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The host immune response plays a critical role in the immunopathology of SARS-CoV2. Here the authors combine a systems biology approach to implicate monocytes as key drivers of cytokine storm and disturbed neutrophil activation in COVID-19 disease severity.

The topic of sleep-related breathing disorders is always evolving, and during the European Respiratory Society (ERS) International Congress 2023 in Milan, Italy, the latest research and clinical topics in respiratory medicine were presented. The most interesting issues included new diagnostic tools, such as cardiovascular parameters and artificial intelligence, pathophysiological traits of sleep disordered breathing from routine polysomnography or polygraphy signals, and new biomarkers and the diagnostic approach in patients with excessive daytime sleepiness. This article summarises the most relevant studies and topics presented at the ERS International Congress 2023. Each section has been written by early career members of ERS Assembly 4., Competing Interests: Conflict of interest: M. Bradicich reports an ERS faculty participation grant for the ERS International Congress 2023, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from ERS faculty participation grant for the ERS International Congress 2023, outside the submitted work; support for attending meetings and/or travel from ERS faculty participation grant for the ERS International Congress 2023, outside the submitted work; and is ERS ECMC Representative for Assembly 4, outside the submitted work. Conflict of interest: D. Testelmans reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Resmed and Nyxoah, outside the submitted work. Conflict of interest: M. Sánchez-de-la-Torre reports grants or contracts from Instituto de Salud Carlos III (Spain Goverment), outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Jazz Pharmaceuticals and Philips, outside the submitted work; and support for attending meetings and/or travel from Jazz Pharmaceuticals and Resmed, outside the submitted work. Conflict of interest: W. Randerath is an associate editor of this journal. Conflict of interest: E.I. Schwarz reports grants or contracts from Philips Respironics, Löwenstein and the Swiss National Science Foundation, outside the submitted work; payment or honorara for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from ResMed, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for ERS Secretary of Assembly 4, outside the submitted work. Conflict of interest: S. Schiza reports being ERS secretary of Assembly 4 (until September 2023), unpaid, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Introduction: Subclinical epileptiform activity (SEA) and sleep disturbances are frequent in Alzheimer's disease (AD). Both have an important relation to cognition and potential therapeutic implications. We aimed to study a possible relationship between SEA and sleep disturbances in AD., Methods: In this cross-sectional study, we performed a 24-h ambulatory EEG and polysomnography in 48 AD patients without diagnosis of epilepsy and 34 control subjects., Results: SEA, mainly detected in frontotemporal brain regions during N2 with a median of three spikes/night [IQR1-17], was three times more prevalent in AD. AD patients had lower sleep efficacy, longer wake after sleep onset, more awakenings, more N1%, less REM sleep and a higher apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). Sleep was not different between AD subgroup with SEA (AD-Epi+) and without SEA (AD-Epi-); however, compared to controls, REM% was decreased and AHI and ODI were increased in the AD-Epi+ subgroup., Discussion: Decreased REM sleep and more severe sleep-disordered breathing might be related to SEA in AD. These results could have diagnostic and therapeutic implications and warrant further study at the intersection between sleep and epileptiform activity in AD., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

One fifth of today's workforce is engaged in shift work and exposed to various mental and physical health risks including shift work disorder. Efficiently recovering from shift work through physical and mental interventions allows us to mitigate negative effects on health, enables a better work-life balance and enhances our overall wellbeing. The aim of this review is to provide a state-of-the-art overview of the available literature. The role of sleep timing and naps, light therapy and psychotherapy, diet and exercise in recovery from shift work is presented here. We further review the impact of shift schedules and social support on post-shift unwinding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalkanis, Demolder, Papadopoulos, Testelmans and Buyse.)

Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT)., Methods and Results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0 kg/m 2 , apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9 h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7 mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8 mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders., Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA., Competing Interests: Conflict of interest: The ESADA study group received unrestricted funding grants from Respironics and Resmed Foundations (2008–11) and an unrestricted collaboration grant from Bayer AG (2018–22). S.S., corresponding author, reports no COI. He has grants from the Swedish Heart and Lung Foundation. J.H. reports no COI related to the content of the manuscript. He has institutional grants from Gothenburg University, Swedish Government Research and Educational grant LUA/ALF and grants from the Swedish Heart and Lung Foundation. Outside of the current manuscript, he has EU grants Horizon 2020, Eureka, and Inter Funding: Sleep Across Waters. He has consulting fees from SomnoMed (advisory input), has received research equipment from Itamar, and owns stock in Cereus Pharma. S.B. reports no COI. F.F. reports no COI. H.H. reports no COI. C.L. reports no COI. O.L. reports no COI. S.M. reports no COI. G.P. reports no COI; he has honoraria for lectures from Merck. A.P. reports no COI. S.S. reports no COI. S.T. reports no COI. D.T. reports no COI; he has payment to his Institution for lectures from Nyxoah. D.Z. reports no COI. L.G. reports no COI related to the content of the manuscript. He has institutional grants from LUA/ALF and the Swedish Heart and Lung Foundation. Outside the current manuscript, he provided lectures for Resmed, Philips, Astra Zeneca, and Lundbeck; and he has ownership in a patent licensed to Desitin GMBH related to sleep apnoea therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD., Methods: 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure ( P I,max ), n=10) or sham training (10% P I,max , n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal ( P es ) and gastric ( P ga ) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise., Results: The IMT group (from 45±6 to 62±23% P I,max ) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. P I,max , TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH 2 O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, P es , P ga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05)., Conclusion: The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles., Competing Interests: Conflict of interest: Training devices were provided on loan for the study duration by HaB International Ltd. R. Gosselink reports personal fees from Elsevier. D. Langer reports a grant from Research Foundation Flanders and a leadership role with the European Respiratory Society. M.R. Schaeffer, Z. Louvaris, A. Rodrigues, D. Poddighe, G. Gayan-Ramirez, T. Gojevic, L. Geerts, E. Heyndrickx, M. Van Hollebeke, L. Janssens and D. Testelmans do not have any disclosures., (Copyright ©The authors 2023.)

This paper presents some of the highlights of the Sleep and Breathing Conference 2023 https://bit.ly/46MxJml., Competing Interests: Conflict of interest: M. Bradicich reports receiving support to attend meetings and/or travel from the European Respiratory Society as an ERS officer and ERS International Congress faculty; and is the early career member representative of ERS Assembly 4, disclosure made outside the submitted work. W. Randerath reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Heinen & Löwenstein, Philips Respironics, and Habel Medizintechnik, outside the submitted work; and is Head of ERS Assembly 4, Sleep Disordered Breathing (unpaid position) and the German Respiratory Society Secretary General (unpaid position), disclosures made outside the submitted work. J. Cruz is the early career member representative of ERS Assembly 9, disclosure made outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©ERS 2023.)

