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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.

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 β 0.158; p<0.001), along with nocturnal hypoxaemia, predicted HbA1c. Adjusted mean HbA1c levels were lower in the lowest AHI quartile (5.24%, 95% CI 5.21-5.27%) than in the second (5.37%, 95% CI 5.34-5.40%), third (5.44%, 95% CI 5.41-5.47%) or highest (5.50%, 95% CI 5.46-5.53%) quartiles. Subjects in the higher quartiles had significantly greater adjusted odds ratios of HbA1c level ≥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., (© ERS 2014.)

There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ε2 carriers and the ε3/ε3 genotype only. Nevertheless, the ε4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ε4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ε4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.

Background: Osteoprotegerin (OPG), a potent inhibitor of osteoclastogenesis, decreases bone resorption and has protective effects on bone mineral density (BMD). Recently we have shown that the adipose-tissue derived OPG relates to BMD in patients with chronic obstructive pulmonary disease (COPD), a condition associated with increased risk of osteoporosis., Objective: Here we aimed to investigate the potential of circulatory OPG to reflect hip BMD in patients with COPD., Patients and Methods: In 56 subjects with COPD [age, 61.7 ± 6.7 years; forced expiratory volume in 1 s (FEV1), 53.6 ± 19.2% predicted], total femur BMD was assessed by dual energy X-ray absorptiometry, serum OPG and β-crosslaps, a marker of increased bone resorption, by commercially available assays., Results: From patients with normal hip BMD (n = 32, T-score 0.1 ± 0.8) to those with osteopenia (n = 14, T-score -1.6 ± 0.4) and osteoporosis (n = 10, T-score -3.4 ± 0.7) serum OPG levels significantly increased (6.6 ± 1.8 versus 7.2 ± 2.9 and versus 8.6 ± 1.5 pmol/l, p = 0.036). In addition, hip T-scores were directly related to FEV1, and inversely to β-crosslaps (R = 0.40, p = 0.002; R = 0.38, p = 0.01, respectively). In multivariate analysis, OPG independently predicted hip T-scores after adjustments for age, gender, FEV1, and β-crosslaps (p = 0.011, adjusted R(2) = 0.354). Area under receiver operator curve for OPG as a discriminator of osteoporosis was 0.787 (95% CI, 0.653-0.921) (p = 0.005)., Conclusions: Present results suggest that osteoporosis of the hip is associated with increased circulatory levels of OPG in patients with COPD. OPG might serve as a biomarker of this COPD-related comorbidity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular (in particular hypertensive) patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients. The present document is the result of work performed by a panel of experts participating in the European Union COST (Cooperation in Scientific and Technological research) Action B26 on OSA, with the endorsement of the European Respiratory Society and the European Society of Hypertension. In particular, these recommendations are aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are also aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size (P = .007), due to a reduction in large LDL-I particles (P = .002) and an increase in small, dense LDL-IIIA (P = .048) and LDL-IIIB (P = .037). The size of LDL correlated inversely with age (r = -.268, P = .042) and serum triglycerides (r = -.364, P = .005), and positively with serum high-density lipoprotein cholesterol levels (r = .335, P = .010). In multiple regression analysis, the presence of the MetS was the only independent predictor of LDL size (P = 0.015). In patients with OSA, MetS is an independent predictor of LDL size and subclasses, whereas the severity of OSA does not contribute independently to alterations in LDL phenotype.

This article is aimed at addressing the current state of the art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnea (OSA) in cardiovascular (particularly hypertensive) patients, as well as for the management of cardiovascular diseases (particularly arterial hypertension) in OSA patients. The present document is the result of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH). These recommendations are particularly aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are at the same time aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.

Aims: 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., Patients and Methods: One hundred and one patients with type 2 diabetes who failed to achieve HbA1c<7% 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., Results: 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)., Conclusions: 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., (Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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<0.001) were the only significant independent predictors of ΔFPG (R2=0.48)., Conclusions: Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype.

