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Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Cardiopulmonary Exercise Testing (CPET) is a standardized, non-invasive procedure assessing pulmonary, cardiovascular, hematopoietic, and skeletal muscle functions during a symptom-limited test. Few studies have examined whether CPET is of prognostic value in Systemic Sclerosis (SSc), a disease characterized by highly increased cardiorespiratory morbidity and mortality. To examine the prognostic value of CPET in SSc patients without baseline pulmonary hypertension (PH). Sixty-two consecutive SSc patients underwent CPET, Pulmonary Function Tests (PFTs) and echocardiography at baseline. Four patients with Right Ventricular Systolic Pressure ≥ 40 mmHg, were excluded. Participants repeated PFTs approximately every 3 years. At the end of the follow-up period [median (IQR): 9.79 (2.78) years] patient vital status was recorded. Cox Regression analysis was used to identify predictors of deterioration of PFTs and 10-year survival. Median (IQR) age of 58 patients (90% women) at baseline was 54.0 (15.0) years, whereas 10-year survival was 88%. Baseline respiratory Oxygen uptake (VO2max) predicted PFT deterioration, defined either as a decline in FVC ≥ 10% or a combined decline in FVC 5%-9% plus DLCO ≥ 15%, during follow-up, after correction for age, gender and smoking status (HR: 0.874, 95%CI: 0.779–0.979, p = 0.021). In addition, lower baseline VO2max (HR = 0.861, 95%CI:0.739–1.003, p = 0.054) and DLCO (HR = 0.957, 95%CI: 0.910–1.006 p = 0.088), as well as male gender (HR = 5.68, 95%CI: 1.090–29.610 p = 0.039) and older age (HR = 1.069, 95%CI: 0.990–1.154, p = 0.086) were associated, after adjustment, with an increased risk for death. In the absence of baseline PH, CPET indices may predict pulmonary function deterioration and death in SSc patients during a nearly 10-year follow-up period.

Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea-Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy.The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented.Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS.The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well.

Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time.Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice.Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.

Introduction Several epidemiological studies have demonstrated that Obstructive Sleep Apnea (OSA) is a highly prevalent disorder in the general population and increases over time all over the world. The high prevalence is in part due to increasing rates of obesity. However, estimates of OSA prevalence in Southern Europe are generally lacking. Aim The aim of our study was to predict the risk of OSA in the general population of Cyprus, the southeast part of Europe, by using a dedicated questionnaire like STOP-Bang. Subjects and method We screened 5736 sample housing units for eligible adults and a total population of 4118 eligible responders completed the STOP-Bang questionnaire. Participants were all adults, age 18 + residing in Cyprus. The sample was stratified according to the last demographic report (2016) by district, rural or urban area, gender and age and the estimated sample size needed was 2000. Our survey was conducted by Computer Aided Telephone Interviewing (CATI) method. The question about Neck Circumference was removed from the final evaluation due to the uncertainty of most of the participants and the risk of bias. Results From a total of 4118 participants (2252 males – 54.7%, 1862 females – 45.3%), with 46.6% over 50 years old, 2641 (64.1%) were at low risk for OSA (0–2 positive answers), 1200 (29.1%) at intermediate risk (3–4 positive answers) and 277 (6.7%) at high risk (≥5 positive answers). In sum, 29.9% responded positively for snoring, 39.3% for feeling tired or sleepy during the day, 12.3% for observed apnea during sleep, and 24.6% for having or being treated for hypertension. Class II and III obesity with Body Mass Index (BMI) > 35 kgr/m2 was observed in 192 subjects (4.7%). In the subpopulation of obese participants (BMI>30 kg/m2), intermediate to high risk of OSA was present in 45%, whereas in obesity class II and III the percentage reached almost 90%. Conclusions Our survey yielded that the prevalence of intermediate to high risk for OSA was 50% in males and 18% in females, in the general population of Cyprus. These findings were similar to previously reported high OSA prevalence worldwide, considering the fact that a single questionnaire is only a screening tool and cannot alone diagnose sleep apnea.

The aim of the present study was to evaluate the possible correlations between sleep, physical activity, and diet in the general population of Greece during the second lockdown due to COVID-19 pandemic. A web-based questionnaire including 28 items was completed by 494 adults (age 31.5 ± 12.4 years). Half of the participants (49.8%) reported good, 44.1% moderate, and 6.1% bad quality of sleep, whereas 17.2% answered that the quality of sleep improved, 56.5% did not change, and 26.3% worsened compared to a normal week. Compared to normal, sleep duration in lockdown increased by 0.24 h (95% CI, 0.13, 0.35, p &lt, 0.001, d = 0.198). More under-weight (32.4%) and obese (34.1%) respondents reported worsened quality of sleep in lockdown compared with normal (25.6%) and overweight participants (22.7%) (p = 0.006, Cramer’s φ = 0.191). A small effect for BMI group on sleep duration was observed (p = 0.011, η2 = 0.023), where overweight and obese slept less (–0.44 h and –0.66 h, respectively) than normal weight participants. Subjects with the highest percentage of increased food consumption reported decreased sleep duration (p = 0.012) and worsened sleep quality (p = 0.003). Compared with a normal week, physical activity of a high and moderate intensity decreased for 43.0% and 37.0% of participants, did not change in 32.9% and 36.1% of participants, and increased in 24.1% 26.9%, respectively, whereas walking time decreased in 31.3%, did not change in 27.3%, and increased in 41.5% of participants. Increased high and moderate intensity physical activity was related with an improvement in sleep quality (p &lt, 0.001). Those with decreasing walking time reported the highest percentage of decreased sleep quality (p = 0.006) and worsened sleep quality (p = 0.016). In conclusion, both quality and quantity of sleep were impaired during the second lockdown and the observed changes were associated with diet and physical activity.

The aim of this study was to determine if the lockdown measures applied due to the pandemic of Coronavirus Disease 2019 (COVID-19) affected the sleep of the general population and health professionals in six different countries (Greece, Switzerland, Austria, Germany, France, and Brazil). We used a web-based survey with a short questionnaire of 13 questions, translated into four languages (Greek, German, French, and Portuguese). The questionnaire included information about demographic and professional data, quantitative and qualitative characteristics of sleep, degree of abidance in lockdown measures, and data about illness or close contact with active confirmed cases of COVID-19. Initially, 2093 individuals participated. After exclusion of those who did not report their duration of sleep, the final sample comprised 1908 participants (Greek, n = 1271, German, n = 257, French, n = 48, Portuguese, n = 332), aged 42.6 &plusmn, 12.7 years, who were considered for further analysis. A main effect of the lockdown week on sleep duration was observed (+0.25 h, 95% confidence intervals, CI, 0.17, 0.32, p &lt, 0.001), with the total sleep time of the lockdown week being longer than that under normal conditions. A week*occupation interaction on sleep duration was demonstrated (p &lt, 0.001, &eta, 2 = 0.012). Sleep duration remained stable in health professionals (&minus, 0.18 h, 95% CI &minus, 0.36, 0.01, p = 0.063), whereas it increased in other occupations by 0.31 h (95% CI, 0.24, 0.39, 0.001). In terms of sleep quality, 15% of participants characterized their sleep as bad and 37.9% as average during the lockdown week. Almost 1 in 3 individuals (31.3%) reported worse quality of sleep during the lockdown week than under normal conditions. Sleep during the lockdown week was characterized as good by 47.1%, but only 38% of the health professionals group. In conclusion, the COVID&minus, 19 pandemic and lockdown affected sleep in different ways, depending on age, level of education, occupation, and country of residence.

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V., ResMed Foundation European Respiratory Society, ERS European Respiratory Society, ERS European Respiratory Society, ERS, The ESADA network has received support from the European Union COST action B26 and the European Respiratory Society (ERS) funded Clinical Research Collaboration (CRC). Unrestricted seeding grants from the ResMed Foundation and the Philips Respironics Foundation for establishment of the database in 2007 and 2011 are gratefully acknowledged. The ESADA network has a scientific collaboration with Bayer AG., Nonfinancial support was provided by the European Sleep Research Society (ESRS) and the European Respiratory Society (ERS) in terms of logistics for communication, meetings and data presentations for the ESADA collaborators., Dr. Verbraecken reports grants and personal fees from ResMed, Bioprojet, Jazz Pharmaceutics; personal fees from Philips, Sanofi, Agfa-Gevaert, grants from AirLiquide; personal fees from Springer, Westfalen Medical, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, AstraZen, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Dr. Hedner reports grants from ResMed, Philips Respironics, and the European Respiratory Society all related to maintenance of database on behalf of the ESADA group during the conduct of the study. Dr. Grote reports grants from Bayer, Resmed, Respironics/Philips, and from the European Respiratory Society during the conduct of the study; non-financial support and other from Itamar Medical, Resmed, Philips, and Astra Zeneca, outside the submitted work. In addition, Dr. Grote has a patent on sleep apnea therapy licensed. The remaining co-authors have no conflict of interest to declare.

High-flow oxygen through nasal cannula (HFNC) provides adequate oxygenation and can be an alternative to noninvasive ventilation (NIV) for patients with hypoxemic respiratory failure. The aim of the present study was to assess the efficacy of HFNC versus NIV in hypercapnic respiratory failure. Patients (n = 40) who were admitted to the Emergency Department of Alexandra Hospital due to hypercapnic respiratory failure (PaCO2 &ge, 45 mmHg) were randomized assigned into two groups, i.e., an intervention group (use of HFNC, n = 20) and a control group (use of NIV, n = 20). During their hospitalization in the Intensive Care Unit, vital signs (respiratory and heart rate, arterial blood pressure) and arterial blood gases (ABG) were closely monitored on admission, after 24 h and at discharge. No difference between the two groups regarding the duration of hospitalization and the use of HFNC or NIV was observed (p &gt, 0.05). On admission, the two groups did not differ in terms of gender, age, body mass index, APACHE score, predicted death rate, heart rate, arterial blood pressure and arterial blood gases (p &gt, 0.05). Respiratory rate in the HFNC group was lower than in the NIV group (p = 0.023). At discharge, partial carbon dioxide arterial pressure (PaCO2) in the HFNC group was lower than in the NIV group (50.8 &plusmn, 9.4 mmHg versus 59.6 &plusmn, 13.9 mmHg, p = 0.024). The lowerPaCO2 in the HFNC group than in the NIV group indicated that HFNC was superior to NIV in the management of hypercapnic respiratory failure.

Supplemental Digital Content is available in the text., Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors–matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41–13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17–3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45–12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

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

Pre-existing pulmonary disease may affect treatment choices, toxicity, and survival of patients with multiple myeloma (MM). However, data on the prognostic value of pulmonary function tests (PFTs) in myeloma patients’ outcome, at the time of initial assessment of newly diagnosed patients, are scarce. Here, we prospectively performed PFTs in 121 newly diagnosed MM patients, before initiation of treatment, and we evaluated possible associations of lung function with their outcomes. Fifty-four patients (44.63%) had either obstructive or restrictive pulmonary function defects, even among those not reporting a history of lung disease. The survival was significantly worse in those with obstructive pulmonary defect (median OS 32.8 months) vs. those with restrictive (median OS 52.5 months) or normal lung function (median not reached, 3-year survival 76%) (p = 0.013), independently of other myeloma-related factors. Forced vital capacity (FVC) (lt) (p = 0.012), forced expiratory volume in 1 s (FEV1) (lt) (p = 0.018), peak expiratory flow (PEF) (lt/min) (p = 0.008), carbon monoxide diffusion capacity (DLCO) (p = 0.012), and expiratory/inspiratory pressures (Pe) (kPa) (p = 0.032)/(Pi) (kPa) (p = 0.023) were significantly associated with OS. Myeloma-related factors associated with survival included ISS stage (p = 0.008), hypercalcemia (p = 0.064), and high-risk cytogenetics (p = 0.004). In the multivariate analysis, only the presence of high-risk cytogenetics and presence of either or both PEF and DLCO

Patients with Chronic Obstructive Pulmonary Disease (COPD) and / or Obstructive Sleep Apnea (OSA) often complain about sleepiness, fatigue, anxiety and depression. However, common screening questionnaires, like Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS) have not been previous evaluated in patients with overlap-coexisting COPD and OSA-syndrome versus patients with OSA alone. Our study compared ESS, FSS and HADS between patients with overlap syndrome and patients with OSA, before and after treatment with Continuous Positive Airways Pressure (CPAP). We examined 38 patients with coexisting COPD and OSA versus 38 patients with OSA-only and 28 subjects without respiratory disease, serving as controls. All patients underwent pulmonary function tests (PFTs), oximetry and overnight polysomnography and completed the questionnaires, before and after 3 months of CPAP therapy. The two patient groups did not differ significantly in terms of age, Body Mass Index (BMI), neck, waist and hip circumferences, and arterial blood pressure values. They also had similar comorbidities. They differed significantly, as expected, in PFTs (Forced Vital Capacity-FVC, 2.53±0.73 vs 3.08±0.85 lt, p = 0.005, Forced Expiratory Volume in 1sec-FEV1, 1.78±0.53 vs 2.60±0.73 lt/min, p

Obstructive sleep apnea syndrome (OSAS) is common in adult population and it is associated with increased morbidity and mortality, especially due to cardiovascular disease (CVD). Both diagnosis, based on polysomnography, and treatment with continuous positive airway pressure (CPAP), carry a potentially high cost. The present study aims to analyze the cost-effectiveness of CPAP treatment versus no treatment, in the long-term, as it examines the effect of this treatment on the incidence of CVD.A Markov model was constructed to observe the disease evolution in patients with OSAS based on published evidence. Data on treatment costs were collected from public hospitals in Greece. Within each cycle of the model, each patient may remain free of CVD, may develop CVD, may die due to a cause related to CVD, or may die from other causes. The model begins at the age of 55 years in a severe OSAS patient (apnea-hypopnea index ≥30/h) and lasts for 45 years.Within the limitation of the model, CPAP was found to be a cost-effective strategy versus no treatment, due to the reduction of the cost for the CVD treatment, when the analysis was restricted to the male population. Moreover, CPAP was found to be clinically more effective than no treatment, as it increases life expectancy in both males and females.CPAP was found to be clinically more effective therapy than no treatment in relation to CVD and a cost-effective strategy in males with severe OSAS.

