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Amnon Ariel,1 Alan Altraja,2,3 Andrey Belevskiy,4 Piotr W Boros,5 Edvardas Danila,6 Matjaz Fležar,7 Vladimir Koblizek,8 Zvi G Fridlender,9 Kosta Kostov,10 Alvils Krams,11 Branislava Milenkovic,12 Attila Somfay,13 Ruzena Tkacova,14 Neven Tudoric,15 Ruxandra Ulmeanu,16 Arschang Valipour17 1Emek Medical Center, Clalit Healthcare Services, Afula, Israel; 2Department of Pulmonary Medicine, University of Tartu, 3Lung Clinic, Tartu University Hospital, Tartu, Estonia; 4Department of Pulmonology, Russian National Research Medical University, Moscow, Russia; 5Lung Pathophysiology Department, National TB and Lung Diseases Research Institute, Warsaw, Poland; 6Clinic of Infectious Chest Diseases, Dermatovenereology, and Allergology, Vilnius University, Centre of Pulmonology and Allergology, Vilnius University Hospital, Vilnius, Lithuania; 7University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; 8Department of Pneumology, University Hospital, Hradec Králové, Czech Republic; 9Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem, Israel; 10Clinic of Pulmonary Diseases, Military Medical Academy, Sofia, Bulgaria; 11Medical Faculty of Latvian University, Riga East University Hospital, Riga, Latvia; 12Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 13Department of Pulmonology, University of Szeged, Deszk, Hungary; 14Department of Respiratory Medicine and Tuberculosis, Faculty of Medicine, PJ Safarik University, Košice, Slovakia; 15School of Medicine, Dubrava University Hospital, Zagreb, Croatia; 16Marius Nasta Institute of Pneumology, Bucharest, Romania; 17Department of Respiratory and Critical Care Medicine, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria Abstract: 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. Keywords: dual bronchodilation, inhaled corticosteroid, LAMA, LABA, tiotropium, anticholinergic

Zuzana Zbozinkova,1 Adam Barczyk,2 Ruzena Tkacova,3 Arschang Valipour,4 Neven Tudoric,5 Kirill Zykov,6 Attila Somfay,7 Marc Miravitlles,8 Vladimir Koblizek91Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 3Department of Respiratory Medicine, Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; 4Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Wien, Austria; 5School of Medicine Zagreb, University Hospital Dubrava, Zagreb, Croatia; 6Laboratory of Pulmonology, Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russia; 7Department of Pulmonology, University of Szeged, Deszk, Hungary; 8Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 9Department of Pneumology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech RepublicIntroduction: Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.Methods/design: The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC ,0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494.Outcomes: The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries.Conclusion: There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.Keywords: COPD, phenotypes, Central Europe, Eastern Europe, study, GOLD, comorbidity

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<0.05) was observed on NIV whereas the stroke volume and cardiac index remained stable throughout all three assessed intervals (p=0.347, p=0.344; respectively). The pre-ejection period increased on NIV (from 113±16 to 127±20 ms, p<0.05), and the left ventricular ejection time increased after NIV termination compared to baseline (from 259±25 to 269±25 ms, p<0.05). CONCLUSION: Volume-targeted NIV may acutely improve systolic time intervals without any negative impact on the left ventricular function in OHS patients. [ABSTRACT FROM AUTHOR]

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 μg.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, r2=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<0.001, r2=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients. [ABSTRACT FROM AUTHOR]