Introduction: The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD., Methods: In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR., Results: Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p=0.015), and directly to serum leptin (p<0.001) and to the total, femoral, and lumbar BMD and T-score (p<0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p<0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p<0.001, adjusted R(2)=0.383; p=0.008, adjusted R(2)=0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions., Conclusion: Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Several large population-based cohort studies identified an association between reduced lung function and increased intima-media thickness (IMT). Nevertheless, a vast majority of subjects in these studies did not suffer from COPD and thus it remains unclear whether IMT differs among various stages of COPD severity. The aim of the present pilot study was to evaluate IMT in central European patients with moderate, severe and very severe COPD., Methods: In forty-nine patients (34 men, 15 women; mean age 66.1 +/- 10.9 years) with COPD, the combined thickness of intima and media layers of the common carotid arteries was measured using B-mode ultrasound imaging., Results: Increased cardiovascular disease risk as evidenced by carotid IMT values greater or equal to 75th percentile were present in 14 (28.6%), whereas IMT hypertrophy (IMT values greater or equal 0.80 mm) was present in 24 (49.0%) of patients. Average IMT in the entire cohort was 0.85 +/- 0.21 mm, with no significant differences from stage II to stages III and IV of COPD., Conclusion: Present results indicate a high prevalence of IMT hypertrophy and increased cardiovascular disease risk as assessed by carotid ultrasonography in COPD patients with a broad spectrum of airway obstruction severity. The lack of differences in carotid IMT between various stages of lung impairment severity suggests that atherosclerosis starts early in the course of COPD. Therefore, the need to screen patients for the presence of concomitant atherosclerosis in early stages of COPD severity may be warranted (Tab. 2, Ref. 33).

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 NH(2)-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, PaO(2), 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO(2) 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 PaO(2), 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., (Copyright © 2010 S. Karger AG, Basel.)

Background: Surfactant protein D (SP-D) is a promising blood biomarker in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, circulating levels of SP-D are not related to pulmonary functions. In the present exploratory study, we created a simple index of plasma to bronchoalveolar lavage (BAL) fluid ratio of SP-D (pSP-D/bSP-D), and determined whether this index would relate to the severity of airflow limitation and hence represent a superior biomarker than pSP-D alone., Material/methods: In 50 ex and current smokers (mean age 57.6±7.8 years, 74% men), SP-D was measured in BAL fluid and plasma samples, and the relationships between spirometric variables and a composite parameter - the pSP-D/bSP-D ratio were determined., Results: There was a significant inverse correlation between the pSP-D/bSP-D ratio and the severity of airflow obstruction, as measured by FEV1/FVC (p=0.012). In contrast, no relationship was observed between FEV1/FVC and pSP-D alone., Conclusions: We suggest that integrating both lung and plasma expression of pneumo-proteins may be more useful than plasma expression alone in developing pneumo-proteins as potential biomarkers in COPD.

Potential links between metabolic derangements and adipose tissue (AT) inflammation in patients with chronic obstructive pulmonary disease (COPD) are unexplored. We investigated AT expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-α, CD68 (macrophage cell surface receptor), caspase-3, and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with COPD (age 62.3 ± 7.2 years). With increasing body mass index, increases in AT expressions of IL-6, TNF-α, and CD68 were observed (P < .001; P = .005; P < .001, resp.), in association with reduced insulin sensitivity (P < .001). No differences were observed between cachectic and normal-weight patients in AT expressions of inflammatory or proapoptotic markers. Adipose tissue CD68 and TNF-α expressions predicted insulin sensitivity independently of known confounders (P = .005; P = .025; R(2) = 0.840). Our results suggest that AT inflammation in obese COPD patients relates to insulin resistance. Cachectic patients remain insulin sensitive, with no AT upregulation of inflammatory or proapoptotic markers.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators. On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment. The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown. We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions. The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation.

