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To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules. 488 patients were studied; the majority were male (68%) with a mean age of 50 yrs, mean AHI of 23 events/hour, and mean BMI of 32 kg/m2. In multivariable linear regression models, all three adhesion molecules were significantly associated with BMI (E-selectin p

Background Distinct symptom subtypes are found in patients with OSA. The association between these subtypes and neurocognitive function is unclear. Objective: The purposes of this study were to assess whether OSA symptom subtypes are present in a cohort of Canadian patients with suspected OSA and evaluate the relationship between subtypes and neurocognitive function. Methods Patients with suspected OSA who completed a symptom questionnaire and underwent testing for OSA were included. Symptom subtypes were identified using latent class analysis. Associations between subtypes and neurocognitive outcomes (Montreal Cognitive Assessment [MoCA], Rey Auditory Verbal Learning Test [RAVLT], Wechsler Adult Intelligence Scale [WAIS-IV], Digit-Symbol Coding subtest [DSC]) were assessed using analysis of covariance (ANCOVA), controlling for relevant covariates. Results Four symptom subtypes were identified in patients with OSA (oxygen desaturation index ≥5 events/hour). Three were similar to prior studies, including the Excessively Sleepy (N=405), Disturbed Sleep (N=382) and Minimally Symptomatic (N=280), and one was a novel subtype in our sample defined as Excessively Sleepy with Disturbed Sleep (N=247). After covariate adjustment, statistically significant differences among subtypes (p=0.037) and among subtypes and patients without OSA (p=0.044) were observed in DSC scores; the Minimally Symptomatic subtype had evidence of higher DSC scores than all other groups, including non-OSA patients. No differences were seen in MoCA or RAVLT. Conclusions Results support the existence of previously identified OSA symptom subtypes of excessively sleepy, disturbed sleep and minimally symptomatic in a clinical sample from Canada. Subtypes were not consistently associated with neurocognitive function across multiple instruments.

Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43–38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.

Rationale: Obstructive sleep apnea (OSA) is associated with an increased risk of mild cognitive impairment (MCI) within the general population. However, MCI risk in sleep-clinic populations of pati...

Obstructive sleep apnea (OSA) is the most common respiratory disorder of sleep. The vast majority (>80%) of adults with moderate to severe OSA remain undiagnosed. The economic costs associated with OSA are substantial for both the individual and society as a whole; expenses are likely to be underestimated given that the disease remains undiagnosed in such a large percentage of individuals. The economic burden of motor vehicle collisions related to OSA alone is significant; it is estimated that 810,000 collisions and 1400 fatalities from car crashes in the United States were attributable to sleep apnea in 2000. The many health consequences of OSA include daytime sleepiness, reduced quality of life, decreased learning skills, and importantly, neurocognitive impairments that include impaired episodic memory, executive function, attention and visuospatial cognitive functions. Untreated OSA leads to numerous medical problems such as cardiovascular diseases that can potentially increase healthcare utilization. Untreated patients with sleep apnea consume a disproportionate amount of healthcare resources, expenditures that decrease after treatment. The gold-standard management of OSA remains treatment with CPAP (Continuous Positive Airway Pressure), which is effective in eliminating sleep fragmentation and preserving nocturnal oxygenation, thereby improving daytime sleepiness and quality of life. However, its impacts in reversing neurocognitive function are still uncertain. A significant impediment to CPAP effectiveness is low adherence rates (ranges from 50% to 75%). It is commonly accepted that CPAP improves excessive drowsiness; hence meliorates attention, and accumulating data suggest that CPAP improves a variety of other outcomes such as the risk of motor vehicle crashes.

To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin).A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules.488 patients were studied; the majority were male (68%) with a mean age of 50 yrs, mean AHI of 23 events/hour, and mean BMI of 32 kg/mAlthough all three adhesion molecules were associated with BMI, only E-selectin was independently associated with OSA severity. Future studies are needed to determine the clinical significance of the relationship between E-selectin and OSA.

