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Background Previous studies have shown conflicting results on the effect of continuous positive airway pressure (CPAP) on quality of life (QoL) in obstructive sleep apnoea (OSA) patients. Objectives To evaluate the effect of CPAP on QoL in OSA patients compared to sham CPAP, placebo pills, and conservative treatment. Methods Studies were identified via Web of Knowledge, PubMed, PsychInfo, CINAHL, EMBASE, OpenGrey, and the Cochrane Library. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of the findings. Results Meta-analysis of 13 randomised controlled trials showed no significant differences in overall and psychological QoL comparing values of CPAP treated patients with controls; however, physical QoL improved. CPAP significantly affected the overall QoL in studies with controls receiving sham CPAP, parallel design, low risk of bias, and mild OSA patients. Conclusion CPAP treatment may help to improve physical symptoms of OSA, whereas impaired psychological QoL still cannot be alleviated.

OBJECTIVE To evaluate the acute effects of volume-targeted non-invasive ventilation (NIV) on hemodynamic parameters assessed by impedance cardiography in patients with obesity hypoventilation syndrome (OHS). BACKGROUND Despite the well-described beneficial effects of NIV using volume-targeted pressure support ventilation modes on respiration in OHS patients, questions were raised about the impact of this treatment on the cardiovascular system. METHODS In 15 patients (10 men; mean age, 55.8±9.3 years) impedance cardiography recordings were taken at baseline, after 120 minutes while on NIV and 20 minutes after NIV termination. A repeated-measures analysis of variance was used for comparisons. RESULTS Compared to baseline, a reduction in heart rate (from 80±11 to 73±10 beats per min, p

Background The COPD Assessment Test (CAT) has been proposed to help guide therapy in chronic obstructive pulmonary disease (COPD). It is important to understand the distribution of scores in different COPD populations and their determinants. Methods The POPE study is an international, observational cross-sectional study of COPD subjects in 11 Central and Eastern European countries aimed at characterizing COPD phenotypes. Here we report the analysis of CAT scores with the objective of identifying their determinants, evaluating symptom load and investigating the distribution of scores among the participating countries. Additionally, we investigated the discrepancies between the CAT and modified Medical Research Council (mMRC) scores when used to classify patients according to the GOLD strategy. Results The study included 3452 patients (69.2% men, mean forced expiratory volume in 1 s (FEV1% predicted) 52.5%). The mean CAT score was 17.5 (SD = 7.8), ranging from 15.1 in Hungary to 21.2 in Bulgaria. Multiple linear regression analysis showed six variables significantly associated with CAT scores: depression, number of previous exacerbations, 6-min walking distance, FEV1(%), mMRC and country and explained 47.2% of the variance of CAT. According to either CAT or mMRC, up to 23.9% patients would be classified in different GOLD groups. Conclusions The CAT score may be predicted by factors related to COPD severity, depression and exercise capacity, with significant differences in the distribution of CAT scores in different countries. According to our results CAT >10 is not equivalent to mMRC >2 for assessing symptom burden. Trial Registration: ClinicalTrials.gov , identifier NCT02119494

Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9 +/- 423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98 +/- 1.01% to 5.93 +/- 0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (-0.15 +/- 1.02, p=0.019), those with severe OSA baseline (-0.10 +/- 0.68, p=0.005), those with morbid obesity (-0.20 +/- 0.81, p5 kilos (-0.38 +/- 0.99, p5 kilos (p

We aimed to assess whether hostility and coping self-efficacy are associated with psychological distress in obstructive sleep apnoea patients. Furthermore, we examined whether coping self-efficacy mediates the association between hostility and psychological distress. We included 150 obstructive sleep apnoea patients (Apnoea-Hypopnoea Index ⩾5; 68% male; mean age: 48.9 ± 9.5 years). Regression models showed that hostility and poor coping self-efficacy were strongly associated with psychological distress in obstructive sleep apnoea patients. All assessed coping self-efficacy dimensions mediated the association between hostility and psychological distress. Coping self-efficacy for stopping unpleasant emotions and thoughts showed the strongest association with a lower level of psychological distress.

We aimed to assess the prevalence of suicidal ideation and to examine the relationships between obstructive sleep apnoea severity, sleep-related problems, social support and suicidal ideation in obstructive sleep apnoea patients. We included 149 patients (68% male; mean age, 48.99 ± 9.57 years) with diagnosed obstructive sleep apnoea (Apnoea–Hypopnoea Index ⩾5) based on full-night polysomnography. The prevalence of suicidal ideation among obstructive sleep apnoea patients was 20.1 per cent. Structural equation modelling showed that suicidal ideation in obstructive sleep apnoea was strongly related to poor sleep quality and high fatigue levels. No relationship between social support and suicidal ideation in obstructive sleep apnoea patients was found.

