Effects of continuous positive airway pressure on resolvin and matrix metalloproteinase-9 in patients with obstructive sleep apnea.

PURPOSE: Resolvin is a checkpoint controller in inflammation. Matrix metalloproteinase-9 (MMP-9) is an airway remodeling regulator. We evaluated the levels of resolvin and MMP-9 protein in the serum and exhaled breath condensate (EBC) before and after continuous positive airway pressure (CPAP) treatment. METHOD: We enrolled 20 non-OSA snorers and 40 patients with moderate to severe OSA scheduled for CPAP treatment. ELISA was used to assess resolvin and MMP-9 levels in the serum and EBC. All patients underwent sleep assessment at baseline and 3 months after CPAP. RESULTS: There was no between-group difference; moreover, there were no differences in the pre- and post-treatment serum levels of resolvin and MMP-9 in patients with OSA. Compared with non-OSA snorers, patients with OSA had lower resolvin and higher MMP-9 levels in the EBC. After CPAP treatment, the EBC levels of resolvin and MMP-9 in patients with OSA returned to normal. CONCLUSIONS: Successful OSA treatment by CPAP can normalize EBC levels of resolvin and MMP-9.

TcCO2 changes correlate with partial obstruction in children suspected of sleep disordered breathing.

INTRODUCTION: Pediatric sleep disordered breathing (SDB) is characterized by long periods of partial upper airway obstruction (UAO) with low apnea-hypopnea indices (AHI). By measuring snoring and stertor, Sonomat studies allow quantification of these periods of partial UAO. AIM: To determine whether transcutaneous CO2 (TcCO2 ) levels correlate with increasing levels of partial UAO and to examine patterns of ΔTcCo2 in the transitions from (a) wakefulness to sleep and (b) non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. METHODS: This was a retrospective review of sleep studies in seven asymptomatic controls aged 7 to 12 years and 62 symptomatic children with suspected SDB and no comorbidities, aged 2 to 13 years. Both groups underwent overnight polysomnography, including continuous TcCO2 , at one of two pediatric hospitals in Sydney. Changes in carbon dioxide levels between wake to NREM (sleep onset) and NREM to REM sleep were evaluated using an all-night TcCO2 trace time-linked to a hypnogram. Paired Sonomat recordings were used to quantify periods of UAO in the symptomatic group. RESULTS: The ΔTcCO2 at sleep onset was greater in SDB children than controls and ΔTcCO2 with sleep onset correlated with the duration of partial obstruction (r = .60; P < .0001). Children with an increase in TcCO2 from NREM to REM had a higher number of snoring and stertor events compared to those in whom TcCO2 decreased from NREM to REM (91 vs 30 events/h; P = < .0001). CONCLUSIONS: In children without comorbidities, the measurement of TcCO2 during sleep correlates with indicators of partial obstruction.

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling.

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea.

BACKGROUND: The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. METHODS: Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. RESULTS: Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 ± 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 ± 10% desmin-abnormal muscle fibres vs. 22 ± 6% in patients without swallowing dysfunction, p = 0.002. CONCLUSION: Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

Nocturnal oximetry in children with obstructive lung disease or sleep-disordered breathing.

OBJECTIVES: Although progress has been made in the standardized interpretation of nocturnal oximetry in children with obstructive sleep-disordered breathing (SDB), no evidence exists on oximetry abnormalities in other respiratory disorders. We aimed to compare obstructive lung disease (OLD) and SDB regarding nocturnal oximetry parameters. METHODS: We analyzed oximetry recordings from children with (i) OLD (obliterative bronchiolitis; cystic fibrosis); (ii) snoring and adenotonsillar hypertrophy (SDB); and (iii) no respiratory disorder (controls). The three groups were compared regarding: (i) oxygen desaturation of hemoglobin index (SpO2 drops ≥3%/h-ODI3) and (ii) basal SpO2 (average SpO2 between SpO2 drops). The associations of oximetry parameters (natural logarithm) with study group were tested using linear regression including age as covariate. RESULTS: Data of 16 subjects with OLD (median age: 7.3 years; Q25, Q75: 5.4, 12), 22 children with SDB (6.3 years; 4, 9) and 22 controls (6.8 years; 5.6, 10.3) were analyzed. Children with OLD or SDB had significantly lower basal SpO2 than controls (91.9% [90.8, 93.4] vs 96.3% [96, 97.4] vs 97.6% [97.1, 97.9]; P < 0.01). No subjects in the SDB or control groups had basal SpO2 < 95%. Children with SDB had significantly higher ODI3 than children with OLD or controls [8.4 episodes/h (6.2, 16.6) vs 4.4 episodes/h (3.6, 6.6) vs 2 episodes/h (1.3, 2.7); P < 0.01]. OLD had the greatest negative effect on basal SpO2 (R2 = 0.62; P < 0.001) and SDB the greatest positive effect on ODI3 (R2 = 0.34; P < 0.001). CONCLUSION: OLD is associated mostly with reduced basal SpO2 , whereas SDB is characterized by elevated ODI3.

