Can the complete blood count be used as a reliable screening tool for obstructive sleep apnea?

PURPOSE: Since hypoxia increases erythropoietin production and inflammation, the complete blood count (CBC) has been proposed as an inexpensive alternative for obstructive sleep apnea (OSA) screening. The objective of this study was to determine whether or not intermittent hypoxia and OSA severity, as measured by the mean oxygen saturation (SpO2) and apnea-hypopnea index (AHI), affect parameters measured by the CBC. METHODS: This retrospective study included a total of 941 surgical patients who had a pre-operative home sleep study. The pre-operative CBC was extracted from the electronic patient records. Patients were stratified according to their AHI scores, into mild (AHI ≥ 5 - < 15), moderate (AHI ≥ 15 - < 30), and severe (AHI ≥ 30) OSA groups. RESULTS: There were 244 patients without OSA, 294 with mild, 223 with moderate, and 180 with severe OSA. Our analysis showed that hemoglobin (P = 0.010), hematocrit (P = 0.027), and basophils (P = 0.006) showed significant changes among the different severities of OSA. For mean SpO2, there were negative associations with body mass index (r = - 0.287; P < 0.001), age (r = - 0.077; P = 0.021), hemoglobin (r = - 0.208; P < 0.001), hematocrit (r = - 0.220; P < 0.001), red blood cells (r = - 0.107; P = 0.001), mean corpuscular volume (MCV) (r = - 0.159; P < 0.001), mean corpuscular hemoglobin (r = - 0.142; P < 0.001), and basophils (r = - 0.091; P = 0.007). All analyzed parameters remained within normal clinical range. Multivariable regression identified hemoglobin, MCV, and basophils to be independent predictors of mean SpO2 and AHI. CONCLUSION: Hemoglobin, MCV, and basophils were independently associated with intermittent hypoxia defined by mean SpO2 and AHI. Adding CBC parameters to other screening tools for OSA may have additional value due to its association with changes in mean SpO2.

Co-activation of rhythms during alpha band oscillations as an interictal biomarker of exploding head syndrome.

BACKGROUND: Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients' quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear. METHODS AND RESULTS: In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied. CONCLUSION: Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.

Neutrophil-to-lymphocyte ratio decreases in obstructive sleep apnea treated with mandibular advancement devices.

PURPOSE: Obstructive sleep apnea has been associated with chronic inflammation triggered by nocturnal hypoxemia. The neutrophil-to-lymphocyte ratio (NLR) is a measure of subclinical systemic inflammation. We hypothesize that NLR levels would improve as chronic inflammation diminishes in obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs). METHODS: We studied patients with OSA who were treated with MAD as a first-line treatment or because they could not tolerate CPAP. We obtained pre-treatment and post-treatment complete blood counts. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the CBCs. Patients with other conditions known to affect NLR were excluded from the study. RESULTS: We compared the values of NLR and oxygen desaturation index (ODI) before and after treatment with MAD in 22 patients who met inclusion criteria and completed the study protocol. There was a significant difference in NLR before and after treatment (p = 0.01). There was also a significant difference in the 3% ODI and 4% ODI before and after treatment with MAD (p = 0.014, 0.007), respectively. A subgroup analysis compared NLR in two groups of patients, the optimally treated and suboptimally treated. There was a significant decrease in the NLR in the optimally treated group (n = 10) (p < 0.01), whereas it did not change in the suboptimally treated group (n = 12) (p = 0.349). CONCLUSION: The neutrophil-to-lymphocyte ratio may be useful in documenting improvement in inflammation for OSA patients treated with mandibular advancement devices. Our results specifically suggest that the NLR values are associated with the decrease in the ODI.

A matched cohort study of postoperative outcomes in obstructive sleep apnea: could preoperative diagnosis and treatment prevent complications?