Coaching as a lifestyle modification approach to weight management is insufficiently explored in obstructive sleep apnoea. We investigated anthropometry and body composition after 20 weeks of Erickson coaching in 26 obstructive sleep apnoea patients (19 males; 47.6 ± 2.4 years). Body weight, neck circumference, waist-to-hip ratio and %body fat significantly decreased after 20 weeks. The mean weight loss was 5.2 per cent ± 1.0 per cent; 20 (77%) participants achieved target reduction of >3 per cent. Coaching session attendance ( p = 0.006) and reaching personal goal related to physical performance ( p = 0.044) were independently associated with weight loss (multiple regression model R2 = 0.608, p

Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1+/-10.3 to 32.3+/-10.9 to 38.1+/-10.3 microg.ml(-1), p=0.015; from 0.52+/-0.09 to 0.58+/-0.06 to 0.62+/-0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r(2)=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

Background: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are independent risk factors for cardiovascular diseases. In patients with OSA and concurrent COPD, continuous positive airway pressure (CPAP) therapy improves survival. Nevertheless, a significant proportion of such patients do not tolerate CPAP. The aim of the present study was to analyze early predictors of CPAP failure in patients with OSA and concurrent COPD, and to evaluate the effects of bilevel positive airway pressure (BiPAP) in this high-risk group of patients.Methods: A post hoc analysis from the database of 2100 patients diagnosed with OSA between 2012 and 2014 identified 84 subjects as having concomitant COPD and meeting inclusion criteria. Demographic data, pulmonary function tests, OSA parameters, blood gases, response to CPAP and BiPAP titration, and two months of therapy were collected. A multivariate model was generated to find determinants of CPAP failure.Results: Primary CPAP failurewas found in 23% of patientswhoweremore obese (p = 0.018), had worse lung function, lower PO2 (p = 0.023) and higher PCO2 while awake (p Conclusions: Daytime hypercapnia and nocturnal hypoxia are independent predictors of early CPAP failure in patients with the OSA-COPD overlap syndrome. (C) 2016 Elsevier B. V. All rights reserved.

Background: Systemic inflammation, endotoxaemia and oxidative stress may represent intermediate pathophysiological mechanisms involved in impaired sleep architecture. Aims: We investigated relationships between sleep architecture and serum endotoxaemia marker lipopolysaccharides-binding protein (LBP), oxidized low-density lipoprotein (oxLDL) and insulinaemia in patients with obstructive sleep apnoea (OSA). Methods: 66 women with OSA [age (mean±SD) 57.2±9.9 years, body mass index (BMI) 34.8±8.4 kg/m2, apnoea-hypoponea index (AHI) 37.4±37.5 events/hour] underwent overnight polysomnography. Serum biomarkers were analyzed using ELISA. Multivariate linear regressions assessed the independent correlates of slow-wave sleep (SWS) and rapid eye movement (REM) proportion of Total Sleep Time (TST). Results: Serum LBP levels were directly associated with TST duration, and inversely with the proportion of REM and SWS (Table). Moreover, OxLDL was inversely related to SWS, and serum insulin to REM sleep. LBP (P=0.047) and insulinaemia (P=0.013) were related to REM independently of age, AHI and BMI (R2=0.282, p Conclusions: Our results suggest that increases in circulating LBP and insulinaemia are related to reduced REM sleep in women with OSA. Further studies are needed to determine the role of various biomarkers in sleep architecture. Support: VEGA 1/0220/17, APPV-16-0158, VEGA 1/0208/16.

Purpose: To examine whether Obstructive Sleep Apnoea severity, sleep-related problems, and anxiety are associated with work functioning in Obstructive Sleep Apnoea patients, when controlled for age, gender and type of occupation. To investigate whether anxiety moderates the associations between sleep-related problems and work functioning. Materials and methods: We included 105 Obstructive Sleep Apnoea patients (70% male; mean age 46.62 ± 9.79 years). All patients completed the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Beck Anxiety Inventory, and the Work Role Functioning Questionnaire-2.0. Results: Obstructive Sleep Apnoea-severity, poor nighttime sleep quality, and anxiety were univariately associated with impaired work functioning. Multivariate analyzes revealed that poor perceived sleep quality was more strongly associated with work functioning than sleep efficiency and daily disturbances. Anxiety was strongly associated with impaired work functioning. After adding anxiety, the explained variance in work functioning increased from 20% to 25%. Anxiety moderated the association between low and medium levels of nighttime sleep quality problems and work functioning. Conclusions: Poor perceived sleep quality and anxiety were strongly associated with impaired work functioning in Obstructive Sleep Apnoea patients. These findings may help to optimize management, standard treatment, and work functioning in people with Obstructive Sleep Apnoea when confirmed in longitudinal studies.Implications for RehabilitationStudies show an impairment of functional status, including work functioning, in obstructive sleep apnea patients.Aside from physical disorders, obstructive sleep apnea patients often experience mental problems, such as anxiety.As many people with obstructive sleep apnea are undiagnosed, our results demonstrate to employers and healthcare professionals the need to encourage patients for obstructive sleep apnea screening, especially in the situation of impaired work functioning, increased anxiety, and poor sleep quality.The associations between obstructive sleep apnea, sleep and anxiety might increase the awareness of health professionals towards optimizing diagnostic accuracy and standard treatment. Studies show an impairment of functional status, including work functioning, in obstructive sleep apnea patients. Aside from physical disorders, obstructive sleep apnea patients often experience mental problems, such as anxiety. As many people with obstructive sleep apnea are undiagnosed, our results demonstrate to employers and healthcare professionals the need to encourage patients for obstructive sleep apnea screening, especially in the situation of impaired work functioning, increased anxiety, and poor sleep quality. The associations between obstructive sleep apnea, sleep and anxiety might increase the awareness of health professionals towards optimizing diagnostic accuracy and standard treatment.