Cough hypersensitivity in patients with obstructive sleep apnea hypopnea syndrome.

PURPOSE: The purpose of this study was to investigate cough hypersensitivity and its potential mechanisms in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Fifteen OSAHS patients, 12 simple snoring patients, and 15 healthy volunteers received cough sensitivity test and induced sputum cytology. Cough thresholds C2 and C5 (the minimum of capsaicin inducing ≥ 2 and ≥ 5 coughs, respectively), total cell count, cell differentials and the levels of bradykinin, histamine, prostaglandin E2, substance P, calcitonin gene-related peptide, pepsin, and interleukin-2 in the induced sputum detected by enzyme-linked immunosorbent assay were compared. The linear correlation between lgC2 and lgC5 and apnea hypopnea index, cell differentials, and inflammatory mediators in the induced sputum was calculated in OSAHS patients. RESULTS: OSAHS patients presented with a significant lower C2 and C5 (P < 0.01), increased lymphocyte but decreased macrophage and neutrophil proportions in the induced sputum (P < 0.01), and higher contents of substance P, calcitonin gene-related peptide and interleukin-2 (P < 0.01) but similar levels of bradykinin, pepsin, prostaglandin E2, and histamine (P > 0.05) in the supernatant of induced sputum, when compared with simple snoring patients and healthy volunteers. However, theses variable were comparable between simple snoring patients and healthy volunteers (P > 0.05). Finally, lgC2 or lgC5 was negatively related to apnea hypopnea index, lymphocyte percentage, and the levels of substance P, calcitonin gene-related peptide or interleukin-2 in the sputum (P < 0.01). There was a positive linear correlation between lymphocyte percentage and interleukin-2 level in the induced sputum (r = 0.63, P = 0.00). CONCLUSION: OSAHS patients have a predisposition of cough hypersensitivity associated with airway inflammation.

Traditional Chinese herbal formula relieves snoring by modulating activities of upper airway related nerves in aged rats.

AIM: The present study investigated whether intraperitoneal treatment with the herbal formula B210 ([B210]; a herbal composition of Gastrodia elata and Cinnamomum cassia) can reduce snoring in aged rats. Also, we studied possible neural mechanisms involved in B210 treatment and subsequent reduced snoring in rats. METHODS AND RESULT: We compared pressure and frequency of snoring, activities of phrenic nerve (PNA), activities of recurrent laryngeal nerve (RLNA) and activities of hypoglossal nerve (HNA), inspiratory time (TI) and expiratory time (TE) of PNA, and pre-inspiratory time (Pre-TI) of HNA in aged rats between sham and B210 treatment groups (30 mg/mL dissolved in DMSO). We found that aged rats that received B210 treatment had significantly reduced pressure and frequency of snoring than rats who received sham treatment. Also, we observed that aged rats that received B210 treatment had significantly increased PNA, RLNA, and HNA, extended TI and TE of PNA, and prolonged Pre-TI of HNA compared to rats that received sham treatment. In other words, B210 treatment may relieve snoring through modulating activities and breathing time of upper airway related nerves in aged rats. CONCLUSION: We suggested that the B210 might be a potential herbal formula for snoring remission.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 + T cells expressing TNFα and IFNγ.

