Sleepiness and Vitamin D Levels in Patients with Obstructive Sleep Apnea.

STUDY OBJECTIVES: The aim of this cross-sectional study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of the Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). METHODS: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS > 10) and those without EDS (ESS < 10). All patients underwent night polysomnography. Measurement of serum 25(OH)D vitamin was performed using a radioimmunoassay. RESULTS: In total, 217 patients with OSA (197 males and 20 females) were included. Patients with EDS had higher AHI (p < 0.001) values and lower mean serum 25(OH)D levels, compared with those of non-somnolent patients [17.4 (12.2-25.7) versus 21.1 (15.3-28.8) ng/mL, respectively, p = 0.005]. In patients with EDS, serum 25(OH)D levels correlated with average oxyhemoglobin saturation during sleep (r = 0.194, p = 0.043), and negatively with ESS score (r = -0.285, p = 0.003), AHΙ (r = -0.197, p = 0.040) and arousal index (r = -0.256, p = 0.019). Binary regression analysis identified Vit D serum levels (ß = -0.045, OR: 0.956, 95% CI: 0.916-0.997, p = 0.035), total sleep time (ß = 0.011, OR: 1.011, 95% CI: 1.002-1.021, p = 0.016) and AHI (ß = 0.022, OR: 1.022, 95% CI: 1.003-1.043, p = 0.026) as independent predictors of EDS in patients with OSA. In patients with EDS, multiple regression analysis indicated that ESS score was negatively associated with Vit D serum levels (ß = -0.135, p = 0.014) and minimum oxyhemoglobin saturation during sleep (ß = -0.137, p = 0.043). CONCLUSIONS: In the present study, EDS in patients with OSA is associated with low levels of Vitamin D, while sleep hypoxia may play a role in this process.

Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.

PURPOSE: Vitamin D deficiency has been associated with the occurrence of obstructive sleep apnea syndrome (OSAS). Megalin (LRP2) and cubilin (CUBN) are implicated in vitamin D metabolism, whereas LRP2 and CUBN polymorphisms have been previously associated with variable serum vitamin D levels. The present study aimed to evaluate the role of LRP2 rs2228171 c.8614C > T and CUBN rs1801222 c.758A > G polymorphisms in OSAS susceptibility, independently or in synergy with vitamin D levels. METHODS: Vitamin D serum concentration of consecutive individuals was measured. PCR-RFLP was used for LRP2 rs2228171 and CUBN rs1801222 genotyping. RESULTS: A total of 176 individuals was enrolled, including 144 patients with OSAS and 32 controls. Frequency of LRP2 rs2228171 c.8614 T and CUBN rs1801222 c.758G alleles was estimated at 22.4% and 79.8%, respectively. LRP2 and CUBN polymorphisms were not associated with OSAS occurrence (rs2228171Τ allele: 22.9% in OSAS group vs. 20.3% in controls, p = 0.651; rs1801222A allele 19.4% in OSAS group vs. 23.4% in controls, p = 0.471). Frequency of CUBN rs1801222A allele carriers was increased in patients with moderate or severe OSAS compared to mild OSAS (p = 0.028). Patients with OSAS homozygous for LRP2 CC and CUBN GG genotypes had lower vitamin D serum concentration compared to controls carrying the same genotype (18.0 vs 27.0 ng/mL, p = 0.006 and 19.0 vs 27.5 ng/mL, p = 0.007, respectively). CONCLUSION: CUBN rs1801222 polymorphism may affect OSAS severity. Among other factors, low vitamin D concentration is associated with OSAS occurrence, irrespectively of LRP2 and CUBN polymorphisms.

Is COPD the Determinant Factor for Myocardial Injury and Cardiac Wall Stress in OSA Patients?