Objective/Background: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). Patients/Methods: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a sub-population, at treatment follow-up (CGI-Improvement). Results: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged

Both loss of muscle mass (ie, sarcopenia) and obesity adversely impact clinically important outcomes in patients with chronic obstructive pulmonary disease (COPD). Currently, there are only a few studies in patients with COPD with sarcopenia and concurrent obesity, termed sarcopenic obesity (SO).To explore the effects of SO on exercise capacity, health status, and systemic inflammation in COPD.Baseline data collected from a total of 2548 participants (2000 patients with COPD, mean age (SD), 63.5 (7.1) years; and 548 controls, 54.8 (9.0) years) from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, a multicenter longitudinal observational study, were used.All participants were divided into 4 body composition phenotypes using bioelectrical impedance analysis: (1) normal body composition, (2) obesity, (3) sarcopenia, and (4) SO. In patients with COPD, the 6-minute walking distance, disease-specific health status, and plasma inflammatory markers were compared among the respective body composition groups.Patients with COPD were 3 times more likely to present with SO compared with controls without COPD (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.0-5.4, P.001). In patients with COPD, SO was related to reduced 6-minute walking distance (-28.0 m, 95% CI -45.6 to -10.4), P.01) and to higher systemic inflammatory burden (an elevation of at least 2 inflammatory markers, OR 1.6, 95% CI 1.1-2.5, P = .028) compared with the normal body composition group after adjustments for age, sex, smoking, body mass index, and airflow limitation.Our findings suggest that SO is associated with worse physical performance and higher systemic inflammatory burden compared with other body composition phenotypes in patients with COPD.ClinicalTrials.gov no. NCT00292552.

Background: Weight management is essential to reduce high cardiometabolic risk in obese patients with obstructive sleep apnoea (OSA). Coaching is an effective method to shape and reinforce desired behaviour including healthy lifestyle and weight management. In patients with OSA coaching was used to increase compliance with CPAP therapy, nevertheless, its potential in weight management remains unexplored. Aim: To investigate changes in anthropometry and body composition after 4 month of coaching intervention in obese patients with OSA. Methods: 26 patients with OSA diagnosed by full attended polysomnography (19 male; age, 48±12 years; AHI 56±29 events/hour) were enrolled. Anthropometry and body composition were assessed at baseline and after 4 months of periodic Ericksonian solution-focused coaching (Caldwell KL et al. Glob Adv Health Med 2013;2:48-57). Results: The body weight, BMI, neck circumference, waist-to hip ratio and % body fat all decreased after 4 months (Table). The mean body weight reduction was 5.2±3.3% of baseline value; the target reduction of >3% (AHA Practice Guidelines) was achieved by 20 (77%) participants. Conclusion: Ericksonian solution-focused coaching is a promising method that may support adherence to healthy lifestyle behaviour and weight/adiposity reduction in obese patients with OSA. Efficacy of coaching intervention needs to be tested in randomized controlled trials in patients with OSA. Support: APVV-16-0158 and VEGA 1/0208/16, Ministry of Education, Slovakia

BACKGROUND: Social support and mastery are important aspects in the treatment of chronic diseases, however their role in connection with Obstructive Sleep Apnoea (OSA) remains unclear.OBJECTIVES: The study examined the associations between social support, mastery, sleep-related problems and functional status in untreated OSA patients.METHODS: All patients in this cross-sectional study completed the Multidimensional Scale of Perceived Social Support, the Pearlin Mastery Scale, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and the Functional Outcomes of Sleep Questionnaire. Multiple linear regression and mediation analyses were used to analyse the data.RESULTS: Participants were 150 newly diagnosed OSA patients (Apnoea-Hypopnoea Index-AHI≥5; 68% male; mean age 48.9 ± 9.5years). Compared with social support, mastery was more strongly associated with functional status. The indirect effects of sleep-related problems on functional status via mastery varied between 17.7% and 23.3%.CONCLUSIONS: Supporting OSA patients' sense of mastery may significantly contribute to better disease management.