Obstructive sleep apnea (OSA) is a sleeping disorder caused by complete or partial disturbance of breathing during the night. Existing screening methods include questionnaire-based evaluations which are time-consuming, vary in specificity, and are not globally adopted. Point-of-care ultrasound (PoCUS), on the other hand, is a painless, inexpensive, portable, and useful tool that has already been introduced for the evaluation of upper airways by anesthetists. PoCUS could also serve as a potential screening tool for the diagnosis of OSA by measuring different airway parameters, including retropalatal pharynx transverse diameter, tongue base thickness, distance between lingual arteries, lateral parapharyngeal wall thickness, palatine tonsil volume, and some non-airway parameters like carotid intima-media thickness, mesenteric fat thickness, and diaphragm characteristics. This study reviewed previously reported studies to highlight the importance of PoCUS as a potential screening tool for OSA.

During the European Respiratory Society (ERS) International Congress 2022 in Barcelona, Spain, the latest research and clinical topics in respiratory medicine were presented. The sleep medicine-focused presentations and symposia provided novel insights into the pathophysiology of sleep disordered breathing, its diagnostics, and new trends in translational research and clinical applications. The presented research trends focused mainly on the assessment of sleep disordered breathing-related intermittent hypoxia, inflammation and sleep fragmentation, and their implications, especially cardiovascular. The most promising methods for assessing these aspects encompass genomics, proteomics and cluster analysis. The currently available options include positive airway pressure and a combination of it and pharmacological agents ( e.g. sulthiame). This article summarises the most relevant studies and topics on these subjects presented at the ERS International Congress 2022. Each section has been written by Early Career Members of the ERS Assembly 4., Competing Interests: Conflict of interest: M. Bradicich declares support from the European Respiratory Society for acting as faculty at the society's 2022 International Congress; and an unpaid role as Early Career Member Representative for European Respiratory Society Assembly 4 (Sleep Disordered Breathing). W. Randerath declares payment or honoraria from Heinen & Löwenstein, Resmed, Jazz Pharmaceuticals, Inspire, Philips Respironics, Bioprojet and Westfalen Medical; support for attending meetings and/or travel from Heinen & Löwenstein, Jazz Pharmaceuticals, Philips Respironics and Bioprojet; and participation on a data safety monitoring or advisory board from Bioprojet, Jazz Pharmaceuticals, Philips Respironics and Procter & Gamble, all in the 36 months prior to manuscript submission; as well as an unpaid role as head of European Respiratory Society Assembly 4 (Sleep Disordered Breathing). He is an associate editor of this journal. All other authors declare no competing interests., (Copyright ©The authors 2023.)

For more than three decades, type III devices have been used in the diagnosis of sleep disordered breathing in supervised as well as unsupervised settings. They have satisfactory positive and negative predictive values for detecting obstructive and central sleep apnoea in populations with moderately high pre-test probability of symptoms associated with these events. However, standardisation of commercially available type III devices has never been undertaken and the technical specifications can vary widely. None have been subjected to the same rigorous processes as most other diagnostic modalities in the medical field. Although type III devices do not include acquisition of electroencephalographic signals overnight, the minimum number of physical sensors required to allow for respiratory event scoring using standards outlined by the American Academy of Sleep Medicine remains debatable. This technical standard summarises data on type III studies published since 2007 from multiple perspectives in both adult and paediatric sleep practice. Most importantly, it aims to provide a framework for considering current type III device limitations in the diagnosis of sleep disordered breathing while raising research- and practice-related questions aimed at improving our use of these devices in the present and future., Competing Interests: Conflict of interest: T. Penzel reports personal speaker fees from Cerebra, Jazz Pharma, Löwenstein Medical, National Sleep Foundation and Neuwirth; consulting fees from Bayer Healthcare and Cerebra; travel support from Jazz Pharma and Nukute; participation on advisory boards for Nukute and Cerebra; stock or stock options with The Siestagroup, Nukute and Advanced Sleep Research; receipt of equipment from Neurovirtual; institutional fees and research grants from Bayer Healthcare, Cidelec, Löwenstein Medical, Novartis and Springer Publisher. T. Penzel also reports the following leadership roles: German Sleep Society (president, unpaid), IEEE Engineering in Medicine and Biology (advisory committee member, unpaid), German Society on Biomedical Engineering (board member, unpaid), DIN – German standardization body (committee member, unpaid). W. Randerath reports institutional fees, research grants and speaking fees from Philips Respironics, Heinen & Löwenstein, Jazz Pharmaceuticals, Weinmann, Resmed, Inspire, Vanda Pharma and Bioprojet, and is head of European Respiratory Society assembly 4 (Sleep Disordered Breathing). R.L. Riha reports one-off personal speaker fees and participation on an advisory board from Jazz Pharmaceuticals, and is also co-director of Sleep Consultancy Ltd. D. Testelmans reports institutional fees and educational grants from AirLiquide, Philips Respironics and Resmed. J. Verbraecken reports institutional fees and educational grants from Accuramed, Agfa-Gevaert, AirLiquide, AstraZeneca, Bekaert Deslee Academy, Bioprojet, Desitin, Ectosense, Fisher & Paykel, Heinen & Löwenstein, Idorsia, Inspire, Jazz Pharmaceutics, Medidis, Mediq Tefa, MSD, NightBalance, OSA Academy, OSG, Oxford Pharmagenesis, Philips Respironics, ResMed, Sanofi, SomnoMed, Springer, Total Care, UCB Pharma, Vivisol, Wave Medical and Westfalen Medical; consulting fees from Vermedia; and reports the following leadership roles: president (up to August 2021) and past president of the Belgian Association for Sleep research and Sleep medicine (since September 2021). M. Celmina reports lecture honoraria from Rare Diseases Conference and Latvian Medical Association; support to attend various conferences (IPSA, Baltic Sleep Meeting, Nordic Sleep Meeting) provided by Children's Clinical University Hospital (Riga, Latvia); and is a member of the board of the Latvian Sleep Medicine Society. A. Morley reports lecture honoraria from Sleep Consultancy Ltd and Sleep Scotland; participation on advisory board for the BTS Guideline for Pediatric Sleep Disorders; and is a board member of Association of Respiratory Technology and Physiology – Sleep. L. Roberti reports grants/funding to AAI ETS patient organisations from Resmed, Fisher & Paykel, Jazz Ph, Bioprojet, Vitalaire, Linde, Medicair, Philips, Olympus, Respiraire and Vivisol; and also reports the following leadership roles: President of Associazione Apnoici Italiani ETS (Italian Sleep Apnoea Patient Association), Sleep Apnoea Patient Representative of EMA, and Member of ELF Sleep Apnoea PAG. W. Ruehland reports travel support from Institute for Breathing and Sleep to attend Sleep Downunder and TSANZSRS Conferences, and from Australian and New Zealand Sleep Science Association to attend Sleep Downunder conference; and also reports the following leadership roles: board member of the Australian and New Zealand Sleep Science Association, committee member of the Medical and Scientific Research Committee, Institute for Breathing and Sleep, and is director of Respiratory Quality Assurance Pty Ltd, which provides PSG scoring external proficiency testing program (QSleep) for sleep centres. G. Grundström is Chairman of the Swedish Sleep Apnea Association. B. Cooper, R. Hamutcu-Ersu, A. Kaditis, A. Pataka and A. van Eyck have no conflict of interest to disclose related to the topic discussed in this technical standard., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Study Objectives: To evaluate (determinants of) treatment success of mandibular advancement device application in a selected phenotype of patients with obstructive sleep apnea (OSA)., Methods: Ninety nonobese patients with moderate OSA (obstructive apnea-hypopnea index [OAHI] ≥ 15 and < 30 events/h) without comorbidities were prospectively included. Polysomnography was performed at baseline and with a mandibular advancement device. A drug-induced sleep endoscopy with jaw thrust was performed in 83%., Results: OAHI reduction ≥ 50% was observed in 73%, OAHI reduction ≥ 50% with OAHI < 10 events/h in 70%, and complete OSA resolution (OAHI < 5 events/h) in 40%. Patients with nonpositional OSA showed a significantly higher rate of complete OSA resolution: Posttest probability increased to 67%. In patients with total disappearance of collapse at velum level and at all levels during drug-induced sleep endoscopy with jaw thrust, the drop in OAHI was impressive with an infinitively high positive likelihood ratio. However, the proportion of patients having nonpositional OSA or the drug-induced sleep endoscopy characteristics as described above was < 20%. The change in snoring disturbance based on a visual analog scale was 76% (interquartile range 40-89%, P < .001) and a statistically significant amelioration in Epworth Sleepiness Scale (especially in somnolent subjects) was observed. High adherence was reported., Conclusions: In this predefined OSA phenotype, a mandibular advancement device was effective in reduction of OAHI and in amelioration of symptoms. Stratification by nonpositional OSA and findings on drug-induced sleep endoscopy with jaw thrust increased treatment success defined as reduction in OAHI. However, the clinical relevance can be questioned because only a small number of patients demonstrated these characteristics., Citation: Buyse B, Nguyen PAH, Leemans J, et al. Short-term positive effects of a mandibular advancement device in a selected phenotype of patients with moderate obstructive sleep apnea: a prospective study. J Clin Sleep Med . 2023;19(1):5-16., (© 2023 American Academy of Sleep Medicine.)

Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance the efficiency of a lung cancer diagnosis. BALF analysis is a promising approach to evaluating the tumor progression microenvironment. BALF's cellular and non-cellular components dictate the inflammatory response in a cancer-proliferating microenvironment. Furthermore, it is an essential material for detecting clinically significant predictive and prognostic biomarkers that may aid in guiding treatment choices and evaluating therapy-induced toxicities in lung cancer. In the present article, we have reviewed recent literature about the utility of BALF analysis for detecting markers in different stages of tumor cell metabolism, employing either specific biomarker assays or broader omics approaches.

Background: Immune checkpoint inhibitor (ICI)-related pneumonitis is the most frequent fatal immune-related adverse event associated with programmed cell death protein-1/programmed death ligand-1 blockade. The pathophysiology however remains largely unknown, owing to limited and contradictory findings in existing literature pointing at either T-helper 1 or T-helper 17-mediated autoimmunity. In this study, we aimed to gain novel insights into the mechanisms of ICI-related pneumonitis, thereby identifying potential therapeutic targets., Methods: In this prospective observational study, single-cell RNA and T-cell receptor sequencing was performed on bronchoalveolar lavage fluid of 11 patients with ICI-related pneumonitis and 6 demographically-matched patients with cancer without ICI-related pneumonitis. Single-cell transcriptomic immunophenotyping and cell fate mapping coupled to T-cell receptor repertoire analyses were performed., Results: We observed enrichment of both CD4+ and CD8+ T cells in ICI-pneumonitis bronchoalveolar lavage fluid. The CD4+ T-cell compartment showed an increase of pathogenic T-helper 17.1 cells, characterized by high co-expression of TBX21 (encoding T-bet) and RORC (ROR-γ), IFN-G (IFN-γ), IL-17A , CSF2 (GM-CSF), and cytotoxicity genes. Type 1 regulatory T cells and naïve-like CD4+ T cells were also enriched. Within the CD8+ T-cell compartment, mainly effector memory T cells were increased. Correspondingly, myeloid cells in ICI-pneumonitis bronchoalveolar lavage fluid were relatively depleted of anti-inflammatory resident alveolar macrophages while pro-inflammatory 'M1-like' monocytes (expressing TNF , IL-1B , IL-6 , IL-23A, and GM-CSF receptor CSF2RA, CSF2RB ) were enriched compared with control samples. Importantly, a feedforward loop, in which GM-CSF production by pathogenic T-helper 17.1 cells promotes tissue inflammation and IL-23 production by pro-inflammatory monocytes and vice versa, has been well characterized in multiple autoimmune disorders but has never been identified in ICI-related pneumonitis., Conclusions: Using single-cell transcriptomics, we identified accumulation of pathogenic T-helper 17.1 cells in ICI-pneumonitis bronchoalveolar lavage fluid-a phenotype explaining previous divergent findings on T-helper 1 versus T-helper 17 involvement in ICI-pneumonitis-,putatively engaging in detrimental crosstalk with pro-inflammatory 'M1-like' monocytes. This finding yields several novel potential therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In the past, there was limited research relating to the role of sleep in respiratory diseases. Physicians treating these patients tended to focus mainly on the daily disabling symptoms, overlooking the possible significant role of coexisting sleep disorders such as obstructive sleep apnoea (OSA). Nowadays, OSA has been recognised as an important, highly prevalent comorbidity for respiratory diseases such as COPD, asthma and interstitial lung diseases (ILDs). Overlap syndrome refers to the coexistence of chronic respiratory disease and OSA in the same patient. Although, in the past, overlap syndromes have been poorly studied, recent data underline that they result in increased morbidity and mortality compared with either underlying disorder alone. OSA and respiratory disease may be of different severity, and this, along with the existence of various clinical phenotypes, points to the necessity of an individualised therapeutic plan. Early recognition and OSA management could offer key benefits, such as improved sleep, quality of life and disease outcomes., Educational Aims: Describe pathophysiological aspects of OSA in chronic respiratory diseases such as COPD, asthma and ILDs.Understand the bidirectional clinical importance when OSA coexists in chronic respiratory diseases.Review current knowledge of treatment strategies towards an individualised therapeutic plan resulting in patient-centric outcomes., Competing Interests: Conflict of interest: All authors have no financial or other relationships and no conflict of interest to declare., (Copyright ©ERS 2022.)

While continuous positive airway pressure (CPAP) therapy has a strong evidence base for the treatment of obstructive sleep apnoea (OSA), its impact on cardiovascular comorbidity remains unclear. This journal club reviews three recent randomised controlled trials aimed to evaluate the impact of CPAP therapy in secondary prevention of cerebrovascular and coronary heart disease (SAVE trial), comorbid coronary heart disease (RICCADSA trial) and in patients admitted with acute coronary syndrome (ISAACC trial). All three trials included patients with moderate-to-severe OSA and excluded patients with severe daytime sleepiness. When CPAP was compared with usual care, they all reported no difference in a similar primary composite end-point including death from cardiovascular disease, cardiac events, and strokes. These trials faced the same methodological challenges, including a low primary end-point incidence, the exclusion of sleepy patients, and a low CPAP adherence. Therefore, caution must be taken when broadening their results to the wider OSA population. Although randomised controlled trials provide a high level of evidence, they may not be sufficient to capture the diversity of OSA. Large-scale, real-world data may be able to provide a more rounded and generalisable picture of the effects of routine clinical use of CPAP on cardiovascular morbimortality., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright ©ERS 2022.)