Background Air pollution and OSA are independently associated with systemic inflammation, but it is unknown if these exposures interact to influence systemic inflammation. Research Question The study objective was to determine the relative importance of these factors and their combined potential to influence systemic inflammation in patients under assessment for sleep ailments. Study Design and Methods A total of 315 patients contributed data, including a questionnaire, polysomnogram, and morning serum IL-6 and IL-10 concentrations. For each patient, residential annual average air pollution exposure (nitrogen dioxide [NO2], black carbon [BC], and particulate matter with an aerodynamic diameter ≤ 2.5 μm [PM2.5]) was estimated with a land use regression model. Linear regression modeling was used adjusting for age, sex, apnea-hypopnea index, BMI, smoking, socioeconomic status, and comorbidities. Results In adjusted models, quartile 4 PM2.5 exposure (compared with quartiles 1-3) was associated with increased IL-6 and IL-10 concentrations (estimated adjusted, 7.1 pg/mL [95% CI, 2.5-11.7; P Interpretation Long-term residential PM2.5 exposure was associated with increased IL-6 and IL-10 concentrations in patients evaluated for suspected OSA. BC exposure was also associated with increased IL-6 but only in the subgroup of patients with moderate to severe OSA. These data suggest the potential for joint effects of moderate to severe OSA and air pollution on systemic inflammation.

Study objectivesUntreated obstructive sleep apnea (OSA) patients have an increased risk of cardiovascular disease (CVD). Adhesion molecules, including soluble E-selectin (sE-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1), are associated with incident CVD. We hypothesized that specific genetic variants will be associated with plasma levels of adhesion molecules in suspected OSA patients. We also hypothesized that there may be an interaction between these variants and OSA.MethodsWe measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms.ResultsThe most significant association was between the ABO rs579459 polymorphism and sE-selectin levels (P = 7×10-21), with the major allele T associated with higher levels. The direction of effect and proportion of the variance in sE-selectin levels accounted for by rs579459 (16%) was consistent with estimates from non-OSA cohorts. In a multivariate regression analysis, addition of rs579459 improved the model performance in predicting sE-selectin levels. Three polymorphisms were nominally associated with sICAM-1 levels but none with sVCAM-1 levels. The combination of severe OSA and two rs579459 T alleles identified a group of patients with high sE-selectin levels; however, the increase in sE-selectin levels associated with severe OSA was greater in patients without two T alleles (P = 0.05 test for interaction).ConclusionsThese genetic polymorphisms may help to identify patients at greatest risk of incident CVD and may help in developing a more precision-based approach to OSA care.

Untreated Obstructive sleep apnea (OSA) is associated with an increased risk of cardiometabolic diseases such as diabetes and myocardial infarction. However, it is difficult to predict which patients are at particularly high risk. This systematic review aimed to identify potentially useful circulating biomarkers that could predict cardiometabolic complications in OSA. We searched Cochrane (EBM), EMBASE, Medline, PubMed, and Web of Science databases. Search concepts included: "Obstructive Sleep Apnea", "Biomarkers" and "Risk-Stratification". Manuscripts were included if they studied adults with OSA, circulating (blood) markers, and relationships with clinical outcomes. After screening, 10 were included. Studies addressed cardiovascular disease, type 2 diabetes, end-stage renal disease and metabolic syndrome. In general, levels of inflammatory markers, adhesion molecules, and vascular proteins were associated with the presence of cardiometabolic disease in OSA patients. Although studies regarding prognostic circulating biomarkers in OSA are limited, a number of potentially promising biomarkers were identified in our review. However, more research is needed using prospective cohorts to determine which biomarkers are most robustly associated with and useful in predicting future cardiovascular and metabolic sequelae in OSA patients. Identification of such biomarkers could guide more selective and targeted therapy for OSA in an emerging era of precision-based medicine.

