Intermittent Nocturnal Hypoxemia Research Articles

Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer.

Intermittent hypoxaemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer. Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-β1 (TGF-β1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA. The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-β1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices. Moderate-to-severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established disease.

Association of tau burden with sleep disordered breathing in adults with Down syndrome

AbstractBackgroundAdults with Down syndrome (DS) overproduce the amyloid precursor protein and nearly all evidence clinical symptoms of Alzheimer’s Disease (AD) dementia in later life. Sleep disordered breathing, and specifically, obstructive sleep apnea (OSA), is common in adults with DS. OSA has been associated with risk of AD in adults without DS, and sleep disturbances may have a bidirectional relationship with AD pathology. We hypothesized that greater tau burden is associated with subsequent sleep disordered breathing in a time‐lagged design.MethodsEighty young adults with DS (37±8 yrs, 49% women, 94% cognitively‐stable/6% MCI‐DS) from the ABC‐DS study underwent tau PET ([18F]‐AV1451, Braak stage SUVRs) and were assessed 4±0.7 years after PET using WatchPAT home sleep testing. Sleep variables included oxygen desaturation index (ODI) and apnea‐hypopnea index (AHI). General linear models assessed tau burden on later sleep impairments. Models were run in the whole group and the cognitively‐stable group alone, with and without age adjustment. Analyses were run using overall sleep measures and those in REM and non‐REM (NREM) sleep separately.ResultsIn unadjusted models, greater tau in early, middle, and late Braak stages were associated with a higher ODI, while greater tau in middle Braak stages was associated with a higher AHI. In the cognitively‐stable group alone, greater tau in early and middle, but not late, Braak stages were associated with a higher ODI, while greater tau in middle Braak stages was associated with a higher AHI. Adjusting for age, greater tau in late Braak stages was associated with ODI in the whole group and the cognitively‐stable group alone. Associations for overall sleep measures were driven by NREM measures (Table 1).ConclusionIn adults with DS with a high prevalence of OSA, tau burden was associated with subsequent intermittent nocturnal hypoxemia as measured by the ODI during NREM sleep. These findings align with those in adults without DS, linking AD pathology, disturbed sleep, witnessed apneas, and nocturnal hypoxemia. Both longitudinal and randomized studies are required to clarify cause‐effect relationships, including the presence of mediating and/or moderating variables such as reduction in sleep depth or continuity.

Sleep apnea syndrome associated with gonadal hormone imbalance (Review).

Patients with obstructive sleep apnea exhibit an increased risk of developing gonadal disorders. Because a notable number of people worldwide have sleep respiratory and reproductive disorders, it is essential to recognize the association between local upper airway dysfunction and its gonadal effects. Repeated breathing pauses cause sleep fragmentation, disorganization of sleep cycles and stages, sympathetic activation, intermittent hypoxemia and systemic inflammation. Nocturnal intermittent hypoxemia has a direct central effect on neurotransmitters, with disturbances in the normal production of hypothalamic-pituitary hormones. Awakenings and micro-awakenings at the end of apneic episodes produce a central stress responsible for hormonal changes and subsequent endocrine imbalances. The aim of the present study was to investigate the impact of obstructive sleep apnea syndrome (OSAS) on gonadal hormonal homeostasis and its consequences. Recognizing and understanding how local upper airway dysfunction causes gonadal imbalance may facilitate better care for patients with OSAS. Although there may be a direct relationship between sleep-disordered breathing and gonadal function mediated by hormones via the hypothalamic-pituitary-gonadal axis, to date, current therapies have not been effective.