Cyclophosphamide is considered the treatment of choice for interstitial lung disease (ILD) secondary to systemic sclerosis (SSc), albeit having a minimal effect. Although controlled evidence does not exist, mycophenolate is used increasingly in clinical practice as an alternative. We aimed to compare the long-term efficacy of these drugs. Patients from our SSc cohort who received mycophenolate for over 1 year for progressive ILD were 1:1 matched for age, gender, and baseline forced vital capacity (FVC ±3 %) with cyclophosphamide-treated patients. Changes in FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) scans were compared between groups. Changes in pulmonary function tests (PFTs) over at least 1 year in six unmatched control patients, who had denied mycophenolate or cyclophosphamide, also were examined. FVC, TLC, and DLCO did not change significantly in either mycophenolate (from 79.0 ± 12.5 to 80.2 ± 8.1 to 81.2 ± 11.4, from 71.5 ± 16.1 to 74.3 ± 10.8 to 71.8 ± 13.0, from 56.8 ± 12.0 to 55.2 ± 9.9 to 50.6 ± 8.5, respectively) or cyclophosphamide group (from 77.3 ± 12.5 to 79.7 ± 10.3 to 82.5 ± 12.9, from 64.7 ± 14.9 to 68.6 ± 16.0 to 66.1 ± 15.5, from 53.1 ± 14.3 to 56.4 ± 13.5 to 56.3 ± 6.7, respectively), after 1 or 2 years of treatment. PFTs also remained stable in the control group. In either the mycophenolate or cyclophosphamide groups, six patients remained stable, three improved, and one deteriorated according to the definitions of the American Thoracic Society. However, and despite the fact that patients in the cyclophosphamide group had more extended ILD at baseline, a deterioration of lung HRCT findings at 2 years was noticed after mycophenolate (from 10.0 ± 8.9 to 12.7 ± 8.2, p = 0.039) but not after cyclophosphamide. Although these results derive from patients selected for receiving at least 1 year of treatment and therefore they do not represent an intention-to-treat cohort, an eagerness to replace cyclophosphamide by mycophenolate in SSc-associated ILD treatment is not supported.

The purpose of this study was to investigate the role of a fatty meal before bedtime, on sleep characteristics and blood pressure in patients with obstructive sleep apnea (OSA). Recently diagnosed, by full polysomnography (PSG), patients with OSA (n = 19) were included. These underwent PSG for additional two consecutive nights. Two hours before the PSG examination, a ham and cheese sandwich of 360 kcal was served to all patients, at first night, while a fatty meal of 1,800 kcal was served before the second PSG examination. Comparisons were performed between the last two examinations in terms of PSG data and morning and night blood pressure measurements. After the fatty meal, a significant increase was observed in total sleep time (p = 0.026) in the Apnea–Hypopnea Index (AHI) (p = 0.015), as well as in the absolute number of obstructive and central apneas (p = 0.032 and p = 0.042, respectively) compared to the previous night. Conversely, distribution of sleep stages and indices of nocturnal hypoxia (average and minimum SpO2 and sleep time with SpO2

Obstructive sleep apnea syndrome (OSAS) is associated with obesity and insulin resistance. Visfatin is an insulin-mimicking adipokine, which is considered a link between obesity and insulin resistance. Aim of this study was to evaluate levels of plasma visfatin in patients with severe OSAS and examine their potential correlation with sleep characteristics and several biochemical parameters.Nondiabetic patients with severe OSAS (Apnea Hypopnea Index30/h, n = 32) and healthy controls (Apnea Hypopnea Index5/h, n = 12), examined with polysomnography, underwent a biochemical analysis to estimate fasting levels of visfatin, glucose, insulin, C-peptide, and lipid profile.The two groups were matched for age and body mass index (BMI). OSAS patients had significantly higher fasting insulin levels (p = 0.045), but no difference was shown in visfatin between patients and controls (p = 0.585). In OSAS patients, visfatin levels correlated positively with sleep latency (r = 0.539, p = 0.01) and triglyceride levels (r = 0.584, p = 0.036) and negatively with total sleep time, percentage of stage 2 and REM sleep, and LDL-cholesterol levels (r = -0.659 and p = 0.001; r = -0.496 and p = 0.019; r = -0.577 and p = 0.005; r = -0.804 and p = 0.003, respectively). No association was found, however, between visfatin levels and HOMA index or indices of nocturnal hypoxia.In patients with severe OSAS, visfatin levels are associated with characteristics of sleep architecture. However, there is no correlation between visfatin and insulin resistance or nocturnal hypoxia.

Anastasios Kallianos,1 Athanasios Panoutsopoulos,1 Christoforos Mermigkis,2 Konstantinos Kostopoulos,1 Chrysanthi Papamichail,1 Ioannis Kokkonouzis,3 Christoforos Kostopoulos,1 Ioannis Nikolopoulos,4 Antonis Papaiwannou,5 Sofia Lampaki,5 John Organtzis,5 Georgia Pitsiou,5 Paul Zarogoulidis,5 Georgia Trakada1 1Sleep Disorders Unit, Department of Clinical Therapeutics, “Alexandra” General Hospital, Athens School of Medicine, 2Sleep Disorders Unit, Pulmonary Department, 401 General Army Hospital, 3Pulmonary Department, 251 Hellenic Air Force General Hospital, 4Sleep Disorders Unit, “Sotiria” Regional Chest Diseases Hospital of Athens, Athens, Greece; 5Pulmonary Department – Oncology Unit, George Papanikolaou General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, GreeceIntroduction: There is growing research evidence suggesting the presence of endothelial dysfunction and systemic inflammation in patients with obstructive sleep apnea syndrome (OSAS). Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS; nonetheless, the effects of CPAP on the aforementioned pathophysiologic pathways as well as on the systemic disease that result or coexist with the OSAS remain elusive.Aim: To assess the effect of 3-month CPAP therapy on endothelial-dependent dilation, plasma levels of inflammatory markers, blood pressure (BP), and glucose control on male and female patients with OSAS.Methods: Our study group consisted of 40 (24 males and 16 females) patients with no prior history of cardiovascular disease, with an apnea–hypopnea index ≥15, who were assigned to receive CPAP treatment. Measurements of flow-mediated dilation (FMD), 24-hour ambulatory BP, and blood analysis were performed at baseline and 3months after CPAP therapy.Results: Baseline FMD values were negatively correlated with the apnea–hypopnea index (r=−0.55, P=0.001). After 3months of CPAP, there was an increase in the FMD values (5.40%±2.91% vs 3.13%±3.15%, P

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.