CPAP is used as the first-line treatment for patients with severe OSA, but this machine is not always feasible to use on the long term. We performed a clinical trial to determine whether patients with OSA could use a mandibular advancement splint (MAS) as a short-term treatment alternative to CPAP.Twenty-two patients adherent with CPAP therapy were recruited to the study. Each patient used the MAS for approximately 4 months. The transition between CPAP to MAS was gradual, and patients were asked to start using MAS together with CPAP during the MAS titration until subjective improvement or maximum mandibular advancement was achieved. Sleepiness (ESS), quality of life (SAQLI), and polysomnography were recorded prior to and after MAS titration. Patients recorded CPAP or MAS usage for the following 3 months.Seven women and 12 men with a mean age of 53.8 (± 12.1) years and mean body mass index of 28.1 (± 4.8) kg/m² completed the clinical trial. Prior to MAS, CPAP adherence was 5.8 h/night. AHI decreased significantly with MAS use compared to baseline (30.7 ± 23.1 vs 13.2 ± 11; p0.01). Fourteen patients (74%) had50% decrease in their AHI, while 2 patients had an increase in their AHI. There were no significant differences in SAQLI between MAS and CPAP treatment, while ESS decreased significantly on MAS. MAS self-reported usage was correlated with treatment efficacy (r = 0.52; p0.05). Seventy-five percent of the patients reported being sufficiently satisfied with MAS to continue to use it as an alternative short-term therapy.MAS partially or completely reduced sleep disordered breathing in the majority of selected, successfully CPAP-treated severe OSA patients. Many patients can probably effectively use MAS as a short-term treatment alternative to CPAP.

Objective We sought to determine the clinical implications, predictors and patterns of residual sleep apnea on continuous positive airway pressure (CPAP) treatment in patients with moderate-to-severe obstructive sleep apnea (OSA). Methods We performed a post hoc secondary analysis of data from a previously reported randomized trial. Sleepy patients with a high risk of moderate-to-severe OSA identified by a diagnostic algorithm were randomly assigned to standard CPAP titration during polysomnography (PSG) or ambulatory titration using auto-CPAP and home sleep testing. We observed them for 3 months and measured apnea–hypopnea index (AHI) on CPAP, Epworth sleepiness scale (ESS), sleep apnea quality of life index (SAQLI), CPAP pressure and objective CPAP compliance. Results Sixty-one patients were randomized, 30 to the PSG group and 31 to the ambulatory group. Fifteen patients (25%) had residual sleep apnea (AHI >10/h on CPAP) with similar proportions in the PSG (7/30) and ambulatory (8/31) groups. Baseline variables including age, body mass index (BMI), ESS, SAQLI, respiratory disturbance index (RDI) and CPAP pressure did not differ between the groups. Outcomes including compliance were worse in patients with residual sleep apnea. Periodic breathing was prevalent among patients with residual sleep apnea. Conclusions Residual sleep apnea is common in patients with moderate-to-severe OSA, despite careful CPAP titration, and is associated with worse outcomes.

It is increasingly recognized that disruption of sleep and reduced amounts of sleep can have significant adverse cardiovascular consequences. For example, obstructive sleep apnea (OSA) is a common underdiagnosed disorder characterized by recurrent nocturnal asphyxia resulting from repetitive collapse of the upper airway; this leads to repetitive episodes of nocturnal hypoxemia and arousal from sleep. Risk factors for disease include obesity, increased age, male sex, and family history. In epidemiologic studies, OSA appears to be an independent risk factor for cardiovascular disease (CVD), and treatment is associated with better outcomes. Habitual short sleep duration is common in today's society. In epidemiologic studies, short sleep duration is associated with a number of adverse health effects, including all-cause mortality, weight gain, and incident CVD. Given the links between sleep disorders and adverse health outcomes, obtaining adequate quality and amounts of sleep should be considered a component of a healthy lifestyle, similar to good diet and exercise.