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of postoperative complications. The authors investigated whether preoperative diagnosis and prescription of continuous positive airway pressure therapy reduces these risks. METHODS: Matched cohort analysis of polysomnography data and Manitoban health administrative data (1987 to 2008). Postoperative outcomes in adult OSA patients up to 5 yr before (undiagnosed OSA, n = 1,571), and any time after (diagnosed OSA, n = 2,640) polysomnography and prescription of continuous positive airway pressure therapy for a new diagnosis of OSA, were compared with controls at low risk of having sleep apnea (n = 16,277). Controls were matched by exact procedure, indication, and approximate date of surgery. Procedures used to treat sleep apnea were excluded. Follow-up was at least 7 postoperative days. Results were reported as odds ratio (95% CI) for OSA or subgroup versus controls. RESULTS: In multivariate analyses, the risk of respiratory complications (2.08 [1.35 to 3.19], P < 0.001) was similarly increased for both undiagnosed and diagnosed OSA. The risk of cardiovascular complications, primarily cardiac arrest and shock, was significantly different (P = 0.009) between undiagnosed OSA (2.20 [1.16 to 4.17], P = 0.02) and diagnosed OSA patients (0.75 [0.43 to 1.28], P = 0.29). For both outcomes, OSA severity, type of surgery, age, and other comorbidities were also important risk modifiers. CONCLUSIONS: Diagnosis of OSA and prescription of continuous positive airway pressure therapy were associated with a reduction in postoperative cardiovascular complications. Despite limitations in the data, these results could be used to justify and inform large efficacy trials of perioperative continuous positive airway pressure therapy in OSA patients.

Age modulates the predictive value of self-reported sleepiness for all-cause mortality risk: insights from a comprehensive national database of veterans.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is prevalent and overwhelmingly stems from disturbed sleep. We hypothesized that age modulates the association between EDS and increased all-cause mortality. METHODS: We utilized the Veterans' Health Administration data from 1999-2022. We enrolled participants with sleep related ICD9/10 codes or sleep services. A natural language processing (NLP) pipeline was developed and validated to extract the Epworth Sleepiness Scale (ESS) as a self-reported tool to measure EDS from physician progress notes. The NLP's accuracy was assessed through manual annotation of 470 notes. Participants were categorized into Normal-ESS, n-ESS, (ESS 0-10) and high-ESS, h-ESS, (ESS 11-24). We created three age groups: < 50 years; 50 to < 65 years; and ≥ 65 years. The adjusted odds ratio (aOR) of mortality was calculated for age, BMI, sex, race, ethnicity, and the Charlson Comorbidity Index (CCI), using n-ESS as the reference. Subsequently, we conducted age stratified analysis. RESULTS: The first ESS records were extracted from 423,087 veterans with a mean age of 54.8 (±14.6), mean BMI of 32.6 (±6.2), and 90.5% male. The aOR across all ages was 17% higher (1.15,1.19) in the h-ESS category. The aORs only became statistically significant for individuals aged ≥ 50 years in the h-ESS compared to the n-ESS category (< 50 years: 1.02 [0.96,1.08], 50 to < 65 years 1.13[1.10,1.16]; ≥ 65 years: 1.25 [1.21-1.28]). CONCLUSIONS: High ESS, predicted increased mortality only in participants aged 50 and older. Further research is required to identify this differential behavior in relation to age.

The use of combined thermal/pressure polyvinylidene fluoride film airflow sensor in polysomnography.