Objectives: Continuous positive airway pressure (CPAP) is the 'gold standard' treatment for moderate-to-severe obstructive sleep apnea (OSA); adherence is an important issue. The aim of this paper is to review Belgian data on CPAP users and their adherence over a period of 11 years., Methods: Data delivered annually by the CPAP centers to the Belgian National Institute for Health Insurance (RIZIV/INAMI) were studied. Comments on these results were embedded in a narrative review., Results: On 1 January 2008 27.266 Belgian patients were treated with CPAP, at the end of 2018 this number increased to 121.605. In 2018, the short-term adherence (≤3 months) to CPAP was at least twice as high compared to the United States: the CPAP termination rate in Belgium (mainly due to stop of reimbursement because adherence <4 h/night) was estimated to be 12.4%, considerably lower than the 31.1% of patients on CPAP in the United States using the device <4 h., Conclusion: We speculate that this good adherence might be attributed to a stringent Belgian diagnostic and treatment convention model. This model uses 'gold standard' techniques (including in-hospital polysomnography), imposes a minimum capacity of medical doctors and paramedical collaborators, a strict follow-up of the patients, multidisciplinary care and proof of competency. Taking into account the increasing number of patients, a change in the Belgian care strategy is under consideration focusing on more out-of-centre patient's management; we propose a step-by step approach with careful monitoring of the impact of changing policy on adherence.

We conducted a prospective single-center observational study to determine lung ultrasound reliability in assessing global lung aeration in 38 hospitalized patients with non-critical COVID-19. On admission, fixed chest CT scans using visual (CTv) and software-based (CTs) analyses along with lung ultrasound imaging protocols and scoring systems were applied. The primary endpoint was the correlation between global chest CTs score and global lung ultrasound score. The secondary endpoint was the association between radiographic features and clinical disease classification or laboratory indices of inflammation. Bland−Altman analysis between chest CT scores obtained visually (CTv) or using software (CTs) indicated that only 1 of the 38 paired measures was outside the 95% limits of agreement (−4 to +4 score). Global lung ultrasound score was highly and positively correlated with global software-based CTs score (r = 0.74, CI = 0.55−0.86; p < 0.0001). Significantly higher median CTs score (p = 0.01) and lung ultrasound score (p = 0.02) were found in severe compared to moderate COVID-19. Furthermore, we identified significantly lower (p < 0.05) lung ultrasound and CTs scores in those patients with a more severe clinical condition manifested by SpO2 < 92% and C-reactive protein > 58 mg/L. We concluded that lung ultrasound is a reliable bedside clinical tool to assess global lung aeration in hospitalized non-critical care patients with COVID-19 pneumonia.

Obstructive sleep apnea (OSA) patients would strongly benefit from comfortable home diagnosis, during which detection of wakefulness is essential. Therefore, capacitively-coupled electrocardiogram (ccECG) and bioimpedance (ccBioZ) sensors were used to record the sleep of suspected OSA patients, in parallel with polysomnography (PSG). The three objectives were quality assessment of the unobtrusive signals during sleep, prediction of sleep-wake using ccECG and ccBioZ, and detection of high-risk OSA patients. First, signal quality indicators (SQIs) determined the data coverage of ccECG and ccBioZ. Then, a multimodal convolutional neural network (CNN) for sleep-wake prediction was tested on these preprocessed ccECG and ccBioZ data. Finally, two indices derived from this prediction detected patients at risk. The data included 187 PSG recordings of suspected OSA patients, 36 (dataset "Test") of which were recorded simultaneously with PSG, ccECG, and ccBioZ. As a result, two improvements were made compared to prior studies. First, the ccBioZ signal coverage increased significantly due to adaptation of the acquisition system. Secondly, the utility of the sleep-wake classifier increased as it became a unimodal network only requiring respiratory input. This was achieved by using data augmentation during training. Sleep-wake prediction on "Test" using PSG respiration resulted in a Cohen's kappa (κ) of 0.39 and using ccBioZ in κ = 0.23. The OSA risk model identified severe OSA patients with a κ of 0.61 for PSG respiration and κ of 0.39 using ccBioZ (accuracy of 80.6% and 69.4%, respectively). This study is one of the first to perform sleep-wake staging on capacitively-coupled respiratory signals in suspected OSA patients and to detect high risk OSA patients based on ccBioZ. The technology and the proposed framework could be applied in multi-night follow-up of OSA patients.

Transfer entropy (TE) has been used to identify and quantify interactions between physiological systems. Different methods exist to estimate TE, but there is no consensus about which one performs best in specific applications. In this study, five methods (linear, k-nearest neighbors, fixed-binning with ranking, kernel density estimation and adaptive partitioning) were compared. The comparison was made on three simulation models (linear, nonlinear and linear + nonlinear dynamics). From the simulations, it was found that the best method to quantify the different interactions was adaptive partitioning. This method was then applied on data from a polysomnography study, specifically on the ECG and the respiratory signals (nasal airflow and respiratory effort around the thorax). The hypothesis that the linear and nonlinear components of cardio-respiratory interactions during light and deep sleep change with the sleep stage, was tested. Significant differences, after performing surrogate analysis, indicate an increased TE during deep sleep. However, these differences were found to be dependent on the type of respiratory signal and sampling frequency. These results highlight the importance of selecting the appropriate signals, estimation method and surrogate analysis for the study of linear and nonlinear cardio-respiratory interactions.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Objectives: Sleep time information is essential for monitoring of obstructive sleep apnea (OSA), as the severity assessment depends on the number of breathing disturbances per hour of sleep. However, clinical procedures for sleep monitoring rely on numerous uncomfortable sensors, which could affect sleeping patterns. Therefore, an automated method to identify sleep intervals from unobtrusive data is required. However, most unobtrusive sensors suffer from data loss and sensitivity to movement artifacts. Thus, current sleep detection methods are inadequate, as these require long intervals of good quality. Moreover, sleep monitoring of OSA patients is often less reliable due to heart rate disturbances, movement and sleep fragmentation. The primary aim was to develop a sleep-wake classifier for sleep time estimation of suspected OSA patients, based on single short-term segments of their cardiac and respiratory signals. The secondary aim was to define metrics to detect OSA patients directly from their predicted sleep-wake pattern and prioritize them for clinical diagnosis. Methods: This study used a dataset of 183 suspected OSA patients, of which 36 test subjects. First, a convolutional neural network was designed for sleep-wake classification based on healthier patients (AHI < 10). It employed single 30 s epochs of electrocardiograms and respiratory inductance plethysmograms. Sleep information and Total Sleep Time (TST) was derived for all patients using the short-term segments. Next, OSA patients were detected based on the average confidence of sleep predictions and the percentage of sleep-wake transitions in the predicted sleep architecture. Results: Sleep-wake classification on healthy, mild and moderate patients resulted in moderate κ scores of 0.51, 0.49, and 0.48, respectively. However, TST estimates decreased in accuracy with increasing AHI. Nevertheless, severe patients were detected with a sensitivity of 78% and specificity of 89%, and prioritized for clinical diagnosis. As such, their inaccurate TST estimate becomes irrelevant. Excluding detected OSA patients resulted in an overall estimated TST with a mean bias error of 21.9 (± 55.7) min and Pearson correlation of 0.74 to the reference. Conclusion: The presented framework offered a realistic tool for unobtrusive sleep monitoring of suspected OSA patients. Moreover, it enabled fast prioritization of severe patients for clinical diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huysmans, Borzée, Buyse, Testelmans, Van Huffel and Varon.)

