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7. Continuous Positive Airway Pressure but Not GLP1-mediated Weight Loss Improves Early Cardiovascular Disease in Obstructive Sleep Apnea: A Randomized Proof-of-Concept Study

Author

O’Donnell, Cliona, primary, Crilly, Shane, additional, O’Mahony, Anne, additional, O’Riordan, Brian, additional, Traynor, Mark, additional, Gitau, Rachael, additional, McDonald, Kenneth, additional, Ledwidge, Mark, additional, O’Shea, Donal, additional, Murphy, David J., additional, Dodd, Jonathan D., additional, and Ryan, Silke, additional

Published
2024
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10. Continuous Positive Airway Pressure but Not GLP1-mediated Weight Loss Improves Early Cardiovascular Disease in Obstructive Sleep Apnea: A Randomized Proof-of-Concept Study.

Author

O'Donnell, Cliona, Crilly, Shane, O'Mahony, Anne, O'Riordan, Brian, Traynor, Mark, Gitau, Rachael, McDonald, Kenneth, Ledwidge, Mark, O'Shea, Donal, Murphy, David J., Dodd, Jonathan D., and Ryan, Silke

Subjects
CONTINUOUS positive airway pressure, POSITRON emission tomography computed tomography, SLEEP apnea syndromes, WEIGHT loss, CARDIOVASCULAR diseases
Abstract

Rationale: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) is uncertain. However, most randomized controlled trials have focused on the role of CPAP in secondary prevention, although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. Objectives: The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it with a glucagon-like peptide (GLP)-1-mediated weight loss regimen in patients with OSA. Methods: We performed a randomized proof-of-concept study comparing CPAP, a GLP1-mediated weight-loss regimen (liraglutide [Lir]), and both in combination for 24 weeks in 30 consecutive patients with OSA (apnea–hypopnea index >15 events/h; body mass index 30–40 kg/m2; and no history of diabetes, heart failure, or unstable CV disease). In addition to extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography (18F-FDG PET-CT) for the measurement of aortic wall inflammation (target-to-background ratio) and coronary computed tomography angiography for semiautomated coronary plaque analysis. Results: Baseline characteristics were similar between groups. CPAP alone and in combination resulted in greater reduction in apnea–hypopnea index than Lir alone (mean difference, −45 and −43 events/h, respectively, vs. −12 events/h; P < 0.05). Both Lir and combination treatment led to significant weight loss, but only CPAP alone resulted in significant decrease in vascular inflammation (aortic wall target-to-background ratio from 2.03 ± 0.34 to 1.84 ± 0.43; P = 0.010), associated with an improvement in endothelial function and a decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as a marker of unstable plaque also decreased with CPAP (from 571 ± 490 to 334 ± 185 mm3) and with combination therapy (from 401 ± 145 to 278 ± 126 mm3) but not with Lir. Conclusions: These data suggest that CPAP therapy, but not GLP1-mediated weight loss, improves vascular inflammation and reduces unstable plaque volume in patients with OSA. Further large randomized controlled studies are warranted to assess the benefit of CPAP therapy in modifying early CV disease. Clinical trial registered with www.clinicaltrials.gov (NCT 04186494). [ABSTRACT FROM AUTHOR]

Published
2024
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14. Continuous positive airway pressure but not Liraglutide-mediated weight loss improves early cardiovascular disease in obstructive sleep apnea: Data from a randomized proof-of-concept study.

Author

O'Donnell, Cliona, primary, Crilly, Shane, additional, O'Mahony, Anne, additional, O'Riordan, Brian, additional, Traynor, Mark, additional, Gitau, Rachael, additional, McDonald, Kenneth, additional, Ledwidge, Mark T., additional, O'Shea, Donal, additional, Murphy, David J, additional, Dodd, Jonathan D., additional, and Ryan, Silke, additional

Published
2023
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22. The Sleep Revolution project: the concept and objectives