BACKGROUND: The technologies recommended by the American Academy of Sleep Medicine (AASM) to monitor airflow in polysomnography (PSG) include the simultaneous monitoring of two physical variables: air temperature (for thermal airflow) and air pressure (for nasal pressure). To comply with airflow monitoring standards in the sleep lab setting thus often requires the patient to wear two sensors under the nose during testing. We hypothesized that a single combined thermal/pressure sensor using polyvinylidene fluoride (PVDF) film responsive to both airflow temperature and pressure would be effective in documenting abnormal breathing events during sleep. METHODS: Sixty patients undergoing routine PSG testing to rule out obstructive sleep apnea at two different sleep laboratories were asked to wear a third PVDF airflow sensor in addition to the traditional thermal sensor and pressure sensor. Apnea and hypopnea events were scored by the sleep lab technologists using the AASM guidelines (CMS option) using the thermal sensor for apnea and the pressure sensor for hypopnea (scorer 1). The digital PSG data were also forwarded to an outside registered polysomnographic technologist for scoring of respiratory events detected in the PVDF airflow channels (scorer 2). RESULTS: The Pearson correlation coefficient, r, between apnea and hypopnea indices obtained using the AASM sensors and the combined PVDF sensor was almost unity for the four calculated indices: apnea-hypopnea index (0.990), obstructive apnea index (0.992), hypopnea index (0.958), and central apnea index (1.0). The slope of the four relationships was virtually unity and the coefficient of determination (r (2)) was also close to 1. The results of intraclass correlation coefficients (>0.95) and Bland-Altman plots also provide excellent agreement between the combined PVDF sensor and the AASM sensors. CONCLUSION: The indices used to calculate apnea severity obtained with the combined PVDF thermal and pressure sensor were equivalent to those obtained using AASM-recommended sensors.

Comparison of Ring Pulse Oximetry Using Reflective Photoplethysmography and PSG in the Detection of OSA in Chinese Adults: A Pilot Study.

Objective: A novel ring-worn oximeter (Circul) uses reflective photoplethysmography and automated signal processing to calculate oxygen desaturations. We evaluated the ability of Circul to detect obstructive sleep apnea in Chinese adults. Methods: We recruited 207 Chinese Han subjects: 70% males, mean age 48.2±14.7 years, mean BMI 27.6±4.8 kg/m2 and mean AHI 28.6±25.2 events/h. All participants underwent simultaneous polysomnography (PSG) and Circul testing in a sleep laboratory. Oxygen desaturation index (ODI), mean oxygen saturation (MSpO2), cumulative time at SpO2<90% (CT90), cumulative percentage of sleep time spent with SpO2<90% (CT90/TST) were derived and compared for the Circul and the PSG. Results: The ODI was 25.3±24.5 events/h using PSG and 22.2±24.5 events/h using Circul (P<0.0001), with an intraclass correlation coefficient (ICC) of 0.884. CT90 and CT90/TST between the two methods were not different; the MSpO2 level calculated by PSG was slightly lower than Circul, 95.0% (93.0-96.0%) vs 95.3% (93.9-96.6%), P<0.0001. Circul-ODI had a good correlation (r=0.91, p<0.0001) and close agreement with PSG-AHI (Bland-Altman analysis: Mean Difference 6.4, 95% CI -14.8 to 27.5 events/h). Using a threshold of AHI ≥5 events/h, the Circul had 87% sensitivity, 83% specificity, 5.09 positive likelihood ratio (LR+), 86% accuracy, and 0.929 area under the curve (AUC). Conclusion: Circul ring pulse oximetry can detect OSA with reasonable reliability. The Circul system is a reliable and comfortable choice for OSA assessment.

Prediction of obstructive sleep apnea syndrome in a large Greek population.

PURPOSE: We aimed to evaluate the predictive value of anthropometric measurements and self-reported symptoms of obstructive sleep apnea syndrome (OSAS) in a large number of not yet diagnosed or treated patients. Commonly used clinical indices were used to derive a prediction formula that could identify patients at low and high risk for OSAS. METHODS: Two thousand six hundred ninety patients with suspected OSAS were enrolled. We obtained weight; height; neck, waist, and hip circumference; and a measure of subjective sleepiness (Epworth sleepiness scale--ESS) prior to diagnostic polysomnography. Excessive daytime sleepiness severity (EDS) was coded as follows: 0 for ESS ≤ 3 (normal), 1 for ESS score 4-9 (normal to mild sleepiness), 2 for score 10-16 (moderate to severe sleepiness), and 3 for score >16 (severe sleepiness). Multivariate linear and logistic regression analysis was used to identify independent predictors of apnea-hypopnea index (AHI) and derive a prediction formula. RESULTS: Neck circumference (NC) in centimeters, body mass index (BMI) in kilograms per square meter, sleepiness as a code indicating EDS severity, and gender as a constant were significant predictors for AHI. The derived formula was: AHIpred = NC × 0.84 + EDS × 7.78 + BMI × 0.91 - [8.2 × gender constant (1 or 2) + 37]. The probability that this equation predicts AHI greater than 15 correctly was 78%. CONCLUSIONS: Gender, BMI, NC, and sleepiness were significant clinical predictors of OSAS in Greek subjects. Such a prediction formula can play a role in prioritizing patients for PSG evaluation, diagnosis, and initiation of treatment.