In this work, a detection and classification method for sleep apnea and hypopnea, using photopletysmography (PPG) and peripheral oxygen saturation (SpO 2 ) signals, is proposed. The detector consists of two parts: one that detects reductions in amplitude fluctuation of PPG (DAP)and one that detects oxygen desaturations. To further differentiate among sleep disordered breathing events (SDBE), the pulse rate variability (PRV) was extracted from the PPG signal, and then used to extract features that enhance the sympatho-vagal arousals during apneas and hypopneas. A classification was performed to discriminate between central and obstructive events, apneas and hypopneas. The algorithms were tested on 96 overnight signals recorded at the UZ Leuven hospital, annotated by clinical experts, and from patients without any kind of co-morbidity. An accuracy of 75.1% for the detection of apneas and hypopneas, in one-minute segments,was reached. The classification of the detected events showed 92.6% accuracy in separating central from obstructive apnea, 83.7% for central apnea and central hypopnea and 82.7% for obstructive apnea and obstructive hypopnea. The low implementation cost showed a potential for the proposed method of being used as screening device, in ambulatory scenarios.

Clinical activities regarding sleep disordered breathing (SDB) have been sharply interrupted during the initial phase of the coronavirus disease 2019 (COVID-19) epidemic throughout Europe. In the past months, activities have gradually restarted, according to epidemiological phase of COVID-19 and national recommendations. The recent increase in cases throughout Europe demands a reconsideration of management strategies of SDB accordingly. Diagnosis of SDB and initiation of treatment pose some specific problems to be addressed to preserve the safety of patients and health personnel. This perspective document by a group of European sleep experts aims to summarise some different approaches followed in Europe and United States, which reflect national recommendations according to the epidemiological phase of the COVID-19 infection. Respiratory sleep medicine is likely to change in the near future, and use of telemedicine will grow to avoid unnecessary risks and continue to provide optimal care to patients. In addition, the document covers paediatric sleep studies and indications for titration of noninvasive ventilation, as well as precautions to be followed by patients who are already on positive airway pressure treatment. A single consensus document developed by the European Respiratory Society and national societies would be desirable to harmonise SDB management throughout Europe., Competing Interests: Conflict of interest: S. Schiza has nothing to disclose. Conflict of interest: A. Simonds has nothing to disclose. Conflict of interest: W. Randerath has nothing to disclose. Conflict of interest: F. Fanfulla has nothing to disclose. Conflict of interest: D. Testelmans has nothing to disclose. Conflict of interest: L. Grote has nothing to disclose. Conflict of interest: J.M. Montserrat has nothing to disclose. Conflict of interest: J-L. Pepin has nothing to disclose. Conflict of interest: J. Verbraecken has nothing to disclose. Conflict of interest: R. Ersu has nothing to disclose. Conflict of interest: M.R. Bonsignore has nothing to disclose., (Copyright ©ERS 2021.)

How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8 + resident-memory (T RM ) and CD4 + T-helper-17 (T H17 ) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4 + T-cells with T-helper-1 characteristics (T H1 -like) and CD8 + T-cells expressing exhaustion markers (T EX -like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.

Respiratory sinus arrhythmia (RSA) is a form of cardiorespiratory coupling. It is observed as changes in the heart rate in synchrony with the respiration. RSA has been hypothesized to be due to a combination of linear and nonlinear effects. The quantification of the latter, in turn, has been suggested as a biomarker to improve the assessment of several conditions and diseases. In this study, a framework to quantify RSA using support vector machines is presented. The methods are based on multivariate autoregressive models, in which the present samples of the heart rate variability are predicted as combinations of past samples of the respiration. The selection and tuning of a kernel in these models allows to solve the regression problem taking into account only the linear components, or both the linear and the nonlinear ones. The methods are tested in simulated data as well as in a dataset of polysomnographic studies taken from 110 obstructive sleep apnea patients. In the simulation, the methods were able to capture the nonlinear components when a weak cardiorespiratory coupling occurs. When the coupling increases, the nonlinear part of the coupling is not detected and the interaction is found to be of linear nature. The trends observed in the application in real data show that, in the studied dataset, the proposed methods captured a more prominent linear interaction than the nonlinear one., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morales, Borzée, Testelmans, Buyse, Van Huffel and Varon.)

The electrocardiogram (ECG) is an important diagnostic tool for identifying cardiac problems. Nowadays, new ways to record ECG signals outside of the hospital are being investigated. A promising technique is capacitively coupled ECG (ccECG), which allows ECG signals to be recorded through insulating materials. However, as the ECG is no longer recorded in a controlled environment, this inevitably implies the presence of more artefacts. Artefact detection algorithms are used to detect and remove these. Typically, the training of a new algorithm requires a lot of ground truth data, which is costly to obtain. As many labelled contact ECG datasets exist, we could avoid the use of labelling new ccECG signals by making use of previous knowledge. Transfer learning can be used for this purpose. Here, we applied transfer learning to optimise the performance of an artefact detection model, trained on contact ECG, towards ccECG. We used ECG recordings from three different datasets, recorded with three recording devices. We showed that the accuracy of a contact-ECG classifier improved between 5 and 8% by means of transfer learning when tested on a ccECG dataset. Furthermore, we showed that only 20 segments of the ccECG dataset are sufficient to significantly increase the accuracy.

