In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Vitamin D deficiency: A forgotten aspect in sleep disorders? A critical update.

Over the past few years, there has been a surge in interest regarding the connection between sleep duration and quality, sleep disorders, mainly Obstructive sleep apnoea (OSA) and Vitamin D. There is growing evidence to support a new role of Vitamin D in the maintenance and regulation of optimal sleep. Furthermore, a notable link has been identified between OSA and a decrease in serum Vitamin D levels, which appears to intensify as the severity of sleep apnea worsens. Vitamin D status could also potentially serve as a mediator or provide an explanation for the association between OSA and cardiometabolic morbidity, but the current state of research in this area is inadequate. Studies have indicated that the supplementation of Vitamin D can optimize sleep quality, presenting more proof of the connection between insufficient vitamin D levels and sleep disorders. However, it is unclear whether low serum Vitamin D levels are a contributing factor to OSA development or if OSA predisposes individuals to Vitamin D deficiency. As a result, various studies have endeavored to examine the complex relationship between OSA and Vitamin D deficiency. In children and adolescents, while data is limited, there seems also to be a link between sleep disorders and Vitamin D levels. Therefore, the objective of this review is to provide a comprehensive overview of the current evidence on the association between Vitamin D and sleep disorders in both adults and children.

Beat-to-beat cardiac repolarization lability increases during hypoxemia and arousals in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (ß = 0.405, P < 0.01), STVQT (ß = 0.151, P < 0.01), and QTVI (ß = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

Distance follow-up by a remote medical care centre improves adherence to CPAP in patients with obstructive sleep apnoea over the short and long term.

BACKGROUND: Adherence to continuous positive air pressure (CPAP) in patients with obstructive sleep apnoea (OSA) has remained invariably low over the last decades. Remote monitoring of the nocturnal CPAP treatment, within telemedicine (TM)-based follow-up programs, in these patients has been suggested as a potential tool to improve adherence and release the workload of sleep units. The aim of this study was therefore to assess whether a follow-up program carried out by a Remote Medical Care Centre (RMCC), outside the sleep unit, improves adherence to CPAP in the short and long term in patients with OSA. METHODS: In this pilot protocol, we enrolled 37 patients starting CPAP in our Sleep Centre (SC). After three months of standard care in our SC, patients initiated a six-month remote follow-up carried out by the RMCC, functioning as an intermediary between patients and SC. Monthly reports and indication for face-to-face visits were sent to the SC for six months. After this period patients returned to usual care for one year. Results were compared with those obtained in 38 patients (controls) followed with usual care over the same time range. RESULTS: Mean nightly use of CPAP increased from 3.2 ± 2.4 h pre-RMCC to 5.2 ± 1.9 h post-RMCC (p < 0.0001). Nights/month of CPAP use improved from 19.8 ± 9.2 to 25.2 ± 2.5 (p < 0.05) and nights/month with CPAP use >4 h from 12.5 ± 10 to 21.03 ± 8.9 (p < 0.05). This improvement remained stable after 12 months from the return of patients to usual care. No significant changes in CPAP use were observed in controls over the time. CONCLUSION: A six-month follow-up through a remote facility can significantly improve adherence to CPAP in the short and long term. This pilot study provides a solid base for the design of multicentre randomized trials focusing on new models which are able to increase the long-term efficacy of TM programs.

REM sleep obstructive sleep apnoea.

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.

Electrochemical remediation of synthetic and real marine sediments contaminated by PAHs, Hg and As under low electric field values.

To date, remediation, protection, and restoration of contaminated sites is a global concern. The current technologies to restore sediments characterized by heterogeneous characteristics, several pollutants, fine grains, and low hydraulic permeability are poorly effective; hence their remediation is still challenging. A promising approach for the sediment's remediation could be the electrochemical route since it is a not-expensive, effective and noninvasive in situ technology. Electrochemical remediation (ER) is commonly studied under relatively high electric fields (E ≥ 1 V cm-1) and using costly processing fluids in a three compartments cell aiming to desorb and transport the contaminants into the processing fluids (secondary dangerous effluent). In this work, contaminated marine sediments were electrochemically treated focusing on the insertion of electrodes directly in the sediments and adopting, for the first time for real sediments, low E values (≤ 0.25 V cm-1) for 4-days period. It was observed that PAHs can be simultaneously transported and degraded in situ preventing the production of a secondary dangerous effluent and reducing the energy consumption. Firstly, clay marine sediments dragged from Capo Granitola Coast (Trapani, Italy) spiked with five PAHs congeners (5PAHs), Hg and As were used as a simplified model matrix and treated to simulate a real case study. A total PAHs removal efficiency of 57% was reached after 96 h of treatment under 0.05 V cm-1. Then, real polluted marine sediments from Augusta Bay (Syracuse) and Bagnoli-Coroglio Bay (Naples) in the southern Italy were treated as real contaminated sediments to be restored, to validate the proposed approach for real cases. A quite good removal efficiency of PAHs was reached after 96 h of electrochemical treatment coupled with a low energetic consumption due to the rather E values adopted. In addition, it was observed that this approach, under the adopted conditions, is unsuitable for the remediation of Hg and As.

