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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.

CPAP treatment decreases BP in OSA patients, especially in severe OSA, and in patients with poorly controlled BP. OSA adversely affects heart function and remodelling, but its role in the pathogenesis of HF remains unclear. Similarly, the impact of CPAP is uncertain, and results of the ongoing ADVENT-HF trial will provide more information. Several experimental studies in animals and humans indicate a central role of intermittent hypoxia in atherogenesis through multiple mechanisms. However, randomised controlled trials (RCTs) in patients with CAD and OSA found no difference in outcomes between CPAP-treated and untreated patients. The negative results of secondary prevention RCTs may be the result of exclusion of severely sleepy patients and poor compliance with CPAP treatment. In addition, room for improvement after substantial cardiac interventions may be very limited. Knowledge on arrhythmias in OSA has expanded in recent years, especially regarding AF and ventricular arrhythmias including sudden cardiac death. However, studies on the effects of CPAP are limited and controversial.

[No Abstract Available]

STUDY OBJECTIVES: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. METHODS: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild(AHI 5

The concentration of As, Cd, Cr, Cu, Hg, Ni, Pb and Zn were analyzed in the edible part of several species of fish, crustaceans, molluscs and echinoderms collected in sensitive areas of the Tuscany coast (northern Italy). The concentration of As (0.39–78.1 μg g−1) and Hg (0.01–1.56 μg g−1) resulted in most cases higher than reference thresholds. Target hazard quotient (THQ) and lifetime cancer risk (TR) indexes were calculated to assess cancer and non-cancer risk due to oral exposure; the highest THQ values referred to As and Hg, with values ≥ 1 in 39% and 48% of cases, respectively. Total target hazard quotients (TTHQ) values suggested that the local population could experience adverse health effects due to consumption of local seafood, mainly of demersal and benthic species. Cancer risk was mainly associated with As exposure, and with Cd intake, especially through molluscs consumption. The NMDS model highlighted species specific bioaccumulation processes and specific sensitivity of species to different bioavailable heavy metals. Specifically, Mullus spp. and Scorpaena porcus preferentially accumulate Hg and Cr, Octopus vulgaris specimens were discriminated by the presence of Pb and Zn, while an evident preference for Cd and Cu was recorded in Squilla mantis. In addition, the distribution of heavy metals in organisms revealed sound differences between Follonica and Livorno sampling sites, demonstrating a highly heterogeneous anthropogenic impact in terms of heavy metals input from the industrial activity resting on land.

Obstructive sleep apnea (OSA) is often associated with hypertension and other cardiovascular diseases. Blood pressure (BP) variability is part of the assessment of cardiovascular risk. In OSA, BP variability has been studied mainly as very short-term (beat-by-beat) and short-term (24-hour BP profile) variability. BP measured on consecutive heartbeats has been demonstrated to be highly variable, due to repeated peaks during sleep, so that an accurate assessment of nocturnal BP levels in OSA may require peculiar methodologies. In 24-hour recordings, BP frequently features a "nondipping" profile, ie

The upper Aptian-lower Albian stratigraphic interval documents important perturbations in the carbon cycle associated with the Oceanic Anoxic Event 1b (OAE 1b) tentatively connected with pulses in volcanic activity and the formation of the southern Kerguelen Plateau. However, uncertainties in existing age models for this interval preclude a robust and definitely convincing cause-effect connection between these two events. A sedimentary record from the Poggio le Guaine section, Umbria-Marche Basin, shows anomalously high levels of mercury during the upper Aptian-lower Albian interval. The persistence of the anomalies of [Hg] after normalization against TOC, Al, and Fe suggests that chemical and physical processes related to organic-matter scavenging, adsorption onto clay minerals, hydrous iron oxides and sulphur only played a secondary role as mechanisms for Hg accumulation in the sediments. In agreement with previous studies in which anomalous enrichments of Hg in sedimentary records were interpreted as monitors of enhanced volcanic activity, we speculate that the Hg enrichments documented in the Poggio le Guaine section reflect a rapid increase in atmospheric Hg content associated with a massive release of volcanic Hg, and possibly suggest a multi-phase emplacement of the southern Kerguelen Plateau (SKP) as a realistic source. Nonetheless, comparison of Hg profiles and micropalaeontological data from the Poggio le Guaine section reasonably excludes the possibility that the global biotic turnover horizon documented in the upper Aptian could be directly attributed to the volcanic pulses of the SKP emplacement.