Aims and Background: An increased incidence of neuroendocrine tumors in the last decade has been noticed worldwide. Our purpose was to study the characteristics, surgical approaches and outcome in patients with primary bronchopulmonary carcinoid tumors., Methods: Between 2001 and 2007, bronchopulmonary carcinoid tumors were removed in 11 of a total of 287 patients who underwent surgery for primary lung malignancies in our tertiary referral center., Results: The patient group consisted of 3 men and 8 women (mean age 52.9 +/- 5.2 years, range 19-76 years). At presentation, 10 of 11 patients were symptomatic, with cough, pneumonia, breathlessness and hemoptysis being the most frequent symptoms. Histological findings revealed typical carcinoid in 10 patients and atypical carcinoid in one. The surgical approach included 8 lung resections (6 lobectomies, 1 bilobectomy, 1 segmentectomy), and 3 bronchoplastic tumor removals. In 2008, clinical examination and chest X-ray revealed no recurrence of the carcinoid and no long-term postoperative complications in any patient., Conclusions: In the light of our study and the review of the literature we conclude that early recognition of primary bronchopulmonary carcinoid tumors followed by adequate surgical removal of the malignancy are essential for complete remission of the disease.

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.

Background: Knowledge of the effects of undernourishment on the severity of respiratory impairment, systemic inflammation and oxidative stress during acute exacerbations of COPD (AECOPD) is limited. In patients with AECOPD, we assessed the relationships between BMI, lung function, and markers of systemic inflammation and oxidative stress., Material/methods: We measured pulmonary function, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, malondialdehyde (MDA), erythrocytic glutathione-peroxidase (GPx), superoxiddismutase (SOD), and catalase (CAT) in 113 patients admitted to the hospital due to an AECOPD (80 males, age 66.2+/-11.0 years, FEV1 41.5+/-13.7% predicted)., Results: From the low (<21 kg/m2) towards the normal (21-24.9 kg/m2), high (25-29.9 kg/m2) and obese (>30 kg/m2) BMI groups, FEV1, FEV1-to-forced vital capacity (FVC) ratio, inspiratory capacity (IC), and the IC-to-total lung capacity (IC/TLC) ratio increased (p<0.01; p<0.001; p=0.039; p=0.002, respectively), while residual volume (RV), TLC and RV/TLC ratio were reduced (p<0.001; p<0.001; p=0.018, respectively). Patients with low BMI had significantly lower FEV1, FEV1/FVC, IC and IC/TLC, and higher RV and TLC values compared to the high and obese BMI groups. From the low towards the normal, high and obese BMI, reductions in serum CRP, and a trend towards increases in erythrocytic GPx were observed (p=0.023; p=0.056, respectively). No differences were seen in circulating TNF-alpha, IL-6 or IL-8, MDA or erythrocytic CAT and SOD between the groups., Conclusions: In patients with acute exacerbations of COPD, low BMI is associated with higher degree of bronchial obstruction and pulmonary hyperinflation, in association with higher circulating CRP levels.

Patients with obstructive sleep apnoea are at increased risk of atherosclerotic morbidity and mortality. Abnormalities in lipid metabolism that occur in response to chronic intermittent hypoxia in patients with sleep-disordered breathing may increase the cardiovascular risk in an already susceptible population. Atherogenic lipoprotein phenotype and small, dense LDL have an independent predictive role for future cardio- and cerebro-vascular events in patients with the metabolic syndrome. Therefore, testing the hypothesis that therapy of obstructive sleep apnoea may reduce atherogenic lipoprotein phenotype might have significant clinical implications. We suggest that abolition of obstructive sleep apnoea by continuous positive airway pressure results in reductions in circulatory levels of small, dense LDL by improvements in oxygen saturation, reductions in oxidative stress, improvements in insulin sensitivity, and reductions in triglyceride biosynthesis. Testing the proposed hypothesis may contribute to improvements in clinical management of patients with obstructive sleep apnoea by early recognition of atherogenic dyslipidaemia followed by both, vigorous treatment of the underlying sleep-disordered breathing by noninvasive ventilation and targeted therapeutic modulation of hypertriglyceridaemia, low HDL-cholesterol and increased levels of small, dense LDL. Implementing this strategy to patients with obstructive sleep apnoea may potentially contribute to substantial reduction of their high cardiovascular risk.

