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1.
Effects of sleep apnea hypopnea syndromes on cardiovascular events: a systematic review and meta-analysis.
Xie, L, Zhen, P, Yu, F, Yu, X, Qian, H, Yang, F, Tong, J
Sleep & breathing = Schlaf & Atmung. 2022;(1):5-15
Abstract
PURPOSE Previous studies suggest that sleep apnea hypopnea syndrome (SAHS) is an independent risk factor that contributes to certain cardiovascular events. However, there are studies arguing that patients with SAHS had lower peak troponin levels when suffering cardiovascular events compared to patients without SAHS, which indicates that there may potentially be a protective effect of SAHS. This meta-analysis aimed to assess the impact of SAHS on cardiovascular events. METHODS Databases were searched for studies that examined cardiac biomarkers or reported angiographic data when patients with SAHS experienced cardiovascular events. The data about peak cardiac biomarkers and angiographic coronary lesion were extracted and then used to compute the pooled standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS Among 26 studies included in the meta-analysis, there was not a definite difference between the SAHS group and the control group for troponins (SMD, 0.05; 95% CI, [- 0.16, 0.26]), creatine kinase (SMD, - 0.08; 95% CI, [- 0.38, 0.22]), and CK-MB (SMD, - 0.11; 95% CI, [- 0.51, 0.29]). However, patients with SAHS revealed worse coronary lesion condition grading via both Gensini score (SMD, 0.63; 95% CI, [0.31, 0.95]) and SYNTAX score (SMD, 0.99; 95% CI, [0.31-1.67]). CONCLUSIONS Ischemic preconditioning induced by the intermittent hypoxia at the early stage could generate a cardiac protection effect, which would then benefit SAHS patients encountering a major adverse cardiovascular event.
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The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction.
Khalyfa, A, Sanz-Rubio, D
International journal of molecular sciences. 2021;(9)
Abstract
Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).
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The effect of obstructive sleep apnea on peripheral blood amino acid and biogenic amine metabolome at multiple time points overnight.
Kiens, O, Taalberg, E, Ivanova, V, Veeväli, K, Laurits, T, Tamm, R, Ottas, A, Kilk, K, Soomets, U, Altraja, A
Scientific reports. 2021;(1):10811
Abstract
There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the serum of OSA patients with apnea-hypopnea index (AHI) ≥ 15/h and control individuals. Peripheral blood was obtained at 3 different time points overnight: 9:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of serum concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.
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4.
Barbed Reposition Pharyngoplasty versus Expansion Sphincter Pharyngoplasty: A Meta-Analysis.
Neruntarat, C, Khuancharee, K, Saengthong, P
The Laryngoscope. 2021;(6):1420-1428
Abstract
OBJECTIVE This study was to compare barbed reposition pharyngoplasty (BRP) and expansion sphincter pharyngoplasty (ESP) in the treatment of obstructive sleep apnea (OSA). METHODS Relevant 907 articles were searched from various databases until August 2020, including PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science and Scopus, and reference lists. RESULTS Four studies with a total of 208 participants were included. The mean reduction of apnea-hypopnea index (AHI) in the BRP group was 74.03% and the mean reduction of AHI in the ESP group was 60.17%. The mean success rate in the BRP group and the ESP group was 84.96% and 79.87%, respectively. The mean difference (MD) of the change in AHI between groups was not significantly different (MD = -1.24 event/hr, 95% CI [-11.86, 9.36], P = .82). There was no significant difference in postoperative AHI, postoperative Epworth Sleepiness Scale, pain, hospital stay, time to oral diet, and the change in oxygen desaturation index in both groups whereas the analgesic requirement was lower in the BRP group. Operative time was lower in the BRP group (MD = 21.72 minutes, 95% CI [18.85, 24.60], P < .0001). CONCLUSION The outcomes in both procedures are comparable in the improvement of OSA with palatal collapse. BRP is superior to ESP in term of surgical time. However, randomized clinical controlled trials with multicenter cooperation and long-term follow-up are essential to further demonstrate the efficacy of these procedures. Laryngoscope, 131:1420-1428, 2021.
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The effectiveness of a weight-loss Mediterranean diet/lifestyle intervention in the management of obstructive sleep apnea: Results of the "MIMOSA" randomized clinical trial.