Author

Arnardottir, Erna S., Islind, Anna Sigridur, Óskarsdóttir, María, Ólafsdóttir, Kristín A., August, Elias, Jónasdóttir, Lára, Hrubos‐Strøm, Harald, Saavedra, Jose M., Grote, Ludger, Hedner, Jan, Höskuldsson, Sveinbjörn, Ágústsson, Jón Skírnir, Jóhannsdóttir, Kamilla Rún, McNicholas, Walter T., Pevernagie, Dirk, Sund, Reijo, Töyräs, Juha, Leppänen, Timo, Dammen, Toril, Jagomägi, Triin, Oddsson, Sæmundur, Skifjeld, Knut, Verbraecken, Johan, Georgia, Trakada, Penzel, Thomas, Ryan, Silke, Steiropoulos, Paschalis, Pépin, Jean‐Louis, Schiza, Sophia E, Basoglu, Ozen Kacmaz, Bušková, Jitka, Testelmans, Dries, Staats, Richard, Gouveris, Haralampos, Lombardi, Carolina, Bonsignore, Maria Rosaria, Fanfulla, Francesco, Hein, Holger, Randerath, Winfried J., Pataka, Athanasia, Mihaicuta, Stefan, Saaresranta, Tarja, Anttalainen, Ulla, Dogas, Zoran, Śliwiński, Paweł, Drummond, Marta, and Nemeth, Petra

Subjects
digital management platform, Cognitive Neuroscience, Polysomnography, participatory, costs, sleep revolution, lifestyles, Disorders of Excessive Somnolence, PATIENT, PARAMETERS, outcome measures, Behavioral Neuroscience, polysomnography, APNEA, Medicine and Health Sciences, Humans, patient-reported, neurocognitive tests, sleep, Retrospective Studies, Sleep Apnea, Obstructive, exercise, MEDICINE, apnea-hypopnea index, self-applied home testing, NEED, General Medicine, mobile application, machine learning, SEVERITY, OBSTRUCTION EVENTS, TASK, e-health, P4 medicine, diary, telemedicine, Sleep
Abstract

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.

Published
2022

26. Positive airway pressure level based upper airway collapsibility classification – the European Sleep Apnea Database (ESADA)

Author

Zou, Ding, primary, Schiza, Sophia, additional, Saaresranta, Tarja, additional, Pataka, Athanasia, additional, Verbraecken, Johan, additional, Lombardi, Carolina, additional, Hein, Holger, additional, Joppa, Pavol, additional, Ludka, Ondrej, additional, Bonsignore, Maria R., additional, Ryan, Silke, additional, and Basoglu, Ozen K., additional

Published
2021
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28. The sleepy phenotype in mild Obstructive Sleep Apnoea (OSA) patients: from clinical characteristics to cardiometabolic risk. Data from the European Sleep Apnea Database (ESADA)

Author

Bouloukaki, Izolde, primary, Bonsignore, Marisa, additional, Grote, Ludger, additional, Mcnicholas, Walter, additional, Hedner, Jan, additional, Verbraecken, Johan, additional, Ryan, Silke, additional, Lombardi, Carolina, additional, Basoglu, Ozen, additional, Pataka, Athanasia, additional, Fanfulla, Fransesco, additional, Bailly, Sebastien, additional, Pepin, Jean-Louis, additional, Steiropoulos, Paschalis, additional, and Schiza, Sophia, additional

Published
2021
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29. Polygraphic parameters do not correlate with obstructive sleep apnoea (OSA) symptoms according to Baveno

Author

Randerath, Winfried, primary, Treml, Marcel, additional, Herkenrath, Simon, additional, Grote, Ludger, additional, Hedner, Jan, additional, Bonsignore, Maria R., additional, Pépin, Jean-Louis, additional, Ryan, Silke, additional, Schiza, Sophia E., additional, Verbraecken, Johan, additional, Mcnicholas, Walter T., additional, Pataka, Athanasia, additional, Śliwiński, Paweł, additional, and Basoglu, Özen K., additional

Published
2021
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32. European Respiratory Society statement on sleep apnoea, sleepiness and driving risk

Author

Bonsignore, Maria R., Randerath, Winfried, Schiza, Sofia, Verbraecken, Johan, Elliott, Mark W., Riha, Renata, Barbe, Ferran, Bouloukaki, Izolde, Castrogiovanni, Alessandra, Deleanu, Oana, Goncalves, Marta, Leger, Damien, Marrone, Oreste, Penzel, Thomas, Ryan, Silke, Smyth, Dan, Teran-Santos, Joaquin, Turino, Cecilia, McNicholas, Walter T., Bonsignore, Maria R., Randerath, Winfried, Schiza, Sofia, Verbraecken, Johan, Elliott, Mark W., Riha, Renata, Barbe, Ferran, Bouloukaki, Izolde, Castrogiovanni, Alessandra, Deleanu, Oana, Goncalves, Marta, Leger, Damien, Marrone, Oreste, Penzel, Thomas, Ryan, Silke, Smyth, Dan, Teran-Santos, Joaquin, Turino, Cecilia, and McNicholas, Walter T.

Abstract

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.