A chemical remediation technique for a nearly-total removal of arsenic and mercury from contaminated marine sediments.

After decades of industrial exploitation of the coast and consequent contamination of the sites and marine sediments, it became essential to recover the marine ecosystem by remediation methods to remove toxic contaminants. In this work, a remediation method was developed to clean marine sediments contaminated by arsenic (As) and mercury (Hg). The method can be applied to mobile platforms and is based on an environmentally friendly approach designed to minimise further contamination. The method was tested on two artificially contaminated sediments and two real samples collected from two highly contaminated sites in southern Italy, Augusta Bay and Bagnoli Gulf, characterised by high Hg and As concentrations, respectively. The method consists of four steps: washing with sodium hydroxide (NaOH) to remove metals associated with humic acid; Fenton-reaction using α-CycloDextrin (aCD) to stabilise Fe(II) at natural pH and oxidise As (III) and Hg (0 or I); complexation reaction with aCD; and complexation with sodium sulfide (Na2S) to remove Hg as soluble Hg-polysulfides. Compared to other remediation experiences in literature, this technique provides the best removal efficiency for As and Hg (ranging between 26 -71 % and 57-95 %, respectively). Considering the residual concentrations of As and Hg and the contamination threshold fixed by European Regulation for re-use, the treated sediment can be used in several civil and industrial contexts. The presented method operates in line with the principles of the circular economy to preserve natural resources, prevent secondary pollution, and promote the effective re-use of clean environmental matrices (soils, sediments and aqueous solutions), thus minimising landfill waste.

What to expect from the ERS International Congress 2023.

This article provides an overview of the reasons to attend the 2023 ERS Congress, including a summary of the ECM session and the NEXT programme. https://bit.ly/46ghP4g.

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database.

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 (ß) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (ß -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.

Clinical characteristics and positive airway pressure adherence among elderly European sleep apnoea patients from the ESADA cohort.

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<0.001). The 70-79-year-old group adhered to PAP therapy equally well as the younger age groups with a mean PAP use of 5.59 h·day-1 (95% CI 5.44-5.75). PAP adherence did not differ between clinical phenotypes based on subjective daytime sleepiness and sleep complaints suggestive of insomnia in the oldest age group. A higher score on the Clinical Global Impression Severity (CGI-S) scale predicted poorer PAP adherence. Conclusion: The elderly patient group was less obese, less sleepy, had more insomnia symptoms and less severe OSA, but were rated to be more ill compared with the middle-aged patients. Elderly patients with OSA adhered to PAP therapy equally well as middle-aged patients. Low global functioning (measured by CGI-S) in the elderly patient predicted poorer PAP adherence.

Adaptive responses to chronic intermittent hypoxia: contributions from the European Sleep Apnoea Database (ESADA) Cohort.

Obstructive sleep apnoea (OSA) is a common disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favours upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of the respiratory drive, and the arousal threshold. OSA causes chronic intermittent hypoxia, inflammatory activation and autonomic imbalance with diurnal and nocturnal sympathetic hyperactivity. Disentangling so many components to investigate the pathogenesis of OSA's consequences is very hard clinically. However, albeit imperfect, clinical medicine constitutes a major source of inspiration for basic research, and a mutual exchange of information is essential between clinicians and physiologists to improve our understanding of disease states. OSA is no exception, and this narrative review will summarize the results of clinical studies performed over the years by the European Sleep Apnoea Database (ESADA) Study Group, to explore the variables linked to markers of intermittent hypoxia as opposed to the traditional assessment of OSA severity based on the frequency of respiratory events during sleep (the Apnoea Hypopnoea Index). The results of the clinical studies indicate that intermittent hypoxia variables are associated with several comorbidities, although evidence of a cause-effect relationship is still missing in many cases. It is also possible that adaptive rather than maladaptive responses could be evoked by intermittent hypoxia. The intensity, duration and frequency of intermittent hypoxia episodes causing adaptive rather than maladaptive responses, and their clinical implications, deserve further investigation.

Hypertension treatment in patients with sleep apnea from the European Sleep Apnea Database (ESADA) cohort - towards precision medicine.

We recruited 5,970 hypertensive patients with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta-blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta-blocker was associated with lower systolic blood pressure, particularly in non-obese middle-aged males with hypertension. Conversely, the combination of a beta-blocker and a diuretic was associated with lower systolic and diastolic blood pressure in hypertensive patients with moderate-severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross-sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in hypertensive OSA patients. Controlled trials are warranted.

Co-existence of OSA and respiratory diseases and the influence of gender.