The proinflammatory cytokines, TNFalpha and IL-6, are elevated in obstructive sleep apnea (OSA) and have been proposed as mediators of excessive daytime sleepiness in humans. We tested the effects of etanercept, a medication that neutralizes TNFalpha and is approved by the FDA for the treatment of rheumatoid arthritis, in eight obese male apneics. These patients participated in a pilot, placebo-controlled, double-blind study during which nighttime polysomnography, multiple sleep latency test, and fasting blood glucose and plasma levels of IL-6, C-reactive protein, insulin, and adiponectin were obtained. There was a significant and marked decrease in sleepiness by etanercept, which increased sleep latency during the multiple sleep latency test by 3.1 +/- 1.0 min (P < 0.05) compared with placebo. Also, the number of apneas/hypopneas per hour was reduced significantly by the drug compared with placebo (52.8 +/- 9.1 vs. 44.3 +/- 10.3; adjusted difference, -8.4 +/- 2.3; P < 0.05). Furthermore, IL-6 levels were significantly decreased after etanercept administration compared with placebo (3.8 +/- 0.9 vs. 1.9 +/- 0.4 pg/ml; adjusted difference, -1.9 +/- 0.5; P < 0.01). However, no differences were observed in etanercept vs. placebo in the levels of fasting blood glucose and plasma C-reactive protein, insulin, and adiponectin. We conclude that neutralizing TNFalpha activity is associated with a significant reduction of objective sleepiness in obese patients with OSA. This effect, which is about 3-fold higher than the reported effects of continuous positive airway pressure on objective sleepiness in patients with OSA (0.9 vs. 3.1 min), suggests that proinflammatory cytokines contribute to the pathogenesis of OSA/sleepiness.

Pregnancy is associated with significant alterations in respiratory function. Changes during pregnancy include reduced functional residual capacity (FRC) and residual volume (RV), increased alveolar-arterial difference for oxygen (A-αPO 2 ) and in the supine position, reduced cardiac output. In conjunction with sleep-related apneas or hypopneas, these could lead to maternal oxygen desaturation during sleep. Because of the conflicting data from sleep studies in late pregnancy, we performed complete polysomnography on 11 pregnant women at 36 weeks of gestation and again postpartum. We also measured the PaO 2 , every 2h. The frequency of apneas and hypopneas was significantly lower during pregnancy compared with that on the postpartum control night. PaO 2 levels in the supine position, during sleep, were also significantly lower during pregnancy compared to the postpartum period. No correlation was observed between PaO 2 levels and apneas or hypopneas or percent of REM sleep.

Background: Endothelin-1 (ET-1) has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and sputum and fails with treatment of the exacerbations. Hypoxemia stimulates ET-1 secretion. Objective: The aim of this study was to examine the serum ET-1 levels in stable asthmatic and COPD patients. Materials and methods: We examined 48 COPD and 26 asthmatic patients and 34 normal subjects. We collected arterial samples to measure baseline ET-1 levels in all patients and in the control group, during the day. All the patients underwent formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, and oxyhemoglobin desaturation. Twelve of the COPD patients and six of the asthmatic patients were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of the COPD patients desaturated below a baseline sleep saturation of 90% for 5min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, 5min after the first period of desaturation in each of the 19 desaturators COPD patients. None of the 20 asthmatic patients exhibited oxyhemoglobin desaturation during sleep. Results: Baseline arterial ET-1 levels during the day were significantly higher in “desaturators” COPD patients (2.08±0.28pg/ml) compared to “non-desaturators” COPD patients (1.38±0.16pg/ml) (P

Marathon racing is a strenuous exercise that has a profound effect on many laboratory parameters. Participants in marathon races may require abstinence of exercise and the performance of laboratory assays several days after the event. The aim of this study was to evaluate the possible changes in blood cell count and biochemical parameters observed in participants in a marathon 3 days before and 3 days after and before and immediately after a cardiopulmonary exercise test. Incremental cycle ergometry up to maximal capacity was performed in 7 marathon runners, 3 days before and 3 days after the race. The % peak oxygen consumption (peak %VO(2)) achieved was statistically significantly lower after than before the race ( p = 0.02). No statistically significant differences were observed in cardiac frequency ( p = 0.148) or blood cell count ( p = 0.501). Also, the concentration of sodium, potassium, calcium, magnesium, lactate dehydrogenase (LDH), phosphocreatine kinase (CPK) and glucose, measured before and immediately after the pulmonary exercise test, did not differ significantly ( p < 0.5). A significant percentage of the laboratory results were outside the standard reference rates. According to our data, exercise performance, as expressed by peak %VO(2), continued to be decreased in marathon runners 3 days after the race. The blood cell count and biochemical parameters did not differ significantly but many marathon runners were outside the standard reference rates. Unfortunately, only 7 subjects were available for this study. Further studies with larger samples and with samples obtained at multiple times during and after exercise are needed to clarify the effects of long-distance running.

