The relationship between periodic limb movement during sleep and dyslipidaemia in patients with obstructive sleep apnea.

Periodic limb movements during sleep and obstructive sleep apnea are both associated with increased sympathetic tone, and have been proposed as risk factors for heart diseases and, in particular, cardiovascular disease. As sympathetic system activation may lead to dyslipidaemia, periodic limb movements during sleep could be an additional risk factor for cardiovascular disease in patients with obstructive sleep apnea. The aim of the study was to determine whether the presence of periodic limb movements during sleep affects serum lipid levels in obstructive sleep apnea. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non- high-density lipoprotein cholesterol and triglyceride levels were investigated in 4138 patients with obstructive sleep apnea in the European Sleep Apnea Database (ESADA) cohort, divided into those with periodic limb movements during sleep index ≥ 15 per hr (n = 628) and controls (n = 3510). ANCOVA adjusted for age, sex, body mass index, apnea-hypopnea index, alcohol intake, smoking status, diabetes, insomnia and study site was used to assess differences in lipids between periodic limb movements during sleep and controls. Patients with periodic limb movements during sleep (24% female, 54.4 ± 12.1 years, body mass index 31.9 ± 5.8 kg m-2 , apnea-hypopnea index 36.7 ± 25.4 per hr) had higher triglyceride (1.81 ± 1.04 versus 1.69 ± 0.90 mmol L-1 , p = 0.002) and lower high-density lipoprotein cholesterol (1.19 ± 0.34 versus 1.24 ± 0.37 mmol L-1 , p = 0.002) levels, whilst there was no difference in either total cholesterol (4.98 ± 1.10 versus 4.94 ± 1.07 mmol L-1 ), low-density lipoprotein cholesterol (3.04 ± 0.96 versus 2.98 ± 0.98 mmol L-1 ) or non- high-density lipoprotein cholesterol (3.78 ± 1.10 versus 3.70 ± 1.05 mmol L-1 ) concentrations (all p > 0.05). The results remained unchanged after most sensitivity analyses. Patients with obstructive sleep apnea with periodic limb movements during sleep had more prevalent cardiovascular disease (11% versus 6%, p < 0.01). Periodic limb movements during sleep in obstructive sleep apnea is associated with dyslipidaemia independently of important confounders. Our results highlight periodic limb movements during sleep as an additional risk factor for cardiovascular disease in obstructive sleep apnea.

Bed partner perception of CPAP therapy on relationship satisfaction and intimacy-A European perspective from the ESADA network.

Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database.

Aim: The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods: This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. Results: After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (ß) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (ß -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion: Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.

Clinical characteristics and positive airway pressure adherence among elderly European sleep apnoea patients from the ESADA cohort.

Background: The prevalence of obstructive sleep apnoea (OSA) is growing as the population is ageing. However, data on the clinical characteristics of elderly patients with OSA and their adherence to positive airway pressure (PAP) treatment are scarce. Methods: Data from 23 418 30-79-year-old OSA patients prospectively collected into the ESADA database during 2007-2019 were analysed. Information on PAP use (h·day-1) in association with a first follow-up visit was available for 6547 patients. The data was analysed according to 10-year age groups. Results: The oldest age group was less obese, less sleepy and had a lower apnoea-hypopnoea index (AHI) compared with middle-aged patients. The insomnia phenotype of OSA was more prevalent in the oldest age group than in the middle-aged group (36%, 95% CI 34-38 versus 26%, 95% CI 24-27, p<0.001). The 70-79-year-old group adhered to PAP therapy equally well as the younger age groups with a mean PAP use of 5.59 h·day-1 (95% CI 5.44-5.75). PAP adherence did not differ between clinical phenotypes based on subjective daytime sleepiness and sleep complaints suggestive of insomnia in the oldest age group. A higher score on the Clinical Global Impression Severity (CGI-S) scale predicted poorer PAP adherence. Conclusion: The elderly patient group was less obese, less sleepy, had more insomnia symptoms and less severe OSA, but were rated to be more ill compared with the middle-aged patients. Elderly patients with OSA adhered to PAP therapy equally well as middle-aged patients. Low global functioning (measured by CGI-S) in the elderly patient predicted poorer PAP adherence.