Georgoulis, M, Yiannakouris, N, Kechribari, I, Lamprou, K, Perraki, E, Vagiakis, E, Kontogianni, MD
Clinical nutrition (Edinburgh, Scotland). 2021;(3):850-859
Abstract
BACKGROUND & AIMS Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), lifestyle interventions have also emerged as complementary therapeutic choices. We aimed to explore whether the addition of a weight-loss Mediterranean diet/lifestyle intervention to OSA standard care, i.e. CPAP prescription and brief written healthy lifestyle advice, has an incremental effect on improving OSA severity, over the effect of standard care alone. METHODS We designed a parallel, randomized, controlled, superiority clinical trial. Eligible participants were adult, overweight men and women, diagnosed with moderate-to-severe OSA [apnea-hypopnea index (AHI)≥ 15 events/h] through an attended overnight polysomnography. Participants were blindly randomized to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three study groups were prescribed with CPAP. The SCG additionally received written healthy lifestyle advice, while intervention arms were subjected to a 6-month behavioral intervention aiming at weight loss and increasing adherence to the Mediterranean diet. The MLG also received counselling on physical activity and sleep habits. Polysomnographic data and OSA symptoms were evaluated pre- and post-intervention. RESULTS A total of 187 OSA patients were recruited. Seven patients were excluded post-randomization and 53/180 (29%) were lost to follow-up. No harms from the interventions applied were reported. According to intention-to-treat analysis (n = 180), mean (95% confidence interval) AHI change was -4.2 (-7.4, -1.0) for the SCG, -24.7 (-30.4, -19.1) for the MDG and -27.3 (-33.9, -20.6) for the MLG. Post-intervention age-, sex-, baseline- and CPAP use-adjusted AHI was significantly lower in the MDG and the MLG compared to the SCG (mean difference: -18.0, and -21.2, respectively, both P < 0.001), and the differences remained significant after further adjustment for body-weight change (P = 0.004 and 0.008, respectively). Other respiratory event indices, daytime sleepiness and insomnia were also significantly lower in both intervention arms compared to the SCG (all P < 0.05). The MLG only presented higher percent rapid-eye-movement sleep and lower daytime sleepiness compared to the MDG (both P < 0.05). Results were similar in the per-protocol analysis (n = 127). CONCLUSIONS A dietary/lifestyle intervention on top of standard care leads to greater improvements in OSA severity and symptomatology compared to standard care alone. Benefits are evident regardless of CPAP use and weight loss. TRIAL REGISTRATION Clinicaltrials.gov NCT02515357, https://clinicaltrials.gov/ct2/show/NCT02515357.
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Oxidative Stress Markers among Obstructive Sleep Apnea Patients.
Stanek, A, Brożyna-Tkaczyk, K, Myśliński, W
Oxidative medicine and cellular longevity. 2021;:9681595
Abstract
Obstructive sleep apnea (OSA) is a chronic respiratory disorder, which can be present in up to 50% of the population, depending on the country. OSA is characterized by recurrent episodes of partial or complete obstruction of the upper airways with consistent movement of the respiratory musculature during sleep. Apneas and hypopneas can lead to a decrease in oxygen saturation, an increase in carbon dioxide in the blood, and subsequent arousals and sleep fragmentation caused by repetitive activation of the central nervous system. As a consequence, intermittent hypoxemia and consequent reoxygenation result in the production of reactive oxygen species, leading to systematic oxidative stress, which is postulated to be a key mechanism of endothelial dysfunction and increased risk for cardiovascular disorders in patients with OSA. In this review, various biomarkers of oxidative stress, including high-sensitivity C-reactive protein, pregnancy-associated plasma protein-A, superoxide dismutase, cell-free DNA, 8-hydroxy-2-deoxyguanosine, advanced oxidation protein products, lipid peroxidation products, receptor for advanced glycation end-products, and thioredoxin are discussed. Biomarkers of oxidative stress have the potential to be used to assess disease severity and treatment response. Continuous positive airway pressure (CPAP) is one of the most common noninvasive treatments for OSA; it keeps the upper airways open during sleep. This reduces episodes of intermittent hypoxia, reoxygenation, and arousal at night. CPAP has been shown to have anti-inflammatory properties and decrease oxidative stress. The administration of certain compounds, like vitamins A, C, and E as well as N-acetylcysteine and allopurinol, can decrease oxidative stress markers. However, their role in the treatment of OSA remains unclear.
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7.
Xerostomia and hyposalivation in patients with obstructive sleep apnoea.