Objective: The aim of this study was to determine prognostic factors for outcome in patients with lower respiratory tract infections (LRTI). LRTI are an heterogeneous group of disorders, including acute bronchitis, pneumonia, superinfection of chronic bronchitis and influenza. Methodology: A total of 616 patients with LRTI were retrospectively reviewed with regard to epidemiological, clinical, laboratory and radiographical data. Prognostic analysis included a univariate as well as a multivariate approach, in order to identify parameters associated with death. Results: The parameters found to be significantly different between survivors and non-survivors in the univariate analysis, were respiratory rate, Pao2, heart rate, systolic and diastolic blood pressure, platelet count, urea, creatinine, previous admission to the hospital in the last year and cavitations visible on the chest radiograph. Conclusions: LRTI remain a widespread problem and have a significant impact on primary healthcare resources. The great variability seen in rates of hospital admission and lengths of stay in part reflects uncertainty among physicians in assessing the severity of the illness. According to our data, Pao2 and heart rate were most closely associated with patient death and are readily defined and available at presentation.

Background: Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COPD). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bronchoconstriction and activation of alveolar macrophages. Objective: The aim of this study was to examine a possible correlation between ET-1 levels and nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with COPD. Methods: We examined 48 COPD patients with formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of them desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, after 5 min of the first period of desaturation, in each of the 19 patients. We also collected arterial samples in the morning, before the study, to measure baseline ET-1 levels in all patients. Results: Baseline arterial ET-1 levels during the day were very significantly higher in ‘desaturator’ COPD patients (2.058 ± 0.252 pg/ml) compared to ‘non-desaturator’ COPD patients (1.382 ± 0.159 pg/ml; p < 0.001). Also in ‘desaturator’ COPD patients ET-1, levels during the night were significantly higher (4.297 ± 1.107 pg/ml) compared to those during the day (p ≤ 0.001) and a significant negative correlation was observed between ET-1 levels and degree of desaturation (p < 0.0001, r = 0.9305). Conclusions: According to our study we can conclude that (1) ET-1 levels are significantly higher in ‘desaturator’ COPD patients both during the day and during the night, and (2) ET-1 levels correlate negatively significant with the degree of the oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role in the pathophysiological manifestations of COPD patients.

Endothelins are a family of peptide mediators that have a number of biological properties, including the ability to act as bronchoconstrictors and vasoconstrictors of isolated airways and vessels. Endothelin-1 (ET-1) is the more potent peptide compared with the other two peptides of the family. To examine a possible involvement of ET- 1 in the pathogenesis of asthma, we measured arterial ET-1 levels in 11 patients with atopic asthma during attack and during remission, and in 11 healthy control subjects. We also performed fiberoptic bonchoscopy and bronchoalveolar lavage (BAL) to measure ET-1 levels in the 11 asthmatic patients during remission, and in the 11 healthy control subjects. ET-1 concentrations in arterial blood and in BAL were measured by a radioimmunoassay method. Arterial ET-1 levels were very significantly higher in asthma attack (3.67 +/- 0.51 pg ml(-1)) and in asthma remission (2.65 +/- 10.62 pg ml(-1)) compared with those of the healthy controls (1.37 +/- 0.14 pg ml(-1)) (P < 0.001). Arterial ET-1 levels were also very significantly higher during asthma attack compared with those in asthma remission (P < 0.001). BAL ET-1 levels were significantly higher in asthma remission (0.73 +/- 0.53 pmol g(-1)) compared with those of the healthy controls (0.16 +/- 0.02 pmol g(-1)) (P < 0.05). No correlation was observed between arterial and BAL ET-1 levels, PaO2 and peak expiratory flow rate (PEFR). These data are consistent with the hypothesis that ET-1 contributes to the pathophysiology of asthma. However, it is likely that the true importance of this vasoconstrictor peptide will only be revealed by pharmacological studies with specific receptor antagonists.

BACKGROUND Continuous positive airway pressure (CPAP) is the most effective method for treating obstructive sleep apnea syndrome (OSAS) and alleviating symptoms. Improved sleep quality with effective CPAP therapy might also contribute to attenuated systemic inflammation and improved endothelial function, with subsequent reduction of cardiovascular risk. The aim of this study was to assess the effect of 3-month CPAP therapy on brachial artery flow-mediated dilation (FMD) and plasma C-reactive protein (CRP) levels in patients with OSAS. MATERIAL/METHODS Our study group consisted of 38 male patients with no prior history of cardiovascular disease. Twenty patients with an Apnea-Hypopnea Index (AHI) ≥15 were assigned to receive CPAP treatment and 18 subjects with an AHI