Background and Objectives: Evidence shows that COPD-OSA overlap syndrome (OS) is more frequently accompanied by cardiovascular disease (CVD) in comparison to either disease alone. The aim of the study was to explore whether patients with OS have a higher burden of subclinical myocardial injury and wall stress compared with OSA patients. Materials and Methods: Consecutive patients, without established CVD, underwent polysomnography and pulmonary function testing, due to suspected sleep-disordered breathing. An equal number of patients with OS (n = 53, with an apnea hypopnea index (AHI) > 5/h and FEV1/FVC < 0.7) and patients with OSA (n = 53, AHI > 5/h and FEV1/FVC > 0.7) were included in the study. The detection of asymptomatic myocardial injury and wall stress was performed via the assessment of serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), respectively. Results: OS patients were older (p < 0.001) and had worse hypoxemic parameters, namely average oxyhemoglobin saturation (SpO2) (p = 0.002) and time spent with SpO2 < 90% (p = 0.003) during sleep as well as daytime pO2 (p < 0.001), than patients with OSA. No difference was observed between groups in terms of Epworth Sleepiness Scale (p = 0.432) and AHI (p = 0.587). Both levels of hs-cTnT (14.2 (9.1-20.2) vs. 6.5 (5.6-8.7) pg/mL, p < 0.001) and NT-proBNP (93.1 (37.9-182.5) vs. 19.2 (8.3-35.4) pg/mL, p < 0.001) were increased in OS compared to OSA patients. Upon multivariate linear regression analysis, levels of NT-proBNP and hs-cTnT correlated with age and average SpO2 during sleep. Conclusions: Our study demonstrated higher levels of hs-cTnT and NT-proBNP in OS patients, indicating an increased probability of subclinical myocardial injury and wall stress, compared with OSA individuals.

Effect of compliance to continuous positive airway pressure on exacerbations, lung function and symptoms in patients with chronic obstructive pulmonary disease and obstructive sleep apnea (overlap syndrome).

INTRODUCTION: Patients with overlap syndrome (OS), that is obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), are at increased risk of acute exacerbations related to COPD (AECOPD). We assessed the effect of CPAP compliance on AECOPD, symptoms and pulmonary function in OS patients. METHODS: Consecutive OS patients underwent assessment at baseline and at 12 months under treatment with CPAP of: AECOPD and hospitalizations, COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) questionnaires, pulmonary function testing and 6-min walking test (6MWT). RESULTS: In total, 59 patients (54 males) with OS were followed for 12 months and divided post hoc according to CPAP compliance into: group A with good (≥4 h CPAP use/night, n = 29) and group B with poor (<4 h CPAP use/night, n = 30) CPAP compliance. At 12 months, group A showed improvements in FEV1 (p = 0.024), total lung capacity (p = 0.024), RV/TLC (p = 0.003), 6MWT (p < 0.001) and CAT (p < 0.001). COPD exacerbations decreased in patients with good CPAP compliance from baseline to 12 months (17 before vs. 5 after, p = 0.001), but not in those with poor compliance (15 before vs. 15 after, p = 1). At multivariate regression analysis, COPD exacerbations were associated with poor CPAP compliance (ß = 0.362, 95% CI: 0.075-0.649, p = 0.015). CONCLUSIONS: When compared to poorly compliant patients, OS patients with good CPAP compliance had a lower number of AECOPD and showed improved lung function and COPD related symptoms.

Vitamin D Levels in Patients with Overlap Syndrome, Is It Associated with Disease Severity?

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in patients with OVS is scarce. The aim of the present study was to evaluate Vit D serum levels and to explore the association of those levels with anthropometric, pulmonary function and sleep parameters in patients with OVS. Methods: Vit D serum levels were measured in patients diagnosed with OVS, as confirmed by overnight polysomnography and pulmonary function testing. Results: A total of 90 patients (79 males and 11 females) were included in the analysis. The patients were divided into three groups matched for age, gender, and BMI: the control group that included 30 patients (27 males and 3 females), the OSA group that included 30 patients (26 males and 4 females), and the OVS group that included 30 patients (26 males and 4 females). Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients and controls (14.5 vs. 18.6 vs. 21.6 ng/mL, p < 0.001). In the OVS group, multiple linear regression analysis identified AHI and FEV1, as predictors of serum 25(OH)D levels (p = 0.041 and p = 0.038, respectively). Conclusions: Lower Vit D levels have been observed in patients with OVS compared with OSA patients and non-apneic controls, indicating an increased risk of hypovitaminosis D in this population which might be associated with disease severity.