The impact of obstructive sleep apnea (OSA) on the development of atherosclerotic cardiovascular disease (CVD) in the absence of overt CVD or risk factors is unclear. Our purpose was to assess whether patients with OSA without overt CVD or risk factors have subclinical atherosclerosis as evaluated by carotid intima medial thickness (CIMT) compared to matched controls. We measured CIMT in patients >40 years old, who underwent polysomnography for suspected OSA and did not have a history of CVD or risk factors (smoking, hypertension, diabetes, hyperlipidemia). OSA severity was classified according to apnea–hypopnea index. Serum levels of high-sensitivity C-reactive protein, fibrinogen, and lipids were assessed and relationships with OSA severity explored. CIMT measurements from patients with OSA were compared those of to age-, gender-, and BMI-matched controls from a community-based cohort without known CVD or OSA. Fifty-one patients were studied. Of these, patients with severe OSA had an increased CIMT compared to patients without OSA, but the relationship was not significant after controlling for age (p = 0.10). However, 37 patients had OSA and were matched to 105 controls. CIMT was significantly increased in OSA patients versus controls (0.77 vs. 0.68 mm, p = 0.03). The difference between patients and controls was greater for patients with severe OSA (0.83 vs. 0.71 mm) than for patients with mild-to-moderate OSA (0.71 vs. 0.67 mm). Patients with OSA but without a history of or risk factors for CVD have increased CIMT compared to a BMI-, age-, and gender-matched cohort. This provides evidence that OSA is an independent risk factor for the development of CVD.

STUDY OBJECTIVES First-line therapy for patients with moderate to severe obstructive sleep apnea (OSA) is positive airway pressure (PAP). Although PAP is a highly efficacious treatment, adherence to PAP is still a substantial clinical problem. The objective of this study was to determine whether PAP adherence can be improved with a telemedicine monitoring system. DESIGN A nonblinded, single-center, randomized controlled trial that compared standard PAP treatment versus PAP treatment and a telemedicine monitoring system SETTING University sleep disorders program in British Columbia, Canada PATIENTS Adult patients (≥ 19 yr of age) with moderate to severe OSA (apnea hypopnea index (AHI) ≥ 15 events/hr determined by polysomnography) prescribed PAP INTERVENTIONS: Patients were randomized to either standard care with an autotitrating PAP machine or an autotitrating PAP machine that transmitted physiologic information (i.e., adherence, air leak, residual AHI) daily to a website that could be reviewed. If problems were identified from information from the website, the patient was contacted by telephone as necessary. MEASUREMENTS PAP adherence after 3 mo, subjective sleep quality, and side effects RESULTS Seventy-five patients were enrolled; 39 were randomized to telemedicine and 36 to standard care. The mean age ± standard deviation (SD) was 53.5 ± 11.2 yr, mean AHI was 41.6 ± 22.1 events/hr, and 80% of patients were male. After 3 mo, mean PAP adherence was significantly greater in the telemedicine arm (191 min per day) versus the standard arm (105 min per day; mean difference = 87 min, 95% confidence interval (CI): 25-148 min, P = 0.006, unpaired t test). On days when PAP was used, mean adherence was 321 min in the telemedicine arm and 207 min in the standard arm (difference = 113 min, 95% CI: 62-164 min, P < 0.0001). Significant independent predictors of adherence included age, baseline Epworth Sleepiness Scale score, and use of telemedicine. On average, an additional 67 min of technician time was spent on patients in the telemedicine arm compared with the standard arm (P = 0.0001). CONCLUSIONS PAP adherence can be improved with the use of a web-based telemedicine system at the initiation of treatment.

