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Jean-Louis Pepin,1,* Nhat-Nam Le-Dong,2,* Valérie Cuthbert,3 Nathalie Coumans,3 Renaud Tamisier,1 Atul Malhotra,4 Jean-Benoit Martinot3,5 1HP2 Laboratory, Inserm U1300, University Grenoble Alpes, Grenoble, France; 2Sunrise, Namur, Belgium; 3Sleep Laboratory, CHU Université Catholique de Louvain (UCL) Namur Site Sainte-Elisabeth, Namur, Belgium; 4University of California San Diego, La Jolla, CA, USA; 5Institute of Experimental and Clinical Research, UCL Bruxelles Woluwe, Brussels, Belgium*These authors contributed equally to this workCorrespondence: Jean-Benoit Martinot, Centre du Sommeil et de la Vigilance, CHU-UCL Namur Site Ste Elisabeth, 15 Place Louise Godin, Namur, 5000, Belgium, Tel +32 495502608, Fax +32 81570754, Email martinot.j@respisom.bePurpose: Differentiation between obstructive and central apneas and hypopneas requires quantitative measurement of respiratory effort (RE) using esophageal pressure (PES), which is rarely implemented. This study investigated whether the sleep mandibular movements (MM) signal recorded with a tri-axial gyroscopic chin sensor (Sunrise, Namur, Belgium) is a reliable surrogate of PES in patients with suspected obstructive sleep apnea (OSA).Patients and Methods: In-laboratory polysomnography (PSG) with PES and concurrent MM monitoring was performed. PSGs were scored manually using AASM 2012 rules. Data blocks (n=8042) were randomly sampled during normal breathing (NB), obstructive or central apnea/hypopnea (OA/OH/CA/CH), respiratory effort-related arousal (RERA), and mixed apnea (MxA). Analyses were evaluation of the similarity and linear correlation between PES and MM using the longest common subsequence (LCSS) algorithm and Pearson’s coefficient; description of signal amplitudes; estimation of the marginal effect for crossing from NB to a respiratory disturbance for a given change in MM signal using a mixed linear-regression.Results: Participants (n=38) had mild to severe OSA (median AH index 28.9/h; median arousal index 23.2/h). MM showed a high level of synchronization with concurrent PES signals. Distribution of MM amplitude differed significantly between event types: median (95% confidence interval) values of 0.60 (0.16– 2.43) for CA, 0.83 (0.23– 4.71) for CH, 1.93 (0.46– 12.43) for MxA, 3.23 (0.72– 18.09) for OH, and 6.42 (0.88– 26.81) for OA. Mixed regression indicated that crossing from NB to central events would decrease MM signal amplitude by – 1.23 (CH) and – 2.04 (CA) units, while obstructive events would increase MM amplitude by +3.27 (OH) and +6.79 (OA) units (all p< 10− 6).Conclusion: In OSA patients, MM signals facilitated the measurement of specific levels of RE associated with obstructive, central or mixed apneas and/or hypopneas. A high degree of similarity was observed with the PES gold-standard signal.Keywords: obstructive sleep apnea, respiratory effort, mandibular movements, esophageal pressure

Background: Current bilevel positive-pressure ventilators for home noninvasive ventilation (NIV) provide physicians with software that records items important for patient monitoring, such as compliance, tidal volume (Vt), and leaks. However, to our knowledge, the validity of this information has not yet been independently assessed.Methods: Testing was done for seven home ventilators on a bench model adapted to simulate NIV and generate unintentional leaks (ie, other than of the mask exhalation valve). Five levels of leaks were simulated using a computer-driven solenoid valve (0-60 L/min) at different levels of inspiratory pressure (15 and 25 cm H(2)O) and at a fixed expiratory pressure (5 cm H(2)O), for a total of 10 conditions. Bench data were compared with results retrieved from ventilator software for leaks and Vt.Results: For assessing leaks, three of the devices tested were highly reliable, with a small bias (0.3-0.9 L/min), narrow limits of agreement (LA), and high correlations (R(2), 0.993-0.997) when comparing ventilator software and bench results; conversely, for four ventilators, bias ranged from -6.0 L/min to -25.9 L/min, exceeding -10 L/min for two devices, with wide LA and lower correlations (R(2), 0.70-0.98). Bias for leaks increased markedly with the importance of leaks in three devices. Vt was underestimated by all devices, and bias (range, 66-236 mL) increased with higher insufflation pressures. Only two devices had a bias < 100 mL, with all testing conditions considered.Conclusions: Physicians monitoring patients who use home ventilation must be aware of differences in the estimation of leaks and Vt by ventilator software. Also, leaks are reported in different ways according to the device used. [ABSTRACT FROM AUTHOR]