INTRODUCTION: Sleep-disordered breathing (SDB), especially obstructive sleep apnea (OSA), is commonly associated with respiratory diseases, such as COPD, asthma and interstitial lung disease. AREAS COVERED: This narrative review aims to comprehensively synthesize the existing information on SDB in respiratory diseases, investigate the role of gender in this association, and highlight the importance of OSA management in improving sleep, quality of life, and disease prognosis in these specific patient populations. EXPERT OPINION: Research indicates a synergistic link between OSA and chronic respiratory diseases, which leads to greater morbidity and mortality compared to each disorder alone. Given the lack of an optimal OSA screening tool for these patients, a comprehensive patient approach and overnight diagnostic sleep study are imperative. Despite the limited evidence available, it seems that gender has an impact on the prevalence, severity, and susceptibility of this coexistence. Recognizing the role of gender in the coexistence of OSA and other respiratory diseases can enhance everyday medical practice and enable clinicians to adopt a more personalized approach toward optimal screening and diagnosis of these patients.

Epidemiology, Physiology and Clinical Approach to Sleepiness at the Wheel in OSA Patients: A Narrative Review.

Sleepiness at the wheel (SW) is recognized as an important factor contributing to road traffic accidents, since up to 30 percent of fatal accidents have been attributed to SW. Sleepiness-related motor vehicle accidents may occur both from falling asleep while driving and from behavior impairment attributable to sleepiness. SW can be caused by various sleep disorders but also by behavioral factors such as sleep deprivation, shift work and non-restorative sleep, as well as chronic disease or the treatment with drugs that negatively affect the level of vigilance. An association between obstructive sleep apnea (OSA) and motor vehicle accidents has been found, with an increasing risk in OSA patients up to sevenfold in comparison to the general population. Regular treatment with continuous positive airway pressure (CPAP) relieves excessive daytime sleepiness and reduces the crash risk. Open questions still remain about the physiological and clinical determinants of SW in OSA patients: the severity of OSA in terms of the frequency of respiratory events (apnea hypopnea index, AHI) or hypoxic load, the severity of daytime sleepiness, concomitant chronic sleep deprivation, comorbidities, the presence of depressive symptoms or chronic fatigue. Herein, we provide a review addressing the epidemiological, physiological and clinical aspects of SW, with a particular focus on the methods to recognize those patients at risk of SW.

Investigation and management of residual sleepiness in CPAP-treated patients with obstructive sleep apnoea: the European view.

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.

Application of Inverse-Probability-of-Treatment Weighting to Estimate the Effect of Daytime Sleepiness in Patients with Obstructive Sleep Apnea.

Rationale: Continuous positive airway pressure (CPAP), the first line therapy for obstructive sleep apnea (OSA), is considered effective in reducing daytime sleepiness. Its efficacy relies on adequate adherence, often defined as >4 hours per night. However, this binary threshold may limit our understanding of the causal effect of CPAP adherence and daytime sleepiness, and a multilevel approach for CPAP adherence can be more appropriate. Objectives: In this study, we show how two causal inference methods can be applied on observational data for the estimation of the effect of different ranges of CPAP adherence on daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS). Methods: Data were collected from a large prospective observational French cohort for patients with OSA. Four groups of CPAP adherence were considered (0-4, 4-6, 6-7, and 7-10 h per night). Multivariable regression, inverse-probability-of-treatment weighting (IPTW), and inverse propensity weighting with regression adjustment (IPW-RA) were used to assess the impact of CPAP adherence level on daytime sleepiness. Results: In this study, 9,244 patients with OSA treated by CPAP were included. The mean initial ESS score was 11 (±5.2), with a mean reduction of 4 points (±5.1). Overall, there was evidence of the causal effect of CPAP adherence on daytime sleepiness which was mainly observed between the lower CPAP adherence group (0-4 h) compared with the higher CPAP adherence group (7-10 h). There are no differences by considering higher level of CPAP adherence (>4 h). Conclusions: We showed that IPTW and IPW-RA can be easily implemented to answer questions regarding causal effects using observational data when randomized trials cannot be conducted. Both methods give a direct causal interpretation at the population level and allow the assessment of the appropriate consideration of measured confounders.

Treatment options in obstructive sleep apnea.

Treatment of OSA with CPAP is currently the recommended treatment and has the greatest evidence of efficacy on AHI, symptoms and comorbidities. Symptomatic patients with moderate-severe OSA generally have good adherence to CPAP therapy, while those with mild OSA, female, young and generally paucisymptomatic, have lower CPAP adherence, especially in the medium and long term. The recent identification of different clinical and pathophysiological phenotypes of OSA has paved the way for alternative treatments to CPAP, leading to an increasingly personalized therapy. Weight loss and lifestyle modifications are highly recommended in all obese or overweight patients. Mandibular advancement devices (MAD), positional therapy (PT) and hypoglossal nerve stimulation (HSN) are recent and personalized alternative therapies on which there is promising and encouraging data but with still little strong scientific evidence. The purpose of this review is to compare the efficacy, adherence and costs of various therapeutic options for OSA patients in the light of recent evidence and to provide useful guidance for specialists.