Obstructive sleep apnoea (OSA) is a highly prevalent medical condition and amajor cardiovascular risk factor. Obesity is present in ∼70% of patients with OSA, nevertheless, continuous positive airway pressure (CPAP) ventilation - the gold standard therapy for moderate and severe OSA - has no appreciable long-term beneficial effects on obesity, body composition, energy metabolism, physical activities or the incidence of major cardiovascular events. Therefore, effective weight loss strategies in conjunction with CPAP therapy in OSA are critically needed. Since lifestyle interventions may positively impact body weight, there is a strong rationale to testing the hypothesis that Erikson coaching intervention as a form of lifestyle intervention to obese patients with OSA may increase their adherence to healthy lifestyle behaviour and thus result in weight reduction, improved body composition (reduction in %body fat) and improvements in glucose and lipid metabolism. There are three lines of evidence to justify testing this hypothesis: First, health coaching significantly facilitates uptake of healthy behaviours across a broad variety of chronic conditions; second, several randomized clinical trials suggested positive impact of health coaching on weight management and on cardiometabolic risk factors in overweight/obese otherwise healthy persons; third, Erickson coaching approach empowers the three key elements of health coaching (patient-centeredness, patient-determined goals, use of a self-discovery process) further, namely by introducing two other specific core elements into the coaching process: a) solution-focus and outcome frame, b) orientation at the patient-formulated positive outcomes (i.e., positive values resulting from behavioural change). Importantly, results of our recent pilot observational cohort study suggested that Erickson coaching is a powerful tool to address behavioural modification in obesity. In conclusion, testing our hypothesis may have significant clinical implications: if clinical randomized trials indicate that Erickson health coaching is an efficient approach to behavioural change and weight management in OSA then combining Erickson coaching with CPAP therapy may result in reductions in cardiovascular morbidity and mortality in these high-risk patients.

BACKGROUND: The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. METHODS: In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). RESULTS: In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m(2)) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. CONCLUSIONS: fCPAP but not APAP may prevent eGFR decline in OSA.

Objective Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. Methods AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. Results AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. Conclusions The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown.

Obstructive sleep apnoea (OSA) is associated with increased risk of dysglycaemia but the intimate link of these conditions with obesity makes discerning an independent relationship between them challenging. Glycosylated haemoglobin (HbA1c) levels predict adverse cardiovascular outcomes in nondiabetics but there is a lack of population-level data exploring the relationship of HbA1c with OSA. A cross-sectional analysis of 5294 participants in the multinational European Sleep Apnoea Cohort (European Sleep Apnoea Database) study was performed, assessing the relationship of OSA severity with HbA1c levels in nondiabetic subjects, with adjustment for confounding factors. HbA1c levels correlated significantly with OSA severity in univariate analysis. Following adjustment for confounding factors, apnoea-hypopnoea index (AHI) (standardised beta 0.158; p= 6.0% than those in the first quartile. In stratified analyses, OSA severity predicted glycaemic health irrespective of sleep study modality, sex, obesity or daytime sleepiness. OSA severity independently predicts glycaemic health in nondiabetic subjects. Further studies should assess the impact of OSA treatment on glycaemic health and elucidate underlying mechanisms.

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, WOS: 000507372402167, [No abstract available], European Respiratory Soc

The distribution of patients based on exacerbations solely is the most profound consequence of the 2017 GOLD Report http://ow.ly/4UJa309fLbM

Background: The COPD assessment test (CAT) is widely used for basic symptom evaluation in patients with COPD. The impact of COPD phenotypes on symptom scores using the CAT, however, remains largely unknown. Methods: The POPE-Study (NCT02119494) is an international, multicentre, observational cross-sectional survey of consecutive patients with COPD in Central and Eastern Europe (CEE). Respiratory symptoms using the modified Medical Research Council (mMRC) dyspnoea scale, and the CAT were recorded. Inclusion criteria: age ≥ 40 years, smoking history ≥ 10 pack-years, post-bronchodilator (BD) FEV1/FVC Results: 3366 COPD subjects (66 ± 8.8 yrs, post-BD FEV1 52.8 ± 18.5 % predicted, CAT 17.4 ± 7.8) were recruited. On the whole 63.3 % were non-exacerbators (NON-AE), 20.4 % frequent exacerbators with chronic bronchitis (AE CB), 9.5 % frequent exacerbators without CB (AE NON-CB), and 6.9 % were patients with asthma-COPD overlap syndrome (ACOS). There were apparent statistically significant differences ( Conclusion: There were noted significant differences in total CAT and individual CAT items between clinical phenotypes of COPD.

Introduction: In Central and Eastern Europe (CEE) the burden of chronic obstructive pulmonary disease (COPD) is high. It remains unknown whether patients are treated in line with GOLD recommendations or according to their phenotypes. Our aim was to analyze the treatment patterns of COPD in CEE. Methods: In the frame of the POPE study (ClinicalTrials.gov - NCT02119494) data including pharmacotherapy were collected in patients with stable COPD across 11 CEE countries. Results: 3366 patients (66±9 yrs, 70% male, FEV 1 53±18%) participated in the study. In all GOLD categories, the most widely used medications were long-acting beta-2 agonists (LABA), followed by long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS). Overall 98.8% of ICS were prescribed in combination with LABA and/or LAMA. LAMA/LABA/ICS was used by 45% patients. ICS were prescribed not in line with GOLD recommendations in 38% of the participants; furthermore 52% of infrequent exacerbators received ICS. In GOLD group A, the asthma-COPD overlap syndrome (ACOS) was the only independent predictor of ICS use. In GOLD group B, independent predictors of ICS and of triple combination use were ACOS, an exacerbation within the last year, and COPD assessment test (CAT) score (p *p Conclusion: In CEE, the adherence to GOLD recommendations or to the phenotypic approach is not optimal. The presence of ACOS, exacerbation history and CAT score predict ICS use in GOLD groups A and B.