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

STUDY OBJECTIVES: Trefoil factor family (TFF) peptides belong to the family of mucin-associated peptides and are expressed in most mucosal surfaces. TFF peptides carry out functions such as proliferation and migration enhancement, anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and interact with them as "linker peptides", thereby influencing mucus viscosity. To test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA) changes occur in the expression of TFF3 and -2 that could contribute to changes in mucus viscosity, leading to an increase in upper airway resistance during breathing. METHODS: RT-PCR, Western-blot, immunohistochemistry and ELISA were performed to detect and quantify TFF3 and -2 in uvula samples. In addition, 99 saliva samples from patients with mild, moderate or severe OSA, as well as samples from rhonchopathy patients and from healthy volunteers, were analyzed by ELISA. RESULTS: TFF3 was detected in all uvula samples. Immunohistochemistry revealed a subjectively decreasing antibody reactivity of the uvula epithelia with increasing disease severity. ELISA demonstrated significantly higher TFF3 saliva protein concentrations in the healthy control group compared to cases with rhonchopathy and OSA. Predisposing factors of OSA such as BMI or age showed no correlation with TFF3. No significant changes were observed with regard to TFF2. CONCLUSIONS: The results suggest the involvement of TFF3 in the pathogenesis of rhonchopathy and OSA and lead to the hypothesis that reduction of TFF3 production by the epithelium and subepithelial mucous glands of the uvula contribute to an increase in breathing resistance due to a change in mucus organization.

Current child, but not maternal, snoring is bi-directionally related to adiposity and cardiometabolic risk markers: A cross-sectional and a prospective cohort analysis.

PURPOSE: Obstructive sleep apnea (OSA), typically manifested as snoring, is closely associated with obesity. However, the directionality of associations of OSA with cardiometabolic risk markers is unclear, as obesity increases risk for OSA, and OSA results in excess weight gain and its metabolic consequences. Less is known about how obesity and OSA may relate in children and adolescents and whether maternal OSA may influence the development of obesity and cardiometabolic dysfunction in offspring. BASIC PROCEDURES: Among 1078 children from the Project Viva cohort, we examined cross-sectionally and prospectively associations of parent-reported child or maternal snoring with cardiometabolic outcomes, including adiposity, adipokines, and insulin resistance. MAIN FINDINGS: Cross-sectionally, child snoring was related to adiposity and metabolic risk, particularly body mass index (BMI; ß 0.61kg/m2, 95% CI 0.33, 0.89; p<0.001), trunk fat mass index (ß 0.23kg/m2, CI 0.12, 0.34; p<0.001), high-density lipoprotein cholesterol (ß -1.47mg/dL, CI -2.69, -0.25; p=0.02), and metabolic risk z-score (ß 0.08, CI 0.02, 0.14; p=0.01) after correction for covariates. Prospectively, adiposity (BMI, trunk fat, fat mass, and waist circumference) and cardiometabolic (leptin, HOMA-IR, CRP, and global metabolic risk) measures at mid-childhood (~7y) were associated with child snoring at the early teen visit (~12y) after correction for covariates. Child snoring at ~9y was related to changes in adiposity between mid-childhood and early teen visits. CONCLUSIONS: Child but not maternal snoring, was related to child adiposity and cardiometabolic outcomes. Adiposity and child snoring are associated with each other cross-sectionally and are each predictive of the other among children/adolescents prospectively. These results suggest similar mechanisms in pediatric/adolescent populations as in adults for the development of sleep-disordered breathing and sleep apnea that will need to be confirmed in randomized clinical trials. Importantly, this research points to the need to target both sleep and obesity in order to break this vicious cycle.

Effects of positive airway pressure therapy on cardiovascular and metabolic markers in males with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular/metabolic complications. Some analytical parameters (homocysteine, glycemic and lipidic profiles) are recognized markers of these consequences. Limited data is available on the association of these markers and OSAS's severity/response to positive airway pressure therapy (PAP). MATERIAL AND METHODS: In this prospective study we analyzed polysomnographic and analytical data of male patients admitted to sleep laboratory. The aim was to evaluate metabolic/cardiovascular markers in snorers and OSAS patients, to relate with sleep parameters and PAP response. One-hundred and three patients were included, and 73 (71%) were OSAS patients. OSAS patients were similar to snorers except for higher body mass index (BMI) and dyslipidemia. Severe OSAS patients showed higher glycemia, HbA1c, insulin, and insulin resistance, and lower HDL cholesterol in comparison to mild-moderate (p<0.05, p<0.05, p<0.001, p<0.001, p<0.05, respectively). Glycemic profile and triglycerides were slightly correlated with OSAS severity. 46 OSAS patients were submitted to 6 months of PAP, with a statistical decrease in mean values of homocysteine, glycemia, total and LDL cholesterol (p<0.05, p<0.05, p<0.05, respectively), and in glycemia and LDL cholesterol in severe group only (p<0.05, p<0.05, respectively). RESULTS: This study demonstrated an association between glucose metabolism parameters and triglycerides with OSAS severity underlying the complexity of the process leading to cardiovascular/metabolic complications in this disorder. Moreover, homocysteine, glycemic and lipidic profiles changed significantly after 6 months of PAP therapy in OSAS, supporting its cardiovascular and metabolic protective effect. CONCLUSION: Our study has reinforced the importance of analytical cardiovascular/metabolic evaluation as complementary tool of diagnosis/treatment response in OSAS.