Effect of menopause and age on vascular impairment

AimsThe prevalence of cardiovascular diseases increases in women after menopause. The aim of the study was to determine the impact of conventional cardiovascular risk factors such as age, blood pressure, smoking, cholesterol, obesity, and glucose balance, but also menopausal state and sleep-disordered breathing on vascular impairment during menopausal transition. Methods89 women initiated the study and 74 of them participated in the 10-year follow-up. Cardiovascular disease risk factor assessments, ultrasound measurements of brachial artery function, including nitroglycerin-mediated vasodilatation and flow-mediated endothelium-dependent vasodilation, and sleep studies were repeated at baseline and at 5-year and 10-year follow-ups. ResultsOver the study period, all the cardiovascular disease risk estimates increased. Both flow-mediated endothelium-dependent vasodilatation (decline 55 %) and nitroglycerin-mediated vasodilatation (decline 18 %) worsened over the 10 years (p < 0.001). Vascular function was not associated with menopausal state (determined with follicle stimulating hormone). Systolic blood pressure (p = 0.009) and smoking (p = 0.006) at baseline were negatively associated with nitroglycerin-mediated vasodilatation at 5-year follow-up and the use of hormonal therapy at 5-year follow-up was positively associated with concurrent nitroglycerin-mediated vasodilatation (p = 0.041). Intermittent nocturnal hypoxemia at baseline was associated with flow-mediated endothelium-dependent vasodilatation at 10-year follow-up (p = 0.043). High body mass index and impaired glucose balance at 5-year follow-up were associated with nitroglycerin-mediated vasodilatation decline at 10-year follow-up (p = 0.022 and p = 0.037, respectively). ConclusionsWe demonstrate how cardiovascular risk factors and vascular function evolve during menopausal transition. Although menopause was not associated with vascular impairment, short-term improvement in vascular function was observed in those using menopausal hormonal therapy. Intermittent nocturnal hypoxemia, obesity and impaired glucose control are early predictors of vascular decline during postmenopause.

P66Shc is increased in peripheral blood mononuclear cells of the patients with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) is characterized by nocturnal intermittent hypoxemia and linked to oxidative stress. Evidence demonstrated that p66Shc plays a key role in regulating oxidative stress. This study aimed to investigate the expression of p66Shc in peripheral blood mononuclear cells (PBMCs) of patients with OSA and the association with polysomnographic parameters. Methods: Fifty-four OSA subjects and 19 no OSA controls were enrolled in this study. All the subjects underwent standard polysomnography. P66Shc mRNA and protein levels in the PBMCs were detected by quantitative real-time polymerase chain reaction and western blotting. Plasma 3-nitrotyrosine (3-NT), oxidized low density lipoprotein (oxLDL), and advanced oxidation protein products (AOPP) were measured by ELISA method. Results: P66Shc mRNA and protein levels in PBMCs were significantly higher in OSA patients than in controls. P66Shc mRNA was positively correlated with plasma 3-NT, oxLDL, AOPP, hypopnea index (AHI), oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation (SaO2) below 90% (CT90), epworth sleepiness scale (ESS) and lymphocytes; negatively correlated with lowest SaO2 (LSaO2) and mean SaO2 (MSaO2). Further multivariate linear regression analysis showed that p66Shc mRNA levels were independently associated with AHI, MSaO2 and CT90. Conclusions: Oxidative stress regulator p66Shc may play a role in the pathophysiology of OSA and might serve as a potential biomarker for this disease.

Correlation between nocturnal intermittent hypoxemia and mild cognitive impairment in the older adult and the role of BDNF Val66Met polymorphism: a hospital-based cross-sectional study.

To explore theprevalence ofnocturnal intermittent hypoxemia (NIH) in a tertiary hospital geriatric department and the relationship between NIH and mild cognitive impairment (MCI) in older adults, and to examinethe role of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. Older adults aged ≥ 60 were enrolled. NIH and cognitive assessments were conducted. BDNF concentrations and BDNF Val66Met polymorphism were detected for a preliminary exploration of the possible mechanism of the process. Of 325 older adults enrolled, 157 (48%) had NIH and were further divided into mild, moderate, and severe NIH groups according to their oxygen desaturation of ≥ 4% per hour of sleep (ODI4). MCI detection rate in the four groups gradually increased, and the differences were statistically significant (chi-square = 4.457, P = 0.035). ODI4 was negatively correlated with MoCA score in all participants (r = - 0.115, P = 0.039) and patients with NIH (r = - 0.199, P = 0.012). After adjusting for sex, age, and cardiovascular risk factors, NIH and MCI remained independently associated (OR = 3.13, 95% CI 1.03-9.53, P = 0.045). BDNF levels were positively correlated with MoCA score (r = 0.169, P = 0.028) and negatively correlated with nocturnal average oxygen saturation in patients with NIH (r = - 0.288, P = 0.008). Older adults with different BDNF Val66Met genotypes did not show significant differences in MCI rate and BDNF levels (P > 0.05). The older adults with NIH have a higher MCI detection rate. BDNF levels may be a potential biomarker for cognitive dysfunction in patients with NIH.