Data concerning sleep-disordered breathing (SDB) after lung transplantation (LTX) are scarce. This study aims to analyze prevalence, associated factors, and impact on survival of moderate to severe SDB in a large cohort of consecutive LTX patients (n = 219). Patients underwent a diagnostic polysomnography 1 year after LTX. Moderate to severe SDB was present in 57.5% of patients, with the highest prevalence in chronic obstructive pulmonary disease/emphysema (71.1%) and pulmonary fibrosis (65.1%). SDB patients were older, mostly male, and had higher body mass index and neck circumference. Nocturnal diastolic and 24-hour blood pressures were higher in SDB patients. In 45 patients, polysomnography was also performed pre-LTX. Compared to pre-LTX, mean apnea/hypopnea index (AHI) increased significantly after LTX. A significant correlation was seen between lung function parameters and AHI, suggesting a role of decreased caudal traction on the pharynx. Presence of SDB had no impact on mortality or prevalence of chronic lung allograft dysfunction. However, survival was better in continuous positive airway pressure (CPAP) compliant SDB patients compared to SDB patients without CPAP treatment. These findings may be pertinent for systematic screening of SDB after LTX., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Studies have shown an increased cardiovascular risk in obstructive sleep apnea (OSA) patients. In order to prioritize treatment of high risk patients, there is a need for improved cardiovascular OSA phenotyping. This study investigates the use of oxygen saturation (SpO 2 ) parameters for cardiovascular risk assessment of OSA patients. To this end, a novel multilevel interval coded scoring (mICS) algorithm is proposed., Methods: The study includes SpO 2 recordings from 1987 overnight polysomnographies, of which 974 are from patients suspected to have OSA, 931 from the general population based Sleep Heart Health Study and 83 from healthy controls. The minimal SpO 2 value, SpO 2 upslope and amplitude ratio of desaturation over resaturation are extracted for all oxygen desaturations and averaged per patient. These three SpO 2 parameters are used together with patient demographics to develop a mICS model to predict the probability that a patient had a cardiovascular condition, or had already experienced a cardiovascular event, at the time of the polysomnography., Results: Including the SpO 2 parameters in the mICS together with age and BMI improves the model's performance by 2.7% and leads to a test area under the curve (AUC) of 69.5% for the detection of any cardiovascular comorbidity. Moreover, an increase in AUC of 5% was obtained for the detection of cardiovascular events, resulting in an AUC of 93.5%., Conclusions: This study shows that parameters based on SpO 2 and the mICS model are useful to predict the cardiovascular comorbidity status of OSA patients., Significance: The proposed model could be used to assist in prioritizing OSA patients for treatment.

Cardiorespiratory monitoring is crucial for the diagnosis and management of multiple conditions such as stress and sleep disorders. Therefore, the development of ambulatory systems providing continuous, comfortable, and inexpensive means for monitoring represents an important research topic. Several techniques have been proposed in the literature to derive respiratory information from the ECG signal. Ten methods to compute single-lead ECG-derived respiration (EDR) were compared under multiple conditions, including different recording systems, baseline wander, normal and abnormal breathing patterns, changes in breathing rate, noise, and artifacts. Respiratory rates, wave morphology, and cardiorespiratory information were derived from the ECG and compared to those extracted from a reference respiratory signal. Three datasets were considered for analysis, involving a total 59 482 one-min, single-lead ECG segments recorded from 156 subjects. The results indicate that the methods based on QRS slopes outperform the other methods. This result is particularly interesting since simplicity is crucial for the development of ECG-based ambulatory systems.

Objectives: Last years, vibrating devices were introduced to treat positional sleep apnoea (POSA). However, few data exist on determinants of effectiveness and adherence in clinical settings. Methods : The NightBalance Sleep Position Trainer (SPT) analyses the patient's position during the first 2 nights, starts to build up vibrations during the following 7 and is 100% performant from night 10 on; and, reports on %supine, usage time, number of (responses on) vibrations. The device was started for a 28-day try-out period in a clinical cohort of 51 consecutive patients with POSA. SPT-stored data were studied on different time points: first 2 nights without vibrations (baseline), first 2 nights on SPT 100% performance (short term) and 2 later nights after having used the full performant device for 14 days (long term). Results : Only 27 patients used the device throughout the long-term period. The baseline %supine was lower than during polysomnography: 22.9 ± 16.2 versus 40.7 ± 20.0% ( p = 0.0005). Apnoea-hypopnoea index calculation taking into account the %supine on SPT revealed that 2/27 patients would not have obstructive sleep apnoea at home. The baseline %supine dropped ( p < 0.0001) on short term without further change on long term. Ten patients could be considered cured and demonstrated higher response on vibrations. Only 29 patients could be considered as adherent, and they demonstrated higher response on vibrations and less side effects; only 13 wanted to purchase the SPT. Conclusion : On polysomnography, the %supine is overestimated. The efficacy and low adherence are influenced by differences in response to vibrations. The training effect is already presented on short term.

Patients with diaphragm dysfunction experience exertional dyspnoea. Respiratory muscle function assessments can identify breathing abnormalities and IMT might help to reduce symptoms (mostly via improvements in non-diaphragmatic muscles). http://bit.ly/2QdxNFP., Competing Interests: Conflict of interest: M. Caleffi Pereira has nothing to disclose. Conflict of interest: S. Dacha has nothing to disclose. Conflict of interest: D. Testelmans has nothing to disclose. Conflict of interest: R. Gosselink has nothing to disclose. Conflict of interest: D. Langer has nothing to disclose., (Copyright ©ERS 2019.)

The high prevalence of sleep apnea syndrome (SAS) and its direct relationship with an augmented risk of cardiovascular disease (CVD) have raised SAS as a primary public health problem. For this reason, extensive research aiming to understand the interaction between both conditions has been conducted. The advances in non-invasive autonomic nervous system (ANS) monitoring through heart rate variability (HRV) analysis have revealed an increased sympathetic dominance in subjects suffering from SAS when compared with controls. Similarly, HRV analysis of subjects with CVD suggests altered autonomic activity. In this work, we investigated the altered autonomic control in subjects suffering from SAS and CVD simultaneously when compared with SAS patients, as well as the possibility that ANS assessment may be useful for the early stage identification of cardiovascular risk in subjects with SAS. The analysis was performed over 199 subjects from two independent datasets during night-time, and the effects of the physiological response following an apneic episode, sleep stages, and respiration on HRV were taken into account. Results, as measured by HRV, suggest a decreased sympathetic dominance in those subjects suffering from both conditions, as well as in subjects with SAS that will develop CVDs, which was reflected in a significantly reduced sympathovagal balance ( p < 0.05). In this way, ANS monitoring could contribute to improve screening and diagnosis, and eventually aid in the phenotyping of patients, as an altered response might have direct implications on cardiovascular health.

There exists a technological momentum towards the development of unobtrusive, simple, and reliable systems for long-term sleep monitoring. An off-the-shelf commercial pressure sensor meeting these requirements is the Emfit QS. First, the potential for sleep apnea screening was investigated by revealing clusters of contaminated and clean segments. A relationship between the irregularity of the data and the sleep apnea severity class was observed, which was valuable for screening (sensitivity 0.72, specificity 0.70), although the linear relation was limited ( R 2 of 0.16). Secondly, the study explored the suitability of this commercial sensor to be merged with gold standard polysomnography data for future sleep monitoring. As polysomnography (PSG) and Emfit signals originate from different types of sensor modalities, they cannot be regarded as strictly coupled. Therefore, an automated synchronization procedure based on artefact patterns was developed. Additionally, the optimal position of the Emfit for capturing respiratory and cardiac information similar to the PSG was identified, resulting in a position as close as possible to the thorax. The proposed approach demonstrated the potential for unobtrusive screening of sleep apnea patients at home. Furthermore, the synchronization framework enabled supervised analysis of the commercial Emfit sensor for future sleep monitoring, which can be extended to other multi-modal systems that record movements during sleep.