Objective: 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).Methods: 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.Results: Obstructive sleep apnoea was diagnosed in 91% Roma and 65% non-Roma subjects (p < 0.001). Roma subjects had higher apnoea-hypopnoea index (AHI) (61.2 ± 7.9 vs. 22.8 ± 2.3 events/h, p < 0.001), lower dip oxygen saturation (56.7 ± 4.9 vs. 79.3 ± 1.3%, p < 0.001), and higher waist circumference as compared to non-Roma subjects (121.3 ± 3.1 vs. 105.2 ± 2.4 cm, p < 0.001). In multiple regression analysis, Roma background (p < 0.001) and waist circumference (p < 0.001) were independent predictors of AHI (R (2) = 0.330). Roma background was associated with significantly higher risk of severe OSA (odds ratio 3.73; 95% confidence interval 1.20-11.65, p = 0.023), independently of age, gender and waist circumference.Conclusions: Among subjects referred for polysomnography, Roma background is associated with significantly higher risk of severe OSA. Knowledge of common OSA pattern in Roma patients may help in identifying high risk individuals and guide early therapy of this disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Several observational studies suggest that therapy with inhaled corticosteroids (ICS) is associated with reduced mortality in patients with chronic obstructive pulmonary disease (COPD). However, none of these has reported survival data in COPD patients with respiratory insufficiency who require domiciliary oxygen therapy. The present study was conducted to examine the association between ICS and all-cause mortality in patients with severe COPD and chronic hypoxemia. Patients and methods: From a tertiary referral clinic, we identified 145 consecutive COPD patients who met the criteria for long-term oxygen therapy between 1996 and 2002. We compared the hazard ratio (HR) for all-cause mortality over 1 year between patients who were () and were not treated with ICS (). Results: In a crude analysis, the use of ICS was associated with a HR of 0.38 (95% confidence interval (CI)=0.18–0.79). After adjustments for age, sex, use of oral steroids, and β 2-agonists, PaO2 and PaCO2, the HR was 0.46 (95% CI=0.21–0.98). Conclusions: Our findings indicate that ICS may reduce all-cause mortality in patients with severe COPD and chronic hypoxemia, who require long-term domiciliary oxygen therapy. These data suggest that ICS may play an important role in improving clinical outcomes in patients with advanced COPD. [Copyright &y& Elsevier]

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, p<0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction >5 kilos (-0.38±0.99, p<0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction >5 kilos (p<0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA., (© 2021 European Sleep Research Society.)

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<0.05) was observed on NIV whereas the stroke volume and cardiac index remained stable throughout all three assessed intervals (p=0.347, p=0.344; respectively). The pre-ejection period increased on NIV (from 113±16 to 127±20 ms, p<0.05), and the left ventricular ejection time increased after NIV termination compared to baseline (from 259±25 to 269±25 ms, p<0.05)., Conclusion: Volume-targeted NIV may acutely improve systolic time intervals without any negative impact on the left ventricular function in OHS patients (Tab. 2, Ref. 17).

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 R 2  = 0.608, p  < 0.001). Erickson solution-focused coaching supports adherence to healthy lifestyle and weight reduction in obstructive sleep apnoea.

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 Rehabilitation 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 subpopulation, 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 ≤65 years, CGI scoring was generally better than in the elderly despite a similar degree of OSA (eg, 'normal, not ill' 24.2% vs 15.3%, p < 0.01, respectively). Independent predictors of CGI rating included age, BMI, AHI, ESS, cardio-metabolic comorbidities, and diagnosis based on polygraphy. CGI-improvement rating (Beta = -0.406, p < 0.01) was superior to sleep apnea severity or ESS-score (Beta = 0.052 and -0.021, p = 0.154 and 0.538 respectively) at baseline for prediction of good CPAP compliance at follow-up., Conclusions: CGI rating is confounded by gender, age class and the type of sleep diagnostic method. As OSA phenotypes differ, CGI may contribute as a clinical tool to reflect the significance of clinical disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