Published
2021

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

Author

Randerath, Winfried J., Herkenrath, Simon, Treml, Marcel, Grote, Ludger, Hedner, Jan, Bonsignore, Maria Rosaria, Pepin, Jean Louis, Ryan, Silke, Schiza, Sophia, Verbraecken, Johan, McNicholas, Walter T., Pataka, Athanasia, Sliwinski, Pawel, Basoglu, Ozen K., Randerath, Winfried J., Herkenrath, Simon, Treml, Marcel, Grote, Ludger, Hedner, Jan, Bonsignore, Maria Rosaria, Pepin, Jean Louis, Ryan, Silke, Schiza, Sophia, Verbraecken, Johan, McNicholas, Walter T., Pataka, Athanasia, Sliwinski, Pawel, and Basoglu, Ozen K.

Abstract

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 14499 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.

Published
2021

34. Polygraphic parameters do not correlate with obstructive sleep apnoea (OSA) symptoms according to Baveno

Author

Randerath, Winfried, Treml, Marcel, Herkenrath, Simon, Grote, Ludger, Hedner, Jan, Bonsignore, Maria R., Pepin, Jean-Louis, Ryan, Silke, Schiza, Sophia E., Verbraecken, Johan, Mcnicholas, Walter T., Pataka, Athanasia, Sliwinski, Pawel, Basoglu, Ozen K., Randerath, Winfried, Treml, Marcel, Herkenrath, Simon, Grote, Ludger, Hedner, Jan, Bonsignore, Maria R., Pepin, Jean-Louis, Ryan, Silke, Schiza, Sophia E., Verbraecken, Johan, Mcnicholas, Walter T., Pataka, Athanasia, Sliwinski, Pawel, and Basoglu, Ozen K.

Published
2021

35. Unique sleep-stage transitions determined by obstructive sleep apnea severity, age and gender

Author

Wächter, Marcel, Kantelhardt, Jan W., Bonsignore, Maria R., Bouloukaki, Izolde, Escourrou, Pierre, Fietze, Ingo, Grote, Ludger, Korzybski, Damian, Lombardi, Carolina, Marrone, Oreste, Paranicova, Ivana, Pataka, Athanasia, Ryan, Silke, Schiza, Sophia E., Sliwinski, Pawel, Steiropoulos, Paschalis, Verbraecken, Johan, Penzel, Thomas, ESADA Study Group, Wächter, Marcel, Kantelhardt, Jan W, Bonsignore, Maria R, Bouloukaki, Izolde, Escourrou, Pierre, Fietze, Ingo, Grote, Ludger, Korzybski, Damian, Lombardi, Carolina, Marrone, Oreste, Paranicova, Ivana, Pataka, Athanasia, Ryan, Silke, Schiza, Sophia E, Sliwinski, Pawel, Steiropoulos, Paschali, Verbraecken, Johan, Penzel, Thomas, ESADA Study Group, SALAS, Danielle, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Martin-Luther-Universität Halle Wittenberg (MLU), Università degli studi di Palermo - University of Palermo, University of Crete [Heraklion] (UOC), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sahlgrenska University Hospital [Gothenburg], Institute of Tuberculosis and Lung Diseases [Warsaw, Poland] (ITLD), IRCCS Istituto Nazionale dei Tumori [Milano], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University Hospital Kosice [Kosice, Slovakia] (UHK), Aristotle University of Thessaloniki [Thessaloniki, Greece] (AUT), University College Dublin [Dublin] (UCD), Democritus University of Thrace (DUTH), Alexandroupolis University Hospital [Alexandroupolis, Greece] (AUH), Antwerp University Hospital [Edegem] (UZA), University of Antwerp (UA), and ESADA Study Group: P Steiropoulos, J Verbraecken, E Petiet, Georgia Trakada, J M Montserrat, I Fietze, T Penzel, Ondrej Ludka, Daniel RodensteinCliniques, J F Masa, I Bouloukaki, S Schiza, B Kent, W T McNicholas, S Ryan, R L Riha, J A Kvamme, L Grote, J Hedner, J L Pépin, S Bailly, Lena Lavie, Peretz Lavie, O K Basoglu, M S Tasbakan, G Varoneckas, P Joppa, R Tkacova, R Staats, F Barbé, C Lombardi, G Parati, Marta Drummond, Mafalda van Zeller, M R Bonsignore, O Marrone

Subjects
Adult, Male, sleep-disordered breathing, medicine.medical_specialty, sleepdisordered breathing, [SDV]Life Sciences [q-bio], Cognitive Neuroscience, sleep dynamics, Excessive daytime sleepiness, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten, power-law distribution, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Internal medicine, Humans, Medicine, exponential distribution, sleep fragmentation, Stage (cooking), Retrospective Studies, Sleep Apnea, Obstructive, business.industry, Confounding, Age Factors, Gender Identity, Sleep apnea, General Medicine, Middle Aged, Anthropometry, medicine.disease, Sleep in non-human animals, [SDV] Life Sciences [q-bio], Obstructive sleep apnea, 030228 respiratory system, sleep dynamic, Cohort, Cardiology, Female, Human medicine, medicine.symptom, Sleep, business, 030217 neurology & neurosurgery
Abstract

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.