Metabolic consequences of snoring in adolescents and younger adults: a population study in Chile.

STUDY OBJECTIVES: To investigate the potential association between snoring and other symptoms indicative of sleep-disordered breathing and metabolic syndrome (MetS) in Hispanic adolescents and younger adults using a large population-based survey. METHODS: Sleep-related information, anthropometric measurements and fasting blood samples markers of MetS were obtained from subjects aged 15-40 years collected through the 2nd Chilean Health Survey. Regression models were constructed to evaluate the associations of snoring with MetS, hypertension and serum cholesterol levels. The modulating effect of sleep duration was accounted for in the models. RESULTS: A total of 2147 subjects (42% males, mean age 27.9±7.6 years) were included. Snoring and short sleep duration were present in 43.5 and 25% of the entire population, respectively. MetS was detected in 19.5% of the subjects. In the adjusted regression model, the odds of MetS among snoring subjects were 2.13 times higher (95% confidence interval (CI): 1.52-2.99; P<0.01), and 1.53-fold higher odds of elevated cholesterol also emerged (95% CI: 1.12-2.10; P<0.01). However, the odds of hypertension were not increased by the presence of snoring after adjusting for confounders. In addition, snoring was associated with an increase of 7.26 and 6.56 mg dl-1 for total and low-density lipoprotein cholesterol, respectively, even after adjusting for age, sex and body mass index. Short sleep duration was associated with a small albeit significant risk increase for high systolic blood pressure. CONCLUSIONS: In this large population-based sample of young Hispanic adults and adolescents, snoring, but not sleep duration, emerged as an independent risk factor for dyslipidemia and MetS, but not for hypertension.

Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers.

Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS), and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine, and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine, and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach, and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.

Expression of cysteinyl leukotriene receptor 1 and 2 (CysLTR1 and CysLTR2) in the lymphocytes of hyperplastic tonsils: comparison between allergic and nonallergic snoring children.

BACKGROUND: Cysteinyl leukotriene receptor 1 and 2 (CysLTR1 and CysLTR2) are involved in allergic processes and play a role in adenotonsillar hyperplasia (AH). Clinically, only CysLTR1 may be blocked by montelukast. Our objective was to compare the expression of CysLTR1 and CysLTR2 in the B and T cells of hyperplasic tonsils of sensitized (SE) and control (NS) snoring children. METHODS: Sixty children, 5 to 10 years of age, referred for adenotonsillectomy, were divided into SE and NS groups, according to their responses to the skin-prick test. Cells from the removed tissues were stained for CysLTR1, CysLTR2, CD19, and CD3 and counted via flow cytometry. messenger RNA (mRNA) expression of the CysLTRs genes was measured real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The SE group showed reduced expression of the small CD3+/CysLTR1+ lymphocytes (4.6 ± 2.2 vs 6.5 ± 5.0; p = 0.04). Regarding the large lymphocytes, the SE group showed lower expression of CD3+/CysLTR1+ (40.9 ± 14.5 vs 47.6 ± 11.7; p = 0.05), CD19+/CysLTR1+ (44.6 ± 16.9 vs 54.1 ± 12.4; p = 0.01), and CD19+/CysLTR2+ (55.3 ± 11.3 vs 61.5 ± 12.6; p = 0.05) lymphocytes. Considering the total number of lymphocytes, the SE group had fewer CD3+/CysLTR1+ lymphocytes (11.1 ± 5.5 vs 13.7 ± 6.2; p = 0.04). All other cell populations exhibited reduced expression in the SE group without statistical significance. The expression of CysLTR2 was significantly higher (p < 0.05) than CysLTR1 in most studied cell populations. The mRNA expression did not show significant differences between the groups. CONCLUSION: The expression of CysLTR is higher in the lymphocytes of the NS children, and CysLTR2 shows greater expression than CysLTR1 Respiratory allergies do not appear to be a stimulus for AH occurrence. Newer drugs capable of blocking both CysLTRs warrant further study.