Polysomnography (PSG), despite limited availability and high cost, is currently recommended for diagnosis of obstructive sleep apnea and titration of effective continuous positive airway pressure (CPAP).To test the utility of a diagnostic algorithm in conjunction with ambulatory CPAP titration in initial management of obstructive sleep apnea.A randomized, controlled, open-label trial that compared standard PSG with ambulatory CPAP titration in high-risk patients identified by a diagnostic algorithm.A tertiary referral sleep disorders program in Vancouver, British Columbia, Canada.68 patients with a high pretest probability of moderate to severe obstructive sleep apnea (apnea-hypopnea index [AHI]15 episodes/h) identified by sequential application of the Epworth Sleepiness Scale (ESS) score, Sleep Apnea Clinical Score, and overnight oximetry.Patients were randomly assigned to PSG or ambulatory titration by using a combination of auto-CPAP and overnight oximetry. They were observed for 3 months.Apnea-hypopnea index on CPAP, ESS score, quality of life, and CPAP adherence.The PSG and ambulatory groups had similar median BMI (38 kg/m2), age (55 years), ESS score (14 points), and respiratory disturbance index (31 episodes of respiratory disturbance/h). Each episode is determined by a computer algorithm based on analysis of oxygen saturation measured by pulse oximetry. After 3 months, there were no differences in the primary outcome, AHI on CPAP (median, 3.2 vs. 2.5; difference, 0.8/h [95% CI, -0.9 to 2.3]) (P = 0.31), between the PSG and ambulatory groups, or in the secondary outcomes, ESS score, Sleep Apnea Quality of Life Index, and CPAP. Adherence to CPAP therapy was better in the ambulatory group than in the PSG group (median, 5.4 vs. 6.0; difference, -1.12 h/night [CI, -2.0 to 0.2]) (P = 0.021).In the initial management of patients with a high probability of obstructive sleep apnea, PSG confers no advantage over the ambulatory approach in terms of diagnosis and CPAP titration. The ambulatory approach may improve adherence to treatment. When access to PSG is inadequate, the ambulatory approach can be used to expedite management of patients most in need of treatment.

Many patients with obstructive sleep apnea (OSA) participate in the work force. However, the impact of OSA and sleepiness on work performance is unclear.To address this issue, we administered the Epworth Sleepiness Scale (ESS), the Work Limitations Questionnaire (WLQ), and an occupational survey to patients undergoing full-night polysomnography for the investigation of sleep-disordered breathing. Of 498 patients enrolled in the study, 428 (86.0%) completed the questionnaires. Their mean age+/-standard deviation (SD) was 49+/-12 years, mean body mass index (BMI) was 31+/-7 kg/m(2) mean apnea hypopnea index (AHI) was 21+/-22 events/h, and mean ESS score was 10+/-5. Subjects worked a mean of 39+/-18 h per week. The first 100 patients to complete the survey were followed up at two years.In the group as a whole, there was no significant relationship between severity of OSA and the four dimensions of work limitation. However, in blue-collar workers, significant differences were detected between patients with mild OSA (AHI 5-15/h) and those with severe OSA (AHI30/h) with respect to time management (limited 23.1% of the time vs. 43.8%, p=0.05) and mental/personnel interactions (17.9% vs. 33.0%, p=0.05). In contrast, there were strong associations between subjective sleepiness (as assessed by the ESS) and three of the four scales of work limitation. That is, patients with an ESS of 5 had much less work limitation compared to those with an ESS 18 in terms of time management (19.7% vs. 38.6 %, p0.001), mental-interpersonal relationships (15.5% vs. 36.0%, p0.001) and work output (16.8% vs. 36.0%; p0.001). Of the group followed up, 49 returned surveys and 33 who were using continuous positive airway pressure (CPAP) showed significant improvements between the initial and second follow-up in time management (26% vs. 9%, p=0.0005), mental-interpersonal relationships (16% vs. 11.0%, p=0.014) and work output (18% vs. 10%; p0.009).We have demonstrated a clear relationship between excessive sleepiness and decreased work productivity in a population referred for suspected sleep-disordered breathing. Screening for sleepiness and sleep-disordered breathing in the workplace has the potential to identify a reversible cause of low work productivity.