To elucidate the dynamics of a suite of organochlorine contaminants (PCBs, HCB), PAHs and Hg and verify the potential of these pollutants as reliable fingerprints of sources, an ensemble of marine sediments and organisms (finfish, shellfish species and Mytilus galloprovincialis) were analysed from the contaminated Augusta Bay (Southern Italy). The Hg and HCB concentration in the sediments exceeded the EQS of the Directive 2000/60/EU. Similarly, ∑PCB and selected PAHs were above the threshold limit set by regulation. The marine organisms showed Hg concentrations above CE 1881/2006. Contaminants in transplanted mussel evidenced an increased accumulation overtime and different distribution patterns between sampling sites. Analysis of the homolog composition of PCB congeners revealed comparable patterns between sediments and marine organisms and offered the opportunity to define a robust fingerprint for tracing contaminants transfer from the abiotic to the biotic compartments. These results were confirmed by the Fluoranthene/Pyrene, Hg and HCB distribution modes.

In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and quadriceps in each experimental group at all time points. Although morphological analysis showed unchanged total area of necrosis/regeneration in the diaphragm after training, there was a trend for larger areas of regeneration than necrosis in the diaphragm of mdx-EX compared to mdx-SD mice. However, the levels of Cx39, a protein associated with active regeneration in damaged muscle, were similar in the diaphragm of mdx-EX and mdx-SD mice. Hsp60 significantly decreased at 45 days in the diaphragm, but not in limb muscles, in both trained and sedentary mdx compared to WT mice. In limb muscles, but not in the diaphragm, Hsp70 and NF-kB p65 levels were increased in mdx mice irrespective of training at 30 and 45 days. Therefore, the diaphragm of mdx mice showed little inflammatory and stress responses over time, and appeared hardly affected by mild endurance training. J. Cell. Physiol. 232: 2044–2052, 2017. © 2016 Wiley Periodicals, Inc.

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, WOS: 000507372400195, [No abstract available], European Respiratory Soc

Background: Patients on home continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) show large variability in compliance to treatment. Aim: To identify predictors of poor compliance, we evaluated compliance to treatment in patients with obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), and OSA-chronic obstructive pulmonary disease (COPD) overlap syndrome. Methods: We analyzed clinical and compliance data provided by a single home care provider, in 602 patients (n=442 OSA, males (M) 308; 38 OHS M=15, and 122 overlap M=111) on home CPAP/NIV in the province of Agrigento, Italy, after one year of treatment. The following variables were considered: age, body mass index (BMI), sex, diagnosis, type of prescribed ventilator, and common comorbidities. Results: Mean (±SD) age and BMI were: 64.6±11.9 yrs, and 34.4±7.3 kg/m2. CPAP was prescribed in 67.1%, AutoCPAP in 12.9%, Bilevel in 9.1%, and volume assured pressure support ventilation in 10.9% of the sample. Mean compliance to treatment was 4.7±2.7 h/day, with 64.3% of the patients showing good compliance (>4 h/night). Patients overestimated CPAP/NIV use by 0.5 h/night. Compliance was not affected by age, diagnosis, severity of sleep disordered breathing, type of ventilation or occurrence of comorbidities, with the exception of depression (p=0.05). BMI was higher in poorly compliant compared to compliant patients (p=0.02). When data were split by gender, compliance was OHS>OSAS>overlap in women (p 0.007); overlap>OSAS>OHS in men (p=0.013) Conclusions: A high degree of obesity and depression were associated with poor compliance to ventilatory treatment.