Backround: Obstructive sleep apnoea (OSA) is associated with increased arterial stiffness and endothelial dysfunction. OSA-related oxidative stress, systemic inflammation and endotoxemia may play a role in vascular derangements. Aims: We investigated effects of continuous positive airway pressure (CPAP) therapy on arterial stiffness, body composition, endotoxemia and oxidative stress. Methods: 40 subjects with OSA [age (mean±SD) 50±8 years, body mass index (BMI) 31.9±4.5 kg/m 2 ] free of cardiovascular diseases except for arterial hypertension were enrolled. Arterial stiffness was assessed by carotid-radial pulse wave velocity (PWV) (Complior®, France), body composition by measuring bioelectrical impedance (Bodystat 1500, UK). PWV, body composition, serum lipopolysaccharides-binding protein (LBP) and oxidized low-density lipoprotein (oxLDL), were measured at baseline and after 3 months of CPAP. Results: Compliance with CPAP was 4.1±1.8 hours/night. Reductions of PWV in association with reductions in oxLDL were observed after 3 months of CPAP (9.7±1.6 to 9.0±1.6 m/s, p=0.003; 501±186 to 381±174 ng/ml, p=0.002, respectively). Improvements in arterial stiffness were observed regardless body weight or body composition change. CPAP had no effect on an endotoxemia marker (serum LBP). Conclusions: Our results suggest that in patients with OSA without overt cardiovascular diseases, elimination of OSA by CPAP results in improvements in arterial stiffness in association with reductions in oxidative stress. Support: APVV-0134-11, VEGA 1/0863/15 and 1/0208/16, Ministry of Education, Slovakia.

Rationale. Genome-wide association studies (GWAS) identified multiple loci associated with blood pressure (BP) control. We evaluated the effects of single nucleotide polymorphisms (SNPs) of JAG1 , GUCY1A3-GUCY 1B3 , SH2B3 , FGF5 , and NPR3-C5orf23 on systolic and diastolic blood pressure (SBP, DBP) in patients with obstructive sleep apnoea (OSA). Methods. 1179 adult subjects evaluated for suspected OSA underwent overnight polysomnography. Genotyping was performed by unlabeled probe melting analysis. Findings. Patients were 69.6% male (mean age 52±11 years, apnoea-hypopnoea index 34±31 /hour). Only JAG1 genotype was associated with BP. Compared to AA homozygotes, G allele carriers (pooled GG and AG genotype) had significantly higher morning and evening SBP (129±18 vs 132±19 mmHg; p=0.009; 132±17 vs 134±18 mmHg, p=0,039, respectively) and DBP (83±10 vs 85±11 mmHg, p=0.004; 84±9 vs 86±10 mmHg, p=0.012, respectively). Differences in morning SBP and DBP remained significant after correction for multiple SNPs testing (p=0.045; p=0.020). In multivariate analyses, oxygen desaturation index (ODI) (p JAG1 genotype (p R 2 =0.163, p R 2 =0.0839, p JAG1 genotype (p R 2 =0.0954, p R 2 =0.0382, p Conclusions. This is a first replication study of the respective SNPs recently linked to arterial hypertension in the general population by GWAS. Our findings suggest that JAG1 genotype is related to BP control in OSA; G allele is associated with higher morning and evening SBP and DBP. Funding APVV-0134-11, VEGA 1/0863/15 and 1/0208/16, Ministry of Education, Slovakia.

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.

Obstructive sleep apnea (OSA) is associated with dyslipidemia and increased cardiovascular risk. We assessed the effects of apolipoprotein E ( APOE) genotype on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and lipid subclasses (separated by gradient gel electrophoresis) in patients with OSA. Stable patients (n = 181) prospectively recruited underwent full polysomnography. Both LDL particle size and LDL I proportion were reduced from ∊3∊3 homozygotes to ∊2 carriers and to ∊4 carriers (analysis of variance: P = .024; P = .040, respectively); carriers of the ∊4 allele of the APOE genotype had significantly lower LDL particle size and LDL I proportion compared to ∊3∊3 homozygotes ( P < .05 for both comparisons). Insulin resistance increased from patients with no OSA to those with mild–moderate and to those with severe OSA ( P < .001). In multivariate analysis, LDL size was independently predicted by APOE genotype, male gender, and the presence of metabolic syndrome (MetS; P = .001, P = .020, P = .027, respectively). The HDL particle size was not affected by APOE genotype. Our data demonstrate that both the ∊4 APOE genotype and MetS are independently related to smaller LDL size in patients with OSA.

Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant.One hundred and one patients with type 2 diabetes who failed to achieve HbA1c7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis.After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04±0.10 vs. 0.79±0.12%, p=0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01-0.32, p=0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n=55).Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.