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, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (ß 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 < 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.

Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter?

STUDY OBJECTIVES: Dyslipidemia in obstructive sleep apnea (OSA) has been attributed to confounding obesity and/or diabetes. This study aimed to examine lipid profiles in nondiabetic, nonobese patients with OSA and identify the possible effects of age and sex. METHODS: We retrospectively evaluated the lipid parameters of 3,050 adults who underwent polysomnography. A total of 2,168 patients were excluded due to obesity (body mass index ≥ 30 kg/m2), diabetes, alcoholism, untreated hypothyroidism, lipid-lowering drug use, missing sleep data, or treatment for suspected OSA. RESULTS: Of 882 patients (75% males, aged 46.8 ± 12.2 years) included in the study, 88.4% had OSA. Levels of total cholesterol (P = .003), low-density-lipoprotein (LDL) cholesterol (P = .005), non-high-density-lipoprotein (non-HDL) cholesterol (P = .001), and triglycerides (P = .007) were significantly higher in patients with OSA than in those without, whereas HDL-cholesterol levels did not differ. The proportion of patients with hypercholesterolemia and/or elevated non-HDL cholesterol (> 160 mg/dL) was significantly higher in OSA than in non-OSA. Correlation analyses by sex revealed stronger and more significant relationships between lipid parameters and apnea-hypopnea index in women than in men (r = .135, P < .001, vs r = .080, P = .043 for total cholesterol; r = .111, P < .001, vs r = .080, P = .046 for non-HDL cholesterol; r = .122, P < .001, vs r = .061, P = .107 for LDL cholesterol, respectively). In regression analysis, the rate of hypercholesterolemia increased with age (P < .001 for women and P = .031 for men); non-HDL- and LDL-cholesterol levels significantly increased with OSA severity (P = .035 and P = .023, respectively) and age (P = .004 and P = .001, respectively) in women. CONCLUSIONS: After excluding confounding obesity and diabetes, patients with OSA have an impaired lipid profile including total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides. A significant association between dyslipidemia and OSA severity was observed in women but not in men. CITATION: Basoglu OK, Tasbakan MS, Kayikcioglu M. Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter? J Clin Sleep Med. 2023;19(5):889-898.

Polygraphic evaluation of the effects of different rapid maxillary expansion appliances on sleep quality: A randomized clinical trial.

BACKGROUND: The purpose of this clinical study was to assess the effects of different rapid maxillary expansion appliances on the severity of obstructive sleep apnea (OSA). MATERIAL AND METHODS: Patients having a narrow maxilla and identified with OSA were divided randomly into three groups: tooth tissue-borne, tooth-borne, and bone-borne expanders. Changes in sleep parameters at baseline and 3-month follow-up detected by polygraphy were the primary outcome. Treatment of the crossbite was the secondary outcome. Dunn-Bonferroni tests, Kruskal-Wallis, and Wilcoxon analysis were applied for intra- and inter-group differences at p < 0.05 significance level. RESULTS: Among 46 patients randomized, apnea-hypopnea index (AHI) changed from baseline to follow-up in all groups (- 1.6, p = 0.280; 0.6, p = 0.691; - 0.45, p = 0.796, respectively), with no between-group difference (p = 0.631). Oxygen desaturation index (ODI) altered from baseline to follow-up in all groups (0.80, p = 0.977; 0.20, p = 0.932; and - 1.00, p = 0.379, respectively), with no between-group difference (p = 0.858). There was no significant difference in minimum oxygen saturation from baseline to follow-up in all groups (0.00, p = 0.401; - 2.00, p = 0.887; 0.50, p = 0.407, respectively). No significant changes were observed in supine AHI from baseline to follow-up in all groups (0.00, p = 0.581; - 1.00, p = 0.393; 0.00, p = 0.972, respectively). The upper intermolar width increased from baseline to follow-up in all groups (5.04, p = 0.000; 3.15, p = 0.001; 5.41, p = 0.00, respectively) with no between-group difference (p = 0.560). Maxillary width increased from baseline to follow-up in all groups (4.25, p = 0.001; 4.74, p = 0.00; 4.49, p = 0.001, respectively) with no inter-group difference (p = 0.963). CONCLUSIONS: The amount of skeletal and dental expansion obtained in the maxilla was similar in all groups. Rapid maxillary expansion was not found to be effective in OSA treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04604392.

