2.55) for mild OSA, 2.05 (0.57-5.47) for moderate OSA, and 2.73 (1.94-3.85) for severe OSA. All-cause mortality (HR 0.66; 0.59-0.73) and cardiovascular mortality (HR 0.37; 0.16-0.54) were significantly lower in CPAP-treated than in untreated patients. There were no differences in cardiovascular mortality in CPAP-treated OSA patients vs. normal control subjects (HR 0.82; 0.52-1.29). CONCLUSIONS Greater attention should be paid to severe OSA, as it is an independent predictor for risk for all-cause and cardiovascular mortality. CPAP is an effective treatment that reduces risk of mortality.
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Abstract
Progress in the modification of conventional coronary risk factors and lifestyle behavior has reduced the incidence of atherosclerotic coronary artery disease; nonetheless, it continues to be the leading cause of mortality in the world. This might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. In the current clinical setting, atherosclerotic coronary artery disease risk is estimated on the basis of identifying and quantifying only traditional risk factors; it does not take into consideration nontraditional risk factors. In addition, most of the prevailing therapies for atherosclerosis are targeted toward traditional risk factors rather than atherosclerosis itself. It is desirable to develop a method that can directly assess the activity of atherogenesis at every moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including nontraditional factors and heretofore unknown factors, and it is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function. Finally, we focus on the effects of major antiatherosclerotic disease therapies on endothelial function and argue the possibility of noninvasive assessment of endothelial function aiming at individualized cardiovascular medicine.
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Phipps AI, Bhatti P, Neuhouser ML, Chen C, Crane TE, Kroenke CH, Ochs-Balcom H, Rissling M, Snively BM, Stefanick ML, Treggiari MM, Watson NF. Pre-diagnostic Sleep Duration and Sleep Quality in Relation to Subsequent Cancer Survival. J Clin Sleep Med 2016; 12:495-503. [PMID: 26612513 PMCID: PMC4795275 DOI: 10.5664/jcsm.5674] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/02/2015] [Indexed: 12/19/2022]
Abstract
STUDY OBJECTIVES Poor sleep quality and short sleep duration have been associated with elevated risk for several cancer types; however, the relationship between sleep and cancer outcomes has not been well characterized. We assessed the association between pre-diagnostic sleep attributes and subsequent cancer survival within the Women's Health Initiative (WHI). METHODS We identified WHI participants in whom a first primary invasive cancer had been diagnosed during follow-up (n = 21,230). Participants provided information on sleep characteristics at enrollment. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between these pre-diagnostic sleep characteristics and cancer-specific survival for all cancers combined and separately for common cancers. Analyses were adjusted for age, study arm, cancer site, marital status, income, smoking, physical activity, and time to diagnosis. RESULTS No individual pre-diagnostic sleep characteristics were found to be significantly associated with cancer survival in analyses of all cancer sites combined; however, women who reported short sleep duration (≤ 6 h sleep/night) combined with frequent snoring (≥ 5 nights/w experienced significantly poorer cancer-specific survival than those who reported 7-8 h of sleep/night and no snoring (HR = 1.32, 95% CI: 1.14-1.54). Short sleep duration (HR = 1.46, 95% CI: 1.07-1.99) and frequent snoring (HR = 1.34, 95% CI: 0.98-1.85) were each associated with poorer breast cancer survival; those reporting short sleep combined with frequent snoring combined had substantially poorer breast cancer survival than those reporting neither (HR = 2.14, 95% CI: 1.47-3.13). CONCLUSIONS Short sleep duration combined with frequent snoring reported prior to cancer diagnosis may influence subsequent cancer survival, particularly breast cancer survival.