Thalamic altered spontaneous activity and connectivity in obstructive sleep apnea syndrome.

Obstructive sleep apnea (OSA) syndrome is a sleep disorder characterized by excessive snoring, repetitive apneas, and nocturnal arousals, that leads to fragmented sleep and intermittent nocturnal hypoxemia. Morphometric and functional brain alterations in cortical and subcortical structures have been documented in these patients via magnetic resonance imaging (MRI), even if correlational data between the alterations in the brain and cognitive and clinical indexes are still not reported. We examined the impact of OSA on brain spontaneous activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional MRI data of 20 drug-naïve patients with OSA syndrome and 20 healthy controls matched for age, gender, and body mass index. Patients showed a pattern of significantly abnormal subcortical functional activity as compared to controls, with increased activity selectively involving the thalami, specifically their intrinsic nuclei connected to somatosensory and motor-premotor cortical regions. Using these nuclei as seed regions, the subsequent functional connectivity analysis highlighted an increase in patients' thalamocortical connectivity at rest. Additionally, the correlation between fALFF and polysomnographic data revealed a possible link between OSA severity and fALFF of regions belonging to the central autonomic network. Our results suggest a hyperactivation in thalamic diurnal activity in patients with OSA syndrome, which we interpret as a possible consequence of increased thalamocortical circuitry activation during nighttime due to repeated arousals.

Impact of obstructive sleep apnea on left ventricular mass index in men with coronary artery disease.

Left ventricular hypertrophy (LVH) is associated with augmented risk for mortality in patients with coronary artery disease (CAD). These patients often have obstructive sleep apnea (OSA). We aimed to evaluate the relationship between OSA and the left ventricular mass index (LVMI) in men with CAD. Consecutive patients with CAD were recruited and underwent overnight portable monitoring for the assessment of OSA. LVMI was ascertained using high-resolution echocardiography. Univariate and multivariate regression analyses were conducted to explore the associations between the OSA parameters and the LVMI levels. Of the 1,053 examined male patients with CAD, 425 (40.4%) had moderate-to-severe OSA (respiratory event index ≥ 15 events/h). The prevalence of LVH (LVMI > 125 g/m²) was 36.0% (n = 379). The mean LVMI values increased with increasing OSA severity (P < .001). Patients with respiratory event index ≥ 30 events/h had 2.30 (95% confidence interval 1.50-3.54, P < .001) times increased risk of LVH than those without OSA (respiratory event index < 5 events/h) independent of confounders. The minimum oxygen saturation levels were the strongest factor correlated with LVMI (β = -0.299, P = .004) of several OSA indices. Patients with minimum oxygen saturation < 70% had an adjusted odds ratio of 3.62 (95% confidence interval 1.81-7.25, P < .001) for LVH development compared with those with minimum oxygen saturation ≥ 90%. OSA severity was associated with a higher likelihood of LVH in men with CAD, which is partially related to severe nocturnal intermittent hypoxemia. Aggressive effort at managing OSA among patients with CAD may further reduce the cardiovascular risk.

Troubles urinaires et génito-sexuels dans le syndrome d’apnée obstructive du sommeil : revue de la littérature