Evidence suggests that obesity hypoventilation syndrome (OHS) is underrecognized and undertreated. Aim of this study was to evaluate the prevalence and clinical characteristics of OHS among patients reporting sleep-related breathing disorders in northern Greece.Individuals (n=276) who consecutively underwent an attended night polysomnography, for possible obstructive sleep apnea syndrome, were recruited. OHS was defined as a combination of obesity (body mass index 30 ≥ kg/m(2)), daytime hypercapnia (PaCO(2) ≥ 45 mmHg), and sleep-disordered breathing, without any other known cause of hypoventilation. Anthropometric and sleep characteristics, daytime sleepiness, spirometry, and arterial blood gases' analysis in awake, were compared between OHS and non-OHS patients.OHS was identified in 38 of the 276 subjects (13.8%). Among study population, OHS patients were older, more obese, and more somnolent. They did not differ significantly in terms of pulmonary function in awake, whereas they differed, as expected, in arterial blood gases values in awake (PaO(2), PaCO(2)). Furthermore, OHS patients displayed lower average and minimum SpO(2) during sleep and spent more time in SpO(2)90% than non-OHS patients. The most common comorbidities were arterial hypertension, diabetes mellitus, and congestive heart failure.In our study population, OHS was accounted for a significant percentage of the patients with reported breathing disorders in sleep. As obesity has become an international epidemic, it is crucial that physicians have the ability to recognize and treat obesity-associated diseases.

Nikolaos Papanas1, Paschalis Steiropoulos2, Evangelia Nena2, Argyris Tzouvelekis2, Efstratios Maltezos1, Georgia Trakada2, Demosthenes Bouros21Outpatient Clinic of Obesity, Diabetes and Metabolism at the 2nd Department of Internal Medicine, 2Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: The aim of this study was to examine the potential correlation of sleep characteristics with glucose metabolism in nondiabetic men with obstructive sleep apnea syndrome (OSAS). Included were 31 male patients (mean age 46.7 ± 11 years), recently diagnosed with OSAS by full polysomnography. There was a significant correlation of fasting glucose and glycosylated hemoglobin (HbA1c) levels with arousal index (P = 0.047 and P = 0.014, respectively). Moreover, HbA1c levels were correlated with apnea hypopnea index (P = 0.009), a widely accepted marker of the severity of OSAS, and with percentage of sleep time with saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO2)

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Conventional treatment is based on non-specific drugs (warfarin, oxygen, diuretics). Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, functional class, exercise tolerance, haemodynamics, echocardiographic parameters and quality of life measures. Intravenous prostacyclin, was the first introduced drug for treatment of PAH and remains the first-line treatment for the most severe patients. Since then the list of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase- 5 inhibitor. Novel drugs have also shown promise in experimental trials and are likely to be added to the list of options. This article reviews the current treatments strategies for PAH.

We present a case of a 43-year-old woman with bipolar disorder who was diagnosed with sleep apnea-hypopnea syndrome (SAHS). After 10 days of treatment with continuous positive airways pressure (CPAP) during sleep, the patient presented a mood switch, from depression to mania and was admitted to the hospital.Withdrawal of CPAP and appropriate therapy controlled the episode.

Premenopausal women with polycystic ovary syndrome (PCOS) are at a much higher risk for excessive daytime sleepiness, fatigue, and insulin resistance than control women. Elevated levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) are presumably part of the pathogenesis of these clinical manifestations. Forty-two obese women with PCOS, 17 body mass index-comparable obese controls, and 15 normal-weight controls free from apnea participated in the study that included one 8-hour nighttime polysomnography, single morning cytokine plasma concentrations, and insulin resistance indices. Women with PCOS exhibited higher plasma concentrations of IL-6 than obese controls, who had intermediate values, or normal-weight controls, who had the lowest values (4.75 +/- 0.5 vs 3.65 +/- 0.4 vs 1.84 +/- 0.3 pg/mL, P < .01). Tumor necrosis factor alpha values were higher in PCOS and obese controls compared with normal-weight controls, but the difference was not statistically significant (4.05 +/- 0.3 vs 3.79 +/- 0.2 vs 3.14 +/- 0.2 pg/mL, P = .103). Based on backward regression analysis, IL-6 levels had a stronger association with the PCOS group than with the obese group, and the sleep or hypoxia variables did not make a significant contribution to either IL-6 or TNF-alpha. Both IL-6 and TNF-alpha correlated positively with body mass index (P < .01) in obese controls but not in women with PCOS. Furthermore, within the PCOS group, IL-6 and TNF-alpha correlated more strongly with indices of insulin resistance than obesity. We conclude that IL-6 levels are elevated in obese women with PCOS independently of obesity or sleep apnea and may represent a pathophysiologic link to insulin resistance.

We present a case of an obese young man who developed ischemic hepatitis, severe coagulopathy, acute renal failure, and encephalopathy. Heart failure and hypovolemia were absent. Oxygen arterial saturation was very low, between 77% and 99% during the day, with no history of respiratory failure. A diagnosis of obstructive sleep apnea was made clinically and confirmed by performing formal polysomnography. The polysomnographic study showed multiple episodes of apneas and hypopneas with severe oxygen desaturation. The patient was treated with continuous positive airway pressure through a nose mask and clinical manifestations related to profound nocturnal desaturation were ameliorated. He was discharged 32 days after admission with normal results of laboratory tests. This case report is presented to support the hypothesis that hypoxic hepatitis was directly related to severe arterial hypoxemia.