Burden of Comorbidities in Patients with OSAS and COPD-OSAS Overlap Syndrome.

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are usually associated with multi-morbidity. The aim of this study was to retrospectively investigate the prevalence of comorbidities in a cohort of patients with OSAS and COPD-OSAS overlap syndrome (OS) patients and to explore differences between these two groups. Materials and Methods: Included were consecutive OS patients and OSAS patients who had been referred to our sleep laboratory, and were matched in terms of sex, age, BMI, and smoking history. Presence of comorbidities was recorded based on their medical history and after clinical and laboratory examination. Results: The two groups, OS patients (n = 163, AHI > 5/h and FEV1/FVC < 0.7) and OSAS patients (n = 163, AHI > 5/h, and FEV1/FVC > 0.7), did not differ in terms of apnea hypopnea index (p = 0.346), and oxygen desaturation index (p = 0.668). Compared to OSAS patients, OS patients had lower average SpO2 (p = 0.008) and higher sleep time with oxygen saturation <90% (p = 0.002) during sleep, and lower PaO2 (p < 0.001) and higher PaCO2 (p = 0.04) in wakefulness. Arterial hypertension was the most prevalent comorbidity for both OS and OSAS, followed by dyslipidemia, cardiovascular disease (CVD) and diabetes. OS was characterized by a higher prevalence of total comorbidities (median (IQR):2 (1-3) vs. 2 (1-2), p = 0.033), which was due to the higher prevalence of CVD (p = 0.016) than OSAS. No differences were observed in other comorbidities. Conclusions: In OS patients, nocturnal hypoxia and impaired gas exchange in wakefulness are more overt, while a higher burden of CVD is observed among them in comparison to sex-, age- and BMI-matched OSAS patients.

Metabolic Syndrome in Patients with Coexistent Obstructive Sleep Apnea Syndrome and Chronic Obstructive Pulmonary Disease (Overlap Syndrome).

Background: Evidence suggests that metabolic syndrome (MetS) is highly prevalent in patients with obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). However, data on the prevalence of MetS in patients having both OSAS and COPD, or overlap syndrome (OS), are scarce. The aim of this study was to evaluate the prevalence and identify predictors of MetS in patients with OS. Methods: MetS was evaluated in consecutive patients who were diagnosed with OS by polysomnography and pulmonary function testing. Results: A total of 163 subjects (138 males and 25 females) were included. MetS was present in 38% of OS patients. Patients were divided into group A (OS without MetS group: 101 patients) and group B (OS with MetS group: 62 patients). Groups were similar in terms of pulmonary function and sleep parameters. In group B, abdominal obesity was the most prevalent component of MetS (100%), followed by hypertension (82.3%), hypertriglyceridemia (72.6%), and hyperglycemia (51.6%). Age (P = 0.009) and body mass index (P = 0.029) were independent predictors of MetS in patients with OS. Conclusions: An increased prevalence of MetS was observed in a group of patients with OS. Early identification and treatment of MetS may play a significant role in prevention of complications related to OS.

Increased risk for cardiovascular disease in patients with obstructive sleep apnoea syndrome-chronic obstructive pulmonary disease (overlap syndrome).