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 [SpO(2)] 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 (>or=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 SpO(2) (r = 0.314, P = 0.028), the lowest sleep SpO(2) (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 SpO(2) 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)-alpha, 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 > or = 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-alpha (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 < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy., 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.

Background: Obstructive sleep apnea (OSA) has been linked to cardiovascular and cerebrovascular diseases in previous studies. However, it remains unclear whether OSA relates to cardiovascular outcomes independently of obesity and/or insulin resistance., Material/methods: At a tertiary referral teaching hospital, this cross-sectional analysis of 98 subjects (28 without, 39 with mild-moderate, and 31 with severe OSA) aimed to determine whether OSA relates to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) cardiovascular risk independently of obesity and insulin resistance. OSA was diagnosed by attended polysomnography. The insulin resistance index (HOMA-IR) was based on a homeostasis model assessment method., Results: Of the patients without to those with mild-moderate to those with severe OSA, significant increases were observed in NCEP ATP III risk [median (25%, 75% quartiles) from 2.0 (1.0, 8.0) to 3.0 (1.0, 12.0) to 16.0 (5.3, 20.0)%, p <0.001 for the trend] in association with increases in HOMA-IR (p<0.001), diastolic (p=0.039) and mean blood pressure (p=0.016), serum triglycerides (p=0.047), apolipoprotein B (p=0.039), plasma fibrinogen (p=0.013), and fasting glucose levels (p=0.002). Compared with subjects without sleep apnea, patients with severe OSA had significantly higher odds for NCEP ATP III risk higher than 10% (moderately high and high cardiovascular risk) (odds ratio: 4.06, 95% confidence interval: 1.02-16.25, p=0.048) after adjustment for body mass index and HOMA-IR., Conclusions: These findings suggest that severe OSA is related to higher cardiovascular risk independently of obesity and insulin resistance.

Background: The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol., Material/methods: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography., Results: Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively)., Conclusions: The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.

Background: In patients with chronic obstructive pulmonary disease (COPD), the inflammatory processes and oxidative stress are closely linked in the lung compartment. However, the relationships between systemic inflammation and parameters of oxidative stress in the systemic circulation during acute exacerbations of COPD remain to be explored., Objective: To analyze relationships between erythrocytic glutathione peroxidase (GPx), a marker of systemic oxidative stress, and parameters reflecting systemic inflammation, such as circulating neutrophils, C-reactive protein (CRP), and interleukin (IL)-6, in patients with acute exacerbations of COPD., Patients and Methods: We measured erythrocytic GPx activity, circulating neutrophil count, and serum high-sensitivity (hs) CRP and IL-6 in 177 patients admitted to the hospital due to an acute exacerbation of COPD (91 males, mean age 66.8+/-0.9 years, mean FEV1 45.3+/-1.3% predicted)., Results: From GOLD Stage II to Stage III and IV, erythrocytic GPx activity significantly decreased [mean+/-SEM: from 44.3+/-1.7 U/g Hb to 40.8+/-1.1 U/g Hb and to 38.4+/-1.5 U/g Hb, p = 0.037], while serum hsCRP increased [median (25th, 75th percentile): from 9.6 (3.0, 23.0) mg/l to 23.3 (6.4, 46.8) mg/l, and to 26.7 (6.5, 117.2) mg/l, p = 0.004]. Erythrocytic GPx activity was significantly inversely related to both, log neutrophil count (r = -0.219, p = 0.003) and log hsCRP (r = -0.199, p = 0.008)., Conclusions: Our study suggests an association between systemic inflammation and systemic oxidative stress reflected by erythrocytic GPx in patients with acute exacerbations of COPD.