Comorbid Insomnia and Sleep Apnea: mechanisms and implications of an underrecognized and misinterpreted sleep disorder.

Sleep-disordered breathing (SDB) and insomnia have long been recognized as important sleep disrupters often associated with increased morbidity and mortality. Although they are often seen as divergent conditions, mainly because their cardinal symptoms (excessive daytime sleepiness, and sleep loss) differ, these two sleep disorders present with many common symptoms, which may hinder diagnosis and treatment. In addition to possible bidirectional pathways between SDB and insomnia, other factors such as circadian timing may play a role. In this paper, we review the mechanisms, differential clinical aspects, and implications of Comorbid Insomnia and Sleep Apnea, sometimes termed COMISA.

Sleep in the Aging Population.

There are normal changes to sleep architecture throughout the lifespan. There is not, however, a decreased need for sleep and sleep disturbance is not an inherent part of the aging process. Sleep disturbance is common in older adults because aging is associated with an increasing prevalence of multimorbidity, polypharmacy, psychosocial factors affecting sleep, and certain primary sleep disorders. It is also associated with morbidity and mortality. Because many older adults have several factors from different domains affecting their sleep, these complaints are best approached as a multifactorial geriatric health condition, necessitating a multifaceted treatment approach.

Flow limitation/obstruction with recovery breath (FLOW) event for improved scoring of mild obstructive sleep apnea without electroencephalography.

OBJECTIVE: Apnea/hypopnea index (AHI), especially without arousal criteria, does not adequately risk stratify patients with mild obstructive sleep apnea (OSA). We describe and test scoring reliability of an event, Flow Limitation/Obstruction With recovery breath (FLOW), representing obstructive airflow disruptions using only pressure transducer and snore signals available without electroencephalography. METHODS: The following process was used (i) Development of FLOW event definition, (ii) Training period and definition refinement, and (iii) Reliability testing on 10 100-epoch polysomnography (PSG) samples and two 100-sample tests. Twenty full-night in-laboratory baseline PSGs in OSA patients with AHI with ≥4% desaturations <15 were rescored for FLOW events, traditional hypopneas with desaturations, respiratory-related arousal (RRA) events (hypopneas with arousals and respiratory-effort related arousals) and non-respiratory arousals (NRA). RESULTS: Scoring of FLOW events in 100-epoch samples had good reliability with intraclass correlation (ICC) of 0.91. The overall kappa for presence of events on two sets of 100 sample events was 0.84 and 0.87 demonstrating good agreement. Moreover, 80% of RRA and 8% of NRA were concurrent with FLOW events. Furthermore, 56% of FLOW events were independent of RRA events. FLOW stratifies patients in traditional AHI categories with 50%/8% of AHI with ≥3% desaturations (AHI3) <5 and 12%/63% of AHI3 >5 in lowest/highest tertiles of AHI3 plus FLOW index. CONCLUSIONS: Scoring of FLOW after training is reliable. FLOW scores a high proportion of RRA and many currently unrepresented obstructive airflow disruptions. FLOW allows for stratification within the current normal-mild OSA category, which may better identify patients who will benefit from treatment.

The subcortical belly of sleep: New possibilities in neuromodulation of basal ganglia?