The sympathetic nervous system participates in the regulation of the basal metabolic rate (BMR) and in the manifestation of the obesity-related metabolic syndrome. A deletion/insertion germline polymorphism of the alpha(2B) adrenergic receptor that is associated with reduced agonist-promoted desensitization has been linked to low BMR in obese subjects and to a predisposition to gain weight. This study investigated an association of the alpha(2B) polymorphism with the BMR and metabolic syndrome-related parameters of morbidly obese patients. Genotype frequencies were similar in patients and in a control group. The patients' BMR, adjusted for fat-free mass, fat mass, sex and age, did not differ between alpha(2B) genotypes. The polymorphism was also not associated with the patients' BMI, systolic and diastolic blood pressure, resting heart rate, total and HDL cholesterol, triglycerides, fasting glucose and uric acid levels. These findings do not support a major functional significance of the alpha(2B) adrenergic receptor polymorphism in the present sample of morbidly obese subjects.

Background: Endothelin (ET)-1 has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and sputum, falling with treatment of the exacerbations. Objective: The aim of this study was to examine the ET-1 blood levels in stable asthmatic patients and stable COPD patients during alertness and sleep. Materials and Methods: We examined 48 COPD and 20 asthmatic patients. All underwent forced spirometry, measurement of SaO2 and of arterial ET-1 levels and nocturnal polysomnography. ET-1 levels were also determined during nocturnal oxyhaemoglobin desaturation. Results: The daytime SaO2 level of our asthmatic patients was higher than that of our COPD patients (p < 0.001). Daytime SaO2 level of our non-desaturator COPD patients was higher than that measured in desaturator COPD patients. Nightime SaO2 level in our asthmatic patients was higher than that in our desaturator COPD patients (p < 0.001). Daytime ET-1 levels in desaturator COPD patients were higher than those observed in normal individuals, in non-desaturator COPD patients and in asthmatic patients. The COPD desaturator patients had higher levels of ET-1 during nighttime than during daytime (p < 0.001). Conclusion: Asthmatic patients did not exhibit desaturation of haemoglobin during the night. ET-1 levels are significantly higher in desaturator COPD patients compared with non-desaturator COPD patients, both during the day and during the night. ET-1 levels in stable COPD patients are significantly higher than in patients with stable asthma. These findings are consistent with the hypothesis that ET-1 is implicated in the pathogenesis of COPD and asthma.

The feasibility and reliability of the combination of several noninvasive methods using a multivariate method of analysis to predict pulmonary artery hypertension (PAH) is evaluated in 20 patients with chronic obstructive pulmonary disease. These methods comprised arterial blood gases (Pao2, Paco2), pulmonary functional parameters (FEV1), echo-Doppler parameters (tricuspid regurgitation jets, acceleration time on pulmonary valve), computed tomography measurements (transhilar distance, hilar thoracic index, and measurement of the descending branch of the right pulmonary artery to the lower lobe). A multiple stepwise regression analysis (including one Doppler parameter, two parameters of arterial blood gases, and one functional parameter) revealed a coefficient of determination (R2) equal to 0.954 for mean pulmonary artery pressure (MPAP) with a standard error of estimate (S.E.E.) of 5.25 mmHg. A stepwise regression analysis including computed tomography and radiographic parameters revealed an R2 equal to 0.970 for PAP with a S.E.E. of 4.26 mmHg. Logistical regression analysis classified correctly 80% of patients with PAH using noninvasive methods such as the diameter of the main pulmonary artery and the diameter of the left pulmonary arterial branch calculated by computed tomography. Not only the presence of PAH but also the level of MPAP can be estimated by the combination of multiple stepwise and logistical regression analyses.

SummaryTracheal stenosis may be attributed to several conditions including trauma, infection, tumour or congenital and collagen vascular diseases. Despite improvement in the design of tracheal tubes, however, tracheal stenosis following intubation still remains an important cause for tracheal obstruction, which may be life threatening and often misdiagnosed. On the other hand, studies have exerted the impact of mechanical ventilation as a risk factor for pulmonary embolism. Here, we describe for the first time, an otherwise healthy patient who was mechanically ventilated due to a labor accident and developed acute pulmonary embolism that was further complicated with post-intubation tracheal stenosis. The patient was treated with anticoagulant therapy and oral corticosteroids and was further referred to a specialist centre for consideration for non-surgical endoscopic treatment.

In obstructive sleep apnea, patients' sleep is fragmented leading to excessive daytime sleepiness and co-morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n=213), moderate (n=235) and severe (n=277) obstructive sleep apnea patients as well as healthy controls (n=105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two-step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two-step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep-states for power-laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake-state durations followed a power-law distribution, while sleep-state durations were characterized by an exponential distribution. Sleep-stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n=425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea-related clinical outcomes like arterial hypertension and daytime sleepiness.