Snoring as a Determinant Factor of Oxidative Stress in the Airway of Patients with Obstructive Sleep Apnea.

PURPOSE: In obstructive sleep apnea-hypopnea syndrome (OSAS), airway collapses and vibrations cause local and systemic inflammatory response and oxidative stress (OS). Our objective was to determine the presence of OS in the airway of patients with OSAS compared with controls without OSAS and determine its relation to treatment with CPAP and other clinical variables. METHOD: We performed a prospective observational case-control study with repeated measures. We recruited consecutive patients with SAHS diagnosed using complete polysomnography, and a parallel control group. We collected a sample of exhaled breath condensate (EBC) prior to nasal continuous positive airway pressure (CPAP) treatment and again after 4 months. The marker of OS used was 8-isoprostane (8-IPN). The variables analyzed were age, sex, anthropometric variables, apnea-hypopnea index (AHI), snoring, oxygenation, and polysomnographic variables. RESULTS: The study included 20 patients and 10 controls. In cases, the initial value of 8-IPN was 6.8 (1.9), and after nasal CPAP, it was 5.3 (1.2) pg/ml (p = 0.02). In controls, the value of 8-IPN was 5.6 (1.1) pg/ml (p = 0.04 compared to initial values). 8-IPN showed significant correlation with snoring, AHI, BMI, nocturnal desaturation index, and non-REM sleep. On multivariate analysis, only snoring was a significant predictor of 8-IPN. CONCLUSIONS: Snoring, and not OSAS severity, could be the phenomenon underlying the presence of local OS measured in the airway of patients with OSAS.

A comparative study on oxidative stress role in nasal breathing impairment and obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a sleep disorder that leads to metabolic abnormalities and increased cardiovascular risk. This study aimed to define the expression and clinical significance of biomarkers involved in oxidative stress in patients with OSAS. A prospective study was designed to compare outcomes of oxidative stress laboratory tests in three groups of subjects. The study involved the recruitment of three groups of subjects, 10 patients with obstructive sleep apnoea syndrome with AHI > 30; 10 patients suffering from snoring at night with AHI < 15; 10 patients with nasal respiratory impairment with AHI < 5. Patients were subjected to skin prick tests for common aero-allergens, nasal endoscopy, active anterior rhinomanometry, fibrolaryngoscopy and polysomnography; and extra-routine diagnostic tests and procedures; analysis of oxidative and antioxidant (plasma thiol groups) biomarkers in blood and urine samples. No statistical differences in age, sex distribution or body mass index were present between the three groups (p > 0.05). There were significant differences in AHI among the three groups of patients (p < 0.05). No statistical significance was found in the Analysis of Variance (ANOVA) test (p > 0.05) between the levels of biomarkers of oxidative stress in the three populations studied. The results of our study show that the nose can play a role in the pathogenesis of OSAS through the production of biomarkers of oxidative stress.

Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.

OBJECTIVE: We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS: Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history. RESULTS: Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes. CONCLUSIONS: Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

Tongue Volume Influences Lowest Oxygen Saturation but Not Apnea-Hypopnea Index in Obstructive Sleep Apnea.

