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In January 2019, a European Respiratory Society research seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide, which occur frequently in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, and to discuss pitfalls of current models and the design of future collaborative studies. In addition, we debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches., Competing Interests: Conflict of interest: S. Ryan has nothing to disclose. Conflict of interest: E.P. Cummins has nothing to disclose. Conflict of interest: R. Farre has nothing to disclose. Conflict of interest: A. Gileles-Hillel has nothing to disclose. Conflict of interest: J.C. Jun has nothing to disclose. Conflict of interest: H. Oster has nothing to disclose. Conflict of interest: J-L. Pepin has nothing to disclose. Conflict of interest: D.W. Ray has nothing to disclose. Conflict of interest: S. Reutrakul reports grants from Merck Sharp and Dohme, personal fees from Medtronic and Sanofi Aventis, outside the submitted work. Conflict of interest: M. Sanchez-de-la-Torre has nothing to disclose. Conflict of interest: R. Tamisier reports travel grants from Agiradom, grants from Resmed, personal fees for lectures from Resmed, Philips and Elivie, personal fees for consultancy from Navigant, Inspire, Jazz Pharmaceutical and Resmed, outside the submitted work. Conflict of interest: I. Isaac Almendros has nothing to disclose., (Copyright ©ERS 2020.)

Obstructive sleep apnoea (OSA) is a major challenge for physicians and healthcare systems throughout the world. The high prevalence and the impact on daily life of OSA oblige clinicians to offer effective and acceptable treatment options. However, recent evidence has raised questions about the benefits of positive airway pressure therapy in ameliorating comorbidities.An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field, and proposed topics for future research on epidemiology, phenotyping, underlying mechanisms, prognostic implications and optimal treatment of patients with OSA.The group concluded that a revision to the diagnostic criteria for OSA is required to include factors that reflect different clinical and pathophysiological phenotypes and relevant comorbidities ( e.g. nondipping nocturnal blood pressure). Furthermore, current severity thresholds require revision to reflect factors such as the disparity in the apnoea-hypopnoea index (AHI) between polysomnography and sleep studies that do not include sleep stage measurements, in addition to the poor correlation between AHI and daytime symptoms such as sleepiness. Management decisions should be linked to the underlying phenotype and consider outcomes beyond AHI., Competing Interests: Conflict of interest: W. Randerath reports grants and personal fees (travel grants and speaking fees) from Heinen & Löwenstein, Weinmann, ResMed, Inspire and Philips Respironics, outside the submitted work. L. Ferini-Strambi reports personal fees from Philips Respironics (honoraria for a lecture and for chairing a scientific meeting in 2015–2016, none of which involved promotion of company products and there was no influence on lecture content) and ResMed (honoraria for participating in an advisory board), outside the submitted work. R. Farre reports other fees from ResMed (a contract between the company and the University of Barcelona (Fundació Bosch Gimpera) for assessing automatic CPAP devices in a bench test) and other fees from ANTADIR (a contract between the company and the University of Barcelona (Fundació Bosch Gimpera) for assessing automatic CPAP devices in a bench test), outside the submitted work. L. Grote reports grants and personal fees (speakers’ bureau) from ResMed and Philips, personal fees from Breas Mecical (consultancy), personal fees and nonfinancial support from Heinen & Löwenstein (consultancy), and grants from the ERS, during the conduct of the study; and personal fees (speakers’ bureau) from AstraZeneca, outside the submitted work. In addition, L. Grote has a patent on pharmacological treatment of OSA pending. J. Hedner has together with the ESADA study group received grants from ResMed and Philips Respironics to enable the ESADA database. He has also received personal speaker bureau fees from AstraZeneca, Takeda and Bayer. M. Kohler reports personal fees from Bayer (advisor fees), outside the submitted work. J-L. Pepin reports unrestricted research grants from Philips, ResMed, Fisher & Paykel, Fondation de la recherche medicale, Direction de la recherche Clinique du CHU de Grenoble and Fond de dotation “Agir pour les maladies chroniques”, and personal fees (travel grants and lecture fees) from Perimetre, Philips, Fisher & Paykel, ResMed, AstraZeneka, SEFAM, Agiradom and Teva, during the conduct of the study. J. Verbraecken reports other fees (sponsoring courses) from Koninklijke Philips Respironics, ResMed, Fisher & Paykel, NightBalance, Heinen & Löwenstein, AirLiquide, Accuramed, OSG, Medidis, MediqTefa, Wave Medical, Vivisol, TotalCare, SomnoMed, UCB Pharma, Olympus Belgium, Takeda, Masimo and Linde Healthcare, outside the submitted work. W.T. McNicholas reports personal fees from Philips Respironics (honoraria for lectures, but none of these lectures related to promotion of company products and the lecture content was not in any way influenced by the company), outside the submitted work., (Copyright ©ERS 2018.)

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h -1 ), mild OSA (AHI 5-15 events·h -1 ) and moderate-severe OSA (AHI >15 events·h -1 ). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable.360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8-68.0) years and AHI 8.55 (2.8-19.5) events·h -1 ). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate-severe OSA: OR 2.35, p=0.013).In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8 + T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human in vitro and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8 + T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8 + T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Little is known about the changes in upper airway calibre in Cheyne-Stokes respiration (CSR) during sleep in patients with congestive heart failure. This study aimed to test the hypothesis that upper airway closure occurs during central CSR events, by assessing upper airway calibre during sleep using the forced oscillation technique (FOT). Nine males with compensated heart failure (left ventricular ejection fraction mean ± sem 27.9 ± 5.1%) and predominant central CSR (apnoea/hypopnoea index 43.9 ± 4.2 events · h(-1)) were studied during overnight polysomnography, which included pneumotachography, inductance plethysmography or oesophageal pressure and FOT-derived impedance signal (|Z|). Baseline |Z| values during stable breathing in stage 2 sleep were 11.0 ± 1.3 cmH(2)O · s · L(-1). Mean |Z| increased to 31.9 ± 6.7 cmH(2)O · s · L(-1) during obstructive apnoeas (7% of events, n = 46). Increases in |Z| consistent with upper airway narrowing (more than two-fold baseline) were common during central apnoeas (50 ± 12% of events) occurring in the middle or end of apnoeas and occurred during some central hypopnoeas (16 ± 10% of events), typically in the expiratory phase. These findings indicate that in heart failure patients, reductions in upper airway calibre are common during CSR apnoeas, and may also occur during central hypopnoeas.

The study was designed to assess the patterns of use of home mechanical ventilation (HMV) for patients with chronic respiratory failure across Europe. A detailed questionnaire of centre details, HMV user characteristics and equipment choices was sent to carefully identified HMV centres in 16 European countries. A total of 483 centres treating 27,118 HMV users were identified. Of these, 329 centres completed surveys between July 2001 and June 2002, representing up to 21,526 HMV users and a response rate of between 62% and 79%. The estimated prevalence of HMV in Europe was 6.6 per 100,000 people. The variation in prevalence between countries was only partially related to the median year of starting HMV services. In addition, there were marked differences between countries in the relative proportions of lung and neuromuscular patients using HMV, and the use of tracheostomies in lung and neuromuscular HMV users. Lung users were linked to a HMV duration of <1 yr, thoracic cage users with 6-10 yrs of ventilation and neuromuscular users with a duration of > or =6 yrs. In conclusion, wide variations exist in the patterns of home mechanical ventilation provision throughout Europe. Further work is needed to monitor its use and ensure equality of provision and access.