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 failure was found in 23% of patients who were more obese (p = 0.018), had worse lung function, lower PO 2 (p = 0.023) and higher PCO 2 while awake (p < 0.001), and more sleep time with an SpO 2  < 90% (CT90%) (p < 0.001) compared to those who responded to CPAP. In multivariate analysis, PCO 2 while awake [odds ratio (OR) 29.5, confidence interval (CI) 2.22-391, p = 0.010] and CT90% (OR 1.06, CI 1.01-1.11, p = 0.017) independently predicted CPAP failure after adjustments for covariates. The BiPAP therapy was well tolerated and effectively alleviated hypercapnia in all patients with primary CPAP failure., Conclusions: Daytime hypercapnia and nocturnal hypoxia are independent predictors of early CPAP failure in patients with the OSA-COPD overlap syndrome., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV 1 decline, respiratory mortality, and systemic inflammation., Objectives: We sought to determine the relationship of AHR with FEV 1 decline, respiratory mortality, and systemic inflammatory burden in patients with COPD in the Lung Health Study (LHS) and the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study., Methods: The LHS enrolled current smokers with mild-to-moderate COPD (n = 5887), and the GLUCOLD study enrolled former and current smokers with moderate-to-severe COPD (n = 51). For the primary analysis, we defined AHR by a methacholine provocation concentration of 4 mg/mL or less, which led to a 20% reduction in FEV 1 (PC 20 )., Results: The primary outcomes were FEV 1 decline, respiratory mortality, and biomarkers of systemic inflammation. Approximately 24% of LHS participants had AHR. Compared with patients without AHR, patients with AHR had a 2-fold increased risk of respiratory mortality (hazard ratio, 2.38; 95% CI, 1.38-4.11; P = .002) and experienced an accelerated FEV 1 decline by 13.2 mL/y in the LHS (P = .007) and by 12.4 mL/y in the much smaller GLUCOLD study (P = .079). Patients with AHR had generally reduced burden of systemic inflammatory biomarkers than did those without AHR., Conclusions: AHR is common in patients with mild-to-moderate COPD, affecting 1 in 4 patients and identifies a distinct subset of patients who have increased risk of disease progression and mortality. AHR may represent a spectrum of the asthma-COPD overlap phenotype that urgently requires disease modification., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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.

Background: 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)., Objective: To explore the effects of SO on exercise capacity, health status, and systemic inflammation in COPD., Design/settings/participants: 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., Measurements: 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., Results: 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., Conclusions: 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., Trial Registry: ClinicalTrials.gov no. NCT00292552., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Polygraphy (PG) and polysomnography (PSG) are used in clinical settings in Europe for diagnosing obstructive sleep apnea (OSA), but their equivalence in unselected clinical cohorts is unknown. We hypothesized that the method would affect both diagnostic outcomes and disease severity stratification. Data from 11 049 patients in the multi-centre European Sleep Apnea Cohort (ESADA) with suspected OSA (male and female, aged 18-80 years) were used in two groups of patients to compare PG (n = 5745) and PSG (n = 5304). Respiratory events were scored using the 2007 American Association of Sleep Medicine (AASM) criteria. In subjects who underwent PSG, mean apnea-hypopnea index (AHI) using sleep time (AHIPSG 31.0 ± 26.1 h(-1) ) and total analysed time (TAT) (AHITAT 24.7 ± 22.0 h(-1) ) were higher than in subjects who underwent PG (AHIPG 22.0 ± 23.5 h(-1) ) (P < 0.0001). The oxygen desaturation index (ODI) was lower in subjects investigated with PG (ODIPG 18.4 ± 21.7 h(-1) ) compared to subjects investigated with PSG (ODIPSG 23.0 ± 25.3 h(-1) ) but not different when the PSG was indexed by TAT (ODITAT 18.6 ± 21.4 h(-1) , P < 0.65). The proportion of patients with an AHI ≥ 15 was 64% in the subjects who underwent PSG and 47% in the subjects who underwent PG (P < 0.001). Overall, patients investigated using PG are likely to have a 30% lower AHI on average, compared to patients investigated by PSG. This study suggests that PG interpreted using standard guidelines results in underdiagnosis and misclassification of OSA. We advocate the development of PG-specific guidelines for the management of OSA patients., (© 2015 European Sleep Research Society.)

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 <5, 5-15, 15-30, >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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2014 The Obesity Society.)

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., (©ERS 2014.)

Background: OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population., Methods: We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects., Results: T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) (P < .001), respectively, for prevalent T2DM. Diabetic subjects with more severe OSA had worse glycemic control, with adjusted mean HbA1c levels 0.72% higher in patients with severe OSA than in those without sleep-disordered breathing (analysis of covariance, P < .001)., Conclusions: Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.