BACKGROUND Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.

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.

We thank doctors Park and Kang for their editorial that well summarized our article. Our common belief is that one of the possible consequences of untreated obstructive sleep apnea (OSA) is an accelerated deterioration of kidney function, and that more knowledge would be necessary on the possible protective effects of OSA treatments. To our knowledge, so far the only OSA therapy whose effects on renal function have been tested is continuous positive airway pressure (CPAP), and most , although not all studies, have demonstrated its benefits. Our own study, while confirming benefits of fixed CPAP, has demonstrated little effect of auto-adjusting CPAP (APAP). This finding may be of relevance as, at present, OSA treatment by APAP is largely used. Then, should we ban APAP as a therapeutic modality for patients with renal problems? Most studies comparing fixed CPAP and APAP have focused on correction of respiratory events during sleep, relief of sleepiness, tolerability and patients’ compliance in subjects with typical pure OSA. In fact, APAP devices have been designed as treatment tools for this subgroup of patients, and not for patients with comorbid OSA with other types of respiratory disorders. Accordingly, current guidelines do not recommend APAP therapy for OSA patients with comorbidities like chronic obstructive pulmonary disease (COPD) or congestive heart failure although, more recently, small studies have been published suggesting effectiveness of APAP in patients with both OSA and COPD (overlap syndrome). Other diseases are not specifically mentioned in guidelines as contraindications to APAP. However, efficacy of OSA treatment should not be evaluated just in terms of polysomnographic parameters or symptoms, but also for its ability to prevent or counteract OSA deleterious effects on various organs and functions. In that respect, many studies have been published about effects of CPAP treatment, but few of them compared effects of fixed CPAP and APAP. We are aware of some studies comparing effects of these treatment modalities on blood pressure, autonomic activity or insulin resistance. Most of them showed superiority of fixed CPAP but, altogether, they are few, and more data would be required. Inflammatory activation and enhanced renin aldosterone angiotensin system activity in OSA may contribute to accelerate the age-related decline in estimated glomerular filtration rate (eGFR). Several, although not all, studies suggested beneficial effects of CPAP treatment on those factors, but to our knowledge possible differential effects of fixed CPAP and APAP have not been investigated, and could account for a different evolution of renal function in patients treated by each CPAP modality. Investigations should be extended to effects of APAP devices working with different algorithms. Besides, effects of setting different pressure ranges on the APAP machines, implying different degrees of variability of the administered pressure, should be tested. Although changes in eGFR over time differed significantly between our patients treated by fixed CPAP and APAP, standard deviations of changes were large in both groups. This finding suggests that the rate of eGFR decline may show high interindividual variability in treated OSA patients. What could make an OSA patient more susceptible to renal injury is not entirely clear. One longitudinal study showed that spending ≥12% of sleep time with an oxygen saturation

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.

Air pollution is a major problem worldwide, which could be even more serious for athletes who train in urban environments. Exercise increases minute ventilation and exposure to pollutants, but the literature on the effects of air pollution in athletes is relatively scarce, with the exception of chlorine exposure in athletes of aquatic sports and air pollution secondary to ice resurfacing in athletes performing in ice arenas. Although air pollution may exert detrimental effects on athletic performance, little has been published on this topic. The largest body of information regards the impact of air pollution during urban active transport, i.e., walking and cycling in cities, due to the potential risk of air pollution in citizens and the need to rethink urban transportation strategies accordingly. In healthy subjects, the benefits of physical activity largely outweigh the disadvantages of exposure to air pollutants. In susceptible individuals, however, such as patients with cardiac or respiratory disease and children, detrimental effects have been demonstrated. Improvement in air quality, individual protective behaviors, and prompt communication to the population of dangerous air quality may help to limit the negative effects of air pollution on respiratory health.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, Riha, Renata/0000-0001-8983-9985, WOS: 000507372405424, [No abstract available], European Respiratory Soc

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, WOS: 000507372400192, [No abstract available], European Respiratory Soc