The objective of this work was to make a review of urinary tract symptoms and erectile dysfunction involved in obstructive sleep apnea (OSA) but also to study their physiopathology and potential treatments. We conducted a literature review in the Pubmed database using PRISMA guidelines and the MeSH terms: sleep apnea, urinary incontinence, erectile dysfunction, sexuality. All French and English articles published up to 2020 were evaluated. The initial evaluation identified 240 articles from which 30 were included. References lists review allowed the inclusion of 26 additional articles. Nocturia, overactive bladder (OAB) and erectile dysfunction (ED) were associated with OSA. Increased levels of natriuretic peptides are behind nocturia. Nocturia is associated with higher Apnea/Hypopnea Index (AHI) (49±11 vs 24±8 episodes/hour with P=0.0001). The severity of nocturia is proportional to the severity of OSA with a positive predictive value of 71%. Intermittent nocturnal hypoxemia causes peripheral axonal damage with subsequent urgency incontinence. There is correlation between severity of OAB and the severity of OSA especially when the latter is moderate or severe. An odds ratio of 0.45 (CI95%: 0.18-0.71) is found for ED in patients who don't have OSA, associating the latter to an increased risk of ED. Intermittent nocturnal hypoxemia, the decrease in the levels of nitric oxide, and the increase in blood pressure and levels of endothelin 1 contribute to the development of ED. An early treatment of OSA with continuous positive airway pressure (CPAP) may allow a partial but significant control of urinary symptoms and erectile dysfunction associated with OSA. OSA is associated with urinary tract symptoms (nocturia and OAB) and erectile dysfunction. The severity of associated symptoms is related to the severity of OSA. Urinary and sexual troubles are reversible after treatment of OSA by CPAP. OSA research is reasonable in case of pathologic nocturia or ED with loss of morning erections.

Aberrant Awake Spontaneous Brain Activity in Obstructive Sleep Apnea: A Review Focused on Resting-State EEG and Resting-State fMRI.

As one of the most common sleep-related respiratory disorders, obstructive sleep apnea (OSA) is characterized by excessive snoring, repetitive apnea, arousal, sleep fragmentation, and intermittent nocturnal hypoxemia. Focused on the resting-state brain imaging techniques, we reviewed the OSA-related resting-state electroencephalogram and resting-state functional magnetic resonance imaging (rsfMRI) studies. Compared with the healthy control group, patients with OSA presented increased frontal and central δ/θ powers during resting-state wakefulness, and their slow-wave activity showed a positive correlation with apnea–hypopnea index. For rsfMRI, the prefrontal cortex and insula may be the vital regions for OSA and are strongly related to the severity of the disease. Meanwhile, some large-scale brain networks, such as the default-mode network, salience network, and central executive network, play pivotal roles in the pathology of OSA. We then discussed the contribution of resting-state brain imaging as an evaluation approach for disease interventions. Finally, we briefly introduced the effects of OSA-related physiological and mental diseases and discussed some future research directions from the perspective of resting-state brain imaging.

Increased platelet activation in sleep apnea subjects with intermittent hypoxemia

Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia. Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry. Epinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state. Increased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease. NCT00859950.

Nocturnal Hypoxemia Is Associated with Altered Parahippocampal Functional Brain Connectivity in Older Adults at Risk for Dementia.

Obstructive sleep apnea is associated with an increased risk of developing mild cognitive impairment and dementia. Intermittent nocturnal hypoxemia in obstructive sleep apnea is associated with brain changes in key regions that underpin memory. To determine whether older adults with severe nocturnal hypoxemia would exhibit reduced functional connectivity within these regions, with associated deficits in memory. Seventy-two participants 51 years and over underwent polysomnography with continuous blood oxygen saturation recorded via oximetry. The oxygen desaturation index (ODI, 3% dips in oxygen levels per hour) was the primary outcome measure. ODI was split into tertiles, with analyses comparing the lowest and highest tertiles (N = 48). Thirty-five of the 48 participants from these two tertiles had mild cognitive impairment. Participants also underwent resting-state fMRI and comprehensive neuropsychological, medical, and psychiatric assessment. The highest ODI tertile group demonstrated significantly reduced connectivity between the left and right parahippocampal cortex, relative to the lowest ODI tertile group (t(42) = -3.26, p = 0.041, beta = -1.99).The highest ODI tertile group also had poorer working memory performance. In the highest ODI tertile group only, higher left-right parahippocampal functional connectivity was associated with poorer visual memory recall (between-groups z = -2.93, p = 0.0034). Older adults with severe nocturnal hypoxemia demonstrate impaired functional connectivity in medial temporal structures, key regions involved in sleep memory processing and implicated in dementia pathophysiology. Oxygen desaturation and functional connectivity in these individuals each relate to cognitive performance. Research is now required to further elucidate these findings.

Therapeutic effects of CPAP on cognitive impairments associated with OSA.