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Affiliation(s)
- Amanda I. Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Epidemiology Department, School of Public Health, University of Washington, Seattle, WA
| | - Parveen Bhatti
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Epidemiology Department, School of Public Health, University of Washington, Seattle, WA
| | - Marian L. Neuhouser
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Chu Chen
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Tracy E. Crane
- Health Promotion Sciences Division, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ
| | - Candyce H. Kroenke
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Heather Ochs-Balcom
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY
| | | | - Beverly M. Snively
- Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Marcia L. Stefanick
- Stanford Prevention Research Center, Stanford University, School of Medicine, Palo Alto, CA
| | - Miriam M. Treggiari
- Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR
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36
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Duffy SL, Lagopoulos J, Terpening Z, Lewis SJG, Grunstein R, Mowszowski L, Cross N, Hermens DF, Hickie IB, Naismith SL. Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At-Risk for Dementia. Sleep 2016; 39:899-906. [PMID: 26856906 DOI: 10.5665/sleep.5650] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 12/14/2015] [Indexed: 12/19/2022] Open
Abstract
STUDY OBJECTIVES Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy ((1)H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. METHODS Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent (1)H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr). RESULTS Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037). CONCLUSIONS Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted.
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Affiliation(s)
- Shantel L Duffy
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Jim Lagopoulos
- Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Zoe Terpening
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia
| | - Simon J G Lewis
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Ron Grunstein
- Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Loren Mowszowski
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia
| | - Nathan Cross
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.,Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Daniel F Hermens
- Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia
| | - Ian B Hickie
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
| | - Sharon L Naismith
- Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.,Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.,Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.,National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia
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37
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Paz Y Mar HL, Hazen SL, Tracy RP, Strohl KP, Auckley D, Bena J, Wang L, Walia HK, Patel SR, Mehra R. Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial. Chest 2016; 150:80-90. [PMID: 26997243 DOI: 10.1016/j.chest.2016.03.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 02/26/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures. METHODS We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index ≥ 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia. RESULTS Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to -0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively. CONCLUSIONS In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences. TRIAL REGISTRATION ClinicalTrials.govNCT00607893.
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Affiliation(s)
- Hugo L Paz Y Mar
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH
| | - Stanley L Hazen
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Russell P Tracy
- Departments of Biochemistry and Pathology, University of Vermont, Burlington, VT
| | - Kingman P Strohl
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH
| | - Dennis Auckley
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH
| | - James Bena
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Lu Wang
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Harneet K Walia
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH
| | - Sanjay R Patel
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Reena Mehra
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
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38
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Oyama JI, Nagatomo D, Yoshioka G, Yamasaki A, Kodama K, Sato M, Komoda H, Nishikido T, Shiraki A, Node K. The relationship between neutrophil to lymphocyte ratio, endothelial function, and severity in patients with obstructive sleep apnea. J Cardiol 2016; 67:295-302. [DOI: 10.1016/j.jjcc.2015.06.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 05/28/2015] [Accepted: 06/17/2015] [Indexed: 01/04/2023]
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39
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Pan Z, Zhuang X, Li X, Huang S, Zhang L, Lou F, Chen S, Ni Y. Significance of vaspin in obstructive sleep apnea-hypopnea syndrome. Exp Ther Med 2016; 11:841-845. [PMID: 26998001 PMCID: PMC4774374 DOI: 10.3892/etm.2016.2997] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Accepted: 11/18/2015] [Indexed: 01/06/2023] Open
Abstract
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a commonly-diagnosed chronic sleep disorder. It is considered to be an important independent risk factor in the development of insulin resistance (IR). Patients with OSAHS exhibit a variety of metabolic disorders, including obesity and metabolic syndrome. Visceral adipose tissue-derived serpin (vaspin) is an adipokine that is considered to be a link between obesity and IR. The present study aimed to evaluate the levels of plasma vaspin in patients with OSAHS and examine their potential correlation with sleep characteristics. A total of 20 healthy male subjects and 42 male patients with OSAHS were selected, and patients were divided into mild (n=22) and severe (n=20) OSAHS groups. The 20 patients in the severe OSAHS group received nasal continuous positive airway pressure (nCPAP) treatment for 2 months. Venous blood samples were drawn from all patients in a fasting state prior to and subsequent to nCPAP treatment, which were used to measure the levels of biochemical indicators. The sleep parameters and serologic index changes were compared prior to and following treatment. The values of contractive pressure (SBP), neck circumference (NC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI) and hip circumference (HC) in the two OSAHS groups were significantly increased compared with those in the control group. In addition, the levels of vaspin in OSAHS patients were markedly increased and vaspin was revealed to be positively associated with fasting blood sugar, fasting insulin, triglycerides, homeostasis model assessment-IR, apnea-hypopnea index (AHI), NC, WC, BMI and WHR (P<0.05). After 2 months of nCPAP treatment, the SBP and AHI were significantly reduced. In conclusion, vaspin may have an important role in OSAHS patients with IR and treatment using nCPAP may improve the condition of OSAHS patients.
