OBJECTIVES:Hypoxic burden (HB) quantifies obstructive sleep apnoea (OSA)-associated nocturnal intermittent hypoxemia as the area under the peripheral desaturation curve near an apnoeic or hypopnoeic event. We assessed whether HB is a better marker of the cardiovascular effects of OSA than usual OSA severity markers. METHODS:In a continuous positive airway pressure (CPAP) withdrawal study in OSA patients (apnoea-hypopnoea-index (AHI) > 10/h), randomized in a 1:1 ratio to two weeks of CPAP continuation or sham CPAP, the relationship between the treatment effect on HB (ΔHB) and the treatment effect on office morning blood pressure, heart rate (HR), endothelial function (flow-mediated dilatation, FMD), and urinary catecholamines was assessed using linear regression and multivariate fractional polynomial regression. The capacity of ΔHB in predicting CPAP response of these cardiovascular outcomes was compared with other OSA severity markers. RESULTS:In 40 patients with OSA (age 63.1 ± 5.8y, AHI at diagnosis 37 (26-55)/h), AHI and HB significantly increased after CPAP withdrawal compared to the control group with 28 (19-62)/h and 37.8 (18.8-112.6) %min/h. Controlling for baseline values and confounders, ΔHB was associated with change in urinary catecholamines and morning HR, but not in FMD, morning blood pressure and nocturnal HR. Using a multivariate fractional polynomial regression model, ΔHB predicted the CPAP effect on catecholamines and morning HR better than AHI, oxygen desaturation index (ODI), time<90 % SpO2, and arousal index. CONCLUSIONS:HB in untreated OSA was associated with an increase in urinary catecholamines and morning HR and predicted their CPAP response better than other OSA severity markers. TRIAL REGISTRATION:Controlled-Trials.com, registration number ISRCTN 93153804.

BACKGROUND AND METHODS:Home-mechanical-ventilation in Duchenne muscular dystrophy improves survival and quality of life. In this observational study in Duchenne muscular dystrophy patients, lung function and respiratory muscle strength at the time of ventilation-initiation and their change under home-mechanical-ventilation were investigated. Main outcomes of interest were age and pulmonary function at the time of ventilation-initiation. RESULTS:Age at start of nocturnal home-mechanical-ventilation was 19.8 ± 4.8 years (n = 80) and 23.8 ± 5.4 years when home-mechanical-ventilation was extended to daytime (63/80). 25/80 patients were ventilated via tracheostomy (8% initially, 92% switched after 86 ± 46 months of non-invasive ventilation). Forced vital capacity, maximal inspiratory pressure and sniff nasal pressure at the start of home-mechanical-ventilation were 21 ± 13% predicted, -26.9 ± 15.4 cmH2O, and -20.3 ± 11.7 cmH2O, respectively. Forced vital capacity was an independent negative predictor of sleep-hypoventilation, even after adjustment for body-mass-index and age, whereas inspiratory muscle strength measures were not. Starting home-mechanical-ventilation slowed the decline in forced vital capacity and inspiratory muscle strength. Median survival was 33 (28-39) years. CONCLUSIONS:In summary, indication of home-mechanical-ventilation can be expected at a median age of 20 (16-22) years and at a forced vital capacity of 18% (12-20) predicted in Duchenne muscular dystrophy. Initiation of home-mechanical-ventilation slows the decline in lung function.

Obstructive sleep apnoea (OSA) is characterized by multidimensional variability that complicates diagnosis and treatment. Awareness on these aspects of variability is relevant for optimal treatment concepts. This review focuses on night-to-night variability in apnoea–hypopnoea index (AHI) – highlighting the risk of misclassification of the severity of OSA and the low negative predictive value of a single night sleep study – and its implications for accurately assessing disease severity and treatment response. We also consider other temporal fluctuations, including day-to-day symptom variability, low test-retest reproducibility of patient-reported outcomes such as the Epworth Sleepiness Scale, and night-to-night differences in treatment adherence and residual AHI on positive airway pressure therapy. Long-term changes related to age, weight, menopausal status, and evolving comorbidities further influence OSA expression. Access-related variability, e.g., disparities in availability of sleep clinics, polysomnography, and continuous positive airway pressure (CPAP) or non-CPAP treatments, adds another layer of complexity. Integrating these temporal, treatment-related, and access dimensions is essential for accurate phenotyping, individualized management, and longitudinal monitoring, highlighting the need for precision approaches in the care of patients with OSA.

Background: Continuous positive airway pressure (CPAP) is the most effective treatment for obstructive sleep apnoea (OSA). However, CPAP adherence in randomized controlled trials (RCTs) is frequently inadequate, potentially leading to an underestimation of the therapy's true effect on relevant outcomes. The aim was to identify patient and study characteristics that predict adherence to CPAP therapy in RCTs. Methods: PubMed and the existing meta-analyses were searched (1984 to 31 December 2024). A study-level meta-analysis of RCTs comparing CPAP with inactive control in patients with OSA was conducted. Meta-regressions and subgroup analyses (<4 h vs. ≥5 h usage) were undertaken to identify the predictors of CPAP adherence. Risk-of-bias was assessed using the Cochrane RoB-2 tool. Results: In 136 RCTs reporting on CPAP use, including 8827 patients with OSA (55 [49.5-59.8] years, 77.4 [61.2-89.2]% male, BMI 31 [28.9-33.2] kg/m2, Epworth Sleepiness Scale (ESS) 10.0 ± 2.8, apnoea-hypopnoea-index (AHI) 35.7 ± 13.4/h), mean nocturnal CPAP use was 4.5 ± 1 h. CPAP use of ≥4 h, ≥5 h, and ≥6 h per night was observed in 71.3%, 34.1%, and 7.8% of RCTs, respectively. Higher baseline AHI was the strongest predictor of longer CPAP use in meta-regressions (p < 0.001, β = 0.02, 95% CI 0.01-0.04). Baseline AHI was also significantly higher (40.3 ± 12.8 vs. 29.9 ± 12.6) in the ≥5 h vs. <4 h subgroup (p < 0.01, large effect size d = 0.84). A higher nightly CPAP usage was more likely in smaller (p < 0.05, d = 0.45) and single-centre trials (p < 0.05, h = 0.52). Sex distribution, age, BMI, ESS, and follow-up had no significant effect on nightly CPAP use. Conclusions: Higher baseline AHI independently predicted longer CPAP use in RCTs, while sleepiness and demographics did not. This study was registered at PROSPERO (CRD420250653394) and received no external funding.

Effective management of obstructive sleep apnoea requires accurate patient selection, integrated data analysis and multidisciplinary approaches, with machine learning enhancing disease prediction and treatment outcomes https://bit.ly/4altpxr.

Obesity is associated with an increased risk of sleep-disordered breathing (SDB)-obstructive sleep apnoea (OSA) and sleep hypoventilation-and obesity hypoventilation syndrome (OHS). The aim was to assess the impact of obesity on lung volumes and the prevalence of SDB and OHS and to identify predictors of these. In a cross-sectional analysis, obese patients (body mass index ≥30 kg/m2) who underwent an in-laboratory sleep study, arterial blood gas analysis and pulmonary function tests between 2018 and 2023 were included. Analysis of variance and multivariate regression analysis were used to compare obesity groups and identify predictors of SDB and OHS. In 1065 obese adults (39% female; 48% obesity WHO I, 24% WHO II, 28% WHO III), the prevalence of OSA (apnoea hypopnoea index (AHI) ≥5/hour), severe OSA (AHI ≥30/hour), sleep hypoventilation and OHS was 77%, 29%, 21% and 8%, respectively. The likelihood of OSA, severe OSA and sleep hypoventilation increased with obesity class, while the presence of OHS did not differ between groups. In multivariate regression models including body mass index, neck circumference, age, sex, AHI, bicarbonate and expiratory reserve volume, bicarbonate and forced vital capacity were independent predictors of both sleep hypoventilation and OHS and neck circumference of severe OSA. The area under the receiver operating characteristics curve of bicarbonate for OHS and sleep hypoventilation was 0.92 and 0.72, respectively. Three quarter of obese patients have OSA, and the likelihood of OSA, severe OSA and sleep hypoventilation increase across obesity severity groups. Bicarbonate has a high diagnostic accuracy for OHS.

Sex and gender differences significantly influence lung parenchyma development, beginning as early as the embryonic stages of human life. Although this association is well known in the clinical manifestations of some relevant pulmonary diseases, there is less data available regarding their effects on cell biological programmes across different stages of body development. A deep understanding of these mechanisms could help in defining preventive strategies tailored to a fully personalised approach to respiratory medicine. From this perspective, this review aims to analyse the influence of sex and gender on bronchoalveolar and vascular compartments from embryonic and neonatal stages through to adolescence, adulthood and elder age.

Background:Cardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction and major adverse cardiovascular events (MACE) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory. Methods:A literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effects of OSA and CPAP in adults with OSA on the following cardiovascular end-points: blood pressure, arterial hypertension, endothelial function and MACE (myocardial infarction, stroke, transient ischaemic attack or cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models. Results and conclusions:There is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.

In an unselected obstructive sleep apnoea (OSA) population, continuous positive airway pressure (CPAP) slightly lowers blood pressure (BP). The aim was to investigate the differential effects of CPAP on BP in different OSA severities. Medline was searched through December 2023 for randomised controlled trials (RCTs) on the effect of CPAP compared to an inactive control on office, 24 h, diurnal and nocturnal systolic and diastolic BP in OSA. A random-effects meta-analysis was performed at the study level for the different BP measures; meta-regression and subgroup analyses were used to examine the effects of OSA characteristics and CPAP use. Seventy-five RCTs (10,025 patients) were included. CPAP lowered office, 24 h, diurnal and nocturnal systolic BP (SBP) by -2.5 (95% CI -3.8 to -1.2; nRCTs = 40), -2.6 (95% CI -3.6 to -1.6; n = 29), -2.2 (95% CI -3.2 to -1.3; n = 32) and - 3.5 (95% CI -4.4 to -2.5; n = 32) mmHg, respectively. In the meta-regressions, higher 24 h and diurnal SBP and longer nocturnal CPAP use were significantly associated with greater BP reduction (all p < 0.05). In subgroup analyses, the reduction in 24 h, diurnal, and nocturnal SBP was greater in studies with an apnoea-hypopnoea index ≥ 30/h compared to mild OSA. CPAP use ≥ 5 h/night had a greater impact on lowering 24 h and nocturnal SBP (-4.2 vs. -2.1, p = 0.05, and -4.2 vs. -1.6 mmHg, p = 0.01). CPAP has the strongest BP-lowering effect on nocturnal blood pressure, which is, particularly, relevant prognostically and the effect is stronger at higher baseline BP and with CPAP use of ≥ 5 h. Study Registration: The systematic review and meta-analysis has been registered on PROSPERO: CRD42023477227.