Obstructive sleep apnea (OSA) is the most common type of sleep apnea and caused by upper airway obstructions. Clinically, patients with OSA characteristically experience intermittent nocturnal hypoxemia and impaired sleep quality. Cognitive impairments are commonly seen in patients with an OSA diagnosis. A literature search on OSA, cognitive impairments and CPAP was performed with various electronic databases including Medline, EMBASE and Google Scholar. The chosen evidence was limited to human subject studies only, and reports on either central sleep apnea or non-classified sleep apnea were excluded. Available evidence has been systemically reviewed to ascertain what types of cognitive impairments are related to OSA as well as the pathological connections. In addition, effectiveness of continuous positive airway pressure (CPAP) was analyzed as a standard therapy for improving cognitive performance in patients with OSA. The review contributed in: (1) delineating OSA as a risk factor of cognitive impairments; (2) enumerating cognitive impairments seen in patients with OSA; (3) substantiating the relation between OSA and cognitive impairments from the pathological perspective of AD biomarkers; and (4) revealing duration of CPAP is crucial for its therapeutic effects on improving cognitive performance in patients with OSA.

Plasma α-synuclein levels are increased in patients with obstructive sleep apnea syndrome.

ObjectiveObstructive sleep apnea syndrome (OSAS) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma α‐synuclein levels and hypoxia in the patients with OSAS.MethodsWe recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total α‐synuclein and phosphorylated α‐synuclein levels were measured by ELISA kits.ResultsThe OSAS patients had significant higher levels of plasma total α‐synuclein and phosphorylated α‐synuclein levels. Both of the above indexes were positively correlated with the apnea–hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations.InterpretationThis study suggests that chronic intermittent hypoxia can increase the α‐synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.

Intermittent Hypoxemia in Patients with Heart Failure with Preserved Ejection Fraction

Objective To investigate the characteristics of nocturnal intermittent hypoxemia in patients with heart failure(HF) with preserved ejection fraction(HFpEF).Methods Patients(n=854) who completed sleep test and echocardiography from January 2011 to December 2014 were retrospectively studied. HF patients with an ejection fraction(EF) of ≥50% were included in the HFpEF group(n=112) while HF patients with an EF of <50% included in the group of HF patients with reduced EF(HFrEF)(n=104). Respiratory events and minimum nocturnal saturation(minSaO2) were recorded by home sleep testing,and the percentage of total sleep time with saturation <90%(T90SaO2) were calculated.Results Compared with patients without HF,subjects with HFpEF and HFrEF had more breathing events[13(5,29)/h vs. 18(6,36)/h,and 21(8,45)/h,P<0.001],lower minSaO2[85(80,87)% vs. 82(77,86)% and 83(78,87)%,P<0.001] and relatively longer T90SaO2[3.0(0.4,15.5)% vs. 6.0(1.5,24.8)% and 6.7(1.3,14.4)%,P<0.001]. The HFpEF group had significantly higher odds of moderate-severe hypoxemia(minSaO2<85%) during sleep than those without HF(OR=2.02,95%CI=1.34-3.11,P<0.001),with the significance persisting after adjusting for covariates including age,gender,hypertension,diabetes,coronary heart disease,renal dysfunction,and smoking(OR=1.85,95%CI=1.20-2.90,P=0.006).Conclusion Patients with HFpEF have frequent nocturnal intermittent hypoxemia,which warrants further investigations to evaluate if remission of night-time hypoxemia may improve long-term prognosis in this cohort.

Airway inflammation in patients affected by obstructive sleep apnea

Obstructive sleep apnea (OSA) is characterised by repetitive episodes of upper airway occlusion during sleep. OSA has been shown to be associated with a variable degree of nasal inflammation, uvula mucosal congestion and airway hyperreactivity. The upper airway inflammation, whose clinical importance is uncertain, is characterised by leukocytes infiltration and interstitial oedema. In addition, recent data has shown the presence of neutrophilic inflammation in the lower airways. The current opinion is that airway inflammation is caused by the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involves the intermittent nocturnal hypoxemia that through the phenomenon of the ischemia-reperfusion injury may induce the production of oxygen free radicals and therefore cause local and systemic inflammation. Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesised in the visceral adipose cells. Several authors stress the role of circulating and local inflammatory mediators, such as pro-inflammatory cytokines, exhaled nitric oxide, pentane and 8-isoprostane as the determinants of inflammation in OSA.