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Affiliation(s)
- Zhe Pan
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Xianghua Zhuang
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Xiaobo Li
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Shaoyi Huang
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Liang Zhang
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Fuchen Lou
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Shihong Chen
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
| | - Yihong Ni
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
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40
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Zhang XB, Lin QC, Zeng HQ, Jiang XT, Chen B, Chen X. Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure. ARCHIVES OF SEXUAL BEHAVIOR 2016; 45:235-40. [PMID: 26370402 DOI: 10.1007/s10508-015-0593-2] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 04/25/2015] [Accepted: 06/30/2015] [Indexed: 05/28/2023]
Abstract
In this study, the prevalence of erectile dysfunction (ED) and serum sexual hormone levels were evaluated in men with obstructive sleep apnea (OSA). In these patients, the efficacy of continuous positive airway pressure (CPAP) was determined. The 207 men (mean age 44.0 ± 11.1 years) enrolled in the study were stratified within four groups based on their apnea-hypopnea index score: simple snoring (n = 32), mild OSA (n = 29), moderate OSA (n = 38), and severe OSA (n = 108). The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained from each patient, and blood samples for the analysis of sexual hormones (prolactin, luteotropin, follicle-stimulating hormone, estradiol, progestin, and testosterone) were drawn in the morning after polysomnography. The IIEF-5 test and serum sexual hormone measurements were repeated after 3 months of CPAP treatment in 53 men with severe OSA. The prevalence of ED was 60.6 % in OSA patients overall and 72.2 % in those with severe OSA. Compared with the simple snoring group, patients with severe OSA had significantly lower testosterone levels (14.06 ± 5.62 vs. 17.02 ± 4.68, p = .018) and lower IIEF-5 scores (16.33 ± 6.50 vs. 24.09 ± 1.94, p = .001). The differences in the other sexual hormones between groups were not significant. After 3 months of CPAP treatment, there were no significant changes in sexual hormone levels, but the IIEF-5 score had improved significantly (18.21 ± 4.05 vs. 19.21 ± 3.86, p = .001). Severe OSA patients have low testosterone concentration and high ED prevalence. IIEF-5 scores increased significantly after CPAP treatment, but there was no effect on serum testosterone levels.
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Affiliation(s)
- Xiao-Bin Zhang
- Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, Teaching Hospital of Fujian Medical University, No. 201, Hubin Nan Road, Siming District, Xiamen, Fujian Province, 361004, People's Republic of China.
| | - Qi-Chang Lin
- Department of Respiratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Hui-Qing Zeng
- Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, Teaching Hospital of Fujian Medical University, No. 201, Hubin Nan Road, Siming District, Xiamen, Fujian Province, 361004, People's Republic of China
| | - Xing-Tang Jiang
- Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, Teaching Hospital of Fujian Medical University, No. 201, Hubin Nan Road, Siming District, Xiamen, Fujian Province, 361004, People's Republic of China
| | - Bo Chen
- Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, Teaching Hospital of Fujian Medical University, No. 201, Hubin Nan Road, Siming District, Xiamen, Fujian Province, 361004, People's Republic of China
| | - Xiao Chen
- Department of Respiratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
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41
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Kanagasabai T, Ardern CI. Contribution of Inflammation, Oxidative Stress, and Antioxidants to the Relationship between Sleep Duration and Cardiometabolic Health. Sleep 2015; 38:1905-12. [PMID: 26237775 DOI: 10.5665/sleep.5238] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 06/24/2015] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health. DESIGN Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey. SETTING Nationally representative population sample from the US. PARTICIPANTS Age ≥ 20 y with sleep data; final analytical sample of n = 2,079. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤ 4, 5-6, 7-8, and ≥ 9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (< 0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration- cardiometabolic health relationships were mediated by C-reactive protein (CRP), γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and -systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship. CONCLUSIONS Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results.