Introduction: and Objectives: The clinical presentation of Obstructive Sleep Apnoea (OSA) differs between genders. This study aimed to identify the specific OSA phenotypes of women in the European Sleep Apnoea Database (ESADA) cohort., Materials and Methods: Latent class cluster analysis was applied to data from 9710 female OSA patients. Variables used included age, Body Mass Index (BMI), Epworth Sleepiness Scale (ESS), comorbidities (cardiovascular, pulmonary, psychiatric, metabolic, other) and the Apnoea Hypopnea Index (AHI)., Results: Four different clusters were found: Cluster 1"Women with ischemic heart disease" (38.3 %):middle aged (59 years [53-65]),overweight to obese (BMI 30.1 kg/m 2 [26.9-33.5]), AHI 22.9 events/h[17.4-30], ESS 9 [5,12] with the highest prevalence of ischemic heart disease (56 %). Cluster 2"Elderly women with comorbidities" (23 %): oldest (66 years[60-71]), obese (BMI 36 kg/m 2 [31.6-40.4]),AHI 46 events/h [30-60.1]),ESS 9 [6-13] with the highest prevalence of comorbidities. Cluster 3"Sleepy obese women" (16.2 %): the youngest (49 years [42-55]), sleepiest (ESS 12 [8-16]), most obese(BMI 43 kg/m 2 [37.6-48.9]) females with severe OSA (AHI 53.3 events/h [32-80.5]). Cluster 4 "Women with mild OSA and low comorbidities" (22.5 %): middle aged (53.5 years [46-60]) with BMI 29 kg/m 2 [25-34.1],ESS9 [5,13]),AHI 8.6events/h[6.9-10.4])and low prevalence of comorbidities. The distribution of the clusters differed across Europe. PAP administration was higher in Clusters 2 and 3 but low in Cluster 4., Conclusion: Four distinct female phenotypes were identified with different clinical presentation and comorbidities. Sex-based phenotyping may provide improved risk stratification and personalized treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide. We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the "Bayesian neural network method" on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database. Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis. In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Jean-Christian Borel reports a relationship with Agiradom that includes: employment. Jean-Louis Pepin reports a relationship with Air Liquide Foundation that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Agiradom that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Fisher & Paykel Healthcare Inc that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Mutualia that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Philips that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with ResMed that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with VitalAire France that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Boehringer Ingelheim Ltd that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Jazz Pharmaceuticals that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Night Balance that includes: consulting or advisory and funding grants. Jean-Louis Pepin reports a relationship with Sefam that includes: consulting or advisory and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION)., Methods: BP was recorded for 24 h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.-6 a.m.; definition 2, 10 p.m.-7 a.m.; and definition 3, 10 p.m.-8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10-20%), mild dippers (0-10%), reverse dippers (< 0%), and extreme dippers (> 20%)., Results: The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.-6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%)., Conclusion: In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Obstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, CPAP termination rates remain very high, and adherence to therapy is a major issue. To date, studies targeting predictive factors of CPAP adherence by OSAS patients mainly include clinical data. The social, socioeconomic, psychological, and home environment aspects have been far less studied and largely underestimated. This study aims to obtain solid quantitative results examining the relationship between the determinants of refusal, non-adherence, or termination of CPAP treatment, and in particular the pivotal role played by health literacy., Methods and Analysis: This is a prospective, multicentre, observational study recruiting patients attending the sleep clinic of the Grenoble Alpes University Hospital, France. Consecutive adults (>18 years) recently diagnosed with OSAS and prescribed CPAP treatment with telemonitoring will be enrolled in the present study. They will benefit from home visits by a CPAP technician or nurse at CPAP initiation. Patients will then be followed up for 6 months through the telemonitoring platform of a home-care provider. The primary objective is to evaluate the impact of health literacy (health literacy, measured by the European Health Literacy Survey questionnaire (HLS-EU-16) on the refusal, non-adherence or termination of CPAP treatment in newly diagnosed OSAS patients, during the first 6 months after diagnosis. The target sample size is 250 participants., Ethics and Dissemination: The study protocol, patient information, and the non-opposition form were approved by the French national ethics committee (CPP 2021-92, January 2022). All patients are required to have signed a written informed consent form permitting their anonymised personal and medical data to be used for clinical research purposes. We will publish the results in a peer-reviewed medical journal and on our institutional websites., Trial Registration Number: NCT05385302., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE)., Methods: Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients' characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores., Results: Most COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52)., Discussion: These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae., (© 2023. The Author(s).)

