Nocturnal SaO2 Research Articles

KL‑6, ET‑1 and S100A9 levels in patients with idiopathic pulmonary fibrosis and obstructive sleep apnea.

Obstructive sleep apnea (OSA) and idiopathic pulmonary fibrosis (IPF) frequently coexist. Elevated levels of Krebs von den Lungen-6 (KL-6), endothelin-1 (ET-1) and S100 calcium-binding protein A9 (S100A9) have been observed in patients with IPF, suggesting their potential role as biomarkers for lung fibrosis. The aim of the present study was to measure the levels of KL-6, ET-1 and S100A9 in patients with IPF-OSA and to test the potential of these biomarkers as a characteristic OSA signature with diagnostic and prognostic potential for IPF. A total of 55 subjects with newly-diagnosed IPF participated in the present cross-sectional study. In addition to performing overnight attended polysomnography and pulmonary function tests, serum and bronchoalveolar lavage (BAL) levels of KL-6, along with serum levels of ET-1 and S100A9, were also assessed. A total of 15 patients with IPF and 40 patients with IPF-OSA were included. Age, sex, comorbidities and pulmonary function tests did not differ between the groups. Although there was no significant difference between groups in the levels of KL-6, ET-1 and S100A9 (P>0.05), the serum ET-1 levels tended to be elevated in patients with OSA-IPF compared with patients with IPF (1.78 vs. 1.07 pg/ml; P=0.06). Additionally, a significant association was observed between serum KL-6 levels and the severity of IPF, and also between BAL KL-6 levels and nocturnal mean SaO2 levels, even after taking into account factors such as obesity and smoking. S100A9 levels were associated with the oxygen desaturation index, even after adjustments for obesity, smoking and the gender-age-physiology index, only in the IPF-OSA group. Conclusively, the present findings suggested significant associations between serum ET-1, S100A9 and BAL KL-6 levels and specific OSA severity parameters in the IPF-OSA group. This evidence suggested that these molecules could serve as biomarkers for the identification of patients with IPF-OSA, offering a distinct OSA signature that has diagnostic and potential treatment value. Larger studies are crucial to substantiate the present findings and reinforce this hypothesis.

The Influence of Comorbidities on Chemokine and Cytokine Profile in Obstructive Sleep Apnea Patients: Preliminary Results.

Obstructive sleep apnea (OSA) is frequently associated with a chronic inflammatory state and cardiovascular/metabolic complications. The aim of this study was to evaluate the influence of certain comorbidities on a panel of 45 chemokines and cytokines in OSA patients with special regard to their possible association with cardiovascular diseases. This cross-sectional study was performed on 61 newly diagnosed OSA patients. For the measurement of the plasma concentration of chemokines and cytokines, the magnetic bead-based multiplex assay for the Luminex® platform was used. In the patients with concomitant COPD, there were increased levels of pro-inflammatory cytokines (CCL11, CD-40 ligand) and decreased anti-inflammatory cytokine (IL-10), while in diabetes, there were increased levels of pro-inflammatory cytokines (IL-6, TRIAL). Obesity was associated with increased levels of both pro-inflammatory (IL-13) and anti-inflammatory (IL-1RA) cytokines. Hypertension was associated with increased levels of both pro-inflammatory (CCL3) and anti-inflammatory (IL-10) cytokines. Increased daytime pCO2, low mean nocturnal SaO2, and the oxygen desaturation index were associated with increased levels of pro-inflammatory cytokines (CXCL1, PDGF-AB, TNF-α, and IL-15). In OSA patients with concomitant diabetes and COPD, elevated levels of certain pro-inflammatory and decreased levels of certain anti-inflammatory cytokines may favor the persistence of a chronic inflammatory state with further consequences. Nocturnal hypoxemia, frequent episodes of desaturation, and increased daytime pCO2 are factors contributing to the chronic inflammatory state in OSA patients.