Effect of COVID-19 Pandemic on Sleep Quality and Mental State of Frontline Pulmonologists.

Introduction: This study aims to determine the sleep quality and its relationship with anxiety and depressive symptoms, working conditions and other factors among the frontline pulmonologists on active duty during the COVID-19 pandemic. Method: An online survey was conducted among pulmonologists in Turkey. The survey link was e-mailed to the members of the professional societies of pulmonologists. The volunteers were asked to fill in questions about their sociodemographics, medical and psychiatric history, working and housing conditions, perceived levels of support during the pandemic, as well as the sleep habits before the pandemic. Also, questions investigating the severity/level of their worries were inquired and they were asked to fill in two scale forms (the Hospital Anxiety Depression Scale and Pittsburgh Sleep Quality Index-PSQI). Results: The sample consisted of 179 pulmonologists who were divided into two groups according to PSQI as good sleepers (PSQI ≤5) and poor sleepers (PSQI >5). It was observed that 59.2% of the participants had poor sleep quality during the pandemic. Being anxious (p<0.0001, Odds ratio [OR]=0.139, 95% Confidence Interval [CI] [0.052-0.372]), working in intensive care unit (p=0.046, OR=2.363, 95% CI [1.015-5.497]), worry level about excessive increase of the number of patients above the capacity of the institution they worked in (p=0.018, OR=1.755, 95% CI [1.102-2.794]) and being dissatisfied with ones' sleep before the pandemic (p<0.016, OR=0.272, 95% CI [0.094-0.786]) were found to be the main factors that negatively affected the quality of sleep of pulmonologists during the pandemic. Conclusion: More than half of the pulmonologists in our sample group had low sleep quality during the pandemic. For establishing a good sleep regime for clinicians, its crucial to consider certain interventions on the affecting factors.

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.

Clinical Predictors of Response to Tocilizumab: A Retrospective Multicenter Study.

OBJECTIVE: A substantial number of patients with coronavirus disease-2019 (COVID-19) demonstrate severe infection. Cytokine storm is an underlying condition that worsens clinical outcomes. As an interleukin-6 receptor antagonist, tocilizumab is a promising treatment option for COVID-19. This study aimed to evaluate the clinical predictors of mortality for critically ill COVID-19 patients receiving tocilizumab therapy. MATERIAL AND METHODS: The retrospective cohort study was conducted in 4 centers' both wards and intensive care units between March 20 and May 20, 2020. Demographic, clinical, and laboratory data were consecutively drawn from medical records. The primary endpoint was in-hospital mortality. RESULTS: In this study, 39 patients (28.2% female) were included, and the mortality rate was 25.6% (n = 10). There was statistically significant difference between survivor and non-survivor groups regarding age (53.0 (46.5-65.0) vs. 75.0 (68.25-81.25), respectively,P = .001), CALL score (8.0 (7.0-10.0) vs. 12.0 (9.75-13.0), P = .001), GRAM score (119.5 (99.5-142.0) vs. 155.0 (129.8-226.0), P = .004), and white blood cell count (k/mL) (5.6 (3.8-8.6) vs. 8.0 (7.6-9.3), P = .003). The patients who were on invasive mechanical ventilation at the time of tocilizumab administration had a higher mortality rate (100% vs. 25.9%, P < .001). Besides, arterial partial pressure of oxygen/ fraction of inspiratory oxygen (PaO2/FiO2) ratio on day 7, but not on days 0, 1, and 3 of tocilizumab therapy, was associated with mortal- ity. C-reactive protein (mg/dL) tended to be lower in the survivor group; however, it was not statistically significant (68.4 (32.7-157.5) vs. 113.5 (77.7-219.0), P = .058). CONCLUSION: This study demonstrated that advanced age, increased leukocyte count, higher CALL and GRAM scores, and the need for invasive mechanical ventilation revealed a worse prognosis after tocilizumab treatment.