Clinical Correlates of Sleep-Disordered Breathing and Nocturnal Hypoxemia in Sickle Cell Disease

Cardiopulmonary complications are the major cause of morbidity and mortality in sickle cell disease (SCD). In the general population, obstructive sleep apnea (OSA), has been associated with daytime sleepiness and increased risk for all-cause morbidity and mortality due to cardiovascular disease, systemic hypertension, pulmonary hypertension, and stroke-all of which are complications of SCD. Multiple small cohort studies have demonstrated that sleep-disordered breathing (SDB) is common among children and adolescents with SCD, but we do not understand the risk factors and clinical consequences of SDB in this population. Additionally, the prevalence of SDB in adults with SCD is unknown. We hypothesized that SDB and nocturnal hypoxemia are common across the lifespan in SCD and that the clinical presentation of SDB among SCD patients may be different from the general population without SCD. We performed a retrospective chart review of the overnight sleep studies performed at Boston Medical Center to gain greater understanding of the risk factors and clinical correlates of SDB in this population. We identified 29 patients with SCD who had a full polysomnogram for clinical purposes between 2012-2015. We obtained medical histories and steady state laboratory test results on these patients. Symptoms of SDB were assessed via the Epworth Sleepiness Scale (ESS). We evaluated the sleep studies for apneas, hypopneas, snoring, and the degree of hypoxemia. Data were analyzed using SAS, version 9.3. The 29 patients had a median age of 15.3 years (range 4 to 60), 66% were male, 43% were overweight or obese, and 86% had either the HbSS or HbSβ0 genotype 82% of these patients had at least one prior episode of the acute chest syndrome and 46% carried a diagnosis of asthma. Overall, the group had a median hemoglobin concentration of 9.7 (range 6.1-13.3) g/dL and median reticulocyte percentage of 7.3% (range 2.8-23.3%). 28% of the subjects had elevated scores on the ESS reflective of increased daytime sleepiness. Moderate to severe snoring, typically associated with OSA in the general population, was observed in 35% of patients. However, 48% of our patients met diagnostic criteria for OSA (defined as an apnea/hypopnea index [AHI] > 5), suggesting that a history of snoring may not be a sensitive marker to identify OSA risk in this population. Additionally, 17% of patients were considered to have nocturnal hypoxemia defined as greater than 5% of total sleep time with an oxygen saturation below 90%; this included 13% of those with OSA and 21% of those without OSA (p=0.65). In total, 38% of SCD patients referred for a sleep study had neither OSA nor nocturnal hypoxemia.Comparing the adults (n=14) and children (n=15) showed some differences across the lifespan. AHI and ESS scores were significantly higher in adults, while the resting oxygen saturation was lower. HbSS or HbSβ0 patients typically had lower BMIs but similar findings on sleep studies compared to those with HbSC disease. Those with moderate to severe OSA were older (p=0.006), more likely to be overweight or obese and had both significantly higher hemoglobin concentrations (p=0.04) and lower reticulocyte counts (p=0.03) compared to those without moderate-severe OSA. Nocturnal hypoxemia was associated with a history of asthma (p=0.01), an increased reticulocyte percentage (p=0.005) and white blood cell count (p=0.006), and a reduced awake oxygen saturation (p=0.002) compared to those without significant nocturnal hypoxemia. Interestingly, increased age, BMI, or ESS scores were not associated with nocturnal hypoxemia.Results from this small retrospective cohort study suggest that SDB in SCD is more complex than in the general population. SDB in SCD is common and not solely due to OSA. Additionally, traditional risk factors for OSA such as snoring and daytime sleepiness may not be present in SCD patients who have polysomnographic abnormalities. While this study needs to be confirmed with a larger prospective screening study, our findings suggest that intermittent nocturnal hypoxemia is potentially a modifiable cardiovascular risk factor in SCD. DisclosuresKlings:Pfizer: Consultancy; Actelion Pharmaceuticals: Research Funding.

Usefulness of reinforcing interventions on continuous positive airway pressure compliance.