Summary Background We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment. Material/Methods Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe. Results The reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95±0.13 vs. 7.50±0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58±0.13 vs. 1.04±0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p

Background: CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily, is activated in response to cellular stress, including hypoxia, and orchestrates the process of inflammation via secondary messengers such as mitogen-activated protein kinase kinase 4 (MKK4) and c-Jun NH2-terminal kinases (JNK). Objectives: We hypothesized that CD40, MKK4 and JNK expression is increased in the adipose tissue of patients with very severe chronic obstructive pulmonary disease (COPD). Methods: In 20 patients with stable COPD, lung function was assessed using body plethysmography, and samples of subcutaneous adipose tissue were analyzed using real-time PCR. Body composition, including fat mass index (FMI), was assessed by bioelectrical impedance. Results: 12 patients in GOLD stage I–III (age 61.6 ± 8.6 years, 4 females, mean partial pressure of oxygen in arterial blood, PaO2, 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO2 7.70 ± 0.37 kPa). Compared to patients in GOLD stage I–III, patients in GOLD stage IV had lower FMI (p = 0.004), being associated with significantly higher adipose tissue expression of CD40, MKK4 and JNK [ΔΔCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p = 0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs. 4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK expression was significantly inversely related to PaO2, respectively. Conclusions: Upregulation of proinflammatory CD40, MKK4 and JNK gene expression in adipose tissue in very severe COPD raises the possibility of a role of chronic systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.

Obesity and metabolic syndrome are common among Roma subjects in Slovakia. We hypothesised that Roma subjects are at high risk to suffer from severe obstructive sleep apnoea (OSA). 137 non-Roma and 23 Roma subjects referred for a diagnostic polysomnography were consecutively recruited. Overnight polysomnography, anthropometric variables and standard biochemical analyses were analysed. Obstructive sleep apnoea was diagnosed in 91% Roma and 65% non-Roma subjects (p

A rare case of duplicate tumor, osteosarcoma and Ewing's sarcoma, complicated by metachronous pulmonary metastasis in a child is reported. A nine-year-old girl's osteosarcoma was treated by neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Four years later, resection of the chest wall to remove an Ewing's sarcoma had to be performed, followed by chemotherapy and radiotherapy. At the age of 17, the girl underwent a metastasectomy of Ewing's sarcoma metastasis to the lung. Five years later, the patient is free from any recognizable malignant disease. We conclude that after the complete surgical removal of two primary tumors, metastasectomy is an optimal treatment procedure in case of a solitary pulmonary metastasis.

OBJECTIVE: Continuous positive airway pressure (CPAP) applied via a tight-fitting mask is the most effective treatment for obstructive sleep apnea (OSA) and has potential to improve the cardiovascular prognosis in such patients. Adequate compliance with the use of CPAP is essential for achieving the cardiovascular and metabolic benefits of this treatment. This prospective study aimed to assess factors related to objective compliance with CPAP treatment in Slovakian patients with metabolic syndrome and newly diagnosed OSA. PATIENTS AND METHODS: Fifty-one patients (42 men) with metabolic syndrome and OSA (mean age, 54.5 ± 1.5 years; mean apnea-hypopnea index 59.0 ± 3.9 events/h of sleep; mean lowest sleep transcutaneous oxygen saturation [SpO2] 66.0 ± 2.7%) underwent pressure titration during overnight polysomnography using the Autoset self-adjusting CPAP device. Metabolic syndrome was diagnosed according to the recent definition of the International Diabetes Federation. Objective compliance was assessed electronically at the 8-week follow-up visit. RESULTS: Obesity was present in all (100%) the patients and arterial hypertension in 48 (94%); fasting plasma glucose levels were increased in 27 (55%) patients and serum triglycerides in 36 (71%); serum HDL cholesterol was reduced in 30 (59%) patients. Two patients did not use CPAP at all and were excluded from further analyses. The remaining 49 patients were divided into two groups: CPAP compliant (≥4 h/night, mean use 5.52 ± 0.19 h/night, n = 30) and CPAP non-compliant (< 4 h/night; mean use 1.94 ± 0.27 h/night, n = 19). Mask leak was significantly higher in the non-compliant patients (43.0 ± 4.4 vs. 31.9 ± 2.7 l/min, P = 0.027). No relationships were observed between CPAP compliance and age, apnea-hypopnea index, arousal index or variables of sleep architecture. In contrast, CPAP compliance was significantly related to mean sleep SpO2 (r = 0.314, P = 0.028), the lowest sleep SpO2 (r = 0.297, P = 0.038) and mask leak (r = –0.376, P = 0.008). A close relationship between BMI and mask leak was also observed (r = 0.579, P < 0.001). In multiple linear regression analyses with CPAP compliance as an independent variable, and age, sex, mask leak, BMI and mean sleep SpO2 as dependent variables, mask leak was the only independent predictor of CPAP compliance (R 2 = 0.382, P = 0.009). CONCLUSION: The study demonstrates the relationship between reductions in mask leak and good compliance with CPAP treatment in central European patients with OSA and concurrent metabolic syndrome. Strategies to maintain low leakage of the CPAP mask are warranted, particularly in grossly overweight patients.