Nocturnal nasal high-flow oxygen therapy in elderly patients with concomitant chronic obstructive pulmonary disease and obstructive sleep apnea

PurposeThe coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is known as “overlap syndrome” (OS). Patients with OS are usually older than patients with OSA alone, suffer from more profound oxygen desaturation during the obstructive events often accompanied by sustained nocturnal hypoventilation. Although oxygen-enriched positive airway pressure (PAP) is the treatment of choice in these patients, this therapy is often poorly tolerated particularly by the elderly. The aim of this study was to assess the usefulness of nocturnal oxygen therapy via nasal high flow (NHF-OT) as a possible alternative to PAP in patients with OS.MethodsPatients > 65 years old with OS and nocturnal respiratory failure (time spent below SaO2 90% (T90) > 30%) had cardio-respiratory monitoring performed at baseline, during NHF-OT, or during conventional oxygen therapy (COT).ResultsA total of 40 patients were enrolled in the study. NHF-OT significantly reduced the apnea–hypopnea index (AHI) in all patients compared to baseline and COT. The mean basal AHI was 25.4 ± 8.6. During COT and NHF-OT, the AHI was 19.4 ± 7 and 5.4 ± 4.6, respectively (P < 0.001) and 19 patients reached an AHI < 5 during NHF-OT. The mean nocturnal SaO2% was 86.2 ± 2.6 at baseline and at equivalent FiO2 it significantly increased to 91.8 ± 2.4 during COT and to 93.9 ± 2.5 during NHF-OT (P < 0.001). The T90% was 48.7 ± 20.1 at baseline, 16.8 ± 11.7 during COT, and 8.8 ± 8.0 during NHF-OT (P < 0.001).ConclusionsIn elderly patients with OS, nocturnal treatment with NHF-OT significantly reduces obstructive episodes and improves oxygenation. As the treatment is generally well tolerated compared to PAP, NHF-OT may be a possible alternative therapy in this subgroup of patients.

Determinants of response to hypercapnia and to progressive and transient hypoxia in obstructive sleep apnea patients.

The knowledge regarding the control of breathing during wakefulness in patients affected by obstructive sleep apnea (OSAS) is still challenging. The aim of this study is firstly to analyze hypoxic and hypercapnic ventilatory response in OSA patients in comparison to controls and secondly, to investigate correlations between chemosensivity and both lung function tests, such as arterial blood gas analysis and spirometric parameters, and clinical characteristics, such as age and BMI. Seventeen never treated OSA patients (16M; 53±13.2 years; BMI=34.5±8.1; AHI=45±14.7) underwent nocturnal cardiopulmonary monitoring test, complete lung function tests (spirometry, lung volumes and arterial blood gas analysis on room air). Read's rebreathing test was used to evaluate hypercapnic ventilatory response (HVR<inf>CO2</inf>); hypoxic ventilatory response (HVR<inf>O2</inf>) was studied through progressive and transient methods. The response was expressed in terms of slope of linear regression for HVR<inf>CO2</inf> and of hyperbolic curve for HVR<inf>O2</inf> between minute ventilation (VE) or mean inspiratory flow (VT/Ti) and PetCO<inf>2</inf> or PetO<inf>2</inf>. The OSA group showed increased transient, but not progressive, HVR<inf>O2</inf> and a lower HVR<inf>CO2</inf>. A lower HVR<inf>CO2</inf> was predicted by greater values of BMI (P<0.01). Progressive HVR<inf>O2</inf> increased with age and lower FEV<inf>1</inf>/VC, while transient HVR<inf>O2</inf> (P<0.05) was inversely correlated with the nocturnal lowest SaO<inf>2</inf> (P<0.01). Nocturnal intermittent hypoxic stimuli increases daytime glomic reactivity to transient hypoxia, while BMI is the main independent determinants of the bulbar response to hypercapnia in normocapnic OSAS patients.

Clinical presentation and comorbidities of obstructive sleep apnea-COPD overlap syndrome.

More advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as 'overlap syndrome' (OVS), impacts on cardiovascular health. To investigate differences between patients with OVS and those with moderate-to-severe OSA alone. A cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017. Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health. 46,786 patients had moderate-to-severe OSA. Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS. A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P <0.02). Similarly, a lower proportion of OVS patients (35.6% versus 39.4%, respectively; P <0.01) experienced sleepiness while driving. In contrast, 63.5% of the OVS population experienced nocturia compared to 58.0% of the OSA population (P<0.01). Apnea hypopnea index (36 [25; 52] vs 33.1 [23.3; 50]), oxygen desaturation index (28 [15; 48] vs 25.2 [14; 45]) and mean nocturnal SaO2 (92 [90; 93.8] vs 93 [91.3; 94]) were significantly more altered in the OVS group. Associated COPD had no effect on the prevalence of hypertension and stroke. After controlling for main confounders, COPD severity was associated in a dose-response relationship with a higher prevalence of coronary heart disease, heart failure and peripheral arteriopathy. In adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy.

0433 IMPACT OF PULMONARY PHYSIOLOGIC AND METABOLIC FACTORS ON ARTERIAL CARBON DIOXIDE LEVELS IN OBESITY HYPOVENTILATION SYNDROME

Although the relationship of respiratory physiology and arterial pCO2 (PaCO2) has been characterized in sleep disordered breathing (SDB), less is known about factors affecting PaCO2 levels in the obesity-hypoventilation syndrome (OHS). We hypothesized that metabolic and mechanical factors would be positively associated with PaCO2 levels in OHS whereas SDB variables would not. In this retrospective study involving adult patients without neuromuscular disease or sedative use, the following variables were collected: 1) SDB - Apnea/hypopnea index (AHI), percent sleep time <90% (PSAT<90), nocturnal SaO2 (nSaO2); 2) Metabolic - bicarbonate (HCO3), fasting blood glucose (FBS), creatinine, body surface area (BSA), metabolic syndrome, chronic kidney disease (CKD); and 3) Mechanical factors - body mass index (BMI), neck circumference, forced vital capacity (FVC), forced expiratory volume in first second (FEV1) and pulmonary disease. The final sample included 81 patients with mean[±SD] age of 62 ± 11 years, 53% female, median[IQR] BMI 39.7kg/m2[34.7,45.5], BSA 2.3m2[2.1,2.5], 95% with OHS and PaCO2 50.0 ± 4mmHg. Median AHI was 28.1[16.8,64.4], PSAT<90% 18.1[3.3,52.2], nSaO2 91.0%[89.0,93.2], HCO3 28.5meq/L[25.0,32.0] and FBS 111.5mg/dl[97.0,165.5]. Metabolic syndrome and pulmonary disease were present in 48.8% and 56.3% respectively. Mean FVC was 65.8 ± 20.9% and FEV1/FVC 73.6 ± 11.2% of predicted. Univariate linear regression showed that pulmonary disease (coefficient, 95%CI) (3.49,0.77-6.22), metabolic syndrome (2.92,0.18-5.65), BMI (0.15,0.03-0.28), HCO3 (0.31,0.07-0.56) and FBS (0.04,0.01-0.06) were positively associated with PaCO2 at p<0.05. Nocturnal SaO2 (-0.35,-0.63 - -0.08) was negatively associated while AHI (-0.01,-0.06-0.03) and PSAT<90% (0.04,-0.01–0.09) were not associated with PaCO2. Presence of pulmonary disease, metabolic syndrome, higher BMI, bicarbonate and FBS were positively associated with PaCO2 in OHS patients with concomitant OSA. In contrast, SDB variables were negatively associated or not associated at all. These results highlight the greater importance of underlying pulmonary-metabolic factors, relative to SDB factors, in the development of hypercapnia in OHS patient with OSA.