OBJECTIVES: The aim of this study was to identify correlations between sleep apnea severity and tongue volume or posterior airway space measured via three-dimensional reconstruction of volumetric computerized tomography (CT) images in patients with obstructive sleep apnea (OSA) for use in predicting OSA severity and in surgical treatment. We also assessed associations between tongue volume and Mallampati score. METHODS: Snoring/OSA male patients (n = 64) who underwent polysomnography, cephalometry, and CT scans were enrolled in this retrospective study. OSA was diagnosed when the apnea-hypopnea index (AHI) was greater than 5 (mild 5-14; moderate 15-29; severe>30). The patients were also categorized into the normal-mild group (n = 22) and the moderate-severe group (n = 42). Using volumetric CT images with the three-dimensional reconstruction technique, the volume of the tongue, posterior airway space volume, and intra-mandibular space were measured. The volumes, polysomnographic parameters, and physical examination findings were compared, and independent factors that are related to OSA were analysed. RESULTS: No associations between tongue volume or posterior airway space and the AHI were observed. However, multivariate linear analyses showed that tongue volume had significantly negative association with lowest O2 saturation (r = 0.365, p = 0.027). High BMI was related to an increase in tongue volume. Modified Mallampati scores showed borderline significant positive correlations with absolute tongue volume (r = 0.251, p = 0.046) and standardized tongue volume (absolute tongue volume / intramandibular area; r = 0.266, p = 0.034). Between the normal-mild and moderate-severe groups, absolute tongue volumes were not different, although the standardized tongue volume in the moderate-severe group was significantly higher. CONCLUSION: Absolute tongue volume showed stronger associations with lowest O2 saturation during sleep than with the severity of AHI. We also found that high BMI was a relevant factor for an increase in absolute tongue volume and modified Mallampati grading was a useful physical examination to predict tongue size.

Oxidative stress in children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with cardiovascular consequences, including accelerated atherosclerosis and endothelial dysfunction. Increased lipid peroxidation, a marker of oxidative stress, has been identified in adults with OSA in a severity-dependent manner, with attenuation following treatment with continuous positive airway pressure therapy. Studies on oxidative stress in children with OSA are sparse and results are inconclusive. The objective of this study was to compare lipid peroxidation in children with OSA to non-OSA children. METHODS: A prospective cross-sectional study of 26 children with polysomnography-confirmed OSA (oAHI ≥ 5/h TST) was conducted. Thirty age- and body mass index z-score-matched children with primary snoring (PS) served as a comparison group (oAHI ≤ 1/h TST). Fasting blood samples were obtained on the morning following the sleep study. Plasma oxidized low-density lipoprotein (oxLDL) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: There were no group differences in patient characteristics and their lipid profiles. The mean oxLDL levels of the OSA group were significantly higher than those of the comparison group (53.1 ± 13.0 vs. 45.7 ± 10.0 U/L, respectively, p = 0.02). There was a significant positive correlation between plasma oxLDL and the apnea hypopnea index (r = 0.29, p = 0.03) and between oxLDL and the oxygen desaturation index (r = 0.51, p = 0.003), and a significant negative correlation between SpO2 nadir and oxLDL (r = -0.29, p = 0.03). CONCLUSIONS: OSA in children is associated with increased lipid peroxidation in a severity-dependent manner. Lipid peroxidation levels correlate with the degree of intermittent hypoxia.

[Evaluation of lipid peroxidation - antioxidant protection in perimenopausal women with sleep disorders].

OBJECTIVE: Our aim was to assess lipid peroxidation - antioxidant protection with the definition of the oxidative stress coefficient in perimenopausal women with sleep disorders. METHODS: 45 perimenopausal women (mean age 49.1±0.32) were examined: 26 patients with sleep disorders, 19 - without sleep disorders. Evaluation of sleep disorders was conducted using a questionnaire of Stanford Centre for the Study of Sleep, test for assessment subjective severity of insomnia, the questionnaire for the quantitative assessment of the risks of sleep apnea, the scale for quantifying the degree of daytime sleepiness Epworth. We used spectrophotometric methods for lipid peroxidation - antioxidant system investigation. Statistical analysis was performed by non-parametric tests. RESULTS: In perimenopausal women sleep disorders often presents falling asleep difficulties (93.3%) and morning awakening difficulties (78.8%). Complaints of snoring detected in 33.3% of patients. Insomnia severity index was 21.3±0.54, the total score on the Epworth scale - 12.2±0.42. The study results showed increase of secondary products of lipid peroxidation (ketodienes and coupled trienes) levels by 2.2 times (p <0.05). Coefficient oxidative stress in women with sleep disorders is higher by 2 times than in group without sleep disorders. CONCLUSION: In perimenopausal women sleep disorders are associated with oxidative stress, which is pathogenic rationale for inclusion in the complex therapy of these patients drugs that inhibit of lipid peroxidation activation.