Published
2019
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36. Evaluation of a multicomponent grading system for obstructive sleep apnoea: the Baveno classification

Author

Randerath, Winfried J., primary, Herkenrath, Simon, additional, Treml, Marcel, additional, Grote, Ludger, additional, Hedner, Jan, additional, Bonsignore, Maria Rosaria, additional, Pépin, Jean Louis, additional, Ryan, Silke, additional, Schiza, Sophia, additional, Verbraecken, Johan, additional, McNicholas, Walter T., additional, Pataka, Athanasia, additional, Sliwinski, Pawel, additional, and Basoglu, Özen K., additional

Published
2021
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41. European Respiratory Society statement on sleep apnoea, sleepiness and driving risk

Author

Bonsignore, Maria R., primary, Randerath, Winfried, additional, Schiza, Sofia, additional, Verbraecken, Johan, additional, Elliott, Mark W., additional, Riha, Renata, additional, Barbe, Ferran, additional, Bouloukaki, Izolde, additional, Castrogiovanni, Alessandra, additional, Deleanu, Oana, additional, Goncalves, Marta, additional, Leger, Damien, additional, Marrone, Oreste, additional, Penzel, Thomas, additional, Ryan, Silke, additional, Smyth, Dan, additional, Teran-Santos, Joaquin, additional, Turino, Cecilia, additional, and McNicholas, Walter T., additional

Published
2020
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43. The sleepy phenotype in mild OSA patients: characteristics and their cardiometabolic risk. Data from the European Sleep Apnea Data Base (ESADA)

Author

Bouloukaki, Izolde, primary, Bonsignore, Marisa, additional, Grote, Ludger, additional, Mcnicholas, Walter, additional, Hedner, Jan, additional, Verbraecken, Johan, additional, Ryan, Silke, additional, Lombardi, Carolina, additional, Basoglu, Ozen, additional, Pataka, Athanasia, additional, Marrone, Oreste, additional, Bailly, Sebastien, additional, Pepin, Jean-Louis, additional, Steiropoulos, Paschalis, additional, and Schiza, Sophia, additional

Published
2020
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45. A novel multicomponent grading system for obstructive sleep apnoea severity applied in the ESADA cohort

Author

Randerath, Winfried, primary, Herkenrath, Simon, additional, Treml, Marcel, additional, Grote, Ludger, additional, Hedner, Jan, additional, Bonsignore, Maria R, additional, Pépin, Jean-Louis, additional, Ryan, Silke, additional, Schiza, Sofia, additional, Verbraecken, Johan, additional, Mcnicholas, Walter T, additional, Pataka, Athanasia, additional, Sliwinski, Pawel, additional, and Basoglu, Ozen K, additional

Published
2020
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46. Tocilizumab therapy in individuals with COVID ‐19 infection and hyperinflammatory state

Author

McCarthy, Cormac, primary, Savinelli, Stefano, additional, Feeney, Eoin R., additional, Butler, Marcus W., additional, O'Broin, Cathal, additional, Ryan, Silke, additional, O'Neill, Lorraine, additional, Murphy, David J., additional, Gallagher, Charles G., additional, McKone, Edward F., additional, Waqas, Sarmad, additional, Cotter, Aoife, additional, Doran, Peter, additional, Keane, Michael P., additional, and Mallon, Patrick W., additional

Published
2020
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49. Understanding the pathophysiological mechanisms of cardiometabolic complications in obstructive sleep apnoea: towards personalised treatment approaches

Author

Ryan, Silke, primary, Cummins, Eoin P., additional, Farre, Ramon, additional, Gileles-Hillel, Alex, additional, Jun, Jonathan C., additional, Oster, Henrik, additional, Pepin, Jean-Louis, additional, Ray, David W., additional, Reutrakul, Sirimon, additional, Sanchez-de-la-Torre, Manuel, additional, Tamisier, Renaud, additional, and Almendros, Isaac, additional

Published
2020
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