BackgroundObstructive sleep apnea (OSA) is a high prevalence sleep disorder characterized by upper airway obstruction during sleep, nocturnal intermittent hypoxemia, poor sleep quality, risk for cardiovascular and metabolic diseases. The adherence to CPAP is the key for an effective management of these patients.The aim of the study was to assess the adherence to CPAP therapy with and without early reinforcing interventions, consisting of motivational reinforcement and technical support in the first month of therapy.MethodsForty patients with OSA undergoing counseling and a one year follow-up on a quarterly basis were included in the study. Twenty subjects (intervention group) underwent reinforcing interventions with telephone interviews in the first month of therapy, and twenty (control group) remained without reinforcing interventions. The two populations were homogeneous for age, severity of illness and BMI.ResultsDuring the first month, intervention group patients showed a higher number of nights with a device use ≥4 hours. Average treatment adherence in the first month (days of therapy with at least 4 hours per night on the total number of days from device delivery) was 77.5% in the intervention group and 55.7% in the control group (p = 0.022). At one year the differences between the two groups were not significant.ConclusionsOur findings suggest that it is important that adequate time and effort is spent to ensure patient comfort at the time of CPAP therapy start to optimize acceptance and adherence to treatment, and suggest that it is necessary to maintain reinforcing interventions over time.

Le syndrome d’apnées obstructives du sommeil : une cause de troubles cognitifs chez les personnes âgées ?

Obstructive sleep apnea syndrome is a chronic disease characterized by repeated upper airway obstructions during sleep, resulting in fragmented sleep with arousals, nocturnal intermittent hypoxemia and diurnal dysfunctions. Despite its high prevalence in elderly, sleep apnea syndrome seems to be underestimated and difficult to be recognized because of the lack of clinical symptoms specificity in this population. Among the numerous consequences of the obstructive sleep apnea syndrome, cognitive impairment prevails on the attention, executive functions and memory. Neuroimaging studies in human and experimental models allowed to highlight neural correlates of these cognitive dysfunctions in obstructive sleep apnea syndrome. The obstructive sleep apnea syndrome with cognitive impairment shares some features with Alzheimer's disease, involving genetic predisposition ApoE4, hippocampus and synaptic plasticity abnormalities. In this context, the question arises whether obstructive sleep apnea syndrome is a possible etiological or aggravating factor of cognitive decline in elderly with mild cognitive impairment or Alzheimer's disease. Although there are conflicting results in studies evaluating therapeutic efficiency of continuous positive air pressure, obstructive sleep apnea syndrome seems nevertheless as a correctable factor, at least for its impact on some cognitive consequences. Looking for sleep apnea syndrome in elderly with cognitive decline should be considered in a global, diagnosis and therapeutic management.

Nocturnal intermittent hypoxemia: utility for the evaluation of severity sleep apnea and cardiovascular comorbidity

Introduction Sleep apnea-hypopnea syndrome (SAHS) is a complex public health problem causing increased risk of cardiovascular diseases. Traditionally, evaluation of the severity of the disease is based on Apnea-Hypopnea Index (AHI). Oxygen desaturation index (ODI) could be a good parameter for the evaluation of the severity of SAHS and its potential cardiovascular consequences. TARGET: the aim of the present study was to examine the relationships between the overnight oxygen desaturation index (ODI), parameters sleep study and cardiovascular events in a sample of patients evaluated in the Unit Respiratory Sleep Disorders. Materials and methods We performed a retrospective study collecting data from 105 patients evaluated in the Unit Respiratory Sleep Disorders. In this study, diagnostic polygraphy recordings were retrospectively analysed. It was studied the correlation of ODI with AHI and the presence or absence of comorbidity, defining this as the presence of ischemic heart disease and / or arrhythmias and / or acute stroke. Results Among the 105 studied patients, 17(16%) had comorbidity. ODI values were correlated with AHI with a correlation coefficient of 0.87. There was a significant relationship between the severity of ODI and the presence of comorbidity (p 0.038), and also a significant association between the AHI and the presence of comorbidity (p 0.024). Conclusion ODI appears a good parameter to estimate the severity of OSA and may be associated with more prevalence of ischemic heart disease, arrhythmias and acute stroke. Acknowledgements Acknowledgements to authors of the study.