Actinomycosis is an infrequent chronic progressive granulomatous and suppurative disease caused by Actinomyces israelii, a natural inhabitant of the gastrointestinal tract. We report a rare case of a 68-year-old man with primary endobronchial actinomycosis who presented in the emergency respiratory ward with massive hemoptysis and dyspnea. An urgent fiberoptic bronchoscopy revealed hypertrophic mucosa and a narrowed lingular bronchus with a pale extruding exophyt. Diffuse bleeding from the mucosa adjacent to the exophyt was present. Histopathologic evaluation revealed chronic inflammation with abscess formation and clusters of Actinomyces colonies. Therapy with clindamycin maintained for 7 weeks prevented recurrence of the disease. In the light of our case and the review of literature we conclude that early recognition of primary endobronchial actinomycosis associated with hemoptysis and proper antibiotic treatment are essential to prevent undesirable complications including unwarranted surgery (Fig. 2, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

Study Objectives: COPD is a systemic disorder that is associated with increases of inflammatory proteins in systemic circulation. However, no data on the potential role of systemic inflammation in pulmonary hypertension secondary to COPD are available. Therefore, our aim was to investigate the degree of systemic inflammation reflected by circulatory levels of C-reactive protein (CRP), tumor-necrosis factor (TNF)-alpha, and interleukin (IL)-6 in COPD patients with and without pulmonary hypertension., Design: Cross-sectional study., Setting: University hospital, tertiary referral setting., Patients and Measurements: In 43 consecutive patients with COPD (mean [+/- SD] age, 65.0 +/- 10.5 years; mean FEV(1), 46.2 +/- 18.1% predicted), lung function was assessed using body plethysmography; pulmonary artery pressure (Ppa) levels were measured by echocardiography. Serum TNF-alpha and IL-6 levels were assessed by enzyme-linked immunosorbent assay, and high-sensitivity serum CRP levels were measured by chemiluminescent immunoassay., Results: Pulmonary hypertension was present in 19 patients and was absent in 24 patients. In patients with pulmonary hypertension, serum CRP and TNF-alpha levels were significantly higher than in those patients without hypertension (median, 3.6 mg/L [25th to 75th percentile, 1.4 to 13.0 mg/L] vs 1.8 mg/L [25th to 75th percentile, 0.8 to 2.8 mg/L; p = 0.034]; and median, 4.2 pg/mL [25th to 75th percentile, 3.4 to 10.9 pg/mL] vs 3.1 pg/mL [25th to 75th percentile, 2.1 to 4.2 pg/mL]; p = 0.042, respectively). No differences were seen in serum IL-6 (median, 10.4 pg/mL [25th to 75th percentile, 8.8 to 12.2 pg/mL] vs 10.5 pg/mL [25th to 75th percentile, 9.4 to 39.1 pg/mL]; p = 0.651) between the groups. In multiple linear regression analysis, the following two variables were independent predictors of systolic Ppa (R(2) = 0.373): Pao(2) (p = 0.011); and log-transformed serum CRP level (p = 0.044)., Conclusion: We conclude that increases in Ppa in patients with COPD are associated with higher serum levels of CRP and TNF-alpha, raising the possibility of a pathogenetic role for low-grade systemic inflammation in the pathogenesis of pulmonary hypertension in COPD patients.

Sleep apnoea in heart failure increases mortality risk, possibly as a result of greater activation of the sympathetic nervous system. In healthy subjects, simulated central apnoeas (holding breath) and obstructive apnoeas (Mueller manoeuvres) increase muscle sympathetic activity equally, primarily through chemoreceptor stimulation. In heart failure, however, Mueller manoeuvres cause greater reductions in blood pressure than breath holds. We hypothesized that in heart failure, the summation of arterial baroreceptor unloading and chemoreceptor stimulation would increase sympathetic activity more during obstructive than central apnoeas. Healthy human subjects and heart failure patients (seven of each) performed 15-s breath holds and 15-s Mueller manoeuvres. Breath holds evoked a progressive increase in muscle sympathetic nerve activity in both groups, but had no effect on blood pressure. In healthy subjects, breath holds and Mueller manoeuvres caused equal peaks in sympathetic activity. In contrast, in heart failure patients, Mueller manoeuvres caused a progressive decrease in blood pressure (P < 0.05) and greater increases in sympathetic activity than breath holds (P < 0.01). In heart failure, simulated obstructive apnoea elicits greater increases in sympathetic activity than simulated central apnoea, due to its additional hypotensive effect. These present findings offer novel insight into the potential role of sleep apnoea in augmenting sympathetic activity and accelerating disease progression in heart failure.