Favipiravir for the treatment of COVID-19 pneumonia: Can we predict the response to treatment?

INTRODUCTION: Early experience with favipiravir in the treatment of COVID-19 is promising, but no clinical data have been published in medical journals. This study aimed to review the experience with favipiravir treatment for COVID-19 pneumonia and to examine whether there are any predictors of treatment response. METHODOLOGY: Fifty-six patients with severe or progressive pneumonia associated with COVID-19 who were treated with favipiravir monotherapy for at least five days were included in this retrospective study. Treatment response was defined as clinical recovery without any need for admission into the intensive care unit and/or anti-cytokine therapy. The demographic, clinical, laboratory and radiographic features of the patients were compared between favipiravir-responders and non-responders. RESULTS: Of the 56 patients, 34 patients (60.7%) responded to treatment and recovered. There was no difference in the demographic, clinical, and radiographic findings between the responders and non-responders. The inflammatory biomarkers were also similar except for the CRP levels on the day favipiravir was started [74 (36-111) vs. 118.5 (46.5-203) mg/L, respectively, p = 0.043]. There was also a significant difference in the median time to defervescence [1 (1-2) vs. 3.5 (1.75-9.25) days, respectively]. Of clinical interest, 27 (79.4%) and 31 (91.2%) of the responders became afebrile within two and four days, respectively. The response rate was lower in patients who presented severe pneumonia associated with respiratory failure. CONCLUSIONS: Patients with non-severe pneumonia at admission and whose fever resolved within two days of treatment are more likely to improve with favipiravir.

Metabolic dysfunction in OSA: Is there something new under the sun?

The growing number of patients with obstructive sleep apnea is challenging healthcare systems worldwide. Obstructive sleep apnea is characterized by chronic intermittent hypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascular and metabolic diseases are common in obstructive sleep apnea, also in lean patients. Further, comorbidity burden is not unambiguously linked to the severity of obstructive sleep apnea. There is a growing body of evidence revealing diverse functions beyond the conventional tasks of different organs such as carotid body and gut microbiota. Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associated with insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoring only hypoxia and hypercapnia but also acting as a metabolic sensor. The emerging evidence shows that obstructive sleep apnea and particularly chronic intermittent hypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to be an important factor in the pathophysiology of obstructive sleep apnea and its consequences. The impact of sleep fragmentation and intermittent hypoxia on the development of metabolic syndrome may be mediated via altered gut microbiota. Circadian misalignment seems to have an impact on the cardiometabolic risk in obstructive sleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleep fragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism and predispose to neurocognitive impairment. Moreover, recent data show that obstructive sleep apnea independently predicts impaired lipid levels. This mini-review will provide novel insights into the mechanisms of metabolic dysfunction in obstructive sleep apnea combining recent evidence from basic, translational and clinical research, and discuss the impact of positive airway pressure treatment on metabolic disorders.

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

BACKGROUND/OBJECTIVE: Obstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients. METHODS: We retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects' lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured. RESULTS: Out of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57-66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation. CONCLUSIONS: Atherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.

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.

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

Impact of temperature on obstructive sleep apnoea in three different climate zones of Europe: Data from the European Sleep Apnoea Database (ESADA).