INTRODUCTION: Accumulating evidence suggests that cardiovascular disease (CVD) is highly prevalent among patients with concurrent obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease, otherwise known as overlap syndrome (OS). OBJECTIVES: The aim of this study was to investigate the 10-year risk for CVD in OS patients compared with OSAS patients and controls. METHODS: Consecutive patients, referred for symptoms suggestive of OSAS, were evaluated with polysomnography and pulmonary function testing. Cardiovascular risk was assessed using the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). RESULTS: Overall, 244 participants (184 males) without CVD and diabetes were divided into 3 groups: controls (n = 63), OSAS (n = 139) and OS (n = 42). Both FRS and SCORE were found to be elevated in the OS group compared with the OSAS and control groups (P < .001 for all). In multivariate analysis, age (ß = .461, P < .001), forced expiratory volume in first second (ß = -.285, P = .036) and oxygen desaturation index (ODI) (ß = .234, P = .007) were major determinants for the SCORE, whereas age (ß = .308, P < .001) and apnoea-hypopnoea index (ß = .252, P = .010) for the FRS. CONCLUSION: In our study, an increased risk for CVD was observed in a group of patients with OS at the time of their initial evaluation. Further studies are needed in the field of OS in order to investigate, prevent and manage early CVD in this population.

Reduced Serum Vitamin D Levels Are Associated with Insulin Resistance in Patients with Obstructive Sleep Apnea Syndrome.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Serum levels of NGAL and cystatin C as markers of early kidney dysfunction in patients with obstructive sleep apnea syndrome.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) has been recently proposed as an independent risk factor for chronic kidney disease. Cystatin C (Cyst C) and neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers for the earlier detection of latent kidney disease. The aim of the study was to assess serum Cyst C and NGAL levels in otherwise healthy OSAS patients and to explore possible associations with sleep parameters. METHODS: Consecutive subjects (n = 96, 79.2% males), without known comorbidities, with symptoms suggestive of OSAS were included. All of them underwent polysomnography (PSG) and blood examination for the measurement of serum Cyst C and NGAL levels. RESULTS: Based on apnea-hypopnea index (AHI), subjects were classified into two groups: 32 controls and 64 OSAS patients, with no significant differences in terms of age (50.1 ± 11.7 vs 51 ± 12.2 years, p = 0.747) and BMI (33.9 ± 8.8 vs 35.9 ± 13.1 kg/m2, p = 0.449). Serum Cyst C and NGAL mean levels were higher in OSAS patients compared to those in controls (1155.2 ± 319.3 vs 966.8 ± 173 ng/ml, p = 0.001, and 43.7 ± 23.2 vs 35.6 ± 13.8 ng/ml, p = 0.035, respectively). After adjustment for age and BMI in OSAS patients, serum NGAL levels were associated with AHI (ß = 0.341, p = 0.015) and minimum oxyhemoglobin saturation during sleep (ß = - 0.275, p = 0.032), while serum Cyst C levels were associated with percentage of time with oxyhemoglobin saturation < 90% (ß = 0.270, p = 0.043), average (ß = - 0.308, p = 0.018), and minimum (ß = - 0.410, p = 0.001) oxyhemoglobin saturation during sleep. CONCLUSIONS: Higher risk for latent kidney disease in otherwise healthy OSAS patients is indicated. Sleep hypoxia seems to be a significant contributor in the pathogenetic process of renal dysfunction in OSAS.

Genetics of Obstructive Sleep Apnea: Vitamin D Receptor Gene Variation Affects Both Vitamin D Serum Concentration and Disease Susceptibility.