Background: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients., Methods: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU., Results: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01)., Conclusion: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic obstructive pulmonary disease (COPD) is the most common indication for long-term domiciliary non-invasive ventilation (NIV) but there is uncertainty in data supporting current guidelines. This study described health trajectories before initiation of at-home NIV in people with COPD, and compared mortality outcomes between groups with different pre-NIV health trajectories., Methods: Data were from the French national health insurance reimbursement system database for individuals with COPD aged ≥40 years and ≥1 reimbursement for NIV between 1 January 2015 and 31 December 2019. Common health trajectories were determined using time sequence analysis through K-clustering (TAK analysis)., Findings: Data from 54,545 individuals were analysed; the population was elderly (median age 70 years) with multiple comorbidities. Four clusters were generated. Cluster 1 (n = 35,975/54,545; 66%) had NIV initiated in ambulatory settings or after the first acute event/exacerbation. Cluster 2 (6653/54,545; 12%) started NIV after ≥2 severe exacerbations in the previous 6 months. Cluster 3 (11,375/54,545; 21%) started NIV after frequent severe COPD-related exacerbations in the previous year. Cluster 4 (652/54,545; 1%) started NIV after many long-lasting severe exacerbations. The four clusters differed in age, sex, comorbidities, pre-NIV investigations, and prescriber/location of NIV initiation. Mortality differed significantly between clusters: highest in Cluster 4 and lowest in Cluster 1., Interpretation: The significant heterogeneity in clinical initiation of NIV probably reflects the current lack of strong evidence and guideline recommendations. Knowledge about the characteristics and outcomes in different clusters should be used to address inequities and facilitate more consistent and personalised use domiciliary NIV in COPD., Funding: JLP and SB are supported by the French National Research Agency in the framework of the "Investissements d'avenir" program (ANR-15-IDEX-02) and the "e-health and integrated care and trajectories medicine and MIAI artificial intelligence (ANR-19-P3IA-0003)" Chairs of excellence from the Grenoble Alpes University Foundation. This work was supported by ResMed., Competing Interests: JLP has received lecture fees or conference travel grants from ResMed, Philips, AstraZeneca, Jazz Pharmaceuticals, Agiradom and Bioprojet, and has received unrestricted research funding from ResMed, Philips, GlaxoSmithKline, Bioprojet, Fondation de la Recherche Medicale (Foundation for Medical Research), Direction de la Recherche Clinique du CHU de Grenoble (Research Branch Clinic CHU de Grenoble), and fond de dotation “Agir pour les Maladies Chroniques” (endowment fund “Acting for Chronic Diseases”). FL and AJ are employees of ResMed. PL, HD and AP are employees of HEVA and their participation in this study was funded by ResMed. APa has received consulting fees from ResMed. APr has received investigator fees for clinical trials funded by ResMed. SB has no conflicts of interest to disclose., (© 2023 The Author(s).)

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD)., Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO 2 , PaO 2 , daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate., Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO 2 was greater with higher baseline PaCO 2 . NIV intensity per se was not associated with improved PaCO 2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO 2 . Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found., Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO 2 , except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities., Study Design and Methods: This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline., Results: After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (β) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation ( S pO 2 ) (β -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal S pO 2 . A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal S pO 2 and T90 (increase in time below S pO 2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes., Conclusion: Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension., Competing Interests: Conflict of interest: J. Verbraecken has reported grants from AirLiquide, AstraZeneca, Bekaert Deslee Academy, Bioprojet, Desitin, Ectosense, Epilog, Fisher & Paykel, Heinen & Löwenstein, Idorsia, Inspire, Jazz Pharmaceutics, Medidis, Mediq Tefa, OSG, Philips, ResMed, Sefam, SomnoMed, Total Care, UCB Pharma, Vivisol, Westfalen Medical and SD Worx, royalties from Epilog, consulting fees from Bioprojet, Desitin, Ectosense, Epilog and Idorsia, lecture fees from AstraZeneca, Bioprojet, Idorsia, Total Care, SD Worx, participation on a data safety monitoring or advisory board for Bioprojet, being a past president Belgian Association for Sleep Research and Sleep Medicine (BASS) and board member up to present, and a trial with Withings. He is an associate editor of this journal. Conflict of interest: C. Lombardi has reported lecture fees from Bioprojet, Idorsia and Jazz Pharmaceutics, and participation on a data safety monitoring or advisory board from Syneos. Conflict of interest: W.T. McNicholas is an associate editor of this journal. Conflict of interest: J-L. Pepin has reported grants Air Liquide Foundation, Agiradom, AstraZeneca, Fisher & Paykel, Mutualia, Philips, Resmed and Vitalaire, and consulting fees Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz Pharmaceuticals, Night Balance, Philips, Resmed and Sefam. Conflict of interest: P. Steiropoulos has reported consulting and lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, MSD, Novartis and Roche, and being a past president of the Polish Respiratory Society and currently board member of the Polish Respiratory Society. Conflict of interest: J. Hedner has reported grants from ResMed Inc., Philips Respironics and Bayer Pharma to develop the ESADA database (grants for institution), speaker bureau of Desitin GmbH and Itamar Medical, two granted patents related to pharmacological therapy in OSA, and advisory boards for DSMB Respicardia and SomnoMed. Conflict of interest: L. Grote has reported an unrestricted collaboration grant with the ESADA network from Bayer AG, Germany, grants from the Swedish Heart and Lung Foundation, LUA-ALF Gothenburg Region, EU Horizon 2020 (Sleep revolution), EUROSTAR (Apnoeaway and WATCH-IT), clinical trial contract and license on pharmacological treatment in OSA for Desitin, lecture fees from AstraZeneca, Lundbeck, ResMed and Philips, chairing national guidelines for treatment in OSA and the National Quality Registry for Sleep Apnoea (SESAR), being a steering group member of the European quality registry for sleep apnoea (ESADA), LRPC member for the European Respiratory Society, Assembly 4, and member of examination committee for the European Sleep Research Society. Conflict of interest: M. Drummond has reported lecture fees from AstraZeneca, Bial, GSK, Medinfar, Teva and Linde, payment for expert testimony from Bial, GSK and Teva, having stock options in Resmed and Philips Respironics, and receiving equipment or materials from Linde and Vivisol. Conflict of interest: The other authors have nothing to declare., (Copyright ©The authors 2023.)

Objectives: Our aim was to describe changes in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and patient outcomes., Design: We extracted data from the OutcomeRea database concerning patients admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of ventilatory support, corticosteroid therapy, antibiotic therapy, and patient survival., Setting: ICUs at 32 French sites., Patients: One thousand eight hundred sixteen patients in the database had a diagnosis of AECOPD., Interventions: None., Measurements and Main Results: Over time, there was a reduction in the prescription of corticosteroids and antibiotics. In a time-series analysis, these changes in practice were not linked with ICU mortality. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an association between decrease in IMV use and reduction in ICU mortality in a time series analysis. Rates of noninvasive ventilation (NIV) failure decreased with an increase in NIV use to support weaning from IMV. There was a reduction in the median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in 2013-2018). We observed an improvement in prognosis, with decreases in overall hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and 2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and 2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013 and 2018)., Conclusions: The length of stay and mortality of patients with AECOPD admitted to ICUs has decreased over the last 20 years, with a wider use of NIV and a reduction in antibiotic and corticosteroid prescriptions., Competing Interests: Dr. Terzi received funding from Pfizer for attending meetings and/or travel. Dr. Hong Tuan Ha disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Conflict of interest: None declared.