Recent studies indicate that ambient temperature may modulate obstructive sleep apnoea (OSA) severity. However, study results are contradictory warranting more investigation in this field. We analysed 19,293 patients of the European Sleep Apnoea Database (ESADA) cohort with restriction to the three predominant climate zones according to the Köppen-Geiger climate classification: Cfb (warm temperature, fully humid, warm summer), Csa (warm temperature, summer dry, hot summer), and Dfb (snow, fully humid, warm summer). Average outside temperature values were obtained and several hierarchical regression analyses were performed to investigate the impact of temperature on the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time of oxygen saturation <90% (T90) and minimum oxygen saturation (MinSpO2 ) after controlling for confounders including age, body mass index, gender, and air conditioning (A/C) use. AHI and ODI increased with higher temperatures with a standardised coefficient beta (ß) of 0.28 for AHI and 0.25 for ODI, while MinSpO2 decreased with a ß of -0.13 (all results p < .001). When adjusting for climate zones, the temperature effect was only significant in Cfb (AHI: ß = 0.11) and Dfb (AHI: ß = 0.08) (Model 1: p < .001). The presence of A/C (3.9% and 69.3% in Cfab and Csa, respectively) demonstrated only a minor increase in the prediction of the variation (Cfb: AHI, R2 +0.003; and Csa: AHI, R2 +0.007; both p < .001). Our present study indicates a limited but consistent influence of environmental temperature on OSA severity and this effect is modulated by climate zones.

Evaluation of a multicomponent grading system for obstructive sleep apnoea: the Baveno classification.

New findings on pathophysiology, epidemiology, and outcome have raised concerns on the relevance of the apnoea-hypopnoea index (AHI) in the classification of obstructive sleep apnoea (OSA) severity. Recently, a multicomponent grading system decision integrating symptomatology and comorbidities (Baveno classification), was proposed to characterise OSA and to guide therapeutic decisions. We evaluated whether this system reflects the OSA population, whether it translates into differences in outcomes, and whether the addition of AHI improves the scheme. A total of 14 499 OSA patients from the European Sleep Apnoea Database cohort were analysed. The groups were homogeneously distributed and were found to clearly stratify the population with respect to baseline parameters. Differences in sleepiness and blood pressure between the groups were analysed in a subgroup of patients after 24-36 months of treatment. Group A (minor symptoms and comorbidities) did not demonstrate any effect of treatment on outcome. However, groups B (severe symptoms, minor comorbidities), C (minor symptoms, severe comorbidities) and D (severe symptoms and comorbidities) were associated with improvement in either or both parameters with treatment. The AHI is an essential prerequisite of the diagnosis; however, adding the AHI did not improve the classification. Rather, it was inferior with respect to guiding the treatment decision. Thus, the Baveno classification allows a better stratification of the OSA population and may provide a better guidance for therapeutic decisions in OSA.

Clinical Outcome of PCR-Negative COVID-19 Patients: A Retrospective Study.

OBJECTIVE: To evaluate the clinical features and outcomes of patients who were admitted with a diagnosis of coronavirus disease 2019 (COVID-19) but who were not confirmed with polymerase chain reaction (PCR) positivity. MATERIAL AND METHODS: This is a retrospective analysis of all patients admitted to two tertiary care centers between March 15 and May 15, 2020, with a diagnosis of COVID-19. From a common database prepared for COVID-19, we retrieved the relevant data and compared the clinical findings and outcomes of PCR-positive patients with those of PCR-negative cases who had been diagnosed on the basis of typical clinical and radiographic findings. RESULTS: A total of 349 patients were included in the analysis, of which 126 (36.1%) were PCR-negative. PCR-negative patients were younger (54.6 ± 20.8 vs. 60.8 ± 18.9 years, P = .009) but were similar to PCR-positive patients in terms of demographics, comorbidities, and presenting symptoms. They had higher lymphocyte counts (1519 ± 868 vs. 1331 ± 737/mm3, P = .02) and less frequently presented with bilateral radiographic findings (68.3% vs. 79.4%, P = .046) than PCR-positive patients. Besides, they had less severe disease and better clinical outcomes regarding admission to the intensive care unit (9.6% vs. 20.6%, P = .023), oxygen therapy (21.4% vs. 43.5%, P < .001), ventilatory support (3.2% vs. 11.2%, P = .03) and length of hospital stay (5.0 ± 5.0 vs. 9.7 ± 5.9 days, P < .001). CONCLUSION: This study confirms that about one-third of the COVID-19 patients are PCR-negative and diagnosed based on clinical and radiographic findings. These patients have a more favorable clinical course, shorter hospital stays, and are less frequently admitted to the intensive care unit.