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Affiliation(s)
| | - Chris I Ardern
- School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
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42
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Roles of interleukin (IL)-6 gene polymorphisms, serum IL-6 levels, and treatment in obstructive sleep apnea: a meta-analysis. Sleep Breath 2015; 20:719-31. [DOI: 10.1007/s11325-015-1288-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 09/21/2015] [Accepted: 11/02/2015] [Indexed: 12/20/2022]
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43
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Canto GDL, Pachêco-Pereira C, Aydinoz S, Major PW, Flores-Mir C, Gozal D. Biomarkers associated with obstructive sleep apnea: A scoping review. Sleep Med Rev 2015; 23:28-45. [PMID: 25645128 PMCID: PMC4447611 DOI: 10.1016/j.smrv.2014.11.004] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 11/12/2014] [Accepted: 11/12/2014] [Indexed: 12/31/2022]
Abstract
The overall validity of biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. We conducted a scoping review to provide assessments of biomarkers characteristics in the context of obstructive sleep apnea (OSA) and to identify gaps in the literature. A scoping review of studies in humans without age restriction that evaluated the potential diagnostic value of biological markers (blood, exhaled breath condensate, salivary, and urinary) in the OSA diagnosis was undertaken. Retained articles were those focused on the identification of biomarkers in subjects with OSA, the latter being confirmed with a full overnight or home-based polysomnography (PSG). Search strategies for six different databases were developed. The methodology of selected studies was classified using an adaptation of the evidence quality criteria from the American Academy of Pediatrics. Additionally the biomarkers were classified according to their potential clinical application. We identified 572 relevant studies, of which 117 met the inclusion criteria. Eighty-two studies were conducted in adults, 34 studies involved children, and one study had a sample composed of both adults and children. Most of the studies evaluated blood biomarkers. Potential diagnostic biomarkers were found in nine pediatric studies and in 58 adults studies. Only nine studies reported sensitivity and specificity, which varied substantially from 43% to 100%, and from 45% to 100%, respectively. Studies in adults have focused on the investigation of IL-6, TNF-α and hsCRP. There was no specific biomarker that was tested by a majority of authors in pediatric studies, and combinatorial urine biomarker approaches have shown preliminary promising results. In adults IL-6 and IL-10 seem to have a favorable potential to become a good biomarker to identify OSA.
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Affiliation(s)
- Graziela De Luca Canto
- Department of Dentistry, Federal University of Santa Catarina, Florianopolis, SC, Brazil; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | | | - Secil Aydinoz
- GATA Haydarpasa Teaching Hospital, Istanbul, Turkey; Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, USA
| | - Paul W Major
- School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | - Carlos Flores-Mir
- School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, USA; Comer Children's Hospital, USA.
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44
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Liu JJ, Dahlin BC, Waldau B. Contrast encephalopathy after coiling in the setting of obstructive sleep apnoea. BMJ Case Rep 2015; 2015:bcr-2014-207503. [PMID: 26409005 DOI: 10.1136/bcr-2014-207503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Obstructive sleep apnoea (OSA) is increasingly recognised as a source of perioperative morbidity and mortality. We describe a patient with severe OSA who developed transient contrast encephalopathy after elective coiling of an anterior communicating artery aneurysm. Contrast extravasation led to cerebral oedema, seizures and delirium, which eventually completely resolved. OSA is known to be associated with a proinflammatory state that leads to hypertension, impaired endothelial repair capacity and endothelial dysfunction. Further studies are needed to clarify whether OSA increases the risk of endovascular procedures.