Maternal-infant outcome of patients with OSAHS and gestational hypertension treated by CPAP

Objective:To explore the clinical characteristics of obstructive sleep apnea hypopnea syndrome (OSAHS) diagnosed during pregnancy.To explore the effect on maternal and infant after treated with CPAP.Method:Data of 117 patients with OSAHS diagnosed by nocturnal blood oxygen saturation (SaO₂) monitoring and PSG during pregnancy were analyzed retrospectively. All the 117 patients were voluntary and divided into intervention group [received continuous positive airway pressure (CPAP) treatment with good compliance under informed consent and conventional drug] 70 cases and control group(received conventional drug) 47 cases. Record the relevant data during the treatment about maternal and infant.Result:There was no statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with mild OSAHS (P> 0.05), there was no statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with moderate OSAHS (P> 0.05) and there were statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with severe OSAHS (P< 0.05 or P< 0.01). There was no statistical significance on the difference of asphyxia neonatorum, fetal growth restriction and fetal distress in the pregnant women with mild OSAHS (P> 0.05), there were statistical significance on the difference of fetal growth restriction and fetal distress in the pregnant women with moderate OSAHS (P< 0.05), and there were statistical significance on the difference of asphyxia neonatorum, fetal growth restriction and fetal distress in the pregnant women with severe OSAHS (P< 0.05 or P< 0.01).Conclusion:Pregnant women who have OSAHS risk factors should be paid attention to during the perinatal care and nocturnal SaO₂ monitoring or PSG should be performed in the suspected OSAHS patients. Strongly advise that those serious OSAHS patients should be treated by CPAP early before delivery. CPAP was a safe and effective treatment to OSAHS patients in pregnancy.

Abstract WMP114: The Role of Hypoxemia and Hypercapnia as Risk Factors for Childhood Stroke

Background: Risk factors for childhood stroke differ significantly from those in adults. Obstructive Sleep Apnea (OSA) is an independent risk factor for adult stroke. Children with Sickle Cell Disease (SCD) have a higher prevalence of OSA than the general pediatric population, and nocturnal hypoxemia in these patients is independently predictive of future CNS events. Hypoxemia and hypercapnia secondary to OSA result in a pro-inflammatory and prothrombotic cascade associated with metabolic dysregulation and endothelial dysfunction. Hypothesis: We hypothesized that OSA, hypoxemia and/or hypercapnia are associated with an increased stroke risk in a pediatric population. Methods: Clinical and radiologic data of consented children seen in the stroke program from 1992-2014 with clinically indicated sleep study/polysomnography (PSG) were retrospectively reviewed and analyzed. Results: Thirty-one children (31/947; 14 male, mean age at PSG 8.4 years) were identified. Twenty-three children had arterial ischemic stroke (AIS) (mean age 7.6 years, SEM 0.99 years) and eight were non-stroke arteriopathy patients (mean age 10.5 years, SEM 1.16 years). Children diagnosed with AIS had significantly higher prevalence of OSA than children with no stroke (69% vs. 25%, p=0.0429) regardless of the timing of sleep study (11/15, 73.3% OSA post-stroke diagnosis and 5/8, 62.5% OSA pre-stroke diagnosis). AIS patients had significantly lower minimum SaO2 values overnight (83.19% vs. 94.56%, p=0.0072), and higher overnight mean end tidal (et) and transcutaneous (tc) CO2 levels (et CO2 42.78 vs. 41.75 mmHg, p=0.4940; tc CO2 42.08 vs. 39.67 mmHg, p=0.3544). Primary risk factors of AIS in children with clinically indicated PSG included 3 moyamoya (33% with OSA), 8 cardiac (63% with OSA), 5 SCD (83% with OSA), and 7 other (86% with OSA). Cardiac patients had the lowest nocturnal SaO2 and highest CO2 levels when compared to moyamoya, SCD and others. Conclusions: In our study, children with AIS were more likely to have OSA and nocturnal hypoxemia, highlighting these as potential risk factors for stroke in childhood. Future prospective studies are required to explore the relationship between stroke, hypoxemia and hypercapnia.

Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level.

Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its genetic contribution has never been studied. Our recent study suggests nocturnal SaO2 is heritable. We performed linkage analysis, association analysis and haplotype analysis of average nocturnal oxyhaemoglobin saturation in participants in the Cleveland Family Study (CFS), followed by gene-based association and additional tests in four independent samples. Linkage analysis identified a peak (LOD = 4.29) on chromosome 8p23. Follow-up association analysis identified two haplotypes in angiopoietin-2 (ANGPT2) that significantly contributed to the variation of SaO2 (P = 8 × 10-5) and accounted for a portion of the linkage evidence. Gene-based association analysis replicated the association of ANGPT2 and nocturnal SaO2. A rare missense SNP rs200291021 in ANGPT2 was associated with serum angiopoietin-2 level (P = 1.29 × 10-4), which was associated with SaO2 (P = 0.002). Our study provides the first evidence for the association of ANGPT2, a gene previously implicated in acute lung injury syndromes, with nocturnal SaO2, suggesting that this gene has a broad range of effects on gas exchange, including influencing oxygenation during sleep.

Treatment and prevention of inflammatory responses and oxidative stress in patients with obstructive sleep apnea hypopnea syndrome using Chinese herbal medicines.

The present study aimed to investigate the therapeutic effects of Chinese herbal medicines for the treatment and prevention of inflammatory responses and oxidative stress in obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 60 patients with OSAHS were randomly divided into two groups (n=30/group): The experimental group, who received the conventional treatment + oral administration of the traditional Chinese herbal formula, Jiawei Di Tan Tang; and the control group, who received the conventional treatment only. OSAHS patients were included in the current study if they presented with snoring and had an apnea-hypopnea index (AHI) of >30 in a polysomnography study, without comorbidities. The therapeutic course lasted 12 weeks in both groups. Alterations to the mean clinical symptom score, Epworth sleepiness scale (ESS) and AHI scores, lowest nocturnal blood oxygen saturation (SaO2) and the serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) prior to and following treatment were observed. The mean clinical symptom score was significantly decreased in the experimental group post-treatment compared with the control group (P<0.05). In addition, the clinical symptoms in the experimental group were significantly improved following treatment compared with pre-treatment symptoms (P<0.05). Furthermore, the ESS and AHI scores, lowest nocturnal SaO2 and serum levels of SOD, MDA, IL-6, TNF-α and CRP were significantly improved in the experimental group post-treatment compared with the control group (P<0.05). These parameters in the experimental group were also significantly improved post-treatment compared with those pre-treatment (P<0.05). The results of the present study suggested that oral administration of the traditional Chinese herbal formula Jiawei Di Tan Tang was able to attenuate oxidative stress and inflammatory responses in patients with OSAHS, and thus may relieve their clinical symptoms.

Relationship Between Chronic Intermittent Hypoxia and Intraoperative Mean Arterial Pressure in Obstructive Sleep Apnea Patients Having Laparoscopic Bariatric Surgery

Background Recurrent nocturnal hypoxemia in obstructive sleep apnea enhances sympathetic function, decreases baroreceptor sensitivity, and weakens peripheral vascular responses to adrenergic signals. The authors hypothesized that the percentage of total sleep time spent at oxyhemoglobin saturation (SaO2) less than 90% and minimum nocturnal SaO2 on preoperative polysomnography are associated with decreased intraoperative mean arterial pressure. Methods The authors examined the records of all patients who had laparoscopic bariatric surgery at Cleveland Clinic between 2005 and 2009 and an available polysomnography study. The authors assessed the relationships between the percentage of total sleep time spent at SaO2 less than 90% and minimum nocturnal SaO2, and the time-weighted average of mean arterial pressure. The authors used multivariable regression models to adjust for prespecified clinical confounders. Results Two hundred eighty-one patients were included in the analysis. The average change in the time-weighted average of mean arterial pressure was -0.02 (97.5% CI, -0.08, 0.04) mmHg for each 1% absolute increase in the percentage of sleep time spent at SaO2 less than 90% (P = 0.50). The average change was -0.13 (97.5% CI, -0.27, 0.01) mmHg, for each 1% absolute decrease in the minimum SaO2 (P = 0.04 > significance criterion of 0.025, Bonferroni correction). An unplanned analysis estimated 1% absolute decrease in minimum SaO2 was associated with -0.22 (98.75% CI, -0.39, -0.04) mmHg, change in mean arterial pressure (P = 0.002) in the time period between endotracheal intubation and trocar insertion. Conclusion Recurrent nocturnal hypoxemia in obstructive sleep apnea is not a risk marker for intraoperative hypotension.