Superior hypertension control with betablockade in the European Sleep Apnea Database.

AIMS: Arterial hypertension is highly prevalent and difficult to control in patients with obstructive sleep apnea (OSA). High sympathoadrenergic activity is a hallmark physiological phenomenon in OSA. We hypothesized that an antihypertensive drug with inhibitory properties on this activity, such as beta blockers (BBs), may be particularly efficacious in OSA patients. METHODS: Hypertensive OSA patients receiving blood pressure-lowing treatment in the European Sleep Apnea Database (ESADA) (n = 5818, 69% men, age 58 ±â€Š11 years, body mass index 33 ±â€Š7 kg/m2, apnea hypopnea index 34 ±â€Š26 events/h) were analyzed. Reported medications [BB, diuretic, renin-angiotensin blocker (RAB), calcium channel blocker (CCB), and centrally acting antihypertensive (CAH)] were classified according to ATC code. Office blood pressure was compared in patients with monotherapy or combination therapy controlling for confounders. RESULTS: Poorly controlled SBP according to the ESC/ESH guidelines was found in 66% of patients. Patients receiving monotherapy with RAB, CCB or CAH had 2.2 (95% CI 1.4-3.0), 3.0 (1.9-4.1) and 3.0 (1.7-4.7) mmHg higher SBP compared with those on BB (adjusted model, P = 0.007, 0.008 and 0.017, respectively). In those with a combination of two antihypertensive drugs, SBP was 5.5 (4.0-7.1), 5.1 (3.7-6.6), 4.3 (2.5-6.1) and 3.1 (1.6-4.6) mmHg higher in those on CCB/RAB, BB/RAB, BB/CCB or diuretic/RAB compared with those on BB/diuretic (adjusted model, P < 0.001, <0.001, 0.018 and 0.036, respectively). CONCLUSION: Poorly controlled blood pressure was common in OSA patients with antihypertensive medication. Treatment with BB alone or BB in combination with a diuretic was associated with the lowest systolic pressure in this large clinical cohort.

Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA).

BACKGROUND AND OBJECTIVE: To personalize OSA management, several studies have attempted to better capture disease heterogeneity by clustering methods. The aim of this study was to conduct a cluster analysis of 23 000 OSA patients at diagnosis using the multinational ESADA. METHODS: Data from 34 centres contributing to ESADA were used. An LCA was applied to identify OSA phenotypes in this European population representing broad geographical variations. Many variables, including symptoms, comorbidities and polysomnographic data, were included. Prescribed medications were classified according to the ATC classification and this information was used for comorbidity confirmation. RESULTS: Eight clusters were identified. Four clusters were gender-based corresponding to 54% of patients, with two clusters consisting only of men and two clusters only of women. The remaining four clusters were mainly men with various combinations of age range, BMI, AHI and comorbidities. The preferred type of OSA treatment (PAP or mandibular advancement) varied between clusters. CONCLUSION: Eight distinct clinical OSA phenotypes were identified in a large pan-European database highlighting the importance of gender-based phenotypes and the impact of these subtypes on treatment prescription. The impact of cluster on long-term treatment adherence and prognosis remains to be studied using the ESADA follow-up data set.