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Affiliation(s)
- Jonathan J Liu
- Department of Neurosurgery, UC Davis, Sacramento, California, USA
| | - Brian C Dahlin
- Department of Radiology, UC Davis, Sacramento, California, USA
| | - Ben Waldau
- Department of Neurosurgery, UC Davis, Sacramento, California, USA
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45
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Innes CRH, Kelly PT, Hlavac M, Melzer TR, Jones RD. Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness. Sleep 2015; 38:699-706. [PMID: 25669185 DOI: 10.5665/sleep.4658] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 03/14/2015] [Indexed: 12/21/2022] Open
Abstract
STUDY OBJECTIVES To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. DESIGN Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. SETTING Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. PARTICIPANTS 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. CONCLUSIONS There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes.
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Affiliation(s)
- Carrie R H Innes
- New Zealand Brain Research Institute, Christchurch, New Zealand.,Medical Physics & Bioengineering, Christchurch Hospital, Christchurch, New Zealand.,Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand
| | - Paul T Kelly
- Sleep Unit, Christchurch Hospital, Christchurch, New Zealand
| | - Michael Hlavac
- Sleep Unit, Christchurch Hospital, Christchurch, New Zealand
| | - Tracy R Melzer
- New Zealand Brain Research Institute, Christchurch, New Zealand.,Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Richard D Jones
- New Zealand Brain Research Institute, Christchurch, New Zealand.,Medical Physics & Bioengineering, Christchurch Hospital, Christchurch, New Zealand.,Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand.,Department of Medicine, University of Otago, Christchurch, New Zealand.,Department of Psychology, University of Canterbury, Christchurch, New Zealand
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46
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Hoyos CM, Melehan KL, Liu PY, Grunstein RR, Phillips CL. Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature. Sleep Med Rev 2015; 20:15-26. [PMID: 25088969 DOI: 10.1016/j.smrv.2014.06.003] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Revised: 06/09/2014] [Accepted: 06/12/2014] [Indexed: 01/29/2023]
Affiliation(s)
- Camilla M Hoyos
- NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
| | - Kerri L Melehan
- NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Y Liu
- Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA
| | - Ronald R Grunstein
- NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Craig L Phillips
- NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia
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47
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De Luca Canto G, Pachêco-Pereira C, Aydinoz S, Major PW, Flores-Mir C, Gozal D. Biomarkers associated with obstructive sleep apnea and morbidities: a scoping review. Sleep Med 2015; 16:347-57. [PMID: 25747333 DOI: 10.1016/j.sleep.2014.12.007] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Revised: 12/16/2014] [Accepted: 12/27/2014] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To map potential biomarkers of obstructive sleep apnea (OSA)-associated morbidities in both adults and children, to identify gaps in current evidence, and to determine the value of conducting a full systematic review. METHODS A scoping review was undertaken of studies in patients with OSA that evaluated the potential value of biological markers in identifying OSA-associated morbidities. Retained articles were only those studies whose main objective was to identify morbidity biomarkers in subjects with OSA, the latter being confirmed with a full overnight polysomnography (PSG) in a laboratory or at-home settings. The methodology of the selected studies was classified using an adaptation of the evidence quality criteria recommended by the American Academy of Pediatrics. Additionally the biomarkers were categorized according to their potential clinical applicability. RESULTS 572 citations were identified of which 48 met inclusion criteria. Thirty-four studies were conducted in adults and 14 involved children. Most of the studies evaluated blood biomarkers, and presented 31 potential diagnostic biomarkers. CONCLUSION The majority of studies that performed explored blood-based biomarkers, with most not identifying definitive morbidity biomarkers. Of the potentially promising morbidity biomarkers, plasma IL-6 and high sensitivity C-reactive protein appear to exhibit a favorable profile, and may discriminate OSA patients with and without morbidities in both adults and children. MRP 8/14 was retained in children as well as cardiovascular morbidity-associated biomarker. Urinary neurotransmitters may also provide a good tool for screening OSA cognitive morbidity in children.