Background: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep., Methods and Results: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate., Conclusions: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.

In patients with congestive heart failure (CHF), elevated, left ventricular (LV) volume might lead to pulmonary congestion and hypocapnia, which would create a predisposition to the development of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In addition, because LV volume affects cardiac output, it should influence the lengths of hyperpneas. We therefore evaluated LV volumes and transcutaneous PCO2 (PtcCO2) during wakefulness and stage 2 sleep in 16 patients with CHF due to nonischemic dilated cardiomyopathy (NIDC). Data were then compared between those with (n = 7) and those without CSR-CSA (n = 9). LV end-diastolic volume (LVEDV) was significantly higher in patients with than those without CSR-CSA (585 +/- 118 versus 312 +/- 41 ml, p < 0.05). Compared with patients without CSR-CSA, those with CSR-CSA had lower mean stage 2 sleep PtcCO2 (36.3 +/- 2.2 versus 41.2 +/- 1.2 mm Hg, p < 0.05) and a lesser change in PtcCO2 from wakefulness to stage 2 sleep (-0.4 +/- 0.3 versus 2.0 +/- 0.4 mm Hg, p < 0.001). Among patients with CSR-CSA, hyperpnea length was inversely related to LVEDV (R = 0.769, p = 0.043) owing to the direct relationship of cardiac output to LVEDV (R = 0.791, p = 0.034). We conclude that CSR-CSA in patients with CHF due to NIDC is associated with increased LV volumes possibly through the direct or indirect influence of LV volume on PaCO2 and cardiac output.

Objectives: We sought to determine the effects of continuous positive airway pressure (CPAP) on mitral regurgitant fraction (MRF) and plasma atrial natriuretic peptide (ANP) concentration in patients with congestive heart failure (CHF)., Background: In patients with CHF, elevated plasma ANP concentration is associated with elevated cardiac filling pressures. Secondary mitral regurgitation may contribute to elevation in plasma ANP concentration in patients with CHF. Because CPAP reduces transmural cardiac pressures and left ventricular (LV) volume, we hypothesized that long-term CPAP application would decrease the MRF and plasma ANP concentration in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA)., Methods: Seventeen patients with CHF and CSR-CSA underwent baseline assessments of plasma ANP concentration and left ventricular ejection fraction (LVEF) and MRF by radionuclide angiography. They were then randomized to receive nocturnal CPAP plus optimal medical therapy (n = 9) or optimal medical therapy alone (n = 8) for 3 months and were then reassessed., Results: In the CPAP-treated group, LVEF increased from (mean +/-SEM) 20.2 +/- 4.2% to 28.2 +/- 5.3% (p < 0.02); MRF decreased from 32.8 +/- 7.7% to 19.4 +/- 5.5% (p < 0.02); and plasma ANP concentration decreased from 140.9 +/- 20.8 to 103.9 +/- 17.0 pg/ml (p < 0.05). The control group experienced no significant changes in LVEF, MRF or plasma ANP concentration. Among all patients, the change in plasma ANP concentration from baseline to 3 months correlated significantly with the change in MRF (r = 0.789, p < 0.0002)., Conclusions: In patients with CHF, CPAP-induced reductions in MRF and plasma ANP concentration in association with improvements in LVEF indicate improved cardiac mechanics. Our findings also suggest that reductions in plasma ANP concentration were at least partly due to reductions in MRF.