Obstructive sleep apnea syndrome (OSAS) is a multifactorial and common disorder affecting 10-17% of men and 3-9% of women. A low vitamin D serum concentration has been reportedly linked to OSAS susceptibility, but the underlying molecular genetic mechanisms are poorly understood thus far. We report here original findings on the ways in which vitamin D receptor (VDR) gene polymorphic variation (FokI, BsmI, ApaI, and TaqI polymorphisms) impacts serum vitamin D concentration and, additionally, susceptibility to OSAS. In a sample of 176 consecutive subjects (144 patients with OSAS and 32 healthy controls) phenotyped by full polysomnography (PSG), we characterized human genetic variation in VDR using the Sequenom MassARRAY iPLEX platform. A logistic regression analysis was employed to account and correct for covariates such as sex, age, body mass index, and comorbidities. Importantly, we observed that the FokI CC genotype frequency was markedly higher in patients with OSAS compared with controls (50.7% vs. 28.1%; p = 0.027). VDR FokI polymorphism explained 14.5% of vitamin D serum concentration variability. Moreover, the VDR FokI polymorphism was also associated with excessive daytime sleepiness (p = 0.016). To the best of our knowledge, this is the first clinical genetics study examining the role of VDR polymorphic variation on OSAS as phenotyped using full PSG. We call for further studies of vitamin D-related mechanisms that might contribute to OSAS risk in independent populations.

The role of vitamin D in obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a common disorder of multifactorial pathogenesis and is associated with obesity, diabetes and cardiovascular disease. Vitamin D is a fat-soluble vitamin with an important function in calcium absorption and homeostasis, which is also implicated in several nonskeletal conditions. The prevalence of vitamin D deficiency is increasing worldwide and is associated with similar metabolic disturbances to OSAS. Moreover, recent data suggest that in OSAS patients serum levels of vitamin D are lower compared with non-apnoeic subjects. However, the mechanisms linking vitamin D deficiency and OSAS are not completely understood and several hypotheses have been advanced. To date, a limited number of studies have assessed the association between lower serum concentrations of vitamin D and OSAS, and have reported inconsistent results. Similarly, contradictory results have been produced by studies which evaluated the effect of continuous positive airway pressure treatment on serum vitamin D levels. The aim of this review is to summarise current knowledge on the association between OSAS and vitamin D levels. KEY POINTS: Vitamin D insufficiency prevalence is increasing worldwide and presents with similar comorbidities and risk factors to OSAS.The nonskeletal actions of vitamin D may contribute to the development of OSAS through immune system modulation, myopathy and inflammation.Studies evaluating serum vitamin D concentrations in OSAS patients and the effect of CPAP treatment report contradictory results, often influenced by confounding factors, such as obesity.There appears to be potential for use of vitamin D supplementation in OSAS patients as a means of reducing the incidence of cardiovascular disease, a comorbidity common in both conditions. EDUCATIONAL AIMS: To assess the potential association between OSAS and serum levels of vitamin D.To discuss the pathogenetic mechanisms linking OSAS and vitamin D insufficiency.To illustrate the effect of CPAP treatment on vitamin D concentration in OSAS patients.

Mean Platelet Volume and Platelet Distribution Width in Patients With Obstructive Sleep Apnea Syndrome and Concurrent Chronic Obstructive Pulmonary Disease.

Evidence suggests that there is platelet activation in obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). Our objective is to evaluate mean platelet volume (MPV) and platelet distribution width (PDW) in patients with overlap syndrome (OS), that is, concurrent COPD with OSAS. Mean platelet volume and PDW were assessed in consecutive patients who had undergone polysomnography and pulmonary function testing. They were divided into the following groups: controls (apnea-hypopnea index [AHI] <5/hour, and forced expiratory volume in 1st second [FEV1]/forced vital capacity [FVC] >70%), OSAS group (AHI ≥5/hour and FEV1/FVC >70%), and OS group (AHI ≥5/hour and FEV1/FVC <70%). A total of 485 patients (360 males and 125 females) were included. Mean platelet volume in controls was lower compared with the other groups: 10 ± 0.9 fL for controls versus 10.3 ± 1.2 fL for OSAS ( P = .006), versus 10.7 ± 1 fL for OS ( P < .001). Additionally, MPV was higher in OS group than OSAS: 10.7 ± 1 fL versus 10.3 ± 1.2 fL, respectively ( P = .002). Platelet distribution width was lower in controls compared with the other groups: 12.9 ± 2 fL for controls versus 13.6 ± 1.9 fL for OSAS ( P = .007), versus 13.8 ± 2.3 fL for OS ( P = .008), while there was no difference between OS and OSAS groups. Mean platelet volume and PDW are increased in patients with OS compared with healthy controls, with respiratory function being the major contributor in platelet activation in this series.