High blood pressure (BP) and non-dipping 24-hour BP profile may help to predict BP decrease after obstructive sleep apnoea treatment by CPAP. However, specific, highly reproducible traits associated with BP responsiveness to CPAP must still be identified.http://bit.ly/2LbS4uV

BACKGROUND: Short sleep duration and poor sleep quality have been reported in chronic kidney disease (CKD). Additionally, sleep disordered breathing (SDB), a well-known cause of disturbed sleep, is highly prevalent in CKD. The majority of studies on sleep quality in CKD were focussed on dialysed patients, were based on subjective reports, and did not consider possible coexistence of SDB.1 Only a small number of studies assessed sleep quality on polysomnographic data in non-dialysed patients with CKD.2 AIM The aim of this study was to evaluate objective sleep quality based on electroencephalographic (EEG) recordings during nocturnal polysomnography in non-dialysed patients with CKD, taking into account coexisting SDB and psychiatric diagnoses. METHODS: The European Sleep Apnea Database (ESADA) cohort includes patients studied for suspected obstructive sleep apnea from numerous European sleep centres. From this cohort, 375 non-dialysed CKD patients who had undergone full polysomnography were matched one-by-one with 375 non-CKD patients. CKD was defined as an estimated glomerular filtration rate (eGFR) of

In continental margins, canyons appear to act as natural conduits of sediments and organic matter from the shelf to deep basins, providing an efficient physical pathway for transport and accumulation of particles with their associated land-produced contaminants. However, these mechanisms have not been yet sufficiently explored by geochemical markers. The continental slope of the south Sardinia has been used as a natural laboratory for investigating mechanisms and times of transfer dynamics of contaminants from land to sea and from shelf to deep sea through an articulated system of submarine canyons. Here, dynamics of contaminants have been investigated in a pilot area of the central Mediterranean basin (Gulf of Cagliari, S Sardinia) where important industrial plants are sited since beginning of the last century. Five sediment cores dated by 210Pb and 137Cs reveal: i) a complex dynamics of organic and inorganic contaminants from point source areas on land to the deep sea and ii) a crucial role played by canyons and bottom morphology as primary pathway conveying sediments and associated contaminants from sources to very far deep sea environments. In particular, this study provides new integrated tools to properly understand mechanisms of connection between coastal sectors and deep sea. This is challenging mostly in regions where coastal pollution could represent critical threats for larger areas of the Mediterranean Sea. © 2018 Elsevier B.V.

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.

Introduction: Automatic event detection (AED) of residual apnea-hypopnea index (AHI) by ventilators is a current practice in sleep and mechanical ventilation Units but this methodology has not been validated in an unselected population of OSA patients. Aim of the present study was to assess in a “real-life” condition the reliability of AED during PAP therapy by the in-built software compared to full polysomnography during follow-up. Methods: We enrolled 300 OSA patients (105 F; AHI 45.3 ± 27.8) already on Positive airway pressure (PAP) therapy: 53% of the patients were on CPAP while other modalities were used in the rest of the sample. Results: Overall, the built-in software identified residual obstructive AHI (AHIPAP) > 5, 10 or 15 in 18.7, 8.6 or 4.6% of patients, respectively. By using AHIPAP, 28.4% of patients were wrongly classified as “well controlled” despite a residual AHIPSG>5 (6% considering a residual AHIVENT >15); 7% of patients were classified as not controlled while AHIPSG was 15). Type of ventilation, ventilator parameters, adherence to treatment and level of baseline or follow-up Epworth Sleepiness Scale score were similar between groups. The sensitivity and positive predicted values were very low. Positive likelihood ratio appears adequate only for residual AHIPAP ≥10, but negative likelihood ratio was inconclusive for all the cut-off considered. Discussion: The results of the present study suggest a more cautious approach in the follow-up of OSA patients, since a protocol based only on AED detection and symptoms assessment may not be accurate especially for AHIPAP

