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.

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.

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.

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.

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.

[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.

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.

Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study.

BACKGROUND: Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes. METHODS: A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively. RESULTS: After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping < or = 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m2) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (> or = 25 kg/m2). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6). CONCLUSIONS: These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.

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.

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.

Tumor necrosis factor-alpha expression in uvular tissues differs between snorers and apneic patients.

BACKGROUND: Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-alpha has been shown to affect diaphragm contractility in mice and rabbit in vivo. OBJECTIVES: To assess total and compartmental TNF-alpha expression in uvular tissues of apneic and nonapneic patients. METHODS: Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-alpha expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections. RESULTS: TNF-alpha was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean +/- SEM] snorers, 100.5 +/- 3.0%; OSA 1 group, 127.1 +/- 6.9%; OSA 2 group, 140.7 +/- 11.0%; p = 0.01). In the muscular area, TNF-alpha levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 +/- 3%; OSA 1 group, 107.4 +/- 0.7%; OSA 2 group, 124.1 +/- 4.2%; p = 0.007). In the muscular area, TNF-alpha was correlated with BMI, but no relationship was found with the apnea-hypopnea index. CONCLUSIONS: We conclude that MU is the major TNF-alpha source in uvular tissue and that TNF-alpha is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.

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.

Behavioral correlates of sleep-disordered breathing in older women.

STUDY OBJECTIVES: To examine the association between SDB and subjective measures of daytime sleepiness, sleep quality, and sleep related quality of life in a large cohort of primarily community-dwelling older women, specifically considering the relative importance of sleep duration in mediating these associations. DESIGN: Cross-sectional. The functional outcome measures of interest were daytime sleepiness (using the Epworth Sleepiness Scale, ESS), sleep-related symptoms (Pittsburgh Sleep Quality Index, PSQI), and sleep related quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ). ANOVA and regression analyses examined the association between SDB severity (measured by indices of breathing disturbances and overnight oxygen saturation) and sleep time (by actigraphy) and these outcome measures. Regression models were adjusted for age, body mass index (BMI), and a medical comorbidity index. We specifically explored whether associations with indices of SDB were mediated by sleep deprivation by adjusting models for actigraphy-determined average total sleep time (TST) during the night. SETTING: Community-based sample examined in home and outpatient settings. PARTICIPANTS: 461 surviving older women from the multicenter Study of Osteoporotic Fractures were examined during Visit 8 from 2002-03. All participants underwent in-home overnight polysomnography for one night and wrist actigraphy for a minimum of 3 24-h periods and completed the above functional outcomes questionnaires. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants were aged 82.9 +/- 3.5 (mean +/- SD) years, had BMI of 27.9 +/- 5.1 kg/m2, and had an apnea-hypopnea index (AHI) of 15.7 +/- 15.1. AHI and TST demonstrated a weak correlation (r = -0.15). ESS score individually demonstrated a modest association with AHI, oxygen desaturation, and TST. The association of ESS score and AHI--but not oxygen desaturation-was attenuated to some extent by adjustment for TST. PSQI and FOSQ scores were not associated with measures of SDB severity or TST. CONCLUSIONS: After adjustment for TST, SDB severity in community-dwelling older women was not independently associated with self-reported daytime sleepiness, although there may be a modest association that is mediated through reduced TST. In older women, SDB severity was not associated with indices of sleep related symptoms or sleep related quality of life.

Upper-airway inflammation triggered by vibration in a rat model of snoring.

STUDY OBJECTIVES: To determine whether the vibratory mechanical stimulus due to snoring induces upper-airway inflammation in an in-vivo rat model. DESIGN: Prospective controlled animal study. SETTING: University laboratory. PATIENTS OR PARTICIPANTS: Sixteen male Sprague-Dawley rats (250-300 g). INTERVENTIONS: The upper trachea of 8 rats was cannulated, and the upper airway was subjected to vibration (60 Hz; +/- 10 cm H2O) with a periodic pattern consisting of 1 second of vibration followed by 3 seconds of no vibration. This snoring-like vibration was applied for 3 hours. The animals breathed spontaneously through a cannula in the lower trachea. In a control group (8 rats), the animals were similarly instrumented, but no upper-airway vibration was applied. MEASUREMENTS AND RESULTS: The effect of vibration was assessed by measuring the vibration-induced increase in gene expression of the pro-inflammatory cytokine tumor necrosis factor-alpha and of the neutrophil attractant chemokine macrophage inflammatory protein-2 in the soft-palate tissue. Real-time reverse-transcription polymerase chain reaction measurement of mRNA showed that vibration induced a significant overexpression of both tumor necrosis factor-alpha and macrophage inflammatory protein-2: 6.01-fold +/- 2.47-fold (p = .005) and 2.38-fold +/- 0.54 -fold (p = .021) increase when compared with control (mean +/- SEM). CONCLUSIONS: The mechanical stimulus of vibration per se triggers an early proinflammatory process in the upper airway.

Oxidative stress markers in pregnant women who snore and fetal outcome: a case control study.

BACKGROUND: To determine the levels of oxidative stress markers in pregnant women who snore and compare with non-snoring pregnant women. Fetal outcome of these 2 groups was also evaluated. MATERIALS AND METHODS: Prospective, case control study. Some 40 pregnant women who snored and 43 non-snoring pregnant women were evaluated. The glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and myeloperoxidase (MPO) levels of the 2 groups were studied. Infant birthweight, Apgar scores, and other indicators of fetal outcome were obtained. RESULTS: The mean level of GSH-Px was significantly lower in the pregnant women who snored (p=0.005), while the mean level of MDA was significantly higher in this group (p=0.005). Levels of MPO were comparable between the groups (p>0.05). The pregnant women who snored did not have infants with evidence of an increase in compromised outcome. CONCLUSION: Although the pregnant women who snored had high levels of MDA, they did not appear to be at increased risk for delivering infants with fetal compromise.

Collagen type analysis in the soft palate after surgical intervention with CO(2) laser and radiofrequency ablation.

BACKGROUND AND OBJECTIVES: Snoring and apnea are social and medical problems that affect as many as 2% of adult women and 4% of adult men. This study compares collagen distribution and type with the intensity of snoring and the degree of drowsiness following uvulopalatoplasty with CO2 laser and radiofrequency ablation. STUDY DESIGN, PATIENTS, AND METHODS: Fragments were taken from the soft palate by biopsies of 16 uvulopalatoplasty patients and 5 controls, 5 weeks after surgery, and they were stained with Sirius red and observed with polarization microscopy. Photographs were taken, and the type and changes in the amount of collagen before and after surgery were compared. RESULTS: A histological analysis 5 weeks postoperatively in 10 patients showed an increased amount of collagen and replacement of type III collagen with type I collagen. CONCLUSIONS: The increase in the amount of collagen after uvulopalatoplasty was significantly larger in patients than in the controls, and all changes from type III to mostly type I collagen occurred in patients who had the surgery. The subjective improvement of both snoring and somnolence is associated with this increase in type I collagen.

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.

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.