Cardiovascular Risk Assessment in a Cohort of Newly Diagnosed Patients with Obstructive Sleep Apnea Syndrome.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. The aim of this study was to assess whether the 10-year risk for cardiovascular disease in newly diagnosed patients with OSAS is increased. MATERIALS AND METHODS: Recently diagnosed, with polysomnography, consecutive OSAS patients were included. The Systematic Coronary Risk Evaluation (SCORE) and the Framingham Risk Score (FRS) were used to estimate the 10-year risk for cardiovascular disease. RESULTS: Totally, 393 individuals (73.3% males), scheduled to undergo a polysomnographic study with symptoms indicative of OSAS, were enrolled. According to apnea-hypopnea index (AHI), subjects were divided in four groups: mild OSAS (AHI 5-14.9/h) was diagnosed in 91 patients (23.2%), moderate OSAS (AHI 15-29.9/h) in 58 patients (14.8%), severe OSAS (AHI > 30/h) in 167 patients (42.5%), while 77 individuals (19.6%) had an AHI < 5/h and served as controls. Increased severity of OSAS was associated with increased SCORE (p < 0.001) and FRS values (p < 0.001). More specifically, a significant correlation was observed both between AHI and SCORE (r=0.251, p < 0.001) and AHI and FRS values (r=0.291, p < 0.001). Furthermore, a negative correlation was observed between FRS values and sleep efficiency (r=-0.224, p=0.006). CONCLUSIONS: The 10-year risk for cardiovascular morbidity and mortality seems to increase with severity of OSAS. Physicians should bear this finding in mind, in order to seek for and consecutively eliminate risk factors for cardiovascular disease and to prevent future cardiovascular events in OSAS patients.

Metabolic Syndrome and Vitamin D Levels in Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Numerous studies have indicated that obstructive sleep apnea syndrome (OSAS), may contribute to the development of metabolic syndrome (MetS) and diabetes. Moreover, OSAS has been associated with lowered vitamin D (Vit D) levels, but reports are inconclusive. Aim of the study was to compare Vit D levels according to the presence of MetS and its components in OSAS patients. METHODS: The presence of MetS was evaluated and serum 25-hydroxy vitamin D [25(OH)D] levels were measured in consecutive newly diagnosed, by polysomnography, subjects with OSAS. RESULTS: A total of 107 subjects (88 men) with OSAS were included in the study. Patients were divided into group A (OSAS with MetS group: 55 subjects) and group B (OSAS without MetS: 52 subjects). There were no differences between the two groups in terms of age, body mass index, and sleep parameters. Patients in group A exhibited higher levels of daytime sleepiness, as expressed by Epworth Sleepiness Scale score (12 ± 5.5 vs. 9.3 ± 4.8 for groups A vs. B, p = 0.008). Serum 25(OH)D levels were significantly decreased in group A, as compared with group B (18 ± 8.6 ng/mL vs. 23.9 ± 14.1 ng/mL, respectively, p = 0.012). Group A was then subdivided in two smaller groups, according to patients' metabolic index: OSAS patients with metabolic score = 3 and OSAS patients with metabolic score >3. Serum 25(OH)D levels were higher in OSAS patients with metabolic score = 3 compared with OSAS patients with metabolic score >3 (19.8 ± 8.9 ng/mL vs. 15.1 ± 7.3 ng/mL respectively, p = 0.038). CONCLUSIONS: OSAS patients with concurrent MetS exhibit lower serum Vit D levels, as compared with those without MetS.