Background Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. Aims Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. Methods 16HBE cells were stimulated with/without cigarette smoke extracts (CSE) and carbocysteine. Flow cytometry and clonogenic assay were used to assess cell proliferation; western blot analysis was used for assessing nuclear expression of SIRT1 and FoxO3. The nuclear co-localization of SIRT1 and FoxO3 was assessed by fluorescence microscopy. Beta galactosidase (a senescence marker) and SIRT1 activity were assessed by specific staining and colorimetric assays, respectively. ChiP Assay and flow cytometry were used for assessing survivin gene regulation and protein expression, respectively. Results CSE decreased cell proliferation, the nuclear expression of SIRT1 and FoxO3 and increased beta galactosidase staining. CSE, reduced SIRT1 activity and FoxO3 localization on survivin promoter thus increasing survivin expression. In CSE stimulated bronchial epithelial cells carbocysteine reverted these phenomena by increasing cell proliferation, and SIRT1 and FoxO3 nuclear expression, and by reducing beta galactosidase staining and survivin expression. Conclusions The study shows for the first time that carbocysteine may revert some senescence processes induced by oxidative stress due to cigarette smoke exposure.

Objective In obstructive sleep apnea (OSA), while both hypothyroidism and hyperthyroidism have been studied, the occurrence of non-thyroidal illness syndrome (NTIS) (normal thyroid stimulating hormone [TSH] with low triiodotironine) has not been investigated. We explored the occurrence of NTIS in patients with moderate to severe OSA and its relationship to the severity of nocturnal respiratory disorders. We also studied the occurrence of subclinical hypothyroidism (SH, ie, high TSH with normal thyroxine) in OSA and changes in circulating TSH, free triiodotironine (fT3) and free thyroxine (fT4) after CPAP treatment. Methods After a nocturnal respiratory polysomnography, 125 consecutive patients with moderate to severe OSA and 60 control subjects with normal nocturnal respiration were recruited. Morning circulating TSH, fT3, and fT4 were measured in all subjects. In a subsample of patients, nocturnal polysomnography and hormonal determinations were repeated after CPAP treatment for five months. Results NTIS was found in 13 (10.4%), and SH in ten (8%) OSA subjects, but not in any control subjects. Patients with NTIS showed worse mean nocturnal oxygen saturation and time with saturation

Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc.

Background: Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF. Objectives: The objective of this study was to explore if circulating relaxin-2 in male OSA subjects may be related to OSA severity, to circulating levels of MMPs, of their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and of VEGF, and if it may protect from hypertension. Patients andMethods: Fifty untreated male subjects with suspected OSA were recruited. After nocturnal polysomnography, a morning venous blood sample was withdrawn. Then, 24-hour ambulatory blood pressure (BP) monitoring was performed. Results: The respiratory disturbance index in the sample was 30.4 [interquartile range (IQR) 15.6-55.2]. Relaxin-2 was detectable in 20 subjects. These subjects did not differ in OSA severity or diurnal and nocturnal BP from subjects with undetectable relaxin-2, but they showed lower TIMP-1 (126.8 ± 29.1 vs. 156.9 ± 41.7 pg/ml, respectively; p = 0.007) and a marginally higher MMP-9/TIMP-1 molar ratio [0.58 (IQR 0.23-1.35) vs. 0.25 (IQR 0.15-0.56); p = 0.052]. Conclusions: Relaxin-2 in male subjects was not related to OSA severity, but it was associated with lower TIMP-1. As it was often undetectable, even when BP values were normal, it is unlikely that it plays a role as a major factor protecting from hypertension in OSA.