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Affiliation(s)
- Graziela De Luca Canto
- Department of Dentistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil; School of Dentistry, Faculty of Medicine and Dentistry, Edmonton Clinic Health Academy, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada
| | - Camila Pachêco-Pereira
- School of Dentistry, Faculty of Medicine and Dentistry, Edmonton Clinic Health Academy, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada
| | - Secil Aydinoz
- GATA Haydarpasa Teaching Hospital, Istanbul, Turkey; Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, USA
| | - Paul W Major
- School of Dentistry, Faculty of Medicine and Dentistry, Edmonton Clinic Health Academy, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada
| | - Carlos Flores-Mir
- School of Dentistry, Faculty of Medicine and Dentistry, Edmonton Clinic Health Academy, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 5721 S. Maryland Avenue, MC 8000, Suite K-160, Chicago, IL 60637, USA.
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48
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Connes P. Obstructive sleep apnea and sickle cell disease: Towards hemorheological abnormalities and vascular dysfunction worsening. Sleep Med Rev 2015; 24:101-2. [PMID: 25743618 DOI: 10.1016/j.smrv.2015.01.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 01/23/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Philippe Connes
- Laboratoire CRIS EA647 - Section "Vascular Biology and Red Blood Cell", Université Lyon 1, COMUE Lyon, Lyon, France; Institut Universitaire de France, Paris, France.
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49
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De Luca Canto G, Pachêco-Pereira C, Aydinoz S, Major PW, Flores-Mir C, Gozal D. Diagnostic capability of biological markers in assessment of obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2015; 11:27-36. [PMID: 25325575 DOI: 10.5664/jcsm.4358] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Accepted: 09/11/2014] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The purpose of this systematic review is to evaluate the diagnostic value of biological markers (exhaled breath condensate, blood, salivary and urinary) in the diagnosis of OSA in comparison to the gold standard of nocturnal PSG. METHODS Studies that differentiated OSA from controls based on PSG results, without age restriction, were eligible for inclusion. The sample of selected studies could include studies in obese patients and with known cardiac disease. A detailed individual search strategy for each of the following bibliographic databases was developed: Cochrane, EMBASE, MEDLINE, PubMed, and LILACS. The references cited in these articles were also crosschecked and a partial grey literature search was undertaken using Google Scholar. The methodology of selected studies was evaluated using the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. RESULTS After a two-step selection process, nine articles were identified and subjected to qualitative and quantitative analyses. Among them, only one study conducted in children and one in adults found biomarkers that exhibit sufficiently satisfactory diagnostic accuracy that enables application as a diagnostic method for OSA. CONCLUSION Kallikrein-1, uromodulin, urocotin-3, and orosomucoid-1 when combined have enough accuracy to be an OSA diagnostic test in children. IL-6 and IL-10 plasma levels have potential to be good biomarkers in identifying or excluding the presence of OSA in adults.
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Affiliation(s)
- Graziela De Luca Canto
- Department of Dentistry, Federal University of Santa Catarina, Florianopolis, SC, Brazil.,School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | | | - Secil Aydinoz
- GATA Haydarpasa Teaching Hospital, Istanbul, Turkey.,Department of Pediatrics, University of Chicago, Chicago, IL
| | - Paul W Major
- School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | - Carlos Flores-Mir
- School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Canada
| | - David Gozal
- Department of Pediatrics, University of Chicago, Chicago, IL
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50
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Biomarkers to improve diagnosis and monitoring of obstructive sleep apnea syndrome: current status and future perspectives. Pulm Med 2014; 2014:930535. [PMID: 25538852 PMCID: PMC4265695 DOI: 10.1155/2014/930535] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 10/23/2014] [Indexed: 02/06/2023] Open
Abstract
Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of upper airway collapse associated with oxygen desaturation and sleep disruption. It is proposed that these periodic changes lead to molecular variations that can be detected by assessing serum biomarkers. Studies have identified inflammatory, oxidative, and metabolic perturbations attributable to sleep-disordered breathing. Given that OSAS is associated with increased cardiovascular and cerebrovascular morbidity, the ideal biomarker should enable timely recognition with the possibility of intervention. There is accumulating data on the utility of serum biomarkers for the evaluation of disease severity, prognosis, and response to treatment. However, current knowledge is limited by data collection techniques, disease complexity, and potential confounding factors. The current paper reviews the literature on the use of serum biomarkers in OSAS. It is concluded that the ideal serum biomarker still needs to be discovered, while caution is needed in the interpretation of hitherto available results.
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