Early studies posited a relationship between sleep and the basal ganglia, but this relationship has received little attention recently. It is timely to revisit this relationship, given new insights into the functional anatomy of the basal ganglia and the physiology of sleep, which has been made possible by modern techniques such as chemogenetic and optogenetic mapping of neural circuits in rodents and intracranial recording, functional imaging, and a better understanding of human sleep disorders. We discuss the functional anatomy of the basal ganglia, and review evidence implicating their role in sleep. Whilst these studies are in their infancy, we suggest that the basal ganglia may play an integral role in the sleep-wake cycle, specifically by contributing to a thalamo-cortical-basal ganglia oscillatory network in slow-wave sleep which facilitates neural plasticity, and an active state during REM sleep which enables the enactment of cognitive and emotional networks. A better understanding of sleep mechanisms may pave the way for more effective neuromodulation strategies for sleep and basal ganglia disorders.

Expenditure on health care in obese women with and without sleep apnea.

STUDY OBJECTIVES: To determine the effect of obesity and sleep apnea on health care expenditure in women over 10 years. DESIGN: Retrospective observational study SETTING: Tertiary university-based medical center PATIENTS AND CONTROLS: Three groups of age-matched women: 223 obese women with OSAS (body mass index: 39.3 +/- 0.6 kg/m2), and from the general population, 223 obese controls (BMI 36.3 +/- 0.4) and 223 normal weight controls (BMI 23.9 +/- 0.4). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We examined health care utilization in the 3 matched groups for the 10 years leading up to the documentation of OSAS. The mean physician fees and the number of physician visits were significantly higher in obese controls than in normal weight controls during the observed period. Physician fees and physician visits progressively increased in the 10 years before diagnosis in the OSAS cases and were significantly higher than in the matched obese controls. Physician fees, in Canadian dollars, one year before diagnosis in the OSAS cases were higher than in obese controls: $547.49 +/- 34.79 vs $246.85 +/- 20.88 (P<0.0001). More was spent for OSAS cases on physician fees for circulatory, endocrine and metabolic diseases, and mental disorders than the obese controls. Physician visits one year before diagnosis in the OSAS cases were more frequent than in the obese controls: 13.2 +/- 0.73 visits vs 7.26 +/- 0.49 visits (P<0.0001). CONCLUSIONS: Obese women are heavier users of health services than normal weight controls. Obese women with OSAS use significantly more health services than obese controls. Since OSAS imposes a greater financial burden, treatment of OSAS may reduce other comorbidities and lower overall medical costs.

The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease.

BACKGROUND: Individuals with moderate to severe chronic obstructive pulmonary disease (COPD) have poor sleep quality. This study evaluated the effects of ramelteon, an MT(1)/MT(2) melatonin receptor agonist indicated for insomnia treatment on respiration in this population. MATERIALS AND METHODS: This double-blind, crossover study enrolled 25 subjects (>or=40 years) with moderate to severe COPD (FEV(1)/FVC <70% and FEV(1) between 50 and 80% of predicted value [moderate], or FEV(1)/FVC <70% and FEV(1) <50% of predicted value [severe]). Subjects received ramelteon 8 mg or placebo for one night 30 min before polysomnographic monitoring, including measurement of oxygen saturation (SaO(2)) and respiratory effort and flow. Subjects crossed to alternate treatment after a 5- to 10-day washout. The primary endpoint was mean SaO(2) for the entire night. RESULTS: No significant difference in SaO(2) for the entire night was observed with ramelteon vs placebo (92.2% vs 92.5%, P = 0.576). Mean SaO(2) was similar between ramelteon and placebo for each hour of the night, each sleep stage, the number of minutes that SaO(2) was <80% and <90%, and mean apnea-hypopnea index. There was a significant difference in total sleep time (389.0 vs 348.4 min, P = 0.019) and sleep efficiency (81.0 vs 72.6%, P = 0.019), and latency to persistent sleep was shorter (23.1 vs 56.9 min, P = 0.051), with ramelteon vs placebo. All adverse events were mild to moderate; none led to study discontinuation. CONCLUSION: Ramelteon did not produce respiratory depressant effects as measured by oxygenation or abnormal breathing events in subjects with moderate to severe COPD. Ramelteon was well tolerated in this population.