Isotopic composition of mercury (Hg) in marine organisms and sediment cores was used to identify sources and reconstruct historical trends of contamination in the coastal-marine area of Rosignano Solvay (Italy), affected by Hg pollution from a chlor-alkali plant on the near land. Sediments show a wide range of Hg concentration and Hg isotope signatures. Particularly, coupled Hg concentration and δ202Hg values trace inputs from different sources. The two depth-profiles clearly indicate three distinct periods: “pre-industrial” (before 1941), “industrial” (between 1941 and 2007) and “post-industrial” (after 2007) ages. This is also corroborated by sediment chronology, using 210Pb dating method, validated through 137Cs. Marine organisms are characterized by Hg isotope signatures comparable to “post-industrial” surface sediments. Notably, specimens of Mullus spp. evidence isotope composition comparable to the “industrial” sediments, thus suggesting a still active role of those sediments as source of Hg for the benthic fish compartment. The small amount of MIF and the Δ199Hg/Δ201Hg ratio recorded in organisms are reasonably consistent with limited processes of MMHg demethylation in the water column.

There are suggestions that the loss of female sex hormones following menopause is critical for the development or progression of sleep-disordered breathing (SDB). We conducted a review of the literature on the role of menopause and hormone replacement therapy (HRT) in SDB risk. There is an increase in SDB during the menopausal transition period, but data on an effect beyond that of increasing age and changes in body habitus are weak or absent. Early community-based, observational studies reported a protective effect by HRT on SDB prevalence, but this could possibly be explained as a healthy user effect. Interventional studies of the effect of HRT on SDB are sparse, with only a few randomized placebo-controlled studies, often performed on small samples of women without clinically significant SDB. HRT regimens have varied and all the studies are fairly old. They do not definitely assure the alleviation of SDB and HRT cannot thus be recommended as treatment for SDB. It is concluded that there is no evidence that female sex hormone changes during menopause per se are able to explain the increase in SDB in midlife women and conclusions on the effect of HRT on SDB cannot be drawn from the current literature.

Background: Available studies show an overall poor correlation between sleep characteristics and symptoms profile in mild obstructive sleep apnoea (OSA) patients. Aim of the study was to explore the relationship of daytime sleepiness, as assessed by Epworth Sleepiness Scale (ESS), with anthropometric, sleep and metabolic characteristics in mild OSA patients (apnoea-hypopnoea index [AHI] 5-15/h) in the ESADA multicenter cohort involving over 20 academic sleep centers. Methods: Data were collected on anthropometrics, ESS, metabolic and sleep variables obtained from overnight polysomnography. Results: A total of 2068 adults (63.6% males) with mean AHI 9.5±2.9/h, age 50.7±12.5 years, BMI 29.1±5.7 kg/m2, and ESS 9.2±5.1, were included in this analysis. ESS was correlated negatively with age (r=-0.115, p

Prevalence of both chronic kidney disease (CKD) and obstructive sleep apnea (OSA) is continuously increasing. Moreover, the prevalence of OSA increases as kidney function declines and is higher among patients with end-stage renal disease (ESRD). In addition, OSA is recognized as a potential nontraditional risk factor for development and progression of CKD. Continuous positive airway pressure (CPAP) plays a pivotal role in the management of OSA, eliminating patients' symptoms and improving their quality of life. Recent studies suggested that CPAP treatment may have beneficial effects on kidney function among patients with OSA. This narrative review summarizes the existing knowledge on the association between CKD and OSA, with emphasis on the epidemiology, the pathophysiology of the development of CKD in OSA and vice versa, as well as the effect of CPAP on renal function.

the clinical and pathophysiological links between obstructive sleep apnea (OSA) and cardiovascular

Trace elements were measured in the edible tissues of target marine species (Sardina pilchardus, Mullus barbatus, Mullus surmuletus, Merluccius merluccius and Parapenaeus longirostris) collected in some of the main ports of the Sicilian coast (southern Italy) in order to evaluate the potential human health risk associated to their consumption. Cadmium, Pb and Hg were below the tolerable limits reported by the European Union in foodstuffs (Commission Regulation (EC) 1881/2006) except for Hg in P. longirostris from one sampling site. The health risk for consumers was assessed both for adults and children calculating the estimated weekly intake (EWI), the target hazard quotient (THQ) and the lifetime cancer risk (CR) for each element. The EWI did not exceed the provisional tolerable weekly intake (PTWI) recommended by the European Food Safety Authority and THQs were 1 in most cases. Further, the probabilistic distributions of health hazard were evaluated through Monte-Carlo simulation which confirmed a non-carcinogenic risk. With some exceptions related to As exposure, the results obtained definitively confirm the goodness of the fishery commercial resources in one of the most important seafood market of the central Mediterranean Sea and represent a positive data for the assessment of the good environmental status for descriptor 9 of the Marine Strategy Framework Directive in this area of the basin.