Objectives: In the last decade significant research has focused on the relationship between physical activity (PA), exercise and obstructive sleep apnea (OSA). The purpose of this study is to provide an overview and interpretation of different studies regarding this subject., Methods: PubMed, Embase and Cochrane Library databases were searched for English articles published before August 21, 2017. Search terms were 'Sleep Apnea, Obstructive' and 'Exercise'., Results: Low levels of PA are associated with higher odds of OSA. A negative correlation between PA level and OSA severity is shown, even after adjusting for baseline differences. OSA also impairs the aerobic exercise capacity significantly. OSA patients have a poor hemodynamic response to exercise, which is related to OSA severity. Findings on the influence of continuous positive airway pressure (CPAP) on PA in OSA are inconsistent in terms of statistical significance. A regular and predominantly aerobic exercise training significantly reduces OSA severity, even without a significant decrease in body weight., Conclusion: The available evidence suggests that further research is necessary to explore the relationships between PA, exercise and OSA and to examine the efficacy of exercise as alternative or additional treatment for OSA.

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a "marker" of disease severity or a "mediator" of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation., (Copyright ©ERS 2017.)

Objectives: Little is known about the effects of noninvasive ventilation (NIV) on sleep quality in amyotrophic lateral sclerosis (ALS). We aim to evaluate the long-term effects of NIV on sleep quality and quality of life in patients with ALS., Methods: In this prospective observational study, 13 ALS patients were followed for one year after initiating NIV. We evaluated sleep quality, quality of life and functional status with several questionnaires: Epworth sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI), Short Form 36 Health Questionnaire (SF-36), McGill Quality of Life questionnaire (McGillQoL) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores (ALSFRS-R)., Results: Median and interquartile range (IQR) at the start of NIV was 59 (53-65) years. The ALSFRS-R at start was 30 (24-37) (median, IQR), with three patients having severe bulbar impairment (ALSFRS-R-bulbar ≤ 9). The P a CO 2 at start of NIV treatment was 48 (43-52) mmHg (median, IQR). During the one-year follow-up period, a significant decrease in the ALSFRS-R was observed. The impact of NIV in a short term (1 month) revealed a statistically significant decrease in ESS, decrease in total PSQI and of four PSQI subscales and improvement of almost all subscales of the McGill questionnaire. Long-term analyses (9 months to 1 year) revealed that amelioration in ESS and total PSQI was sustained., Conclusion: We conclude that accurately titrated NIV in ALS patients can stabilize sleep quality and quality of life for at least one year, despite significant disease progression.

Goal: This paper presents a methodology for the automatic detection of sleep apnea from single-lead ECG., Methods: It uses two novel features derived from the ECG, and two well-known features in heart rate variability analysis, namely the standard deviation and the serial correlation coefficients of the RR interval time series. The first novel feature uses the principal components of the QRS complexes, and it describes changes in their morphology caused by an increased sympathetic activity during apnea. The second novel feature extracts the information shared between respiration and heart rate using orthogonal subspace projections. Respiratory information is derived from the ECG by means of three state-of-the-art algorithms, which are implemented and compared here. All features are used as input to a least-squares support vector machines classifier, using an RBF kernel. In total, 80 ECG recordings were included in the study., Results: Accuracies of about 85% are achieved on a minute-by-minute basis, for two independent datasets including both hypopneas and apneas together. Separation between apnea and normal recordings is achieved with 100% accuracy. In addition to apnea classification, the proposed methodology determines the contamination level of each ECG minute., Conclusion: The performances achieved are comparable with those reported in the literature for fully automated algorithms., Significance: These results indicate that the use of only ECG sensors can achieve good accuracies in the detection of sleep apnea. Moreover, the contamination level of each ECG segment can be used to automatically detect artefacts, and to highlight segments that require further visual inspection.

Study Objective: To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG)., Methods: In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month., Results: In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores., Conclusions: This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality., Commentary: A commentary on this article appears in this issue on page 511., (© 2015 American Academy of Sleep Medicine.)

Introduction: Radial endobronchial ultrasonography miniprobe (rEBUS-MP) is a technique that has increased the diagnostic yield of bronchoscopic occult pulmonary lesions. The purpose of this study was to identify computed tomography (CT) characteristics affecting the success rate of rEBUS-MP in the evaluation of these pulmonary lesions., Methods: Our study encompassed a retrospective review of all consecutive patients who underwent a rEBUS-MP examination between January 2011 and December 2013. CT characteristics including lesion size, lesion location, and bronchus sign were analyzed against two defined outcomes (visualization yield and diagnostic yield). Univariate analysis was employed to examine the individual effects of each CT parameter on visualization yield and diagnostic yield. Multivariate logistic regression was performed to identify significant predictors of diagnostic yield., Results: Seven hundred and sixty lesions (760 patients) were included. The mean ± SD longest lesion diameter was 43 ± 2 mm. rEBUS-MP could visualize 83% and a definitive diagnosis was established in 62%. In a multivariate analysis, longest lesion diameter greater than 20 mm (odds ratio [OR]: 1.97 and p = 0.036), distance lesion to secondary or tertiary carina greater than 40 mm (OR: 0.60 and p=0.016), and lobar segment (1, 3, or 6, respectively) were determined to be significant factors predicting diagnostic yield. Bronchus sign was the only parameter that indirectly influenced the diagnostic yield through enhancing visualization yield (p < 0.001)., Conclusion: Multivariate analysis revealed that lesion size, distance to carina, and segment were predictors of diagnostic yield. The presence of a bronchus sign substantially increased the diagnostic yield through the visualization yield.

In patients with neuromuscular disorders, no randomized studies have been performed whether nasal or oronasal masks should be preferred. Oronasal masks are often used in acute respiratory failure, while nasal masks are preferred in patients with chronic respiratory failure. However, the use of nasal masks can result in mouth leaks with implications on sleep quality. To reduce these leaks, oronasal masks have been applied during home noninvasive ventilation (NIV). Until now, upper airway obstruction during NIV has been thought to be induced by nasal obstruction, pharyngeal collapse, and/or glottis closure. We report a case indicating another cause of upper airway obstruction: use of an oronasal mask can induce obstructive events in the upper airways, possibly resulting in sleep fragmentation and decreased efficiency of NIV., (© 2014 American Academy of Sleep Medicine.)

Unilateral diaphragm paralysis is an often not recognised cause of dyspnoea. We present a patient with a unilateral phrenic nerve paralysis treated with diaphragmatic plication. Patient presented with life-style limiting dyspnoea and pulmonary function showed a decrease in FVC when lying down. Since there was no improvement after respiratory muscle training, plication of the hemidiaphragm was performed by a small thoracotomy. The patient improved with regard to respiratory complaints and lung function. Furthermore, we also demonstrate for the first time a significant improvement in exercise capacity with accompanying striking amelioration of quality of life. The patient is now in follow up up for more than 2 years and the impressive improvement in exercise capacity remains present. Surgical treatment of unilateral diaphragm paralysis has been described in case reports and in small series since 1985. Although comparison of the available data is difficult a diaphragm plication seems an effective and safe procedure for patients with symptomatic, acquired unilateral diaphragm paralysis. Improvement of dyspnoea is present in the majority of patients and we even observed an impressive amelioration in exercise capacity. Consequently, it seems appropriate to propose plication to patients with clear symptoms from the moment spontaneous recovery seems unlikely; yet, prospective randomised controlled studies are needed to prove this.