Cystatin C Levels in Middle-Aged Patients with Obstructive Sleep Apnea Syndrome.

Background. Obstructive sleep apnea syndrome (OSAS) is associated with systemic inflammation and increased risk of cardiovascular and chronic kidney disease. Cystatin C (Cyst C) is a novel biomarker of both latent renal damage and cardiovascular disease. Aim of the study was to measure serum levels of Cyst C, as well as IL-8 and CRP, in otherwise healthy OSAS patients. Methods. 84 individuals examined with polysomnography for OSAS symptoms without known comorbidities were prospectively recruited. Results. According to apnea hypopnea index (AHI) subjects were divided in two groups: OSAS group (AHI > 5/hour, n = 64) and controls (AHI < 5/hour, n = 20), which were age- and BMI-matched. Cyst C levels were higher in OSAS patients versus controls (1176.13 ± 351.33 versus 938.60 ± 245.83 ng/mL, resp.; p = 0.017) while serum IL-8 and CRP levels did not differ significantly. Positive correlation was found between Cyst C levels and respiratory disturbance index (RDI) (r = 0.240, p = 0.039) and percentage of time with oxygen saturation <90% (r = 0.290, p = 0.02) and negative correlation was found between Cyst C levels and average oxygen saturation during sleep (r = -0.291, p = 0.012). After adjustment for age and BMI, RDI was the only independent predictor of Cyst C levels (ß = 0.256, p = 0.039). Conclusion. Cyst C serum levels are increased in OSAS patients without comorbidities, suggesting an increased renal and cardiovascular disease risk.

Bilateral empyema treated by sequential pleuroscopy.

Bilateral empyema associated to infectious pericarditis is an extremely rare, yet life-threatening condition. Pleuroscopy-medical thoracoscopy has proved its efficacy in series of patients with empyema. Yet, all reported cases treated by this technique, concerned patients with pleural infection located to a single hemithorax. We present the case of a 71-year-old man with bilateral empyema treated successfully by sequential pleuroscopy, associated to infectious pericarditis.

Pleuroscopy in 'Idiopathic' eosinophilic pleural effusions.

BACKGROUND: Idiopathic eosinophilic pleural effusions (IEPEs) comprise the eosinophilic pleural effusions for which a specific aetiology cannot be established. There are no reports investigating IEPE on the basis of a systematically applied pleuroscopy approach and entailing an appropriate patient follow-up till the final outcome is established; existing series rather combine clinical and thoracocentesis criteria to establish the idiopathic character of the diagnosis. OBJECTIVES: The aim of our study was to assess the clinical outcome of patients with IEPE, who underwent a systematic diagnostic approach by pleuroscopy. METHODS: We studied 10 patients with IEPE among 175 consecutive patients who underwent pleuroscopy for undiagnosed pleural effusion. Pleural biopsies were obtained from observed lesions. All patients were followed up by means of clinical examination and imaging. RESULTS: The diagnosis of IEPE was established in 10 patients (median age was 50.5 years, range 35-91). Macroscopic examination of the pleura showed diffuse thickening with pleural plaques in eight patients, consistent with diffuse pleural eosinophilic inflammation histologically proven. In two patients, macroscopic examination showed scattered nodules associated with non-caseating granulomas histologically. In all 10 patients, a specific aetiology could not be established. Follow-up was available for all patients ranging from 24-102 months (median 60 months). No patient received a specific treatment during the follow-up period. No relapse of a pleural effusion was documented during this period. CONCLUSION: Pleuroscopy is mandatory in diagnosing IEPE. Negative histology and a long follow-up showed a benign course. These findings suggest that we should call these effusions 'indeterminate'.

Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment.

BACKGROUND AND AIM: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. MATERIALS AND METHODS: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. RESULTS: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 µg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). CONCLUSION: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

BACKGROUND: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. METHODS: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. RESULTS: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. CONCLUSION: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.