Higher nocturnal and awake oxygen saturations in children with sickle cell disease receiving hydroxyurea therapy.

Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented. To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease. This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU. Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P < 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002). In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.

Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort.

Previous data on the associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are conflicting. We examined the prospective associations of nocturnal oxygen saturation (SaO2 ) and cardiovascular disease (CVD) risk factors with carotid intima-media thickness (IMT) and plaques. We used data on 689 Wisconsin sleep cohort participants who had baseline overnight polysomnography followed by carotid ultrasonography a mean (SD) of 7.8 (2.5) years later. Far wall common carotid IMT was measured using B-mode ultrasound. Bilateral common, bifurcation and internal carotid artery segments were evaluated for plaque score. Participants (8) were aged 56 years (55% male); 32% had hypertension and mean body mass index (BMI) was 31 (7) kg m(2). Mean and minimum nocturnal SaO2 were 95% (2) and 86% (7), respectively. Mean percentage sleep time with SaO2 < 90% was 2% (8). Both mean (odds ratio [OR]: 0.60 lower plaque count per 5% higher mean SaO2, 95% confidence interval [CI]: 0.38-0.96, P = 0.033) and minimum SaO2 (OR: 0.88 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.80-0.97, P = 0.013) predicted carotid plaque score after adjusting for age, sex and BMI. Minimum SaO2 predicted future plaque score after adding adjustment for traditional CVD risk factors (OR: 0.90 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.81-0.99, P = 0.038). Mean SaO2 was not associated with carotid IMT after CVD risk factor adjustment. We conclude that minimum nocturnal SaO2 is an independent predictor of future carotid plaque burden. Other nocturnal SaO2 parameters are not associated with future carotid IMT or plaques after adjusting for traditional CVD risk factors.

Effects of exercise and weight loss in older adults with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is prevalent among older individuals and is linked to increased cardiovascular disease morbidity. This study examined the change in OSA severity after exercise training and dietary-induced weight loss in older adults and the association of the changes in OSA severity, body composition, and aerobic capacity with arterial distensibility. Obese adults (n = 25) with OSA, age 60 yr or older, were instructed to participate in supervised exercise (3 d·wk) and follow a calorie-restricted diet. Baseline assessments of OSA parameters, body weight and composition, aerobic capacity, and arterial distensibility were repeated at 12 wk. Nineteen participants completed the intervention. At 12 wk, there were reductions in body weight (-9%) and percentage of total body fat (-5%) and trunk fat (-8%) whereas aerobic capacity improved by 20% (all P < 0.01). The apnea-hypopnea index decreased by 10 events per hour (P < 0.01) and nocturnal SaO2 (mean SaO2) improved from 94.9% at baseline to 95.2% after intervention (P = 0.01). Arterial distensibility for the group was not different from that at baseline (P = 0.99), yet individual changes in distensibility were associated with the change in nocturnal desaturations (r = -0.49, P = 0.03) but not with the change in body weight, apnea-hypopnea index, or aerobic capacity. The severity of OSA was reduced after an exercise and weight loss program among older adults, suggesting that this lifestyle approach may be an effective first-line nonsurgical and nonpharmacological treatment for older patients with OSA.

Relationship between chronic intermittent hypoxia and intraoperative mean arterial pressure in obstructive sleep apnea patients having laparoscopic bariatric surgery.