Makeeva, IM, Budina, TV, Turkina, AY, Poluektov, MG, Kondratiev, SA, Arakelyan, MG, Signore, A, Amaroli, A
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2021;(4):782-787
Abstract
OBJECTIVE (a) To report the xerostomia prevalence and severity in patients with obstructive sleep apnoea (OSA). (b) To assess the saliva pH in patients with OSA. DESIGN Simultaneous cohort observational clinical study. SETTING In Sleep Medicine Centre at Lomonosov Moscow State University from March to June 2019. PARTICIPANTS The study was conducted on 30 patients with OSA aged from 35 to 65 years. MAIN OUTCOMES MEASURES The diagnosis of sleep apnoea was made after standard polysomnography using the Domino programme. The severity of OSA was indicated using the Apnoea-Hypopnea Index. Xerostomia was evaluated using Fox's test. Hyposalivation was evaluated by measurement of salivary flow rate. Determination of the saliva pH was carried out with a pH metre. Statistical analysis was performed by one-way ANOVA and Tukey-Kramer multi-comparison test. RESULTS Twenty-two out of 30 (73.3%) patients were diagnosed with "dry mouth". Hyposalivation was observed in 6 out of 30 (20%). Dry mouth on awakening was observed in 60.0%, 72.7% and 88.9% of patients with mild, moderate and severe OSA, respectively. The average salivary flow rate was 0.28 mL/min, 0.24 mL/min and 0.14 mL/min, respectively. The average pH value in patients with mild, moderate and severe apnoea was 6.40 ± 0.017, 6.15 ± 0.27 and 5.87 ± 0.24, respectively. CONCLUSIONS In patient with mild and moderate OSA, the saliva amount and rate are similar (P > .05). With the increase of OSA severity, both these parameters change (P < .001). The acidity of the saliva was correlated with the level of OSA, and it statistically increased with the increment of the OSA severity (P < .05-P < .001).
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8.
Anti-inflammatory medications for obstructive sleep apnoea in children.
Kuhle, S, Hoffmann, DU, Mitra, S, Urschitz, MS
The Cochrane database of systematic reviews. 2020;(1):CD007074
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Abstract
BACKGROUND Obstructive sleep apnoea (OSA) is characterised by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA, with adenotonsillar hypertrophy being the most common underlying risk factor. Surgical removal of enlarged adenoids or tonsils is the currently recommended first-line treatment for OSA due to adenotonsillar hypertrophy. Given the perioperative risk and an estimated recurrence rate of up to 20% following surgery, there has recently been an increased interest in less invasive alternatives to adenotonsillectomy. As the enlarged adenoids and tonsils consist of hypertrophied lymphoid tissue, anti-inflammatory drugs have been proposed as a potential non-surgical treatment option in children with OSA. OBJECTIVES To assess the efficacy and safety of anti-inflammatory drugs for the treatment of OSA in children. SEARCH METHODS We identified trials from searches of the Cochrane Airways Group Specialised Register, CENTRAL and MEDLINE (1950 to 2019). For identification of ongoing clinical trials, we searched ClinicalTrials.gov and the World Health Organization (WHO) trials portal. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing anti-inflammatory drugs against placebo in children between one and 16 years with objectively diagnosed OSA (apnoea/hypopnoea index (AHI) ≥ 1 per hour). DATA COLLECTION AND ANALYSIS Two authors independently performed screening, data extraction, and quality assessment. We separately pooled results for the comparisons 'intranasal steroids' and 'montelukast' against placebo using random-effects models. The primary outcomes for this review were AHI and serious adverse events. Secondary outcomes included the respiratory disturbance index, desaturation index, respiratory arousal index, nadir arterial oxygen saturation, mean arterial oxygen saturation, avoidance of surgical treatment for OSA, clinical symptom score, tonsillar size, and adverse events. MAIN RESULTS We included five trials with a total of 240 children aged one to 18 years with mild to moderate OSA (AHI 1 to 30 per hour). All trials were performed in specialised sleep medicine clinics at tertiary care centres. Follow-up time ranged from six weeks to four months. Three RCTs (n = 137) compared intranasal steroids against placebo; two RCTs compared oral montelukast against placebo (n = 103). We excluded one trial from the meta-analysis since the patients were not analysed as randomised. We also had concerns about selective reporting in another trial. We are uncertain about the difference in AHI (MD -3.18, 95% CI -8.70 to 2.35) between children receiving intranasal corticosteroids compared to placebo (2 studies, 75 participants; low-certainty evidence). In contrast, children receiving oral montelukast had a lower AHI (MD -3.41, 95% CI -5.36 to -1.45) compared to those in the placebo group (2 studies, 103 participants; moderate-certainty evidence). We are uncertain whether the secondary outcomes are different between children receiving intranasal corticosteroids compared to placebo: desaturation index (MD -2.12, 95% CI -4.27 to 0.04; 2 studies, 75 participants; moderate-certainty evidence), respiratory arousal index (MD -0.71, 95% CI -6.25 to 4.83; 2 studies, 75 participants; low-certainty evidence), and nadir oxygen