Excessive Daytime Sleepiness in Obstructive Sleep Apnea Patients Treated With Continuous Positive Airway Pressure: Data From the European Sleep Apnea Database

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3–13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1–15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea–hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0–3 months, then it was 13–19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment

Cardiopulmonary Exercise Physiology in AL Amyloidosis Patients with Cardiac Involvement and Its Association with Cardiac Imaging Parameters.

Background: Cardiopulmonary exercise testing (CPET) has been widely used for the functional evaluation of patients with heart failure. Patients with amyloidosis and cardiac involvement typically present with heart failure with preserved or mildly reduced ejection fraction. We sought to evaluate the use of CPET parameters in patients with AL amyloidosis for the assessment of disease severity and prognosis and their association with cardiac imaging findings. Methods: A single-center prospective analysis was conducted, which included 23 consecutive ambulatory patients with AL amyloidosis with cardiac involvement, not requiring hospitalization or intravenous diuretics. Patient evaluation included CPET, laboratory testing, echocardiography and cardiac MRI. The cohort was divided according to the presence of high-risk CPET characteristics (below median peak VO2 and above median VE/VCO2). Results: Patients with AL amyloidosis and cardiac involvement (median age was 60 years (56.5% males) had median peak relative VO2 (VO2/kg) of 17.8 mL/kg/min, VE/VCO2 slope of 39.4 and circulatory power of 2362.5 mmHg⋅mL/kg/min. Peak relative VO2 gradually declined across Mayo stages (p = 0.046) and exhibited a significant inverse correlation with NT-proBNP levels (r = −0.52, p = 0.01). Among imaging parameters, peak VO2 positively correlated with global work efficiency (r = 0.61, p < 0.001), and global work index (r = 0.45, p = 0.04). The group of patients with high-risk CPET findings showed evidence of more advanced disease, such as higher NT-proBNP levels (p = 0.007), increased septal and posterior left ventricular wall thickness (p = 0.043 and p = 0.033 respectively) and decreased global work efficiency (p = 0.027) without substantial differences in cardiac MRI parameters. In this group of patients, peak VO2 and VE/VCO2 were not associated significantly with overall survival and cardiac response at one year. Conclusion: In patients with AL amyloidosis, evaluation of exercise capacity with CPET identified a group of patients with more advanced cardiac involvement. The potential of CPET as a risk stratification tool in AL amyloidosis with cardiac involvement warrants further research

Positive airway pressure (PAP) treatment reduces glycated hemoglobin (HbA1c) levels in obstructive sleep apnea patients with concomitant weight loss: Longitudinal data from the ESADA

Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9±423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98±1.01% to 5.93±0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (−0.15±1.02, p=0.019), those with severe OSA baseline (−0.10±0.68, p=0.005), those with morbid obesity (−0.20±0.81, p&lt;0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction &gt;5 kilos (−0.38±0.99, p&lt;0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction &gt;5 kilos (p&lt;0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA

Arterial bicarbonate is associated with hypoxic burden and uncontrolled hypertension in obstructive sleep apnea - The ESADA cohort

Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. Results: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, &lt;0.001, &lt;0.001, and &lt;0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88–1.54], −0.16 [-0.20 to −0.11], −0.51 [-0.64 to −0.37], 1.76 [1.48–2.04], respectively, all p &lt; 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01–1.08], p = 0.013). Conclusion: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA

Profiling of Differentially Expressed Genes Using Suppression Subtractive Hybridization in an Equine Model of Chronic Asthma

Background :\ud Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma.\ud \ud Objective :\ud To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition.\ud \ud Methods :\ud Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay.\ud \ud Results :\ud Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways.\ud \ud Conclusions :\ud Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies

Management of obstructive sleep apnea in Europe-A 10-year follow-up

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/)

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study

Background:Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages.Objective:To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI.Methods:Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years.Results:Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher.Conclusions:Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring

A health-economic analysis of diagnosis and treatment of obstructive sleep apnea with continuous positive airway pressure in relation to cardiovascular disease. The Greek experience.

Purpose: 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.Methods: 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.Results: 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.Conclusions: 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. © 2014, Springer-Verlag Berlin Heidelberg

Sleep during “lockdown” in the COVID-19 pandemic

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 ± 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 &amp;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 &amp;lt; 0.001, η2 = 0.012). Sleep duration remained stable in health professionals (−0.18 h; 95% CI −0.36, 0.01; p = 0.063), whereas it increased in other occupations by 0.31 h (95% CI, 0.24, 0.39; p &amp;lt; 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−19 pandemic and lockdown affected sleep in different ways, depending on age, level of education, occupation, and country of residence. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

High-flow oxygen through nasal cannula vs. Non-invasive ventilation in hypercapnic respiratory failure: A randomized clinical trial

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 ≥ 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 &amp;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 &amp;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 ± 9.4 mmHg versus 59.6 ± 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland