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Summary: Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. Methods: In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640. Findings: Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio. Interpretation: Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Funding: Bioprojet.

Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild–moderate OSA based on the apnoea–hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.

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 (SpO2) (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 SpO2. 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 SpO2 and T90 (increase in time below SpO2 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.

Background The prevalence of obstructive sleep apnoea (OSA) is growing as the population is ageing. However, data on the clinical characteristics of elderly patients with OSA and their adherence to positive airway pressure (PAP) treatment are scarce. Methods Data from 23 418 30–79-year-old OSA patients prospectively collected into the ESADA database during 2007–2019 were analysed. Information on PAP use (h·day−1) in association with a first follow-up visit was available for 6547 patients. The data was analysed according to 10-year age groups. Results The oldest age group was less obese, less sleepy and had a lower apnoea–hypopnoea index (AHI) compared with middle-aged patients. The insomnia phenotype of OSA was more prevalent in the oldest age group than in the middle-aged group (36%, 95% CI 34–38 versus 26%, 95% CI 24–27, p

Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnoea (OSA), defined as the inability to stay awake during the day. Its clinical descriptors remain elusive, and the pathogenesis is complex, with disorders such as insufficient sleep and depression commonly associated. Subjective EDS can be evaluated using the Epworth Sleepiness Scale, in which the patient reports the probability of dozing in certain situations; however, its reliability has been challenged. Objective tests such as the multiple sleep latency test or the maintenance of wakefulness test are not commonly used in patients with OSA, since they require nocturnal polysomnography, daytime testing and are expensive. Drugs for EDS are available in the United States but were discontinued in Europe some time ago. For European respiratory physicians, treatment of EDS with medication is new and they may lack experience in pharmacological treatment of EDS, while novel wake-promoting drugs have been recently developed and approved for clinical use in OSA patients in the USA and Europe. This review will discuss 1) the potential prognostic significance of EDS in OSA patients at diagnosis, 2) the prevalence and predictors of residual EDS in treated OSA patients, and 3) the evolution of therapy for EDS specifically for Europe.

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3–13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1–15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea–hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use 10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

Abstract Obstructive sleep apnea (OSA) is a highly prevalent disease, and is traditionally associated with increased cardiovascular risk. The role of comorbidities in OSA patients has emerged recently, and new conditions significantly associated with OSA are increasingly reported. A high comorbidity burden worsens prognosis, but some data suggest that CPAP might be protective especially in patients with comorbidities. Aim of this narrative review is to provide an update on recent studies, with special attention to cardiovascular and cerebrovascular comorbidities, the metabolic syndrome and type 2 diabetes, asthma, COPD and cancer. Better phenotypic characterization of OSA patients, including comorbidities, will help to provide better individualized care. The unsatisfactory adherence to CPAP in patients without daytime sleepiness should prompt clinicians to examine the overall risk profile of each patient in order to identify subjects at high risk for worse prognosis and provide the optimal treatment not only for OSA, but also for comorbidities.

Study ObjectivesMotor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA.MethodsA 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, “Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?” Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected.ResultsSW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1–1.4; p < 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06–1.18; p < 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15–3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW+ than SW– (22.4% vs. 0.7%; χ2 31, p < 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI (R2 = 0.41).ConclusionSW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia.

Traffic-related air pollution (TRAP) is increasing worldwide. Habitual physical activity is known to prevent cardiorespiratory diseases and mortality, but whether exposure to TRAP during exercise affects respiratory health is still uncertain. Exercise causes inflammatory changes in the airways, and its interaction with the effects of TRAP or ozone might be detrimental, for both athletes exercising outdoor and urban active commuters. In this Mini-Review, we summarize the literature on the effects of exposure to TRAP and/or ozone during exercise on lung function, respiratory symptoms, performance, and biomarkers. Ozone negatively affected pulmonary function after exercise, especially after combined exposure to ozone and diesel exhaust (DE). Spirometric changes after exercise during exposure to particulate matter and ultrafine particles suggest a decrease in lung function, especially in patients with chronic obstructive pulmonary disease. Ozone frequently caused respiratory symptoms during exercise. Women showed decreased exercise performance and higher symptom prevalence than men during TRAP exposure. However, performance was analyzed in few studies. To date, research has not identified reliable biomarkers of TRAP-related lung damage useful for monitoring athletes' health, except in scarce studies on airway cells obtained by induced sputum or bronchoalveolar lavage. In conclusion, despite partly counteracted by the positive effects of habitual exercise, the negative effects of TRAP exposure to pollutants during exercise are hard to assess: outdoor exercise is a complex model, for multiple and variable exposures to air pollutants and pollutant concentrations. Further studies are needed to identify pollutant and/or time thresholds for performing safe outdoor exercise in cities.

The effects of the COVID-19 pandemic on sleep have been widely documented, but longitudinal evaluations during different phases of the “COVID-19 era” are needed to disentangle the specific consequences of the r145estrictive measures on sleep variables. The aim of this study was to assess the immediate effect of the lockdown’s end on sleep and sleep-related dimensions in an Italian sample, also considering the stress and depressive symptoms. We used an online survey to longitudinally collect data on sociodemographic, environmental, clinical, sleep, and sleep-related variables in two time points: during and immediately after the lockdown. The final sample included 102 participants. The large prevalence of poor sleep quality, clinically relevant pre-sleep arousal, and depressive symptoms, as well as poor sleep quality and pre-sleep arousal score observed during the lockdown, remained stable after its end. On the other hand, the prevalence of moderate-to-severe event-related stress and intrusive symptom scores exhibited a drastic reduction after the end of home confinement. Both bedtime and rise time were anticipated after the lockdown, while sleep quality exhibited only a trend of post-lockdown sleep disturbance reduction. Our findings point to a reduced stress level (specific for the intrusive symptomatology) after the end of the lockdown and persistence of sleep problems, suggesting two non-mutually exclusive hypotheses: (a) the strict restrictive measures are not the main cause of sleep problems during the pandemic and (b) home confinement induces long-lasting effects on sleep observable after its end, and a longer period of time might be needed to observe an improvement.

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are usually associated with multi-morbidity. The aim of this study was to retrospectively investigate the prevalence of comorbidities in a cohort of patients with OSAS and COPD-OSAS overlap syndrome (OS) patients and to explore differences between these two groups. Materials and Methods: Included were consecutive OS patients and OSAS patients who had been referred to our sleep laboratory, and were matched in terms of sex, age, BMI, and smoking history. Presence of comorbidities was recorded based on their medical history and after clinical and laboratory examination. Results: The two groups, OS patients (n = 163, AHI > 5/h and FEV1/FVC < 0.7) and OSAS patients (n = 163, AHI > 5/h, and FEV1/FVC > 0.7), did not differ in terms of apnea hypopnea index (p = 0.346), and oxygen desaturation index (p = 0.668). Compared to OSAS patients, OS patients had lower average SpO2 (p = 0.008) and higher sleep time with oxygen saturation p = 0.002) during sleep, and lower PaO2 (p < 0.001) and higher PaCO2 (p = 0.04) in wakefulness. Arterial hypertension was the most prevalent comorbidity for both OS and OSAS, followed by dyslipidemia, cardiovascular disease (CVD) and diabetes. OS was characterized by a higher prevalence of total comorbidities (median (IQR):2 (1–3) vs. 2 (1–2), p = 0.033), which was due to the higher prevalence of CVD (p = 0.016) than OSAS. No differences were observed in other comorbidities. Conclusions: In OS patients, nocturnal hypoxia and impaired gas exchange in wakefulness are more overt, while a higher burden of CVD is observed among them in comparison to sex-, age- and BMI-matched OSAS patients.

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) have long been considered predominantly male-related conditions. The clinical presentation of sleep disordered breathing in females differs from males and can vary with age and physiological status, e.g. menopause and pregnancy. Overall, females appear to be more symptomatic, with lower apnoea–hypopnoea index scores compared to males. Furthermore, they appear to have more prolonged partial upper airway obstruction, and may report insomnia as a symptom of OSAHS more frequently. As a consequence of these differences in clinical presentation, females with sleep disordered breathing are often underdiagnosed and undertreated compared to males. This review is aimed at discussing the epidemiology, clinical presentation, pathophysiology and hormonal and metabolic differences in females who present with OSA/OSAHS in comparison to males.

Obstructive sleep apnoea (OSA) is a highly prevalent disease, and there is an increased demand for OSA diagnosis and treatment. However, resources are limited compared with the growing needs for OSA diagnosis and management, and alternative strategies need to be developed to optimise the OSA clinical pathway. In this review, we propose a management strategy for OSA, and in general for sleep-disordered breathing, to be implemented from diagnosis to follow-up. For this purpose, the best current options seem to be: 1) networking at different levels of care, from primary physicians to specialised sleep laboratories; and 2) use of telemedicine. Telemedicine can contribute to the improved cost-effectiveness of OSA management during both the diagnostic and therapeutic phases. However, although the technology is already in place and different commercial platforms are in use, it is still unclear how to use telemedicine effectively in the sleep field. Application of telemedicine for titration of positive airway pressure treatment, follow-up to improve compliance to treatment through early identification and solution of problems, and teleconsultation all appear to be promising areas for improved OSA management.

Obstructive sleep apnoea (OSA) syndrome affects about 13% of the male and 7–9% of the female population. Hypoxia, oxidative stress and systemic inflammation link OSA and cardiovascular and metabolic consequences, including coronary artery disease. Current research has identified several clinical phenotypes, and the combination of breathing disturbances during sleep, systemic effects and end-organ damage might help to develop personalised therapeutic approaches. It is unclear whether OSA is a risk factor for acute coronary syndrome (ACS) and might affect its outcome. On the one hand, OSA in patients with ACS may worsen prognosis; on the other hand, OSA-related hypoxaemia could favour the development of coronary collaterals, thereby exerting a protective effect. It is unknown whether positive airway pressure treatment may influence adverse events and consequences of ACS. In non-sleepy patients with OSA and stable coronary artery disease, randomised controlled trials failed to show that continuous positive airway pressure (CPAP) treatment protected against cardiovascular events. Conversely, uncontrolled studies suggested positive effects of CPAP treatment in such patients. Fewer data are available in subjects with ACS and OSA, and results of randomised controlled studies on the effects of CPAP are expected shortly. Meanwhile, the search for reliable markers of risk continues. Recent studies suggest that daytime sleepiness may indicate a more severe OSA phenotype with regard to cardiovascular risk. Finally, some studies suggest sex-related differences. The picture is still incomplete, and the potential role of OSA in patients with ACS awaits confirmation, as well as clear definition of subgroups with different degrees of risk.

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive lethal disorder caused by the lack of dystrophin, which determines myofibers mechanical instability, oxidative stress, inflammation, and susceptibility to contraction-induced injuries. Unfortunately, at present, there is no efficient therapy for DMD. Beyond several promising gene- and stem cells-based strategies under investigation, physical activity may represent a valid noninvasive therapeutic approach to slow down the progression of the pathology. However, ethical issues, the limited number of studies in humans and the lack of consistency of the investigated training interventions generate loss of consensus regarding their efficacy, leaving exercise prescription still questionable. By an accurate analysis of data about the effects of different protocol of exercise on muscles of mdx mice, the most widely-used pre-clinical model for DMD research, we found that low intensity exercise, especially in the form of low speed treadmill running, likely represents the most suitable exercise modality associated to beneficial effects on mdx muscle. This protocol of training reduces muscle oxidative stress, inflammation, and fibrosis process, and enhances muscle functionality, muscle regeneration, and hypertrophy. These conclusions can guide the design of appropriate studies on human, thereby providing new insights to translational therapeutic application of exercise to DMD patients.

Educational aims To illustrate the characteristics of endurance exercise training and its positive effects on health.; To provide an overview on the effects of endurance training on airway cells and bronchial reactivity.; To summarise the current knowledge on respiratory health problems in elite athletes.; Endurance exercise training exerts many positive effects on health, including improved metabol­ism, reduction of cardiovascular risk, and reduced all-cause and cardiovascular mortality. Intense endurance exercise causes mild epithelial injury and inflammation in the airways, but does not appear to exert detrimental effects on respiratory health or bronchial reactivity in recreational/non-elite athletes. Conversely, elite athletes of both summer and winter sports show increased susceptibility to development of asthma, possibly related to environmental exposures to allergens or poor conditioning of inspired air, so that a distinct phenotype of “sports asthma” has been proposed to characterise such athletes, who more often practise aquatic and winter sports. Overall, endurance training is good for health but may become deleterious when performed at high intensity or volume.

Maurizio Vignola was a superb and innovative researcher, who wrote seminal papers on the biology of airway epithelium in asthma. Inflammation and remodelling were the main topics of his research, mostly conducted in biopsy specimens from patients with asthma of variable severity, encompassing the entire spectrum of the disease from mild to severe asthma. His observations contributed to define the biology of asthma as we know it today, and opened the way to the personalised treatment of asthma. His group has successfully continued to investigate the biology and clinical aspects of bronchial asthma, with major interest in the clinical use of biomarkers to monitor disease activity, and in the development of new therapeutic perspectives. This review summarises the latest work on these topics proudly conducted by Maurizio's closest collaborators. The results indicate significant progress in our understanding of asthma in the last 10 years, in particular increased knowledge of the complex interaction between inflammatory and remodelling pathways, improved recognition of biological and clinical asthma phenotypes, and development of new treatment strategies, especially for patients with severe corticosteroid-resistant asthma.

In all fields of medicine, major efforts are currently dedicated to improve the clinical, physiological and therapeutic understanding of disease, and obstructive sleep apnoea (OSA) is no exception. The personalised medicine approach is relevant for OSA, given its complex pathophysiology and variable clinical presentation, the interactions with comorbid conditions and its possible contribution to poor outcomes. Treatment with continuous positive airway pressure (CPAP) is effective, but CPAP is poorly tolerated or not accepted in a considerable proportion of OSA patients. This review summarises the available studies on the physiological phenotypes of upper airway response to obstruction during sleep, and the clinical presentations of OSA (phenotypes and clusters) with a special focus on our changing attitudes towards approaches to treatment. Such major efforts are likely to change and expand treatment options for OSA beyond the most common current choices (i.e. CPAP, mandibular advancement devices, positional treatment, lifestyle changes or upper airway surgery). More importantly, treatment for OSA may become more effective, being tailored to each patient's need.

Obstructive sleep apnoea (OSA) is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and non-alcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patients.