saturation (MD 0.59%, 95% CI -1.09 to 2.27; 2 studies, 75 participants; moderate-certainty evidence). Children receiving oral montelukast had a lower respiratory arousal index (MD -2.89, 95% CI -4.68 to -1.10; 2 studies, 103 participants; moderate-certainty evidence) and nadir of oxygen saturation (MD 4.07, 95% CI 2.27 to 5.88; 2 studies, 103 participants; high-certainty evidence) compared to those in the placebo group. We are uncertain, however, about the difference in desaturation index (MD -2.50, 95% CI -5.53 to 0.54; 2 studies, 103 participants; low-certainty evidence) between the montelukast and placebo group. Adverse events were assessed and reported in all trials and were rare, of minor nature (e.g. nasal bleeding), and evenly distributed between study groups. No study examined the avoidance of surgical treatment for OSA as an outcome. AUTHORS' CONCLUSIONS There is insufficient evidence for the efficacy of intranasal corticosteroids for the treatment of OSA in children; they may have short-term beneficial effects on the desaturation index and oxygen saturation in children with mild to moderate OSA but the certainty of the benefit on the primary outcome AHI, as well as the respiratory arousal index, was low due to imprecision of the estimates and heterogeneity between studies. Montelukast has short-term beneficial treatment effects for OSA in otherwise healthy, non-obese, surgically untreated children (moderate certainty for primary outcome and moderate and high certainty, respectively, for two secondary outcomes) by significantly reducing the number of apnoeas, hypopnoeas, and respiratory arousals during sleep. In addition, montelukast was well tolerated in the children studied. The clinical relevance of the observed treatment effects remains unclear, however, because minimal clinically important differences are not yet established for polysomnography-based outcomes in children. Long-term efficacy and safety data on the use of anti-inflammatory medications for the treatment of OSA in childhood are still not available. In addition, patient-centred outcomes like concentration ability, vigilance, or school performance have not been investigated yet. There are currently no RCTs on the use of other kinds of anti-inflammatory medications for the treatment of OSA in children. Future RCTs should investigate sustainability of treatment effects, avoidance of surgical treatment for OSA, and long-term safety of anti-inflammatory medications for the treatment of OSA in children and include patient-centred outcomes.
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Anti-inflammatory medications for the treatment of pediatric obstructive sleep apnea.
Kuhle, S, Urschitz, MS
Paediatric respiratory reviews. 2020;:35-36
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Weight Loss Interventions as Treatment of Obesity Hypoventilation Syndrome. A Systematic Review.
Kakazu, MT, Soghier, I, Afshar, M, Brozek, JL, Wilson, KC, Masa, JF, Mokhlesi, B
Annals of the American Thoracic Society. 2020;(4):492-502
Abstract
Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Weight loss is an important component of management based on clinical rationale, but the evidence supporting weight loss has not been summarized and the optimal approach has not been determined.Objectives: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. The panel asked, "Should a weight loss intervention be performed in patients with OHS?"Methods: Medline, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that assessed weight loss interventions in obese adults with confirmed OHS, suspected OHS, or hypercapnia. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: The search identified 2,994 articles. Six studies were selected, including two randomized trials and four nonrandomized studies without a comparator. Sample size ranged from 16 to 63 subjects. The studies found that a comprehensive weight loss program (including motivational counseling, dieting, and exercise) can reduce weight by 6% to 7% but confers no clinically significant effects compared with standard care. Bariatric surgery, on the other hand, is associated with more robust weight loss (15-64.6%, depending on the type of intervention), reduction of obstructive sleep apnea severity (18-44% reduction of the apnea-hypopnea index), and improvement in gas exchange (17-20% reduction in partial pressure of carbon dioxide in the arterial blood), ultimately leading to the resolution of OHS. Moreover, daytime sleepiness and pulmonary artery pressure also improve with significant weight loss. Bariatric surgery is associated with adverse effects in roughly one-fifth of patients, but serious adverse effects are very rare. The level of certainty in the estimated effects was very low for most outcomes.Conclusions: The guideline panel for which the systematic review was performed made a conditional (i.e., weak) recommendation suggesting a weight loss intervention for patients with OHS, targeting a sustained weight loss of 25% to 30% of actual body weight. This recommendation was based on very low-quality evidence. Although the weight loss target is based on the observation that greater weight loss is associated with better outcomes, there is a need for better-quality studies to ascertain the degree of weight loss necessary to achieve improvement in clinically relevant outcomes in patients with OHS.