Background Bicarbonate above the upper limit of normal is used as an indicator of sleep-related hypoventilation in patients with diseases frequently associated with hypoventilation, such as obesity or neuromuscular diseases.Research question The aim was to evaluate the diagnostic accuracy of bicarbonate from daytime arterial blood gas analysis for sleep-related hypoventilation measured via transcutaneous nocturnal capnometry.Methods In a diagnostic accuracy study, the sensitivity and specificity of bicarbonate concentration for detecting nocturnal hypoventilation were tested using a receiver operating curve (ROC) and logistic regression analysis in patients undergoing both an in-laboratory sleep study with transcutaneous capnometry and daytime arterial blood gas analysis.Results In 510 patients (mean±SD age 52±15 years, BMI 34±10 kg/m2), the area under the ROC curve for bicarbonate (HCO3-) and median nocturnal tcpCO2 ≥50 mm Hg (45% yes, 55% no) was 0.70 (95% CI 0.65 to 0.75). Sensitivity of HCO3- of 26.5 mmol/L and 27.0 mmol/L was 61.0% and 54.1%, specificity 71.3% and 79.6%, and the likelihood ratio for sleep-related hypoventilation (median tcpCO2 ≥50 mm Hg) 2.1 and 2.6. HCO3- was significantly higher in those with (n=231, 27.6±3.0 mmol/L) versus without (n=279, 25.8±1.9 mmol/L) sleep-related hypoventilation (p<0.001). Increasing awake HCO3- was associated with a higher likelihood of nocturnal hypoventilation (OR 1.4 (95% CI 1.3 to 1.5), p<0.001).Conclusions The sensitivity of elevated bicarbonate from awake arterial blood gas analysis using common cut-off values such as 27 mmol/L is only moderate, and bicarbonate as an integral part of the assessment of sleep hypoventilation (likelihood ratio) must be interpreted in the context of other assessments. A normal bicarbonate does not rule out sleep hypoventilation.

Telemedicine as a means of remote patient-physician interaction is gaining popularity in nearly every field, and (respiratory) sleep medicine is no exception. Because obstructive sleep apnoea (OSA) is a chronic condition, and requires a continuous treatment and monitoring of therapy success, telematic communications could be useful to establish diagnostic and therapeutic strategies. This statement summarises the evidence and efficacy of telemedicine options in OSA. An interdisciplinary European Respiratory Society (ERS) task force evaluated the scientific literature based on a systematic search and two-step screening process (title/abstract and full text). Although the task force does not make recommendations for clinical practice, it describes its current practice of telemedicine applications in OSA. The literature shows that telemedicine has been studied in different areas of OSA management, with potential benefits. Telemedicine also served as a major research tool to provide big data related to positive airway pressure therapy. Telemedicine results in similar or improved compliance when compared with traditional face-to-face encounters. Telemedicine-based targeted troubleshooting and support based on individual patient data, and a combination via smartphone apps or coaching websites, are feasible and effective. Expanding evidence suggests that telemedicine is probably cost-effective. However, data do not consistently support staff time savings through telemedicine-based solutions. The potential benefits of telemedicine include improved access to healthcare, and increased adherence to (chronic illness) treatment plans. Benefits should be weighed against the overall costs of telemedicine and risks related to suboptimal compliance.

An international expert group (European Sleep Foundation Think Tank) convened in 2022 to discuss the state of the evidence in the domain of hypersomnolence. The expert group considered the current state of knowledge based on the most relevant recent publications, discussed the current challenges in the field and identified future priorities. The purpose of this white paper is to summarize the definition, diagnosis, and pathophysiology of hypersomnolence, the epidemiology, phenotype, and management of hypersomnolence in obstructive sleep apnea and in neurological and psychiatric disorders, and the impact of hypersomnolence on daily activities, workability and health-related quality of life. The key results of the discussion were that: a) hypersomnolence is both prevalent and heterogeneous in its manifestations in a wide variety of pathological conditions encompassing obstructive sleep apnea and neurological and psychiatric disorders; and b) while multiple pathophysiological pathways are potentially involved in hypersomnolence, knowledge of the specific causal factors in individual patients remains undefined, and the specific factors responsible for excessive daytime sleepiness vs. excessive need for sleep remain largely unclear. The clinical implications of these results are the occurrence of important limitations to the development of personalized approaches to diagnosis, prognosis, and management of hypersomnolence, which is essential considering the high societal and personal costs of hypersomnolence, and its substantial adverse impact on quality of life. Research priorities should address these limitations with improved quantification of hypersomnolence and with an evidence base on the costs and benefit of hypersomnolence management in patients with respiratory, neurologic, and psychiatric disorders.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. 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 of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer’s disease (AD) pathology. Sleep deprivation increases amyloid-β (Aβ) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aβ. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep–wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.