Purpose: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO 2 . Whether this approach may be relevant to other populations, especially slowly progressive neuromuscular diseases (NMD), is unknown., Methods: This study was conducted as a post hoc analysis from a previously published randomized controlled trial (NCT03458507). Patients with NMD treated with domiciliary NIV were stratified according to the level of ventilatory support: high-level tidal volume (HLV T ; mL/kg of predicted body weight [PBW]) or high-level pressure support (HLPS), defined as a value above median value of the whole population (> 6.8 mL/kg PBW or 9.0 cmH 2 O, respectively). Primary outcome was mean nocturnal transcutaneous CO 2 pressure (PtcCO 2 ). Secondary outcomes included adherence to NIV, leaks, and side effects., Results: Of a total of 26 patients, 13 were exposed to HLV T , with significantly lower nocturnal PtcCO 2 (respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg, p = 0.002). A linear correlation between V T (mL/kg PBW ) and mean nocturnal PtcCO 2 was evidenced (r =  - 0.59, 95%CI [- 0.80; - 0.25], p = 0.002). No significant impact of HLV T was found on secondary outcomes., Conclusion: Despite the lack of power of this post hoc analysis, our results suggest that higher levels of ventilatory support are correlated with lower PtcCO 2 in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO 2 evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission., Methods: In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting., Results: Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders., Conclusion: Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28., Competing Interests: NT is supported by Pfizer for attending meetings and/or travel. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests., (Copyright: © 2023 Galerneau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Several sleep-related breathing disorders provoke repeated hypoxia stresses, which potentially lead to neurological diseases, such as cognitive impairment. Nevertheless, consequences of repeated intermittent hypoxia on the blood-brain barrier (BBB) are less recognized. This study compared two methods of intermittent hypoxia induction on the cerebral endothelium of the BBB: one using hydralazine and the other using a hypoxia chamber. These cycles were performed on an endothelial cell and astrocyte coculture model. Na-Fl permeability, tight junction protein, and ABC transporters (P-gp and MRP-1) content were evaluated with or without HIF-1 inhibitors YC-1. Our results demonstrated that hydralazine as well as intermittent physical hypoxia progressively altered BBB integrity, as shown by an increase in Na-Fl permeability. This alteration was accompanied by a decrease in concentration of tight junction proteins ZO-1 and claudin-5. In turn, microvascular endothelial cells up-regulated the expression of P-gp and MRP-1. An alteration was also found under hydralazine after the third cycle. On the other hand, the third intermittent hypoxia exposure showed a preservation of BBB characteristics. Furthermore, inhibition of HIF-1α with YC-1 prevented BBB dysfunction after hydralazine treatment. In the case of physical intermittent hypoxia, we observed an incomplete reversion suggesting that other biological mechanisms may be involved in BBB dysfunction. In conclusion, intermittent hypoxia led to an alteration of the BBB model with an adaptation observed after the third cycle.

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work., Competing Interests: Declaration of competing interest To the best of my knowledge as editor and corresponding author for the above manuscript, neither I nor any of the coauthors or editor have any perceived conflict of interest with respect to the subject matter of this paper. This, by necessity, must be a preliminary statement, as I assume each author must at a later date submit a personal COI statement., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d., Methods: In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy., Results: After 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was -0.84%, compared with 0.54% for placebo, in participants with OSA; and -0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was -1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, -1.2%; 300 mg, -2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of -2.2% and -1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious., Conclusions: Solriamfetol treatment was associated with decreases in body weight in a dose-related manner., Competing Interests: Declaration of competing interest A Malhotra has served as a principal investigator for a Jazz study. He is funded by the NIH and reports income related to medical education from Jazz, Livanova, Equillium and Corvus. ResMed gave a philanthropic donation to the University of California, San Diego, in support of a sleep center. PJ Strollo, Jr has received consultancy fees and honoraria from Inspire Medical Systems, ResMed, Philips-Respironics, Emmi Solutions, Jazz Pharmaceuticals, and Itamar; has received research funding from the National Institutes of Health and Inspire Medical Systems; and has a provisional patent for positive airway pressure with integrated oxygen. J-L Pepin has received lecture fees or conference traveling grants from Resmed, Perimetre, Philips, Fisher and Paykel, AstraZeneca, Jazz Pharmaceuticals, Agiradom, and Teva, and has received unrestricted research funding from ResMed, Philips, GlaxoSmithKline, Bioprojet, Fondation de la Recherche Medicale (Foundation for Medical Research), Direction de la Recherche Clinique du CHU de Grenoble (Research Branch Clinic CHU de Grenoble), and fond de dotation “Agir pour les Maladies Chroniques” (endowment fund “Acting for Chronic Diseases”). P Schweitzer has received consultancy fees from Jazz Pharmaceuticals and Apnimed. Her institution has received research funding from Apnimed, Avadel, Jazz Pharmaceuticals, Inspire Medical Systems, and Suven Life Sciences. GJ Lammers has received consultancy fees and/or honoraria and has been a speakers’ bureau member and/or an advisory board participant for UCB Pharma, Bioprojet, Theranexus, and Jazz Pharmaceuticals. J Hedner has served on the speakers’ bureaus for AstraZeneca, Philips Respironics, Itamar Medical, and BresoTec, and serves as a board member for Cereus Pharma. S Redline: has received grant support and consulting fees from Jazz Pharma as well as consulting fees from Eisai Inc, Eli Lilly Inc, and Respicardia Inc. D Chen and P Chandler are employees of Jazz Pharmaceuticals who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. S Bujanover is a former employee of Jazz Pharmaceuticals who, in the course of this employment, received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. K Strohl has served as an advisory board member and is a principal investigator for Jazz; is a site principal investigator for Inspire Medical Systems; and has received consultancy fees from Sommetrics, GSK (Galvani Bioelectronics), and Seven Dreamers., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)