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Obstructive sleep apnoea (OSA) is a major challenge for physicians and healthcare systems throughout the world. The high prevalence and the impact on daily life of OSA oblige clinicians to offer effective and acceptable treatment options. However, recent evidence has raised questions about the benefits of positive airway pressure therapy in ameliorating comorbidities.An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field, and proposed topics for future research on epidemiology, phenotyping, underlying mechanisms, prognostic implications and optimal treatment of patients with OSA.The group concluded that a revision to the diagnostic criteria for OSA is required to include factors that reflect different clinical and pathophysiological phenotypes and relevant comorbidities (e.g.nondipping nocturnal blood pressure). Furthermore, current severity thresholds require revision to reflect factors such as the disparity in the apnoea–hypopnoea index (AHI) between polysomnography and sleep studies that do not include sleep stage measurements, in addition to the poor correlation between AHI and daytime symptoms such as sleepiness. Management decisions should be linked to the underlying phenotype and consider outcomes beyond AHI.

To determine the relationship between obstructive sleep apnea (OSA) and chronic kidney disease (CKD). Previous population studies of the association are sparse, conflicting and confined largely to studies of administrative data.Cross-sectional analysis in unselected participants of the Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study, aged40 years. Renal data were available for 812 men without a prior OSA diagnosis who underwent full in-home polysomnography (Embletta X100) in 2010-2011. CKD was defined as an estimated glomerular filtration rate (eGFR)60 mL/min/1.73m2 or eGFR≥60 and albuminuria (albumin-creatinine ratio ≥3.0 mg/mmol).CKD (10.5%, n = 85 [Stage 1-3, 9.7%; Stage 4-5, 0.7%]) of predominantly mild severity showed significant associations with OSA (apnea-hypoapnea index [AHI] ≥ 10): odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.02-3.5; severe OSA (AHI ≥ 30/h): OR = 2.6, 95% CI: 1.1-6.2; and respiratory-related arousal index: ≥7.6/h, OR = 2.3, 95%CI: 1.1-4.7; but not measures of hypoxemia after adjustment for age, hypertension, diabetes, smoking, obesity, and NSAID use. There was no association of CKD with daytime sleepiness. In men with CKD, those with OSA were not significantly more likely to report symptoms (sleepiness, snoring, and apneas) or be identified with the STOP OSA screening questionnaire, compared to men without OSA.Predominantly mild CKD is associated with severe OSA and arousals. Further population studies examining the longitudinal relationship between CKD and OSA are warranted. Better methods are needed to identify OSA in CKD which may have few symptoms.

BACKGROUND: The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. METHODS: In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). RESULTS: In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m(2)) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. CONCLUSIONS: fCPAP but not APAP may prevent eGFR decline in OSA.

In recent decades, the study of sleep breathing disorders has accelerated and increased our overall knowledge of sleep disorders in general. This now represents a real challenge to the health system due to the high prevalence, morbidity and mortality with concomitant social and economic repercussions [1]., Sleep medicine: a new approach http://ow.ly/qzVh30iVkWL

The 2017 Annual Congress of the European Respiratory Society (ERS) held in Milan has featured the latest research on clinical physiology and sleep.