Background The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome. Methods In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-α, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm. Results In patients who used CPAP for ≥ 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p=0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-α (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 ± 9.8 to 13.9 ± 9.7%, p=0.001). No significant changes were seen in patients who used CPAP for Conclusions In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk. Trial registration Clinicaltrials.gov Identifier: NCT00635674.

In patients with chronic obstructive pulmonary disease (COPD) classified as moderate onwards, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend regular treatment with one or more long-acting bronchodilators, such as beta(2)-agonists or anticholinergics. In contrast to currently available long-acting beta(2)-agonists, which have a duration of action of 12 h, indacaterol has demonstrated effective 24-h bronchodilation on once-daily dosing. A double-blind, randomised, placebo-controlled study was conducted to compare the safety, tolerability and efficacy of indacaterol with that of placebo, over a 28-day period, in patients with moderate COPD (as defined by GOLD 2001 criteria; equivalent to moderate-to-severe COPD in the GOLD 2005 criteria). Patients were randomised 2:2:1 to receive indacaterol 400 microg or 800 microg or placebo once-daily (between 07:00 and 11:00 h) via a single-dose dry-powder inhaler for 28 days. Assessments included monitoring of adverse events (AEs), blood chemistry (including serum potassium and blood glucose), vital signs (blood pressure and heart rate), electrocardiograms and spirometry. One hundred and sixty-three patients were randomised, with 155 (95%) completing the study. There were no statistically significant differences between treatment groups in the overall incidence of AEs, with AEs reported by 35%, 51% and 25% of patients in the indacaterol 400 microg, 800 microg and placebo groups, respectively. The majority of AEs were mild or moderate in severity, and there were no study-drug related serious AEs. There were no statistically significant differences between indacaterol groups and placebo in mean pulse rate and QTc interval, and isolated statistically significant (p

Introduction: Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries. However, data regarding symptom load and clinical phenotypes of patients with COPD in CEE remain largely unknown. Methods: Participation in the POPE Study (a multicentre, observational cross-sectional survey) was offered to consecutive outpatients with stable COPD in 11 CEE countries if they fulfilled the following criteria: age ≥ 40 years, smoking history ≥ 10 pack-years, post-bronchodilator (BD) FEV 1 /FVC Results: 3504 patients (66 ± 8.7 yrs, 69% male, post-BD FEV 1 53.0 ± 17.5% predicted, Charlson comorbidity index 2.0 ± 1.4, and 1.2 ± 1.6 exacerbations within the last 12 months) were recruited between Apr 2014 and May 2015. The majority of patients were classified as GOLD D or GOLD B (57% and 30.6% of total, respectively). According to predefined phenotypes, 63% of the population were non-exacerbators, 20.5% frequent exacerbators with chronic bronchitis (CB), 9.5% frequent exacerbators without CB, and 7% were patients with asthma-COPD overlap syndrome (ACOS). There were statistically significant differences in symptom load and lung function between these phenotypes. Conclusion: First results of the POPE study offer insight into symptom load, lung function, and phenotypes of COPD in CEE countries.

Background: Patients with obstructive sleep apnoea (OSA) have increased cardiovascular risk. In these patients, intermittent hypoxia increases sympathetic activity, systemic inflammation and oxidative stress which may all contribute to accelerated atherosclerosis. Our aim was to investigate relationships between carotid intima-media thickness (IMT) and OSA severity, markers of oxidative stress and systemic inflammation. Methods: 84 subjects [mean age (mean±SD) 47.1±9.7 years, body mass index (BMI) 30.1±4.1 kg/m2] underwent overnight polysomnography (Alice 4, Respironics, Murrysville, USA). Subjects were divided into three groups: no OSA [apnoea-hypopnoea index (AHI) 3.2±1.1 events/hour]; mild-moderate OSA (AHI 15.8±6.7 events/hour), and severe OSA (AHI 48.3±16.0 events/hour). Carotid IMT was assessed by B-mode ultrasound (Philips HD11 XE), arterial pulse wave velocity (PWV) was measured using the automatic Complior device. Results: Both IMT and PWV increased from subjects with no OSA to patients with mild-moderate, and to those with severe OSA (0.54±0.10 vs 0.59±0.07 vs 0.62±0.11 mm, p=0.037; 8.9±1.0 vs 10.3±1.3 vs 9.8±1.6 m/s, p=0.026, respectively). In addition, circulating oxidized LDL (oxLDL) and lipopolysaccharide binding protein levels increased with OSA severity (p=0.007, p=0.046, respectively). In multivariate analysis, age (p Conclusions: In patients with OSA, older age, nocturnal intermittent hypoxia and oxLDL were independent correlates of ultrasonographic carotid atherosclerosis. Support: APVV-0134-11, Ministry of Education, Slovakia.

Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer.The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography.In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p0.02; 69.1+/-1.6 versus 77.0+/-2.4, p0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p0.02) as a significant independent predictor of FEV1 in this group of patients.The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.