Obstructive sleep apnea (OSA) is inducing oxidative stress and consequently promotes systemic inflammation and cardiovascular morbidity. The respective impact of obesity, sleep apnea and acute cardiovascular events on the profile of inflammatory cytokines has not been extensively evaluated. We examined the profile of circulating cytokines in a case-control study comparing nonobese or obese patients with or without sleep apnea and with or without an acute cardiovascular event. Patients were assessed by sleep studies and inflammatory (hs-CRP, Leptin, RANTES, MCP1, IL6, IL8, TNF-α) and anti-inflammatory (adiponectin, IL1-Ra) cytokines profile. A cardiovascular phenotyping was performed including carotid intima-media thickness, pulse wave velocity and 24h blood pressure monitoring. In comparison with patients without sleep apnea or without comorbidities, patients with the combination of an acute cardiovascular event and pre-existing sleep apnea showed a higher burden of systemic inflammation with significant increase in serum levels of hs-CRP, IL1-Ra, IL-8, IL-6, TNF-α, Rantes and sICAM. Rantes and sICAM serum levels were independently associated with AHI after an acute cardiovascular event. Serum levels of different inflammatory markers were significantly increased in patients with the combination of sleep apnea and an acute cardiovascular event. Since these biomarkers could be associated with worsened cardiovascular outcome, diagnosing and treating associated sleep apnea is potentially important in patients after an acute cardiovascular event., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ovarian cancer is the second most common gynaecologic malignancy. Ovarian carcinomas typically metastasize to multiple sites via exfoliation, lymphatic spread or direct invasion. We present a rare case of a very late recurrence of ovarian carcinoma into the thoracic wall, heralded by thoracic pain in a patient otherwise disease-free for 23 years. This unusual and late presentation of an ovarian cancer metastasis underscores the need for continued awareness and attention to new symptoms in patients with ovarian cancer who show prolonged disease-free intervals.

We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients. We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-kappaB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD. Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IkappaBalpha and IkappaBbeta were decreased in the COPD patients as was NF-kappaB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients. These data show that the ubiquitin-proteasome pathway, the NF-kappaB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.

Introduction: Respiratory muscle weakness is an important risk factor for delayed weaning. Animal data show that mechanical ventilation itself can cause atrophy and weakness of the diaphragm, called ventilator-induced diaphragmatic dysfunction (VIDD). Transdiaphragmatic pressure after magnetic stimulation (TwPdi BAMPS) allows evaluation of diaphragm strength. We aimed to evaluate the repeatability of TwPdi BAMPS in critically ill, mechanically ventilated patients and to describe the relation between TwPdi and the duration of mechanical ventilation., Methods: This was a prospective observational study in critically ill and mechanically ventilated patients, admitted to the medical intensive care unit of a university hospital. Nineteen measurements were made in a total of 10 patients at various intervals after starting mechanical ventilation. In seven patients, measurements were made on two or more occasions, with a minimum interval of 24 hours., Results: The TwPdi was 11.5 ± 3.9 cm H2O (mean ± SD), indicating severe respiratory muscle weakness. The between-occasion coefficient of variation of TwPdi was 9.7%, comparable with data from healthy volunteers. Increasing duration of mechanical ventilation was associated with a logarithmic decline in TwPdi (R = 0.69; P = 0.038). This association was also found for cumulative time on pressure control (R = 0.71; P = 0.03) and pressure-support ventilation (P = 0.05; R = 0.66) separately, as well as for cumulative dose of propofol (R = 0.66; P = 0.05) and piritramide (R = 0.79; P = 0.01)., Conclusions: Duration of mechanical ventilation is associated with a logarithmic decline in diaphragmatic force, which is compatible with the concept of VIDD. The observed decline may also be due to other potentially contributing factors such as sedatives/analgesics, sepsis, or others.

Rationale: Mechanical ventilation is known to induce ventilator-induced diaphragm dysfunction. Patients submitted to mechanical ventilation often receive massive doses of corticosteroids that may cause further deterioration of diaphragm function., Objectives: To examine whether the combination of 24 hours of controlled mechanical ventilation with corticosteroid administration would exacerbate ventilator-induced diaphragm dysfunction., Methods: Rats were randomly assigned to a group submitted to 24 hours of controlled mechanical ventilation receiving an intramuscular injection of saline or 80 mg/kg methylprednisolone, a group submitted to 24 hours of spontaneous breathing receiving saline, or methylprednisolone and a control group., Measurements and Main Results: The diaphragm force-frequency curve was shifted downward in the mechanical ventilation group, but this deleterious effect was prevented when corticosteroids were administered. Diaphragm cross-sectional area of type I fibers was similarly decreased in both mechanical ventilation groups while atrophy of type IIx/b fibers was attenuated after corticosteroid administration. The mechanical ventilation-induced reduction in diaphragm MyoD and myogenin protein expression was attenuated after corticosteroids. Plasma cytokine levels were unchanged while diaphragm lipid hydroperoxides were similarly increased in both mechanical ventilation groups. Diaphragmatic calpain activity was significantly increased in the mechanical ventilation group, but calpain activation was abated with corticosteroid administration. Inverse correlations were found between calpain activity and diaphragm force., Conclusions: A single high dose of methylprednisolone combined with controlled mechanical ventilation protected diaphragm function from the deleterious effects of controlled mechanical ventilation. Inhibition of the calpain system is most likely the mechanism by which corticosteroids induce this protective effect.

Rationale: Controlled mechanical ventilation (CMV) has been shown to result in elevated diaphragmatic proteolysis and atrophy together with diaphragmatic contractile dysfunction., Objectives: To test whether administration of leupeptin, an inhibitor of lysosomal proteases and calpain, concomitantly with 24 hours of CMV, would protect the diaphragm from the deleterious effects of mechanical ventilation., Methods: Rats were assigned to either a control group or 24 hours of CMV; animals in the ventilation group received either a single intramuscular injection of saline or 15 mg/kg of the protease inhibitor, leupeptin., Measurements and Main Results: Compared with control animals, mechanical ventilation resulted in a significant reduction of the in vitro diaphragm-specific force production at all stimulation frequencies. Leupeptin completely prevented this reduction in force generation. Atrophy of type IIx/b fibers was present after CMV, but not after treatment with leupeptin. Cathepsin B and calpain activities were significantly higher after CMV compared with the other groups; this was abolished by treatment with leupeptin. Significant inverse correlations were found between diaphragmatic force generation and cathepsin B and calpain activity, and illustrate the deleterious role of proteolysis in diminishing diaphragmatic force production after prolonged CMV., Conclusions: Administration of the protease inhibitor leupeptin concomitantly with mechanical ventilation completely prevented ventilation-induced diaphragmatic contractile dysfunction and atrophy.