Recurrent nocturnal hypoxemia in obstructive sleep apnea enhances sympathetic function, decreases baroreceptor sensitivity, and weakens peripheral vascular responses to adrenergic signals. The authors hypothesized that the percentage of total sleep time spent at oxyhemoglobin saturation (SaO2) less than 90% and minimum nocturnal SaO2 on preoperative polysomnography are associated with decreased intraoperative mean arterial pressure. The authors examined the records of all patients who had laparoscopic bariatric surgery at Cleveland Clinic between 2005 and 2009 and an available polysomnography study. The authors assessed the relationships between the percentage of total sleep time spent at SaO2 less than 90% and minimum nocturnal SaO2, and the time-weighted average of mean arterial pressure. The authors used multivariable regression models to adjust for prespecified clinical confounders. Two hundred eighty-one patients were included in the analysis. The average change in the time-weighted average of mean arterial pressure was -0.02 (97.5% CI, -0.08, 0.04) mmHg for each 1% absolute increase in the percentage of sleep time spent at SaO2 less than 90% (P = 0.50). The average change was -0.13 (97.5% CI, -0.27, 0.01) mmHg, for each 1% absolute decrease in the minimum SaO2 (P = 0.04 > significance criterion of 0.025, Bonferroni correction). An unplanned analysis estimated 1% absolute decrease in minimum SaO2 was associated with -0.22 (98.75% CI, -0.39, -0.04) mmHg, change in mean arterial pressure (P = 0.002) in the time period between endotracheal intubation and trocar insertion. Recurrent nocturnal hypoxemia in obstructive sleep apnea is not a risk marker for intraoperative hypotension.

Usefulness of Oximetry for Sleep Apnea Screening in Frail Hospitalized Elderly

BackgroundSleep Apnea Syndrome (SAS) prevalence increases with age. In the elderly, symptoms are less specific (falls, cognitive or functional decline, polymedication). Polysomnography, the gold standard technique to diagnose SAS, is challenged by sleep laboratories' waiting lists and high associated costs. Nocturnal oximetry is an easy-to-use tool widely available outside the sleep medicine field identifying intermittent hypoxia, the landmark of SAS. It might be an interesting and easy way to screen for SAS in the functionally and cognitively impaired elderly living in long-term care settings. ObjectivesThe primary goal of this study was to assess the accuracy of the variability index of nocturnal pulse oximetry to detect moderate to severe SAS in patients older than 75 hospitalized in stable condition. The secondary goals were to assess the accuracy of the other indices of pulse oximetry (oxygen desaturation index [ODI]), and to determine the prevalence of moderate to severe SAS in our population. MethodsIn-hospital sleep studies with simultaneous respiratory polygraphy and nocturnal pulse oximetry were performed. Comorbidities were assessed by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) in association with a comprehensive geriatric assessment. ResultsEighty patients (mean age 85.3 ± 5.3 years) were included. Seventy-two percent of the patients exhibited moderate to severe SAS (95% CI 58.9–82.9), including 59.5% of severe SAS (apnea + hypopnea index >30/hour). SaO2 variability index using a threshold of 0.51, the sensitivity and negative predictive value (NPV) were 100%. With a value above 0.88, positive predictive value and specificity were high (respectively 96.6% and 93.8%). ODI of 3% or higher and 4% or higher were highly specific but less sensitive. ConclusionPrevalence of moderate to severe SAS in multimorbid hospitalized elderly patients is high. Automatic analysis of the variability of nocturnal SaO2 is a reliable tool for geriatricians to screen and rule out moderate to severe SAS. Our study suggests an important role of pulse oximetry as the first step in the diagnostic strategy for moderate to severe SAS in this population.

Soluble ligand CD40 and uric acid as markers of atheromatosis in patients with obstructive sleep apnea.