Obstructive sleep apnea subjects the failing heart to adverse hemodynamic and adrenergic loads and may thereby contribute to the progression of heart failure. We hypothesized that treatment of obstructive sleep apnea by continuous positive airway pressure in patients with heart failure would improve left ventricular systolic function.Twenty-four patients with a depressed left ventricular ejection fraction (45 percent or less) and obstructive sleep apnea who were receiving optimal medical treatment for heart failure underwent polysomnography. On the following morning, their blood pressure and heart rate were measured by digital photoplethysmography, and left ventricular dimensions and left ventricular ejection fraction were assessed by echocardiography. The subjects were then randomly assigned to receive medical therapy either alone (12 patients) or with the addition of continuous positive airway pressure (12 patients) for one month. The assessment protocol was then repeated.In the control group of patients who received only medical therapy, there were no significant changes in the severity of obstructive sleep apnea, daytime blood pressure, heart rate, left ventricular end-systolic dimension, or left ventricular ejection fraction during the study. In contrast, continuous positive airway pressure markedly reduced obstructive sleep apnea, reduced the daytime systolic blood pressure from a mean (+/-SE) of 126+/-6 mm Hg to 116+/-5 mm Hg (P=0.02), reduced the heart rate from 68+/-3 to 64+/-3 beats per minute (P=0.007), reduced the left ventricular end-systolic dimension from 54.5+/-1.8 to 51.7+/-1.2 mm (P=0.009), and improved the left ventricular ejection fraction from 25.0+/-2.8 to 33.8+/-2.4 percent (P0.001).In medically treated patients with heart failure, treatment of coexisting obstructive sleep apnea by continuous positive airway pressure reduces systolic blood pressure and improves left ventricular systolic function. Obstructive sleep apnea may thus have an adverse effect in heart failure that can be addressed by targeted therapy.

Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study. Genotyping for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was performed using real-time PCR with subsequent melting-curve analysis. SLC47A1 rs2289669 genotype was significantly associated with the reduction in haemoglobin A1c (HbA1c) after 6 months. Twenty percentage of patients with diabetes that are homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison with the patients carrying G-allele (GG + GA: 0.55 ± 0.09% vs. AA: 1.10 ± 0.18%, p = 0.018). In conclusion, the results of this study might have in future practical implication in personalised treatment of patients with type 2 diabetes.

Background Obstructive sleep apnea (OSA) has been reported to be associated with an increased risk of ventricular arrhythmias and conduction disturbances. The aim of this study was to analyze the QRS complex morphology potentially indicative of intraventricular conduction impairment in patients with mild to severe OSA. Material and methods One hundred ninety-three consecutive patients, who underwent complete overnight polysomnography, were divided into four groups based on the OSA severity: (1) no OSA, (2) mild OSA, (3) moderate OSA and (4) severe OSA (apnea-hypopnea index 30/h, respectively). Resting 12-lead ECG was recorded, the QRS parameters included QRS amplitude in individual leads, QRS spatial vector magnitude (QRSmax), electrical axis (EA), ECG criteria for left ventricular hypertrophy (ECG-LVH) and right ventricular hypertrophy (ECG-RVH), and occurrence of fragmented QRS (fQRS). Results Severity of OSA was significantly associated with a gradual significant shift of the electrical axis to the left (45.5±22.5°; 34.8±17.1°; 32.9±18.2°; 29.8±10.0°; respectively), while the QRSmax values were low in all patient groups, with a significant difference between no OSA and severe OSA groups. The multivariate analysis showed that QRSmax was independently associated with age and the interaction between gender and OSA severity (p=0.001, and p=0.004, respectively; adjusted R 2 =0.178). The electrical axis was found to be independently associated with age and OSA severity (p=0.037, and p=0.026, respectively; R 2 =0.109). Changes of electrical axis and of QRSmax were reflected in corresponding changes in the amplitude of 12-lead ECG and in low occurrence of ECG-LVH and ECG-RVH criteria. The OSA groups had higher occurrence of fQRS. Conclusion OSA patients displayed a combination of changes in QRS complex morphology, the leftward shift of EA, low QRS voltage and fQRS, suggestive of depolarization sequence deterioration that might be indicative of considerable electrical remodeling.

Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT.AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity.AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity.The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown.

International audience; Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European Respiratory Society to deliver a summary of the evidence and description of current practice in nutritional assessment and therapy in COPD, and to provide directions for future research. Task Force members conducted focused reviews of the literature on relevant topics, advised by a methodologist. It is well established that nutritional status, and in particular abnormal body composition, is an important independent determinant of COPD outcome. The Task Force identified different metabolic phenotypes of COPD as a basis for nutritional risk profile assessment that is useful in clinical trial design and patient counselling. Nutritional intervention is probably effective in undernourished patients and probably most when combined with an exercise programme. Providing evidence of cost-effectiveness of nutritional intervention is required to support reimbursement and thus increase access to nutritional intervention. Overall, the evidence indicates that a well-balanced diet is beneficial to all COPD patients, not only for its potential pulmonary benefits, but also for its proven benefits in metabolic and cardiovascular risk.