Obstructive sleep apnoea (OSA) is a major challenge for physicians and healthcare systems throughout the world. The high prevalence and the impact on daily life of OSA oblige clinicians to offer effective and acceptable treatment options. However, recent evidence has raised questions about the benefits of positive airway pressure therapy in ameliorating comorbidities.An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field, and proposed topics for future research on epidemiology, phenotyping, underlying mechanisms, prognostic implications and optimal treatment of patients with OSA.The group concluded that a revision to the diagnostic criteria for OSA is required to include factors that reflect different clinical and pathophysiological phenotypes and relevant comorbidities (

The background and purpose of the HERMES (Harmonising Education in Respiratory Medicine for European Specialists) initiative has been discussed at length in previous articles [1–3]. This article aims to provide more detailed and specific insight into the process and methodology of the Sleep HERMES Task Force in developing a core curriculum in respiratory sleep medicine.

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.

Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep-disordered breathing. Automatic bilevel ventilation can be used to treat obstructive sleep-disordered breathing when CPAP is ineffective, but clinical experience is still limited. To assess the outcome of titration with CPAP and automatic bilevel ventilation, the charts of 356 outpatients (obstructive sleep apnea, n = 242; chronic obstructive pulmonary disease + obstructive sleep apnea overlap, n = 80; obesity hypoventilation syndrome [OHS], n = 34; 103 females) treated for obstructive sleep-disordered breathing from January 2014 to April 2017 were reviewed. Positive airway pressure titration was considered successful in the case of sleep-disordered breathing resolution (apnea-hypopnea index 40 kg/m2(odds ratio 6.16, confidence interval 1.50-25.17, p = 0.011) and CT90% >42% (odds ratio 5.87, confidence interval 1.39-24.83, p = 0.016). During follow-up, automatic bilevel ventilation treatment failed in seven patients (10%), and compliance was similar in CPAP (4.5 ± 2.2 hr) and automatic bilevel ventilation (5.2 ± 2.3 hr, p = 0.09) groups. Automatic bilevel ventilation was useful to treat sleep-disordered breathing, but failed in patients with severe OHS.

A comprehensive assessment of the potential adverse effects on environment and human health generated by the inputs of chemicals from the most important Libyan petrochemical plant is presented. Ecotoxicological risk associated with the presence of As, Hg, Ni, Zn and PAHs in marine sediments is low or moderate, with a probability of toxicity for ecosystem

CPAP is the first-choice treatment for obstructive SDB, but the criteria to prescribe AutoBI are undefined. Trials of AutoBI ventilation in patients under titration for obstructive SDB from January 2015 to January 2017 ((n=67 out of 265 titrations) were reviewed to assess: a) their clinical features, b) the reason to shift from CPAP to AutoBI, and c) long-term compliance to treatment. AutoBI was used in cases of intolerance to high therapeutic CPAP levels (n=23) or incomplete resolution of SDB on CPAP (n=45). AutoBI failed in 11 patients (16.4%): 2 OSA patients (7.7%), 4 overlap patients (21%), and 5 OHS patients (22.7%). The Table reports the differences at diagnosis between patients prescribed CPAP or AutoBI (unpaired t-test, significance p

Background and aim: Obstructive sleep apnea (OSA) and dyslipidemia are both independently well-recognized risk factors for cardiovascular disease. Previous data are inconclusive regarding the relationship between OSA and dyslipidemia. The aim of the present study was to investigate the association between OSA and dyslipidemia in ESADA (European Sleep Apnea Database). Methods: The cross-sectional analysis included 8592 patients (age 50.1±12.7 years, 69.1% male, BMI 30.8±6.6 kg/m2, mean AHI 25.7±25.9 n/h) from the ESADA. The independent relationship between measures of OSA (AHI, ODI, mean and lowest saturation) and lipid profile (total cholesterol [TC], HDL-cholesterol [HDL-C] (n=3289) and fasting triglyceride [TG] (n=4612)) was determined by means of General Linear Model analysis. Patients with known hyperlipidemia and/or lipid-lowering medication were excluded. Results: TC had a strong linear association with ODI (mean±SE [mg/dl] 180.33±2.46, 184.59±2.42, 185.44±2.42 and 185.73±2.44; p Conclusion: OSA has an independent association with dyslipidemia, but the effect size is limited.