The aim of the study was to evaluate the risk of atheromatosis in patients with obstructive sleep apnea (OSA), as based on the concentration of the pro-atherogenic soluble CD40L ligand (sCD40L) in relation to the level of uric acid. The serum levels of sCD40L and uric acid were measured in 79 OSA patients (mean apnea/hypopnea index - AHI 34.4 ± 20.9) and in 40 healthy controls. We found that sCD40L was higher in the OSA patients with hyperuricemia than that in the patients with uric acid in the normal range (sCD40L: 9.0 ng/ml vs. 8.0 ng/ml, respectively, p < 0.05). There was a positive association of sCD40L with AHI (p = 0.01) and a negative one with the mean minimal nocturnal SaO₂(p < 0.05). Uric acid correlated negatively with the mean and minimal SaO₂and positively with the oxygen desaturation index (p < 0.05). OSA patients with hyperuricemia also had a higher prevalence of hypertension and ischemic heart disease. We conclude that OSA patients with increased uric acid concentration have increased risk of atheromatosis, as indicated by a higher level of soluble pro-atherogenic ligand CD40, and a higher prevalence of cardiovascular adverse events.

Sleep, Respiration, and Pain

Sleep, Respiration, and Pain

Glucose Tolerance and Weight Loss in Obese Women with Obstructive Sleep Apnea

BackgroundThe association of obstructive sleep apnea (OSA) with glucose intolerance and the beneficial effect of lifestyle intervention have been poorly investigated in women particularly before menopausal status. The study explored 1) whether OSA is associated with impaired glucose homeostasis in obese non diabetic premenopausal and menopausal women and 2) the effects of a 3- month lifestyle intervention on glucose homeostasis in OSA women.Design and MethodsWe consecutively recruited 98 obese women (39 premenopausal) from those referred for a weight loss intervention. Ambulatory nocturnal polysomnography, body composition, oral glucose tolerance test, insulin sensitivity and β cell function were assessed before and after intervention.Results41% of premenopausal and 64% of menopausal women had OSA which was associated with worse glucose homeostasis before menopausal status. Mean and minimal nocturnal oxygen saturation (SaO2) was associated with neck/height ratio (NHR), independently of total and central obesity. Mean and minimal nocturnal SaO2 and NHR were correlated with insulin sensitivity and fasting glucose. In multivariate analyses, nocturnal mean SaO2 was negatively and independently correlated with fasting glucose (p<0.0001) and NHR with insulin sensitivity (p<0.0001). In OSA women, the intervention induced a 5% weight reduction and a significant increase in minimal nocturnal SaO2, insulin sensitivity and β cell function. Changes in fasting glucose and insulin sensitivity were associated with those in minimal nocturnal SaO2 (p<0.05) and not with weight loss.ConclusionsIn obese women, glucose homeostasis worsens due to nocturnal hypoxia and increased neck circumference through mechanisms partially independent of obesity. OSA is more clearly associated with glucose intolerance in premenopausal than in menopausal women. In OSA women, the improvement of nocturnal hypoxia induced by lifestyle modifications is associated with that of glucose homeostasis.

Sleep-disordered breathing and oxidative stress in preclinical chronic mountain sickness (excessive erythrocytosis)

Chronic mountain sickness (CMS) is considered to be a loss of ventilatory acclimatization to high altitude (>2500m) resulting in marked arterial hypoxemia and polycythemia. This case–control study explores the possibility that sleep-disordered breathing (SDB) and associated oxidative stress contribute to the etiology of CMS. Nocturnal respiratory and SaO2 patterns were measured using standard polysomnography techniques and compared between male high-altitude residents (aged 18–25) with preclinical CMS (excessive erythrocytosis (EE), n=20) and controls (n=19). Measures of oxidative stress and antioxidant status included isoprostanes (8-iso-PGF2alpha), superoxide dismutase and ascorbic acid. EE cases had a greater apnea–hypopnea index, a higher frequency of apneas (central and obstructive) and hypopneas during REM sleep, and lower nocturnal SaO2 compared to controls. 8-iso-PGF2alpha was greater in EE than controls, negatively associated with nocturnal SaO2, and positively associated with hemoglobin concentration. Mild sleep-disordered breathing and oxidative stress are evident in preclinical CMS, suggesting that the resolution of nocturnal hypoxemia or antioxidant treatment may prevent disease progression.