The role of home sleep testing for evaluation of patients with excessive daytime sleepiness: focus on obstructive sleep apnea and narcolepsy.

Excessive daytime sleepiness (EDS) is a common complaint in the general population, which may be associated with a wide range of sleep disorders and other medical conditions. Narcolepsy is a sleep disorder characterized primarily by EDS, which involves a substantial burden of illness but is often overlooked or misdiagnosed. In addition to identifying low cerebrospinal fluid (CSF) hypocretin (orexin) levels, evaluation for narcolepsy requires in-laboratory polysomnography (PSG). Polysomnography is the gold standard for diagnosis of obstructive sleep apnea (OSA) as well as other sleep disorders. However, the use of home sleep apnea testing (HSAT) to screen for OSA in adults with EDS has increased greatly based on its lower cost, lower technical complexity, and greater convenience, versus PSG. The most commonly used, types 3 and 4, portable monitors for HSAT lack capability for electroencephalogram recording, which is necessary for the diagnosis of narcolepsy and other sleep disorders and is provided by PSG. These limitations, combined with the increased use of HSAT for evaluation of EDS, may further exacerbate the under-recognition of narcolepsy and other hypersomnias, either as primary or comorbid disorders with OSA. Adherence to expert consensus guidelines for use of HSAT is essential. Differential clinical characteristics of patients with narcolepsy and OSA may help guide correct diagnosis. Continued EDS in patients diagnosed and treated for OSA may indicate comorbid narcolepsy or another sleep disorder. Although HSAT may diagnose OSA in appropriately selected patients, it cannot rule out or diagnose narcolepsy. Therefore, at present, PSG and MSLT remain the cornerstone for narcolepsy diagnosis.

Centers for Medicare and Medicaid Services Positive Airway Pressure Adherence Criteria May Limit Treatment to Many Medicare Beneficiaries.

STUDY OBJECTIVES: Centers for Medicare and Medicaid Services (CMS) reimbursement for positive airway pressure (PAP) devices for obstructive sleep apnea treatment is dependent on patients meeting adherence expectations within the first 3 months on therapy. Adherence is defined as usage of the device for at least 4 hours per night on 70% of nights during a consecutive 30-day period. We hypothesize that the adherence pattern may be established beyond this initial period, which may limit the opportunity to treat many patients. METHODS: Treatment and adherence data from PAP devices were monitored via wireless modems for 42 consecutive PAP-naïve military veterans who completed 1 year of nightly monitoring. Their baseline characteristics were as follows: age (mean ± standard deviation) 58.5 ± 12.5 years; body mass index 33.7 ± 5.7 kg/m2; diagnostic apnea-hypopnea index (pretreatment) 28.1 ± 18.5 events/h; apnea-hypopnea index on PAP: 4.3 ± 3.3 events/h. We examined daily, monthly, quarterly, semiannual, and annual reports, and the best 30-day adherence report for each quarter. RESULTS: In the first 3 months, 19 of 42 participants were adherent by CMS criteria, and 23 of 42 participants were not. Of the 19 adherent participants, 13 remained adherent and 6 became nonadherent or stopped PAP treatment for the remainder of the year. In the 23 initially nonadherent participants, 16 stopped PAP treatment, and 7 participants (30.4%) became adherent (using CMS criteria) during the rest of the year. Thus, PAP adherence during the first 3 months was predictive for the rest of the year in only 68.4%. PAP nonadherence during the first 3 months was predictive for further nonadherence in only 69.6% of the cases. Overall, this led to a 65% sensitivity and 72% specificity of using adherence at 3 months in predicting adherence at 1 year. CONCLUSIONS: CMS adherence criteria affecting PAP coverage are restrictive and can result in the withholding of therapy in many patients who otherwise might become adherent. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Title: Remote Monitoring in Obstructive Sleep Apnea, Identifier: NCT01678560, URL: https:// clinicaltrials.gov/ct2/show/NCT01678560.