Ding Zou

Impaired vigilance and increased accident rate in public transport operators is associated with sleep disorders

OBJECTIVESnSleep disturbances can impair alertness and neurocognitive performance and increase the risk of falling asleep at the wheel. We investigated the prevalence of sleep disorders among public transport operators (PTOs) and assessed the interventional effects on hypersomnolence and neurocognitive function in those diagnosed with obstructive sleep apnea (OSA).nnnMETHODSnOvernight polygraphy and questionnaire data from 101 volunteers (72 males, median age 48 range [22-64] years, 87 PTOs) employed at the Gothenburg Public Transportation Company were assessed. Treatment was offered in cases with newly detected OSA. Daytime sleep episodes and neurocognitive function were assessed before and after intervention.nnnRESULTSnAt baseline, symptoms of daytime hypersomnolence, insomnia, restless legs syndrome as well as objectively assessed OSA (apnea hypopnea index (AHI, determined by polygraphic recording)=17[5-46]n/h) were highly present in 26, 24, 10 and 22%, respectively. A history of work related traffic accident was more prevalent in patients with OSA (59%) compared to those without (37%, p<0.08). In the intervention group (n=12) OSA treatment reduced AHI by -23 [-81 to -5]n/h (p=0.002), determined by polysomnography. Reduction of OSA was associated with a significant reduction of subjective sleepiness and blood pressure. Measures of daytime sleep propensity (microsleep episodes from 9 [0-20.5] to 0 [0-12.5], p<0.01) and missed responses during performance tests were greatly reduced, indices of sustained attention improved.nnnCONCLUSIONSnPTOs had a high prevalence of sleep disorders, particularly OSA, which demonstrated a higher prevalence of work related accidents. Elimination of OSA led to significant subjective and objective improvements in daytime function. Our findings argue for greater awareness of sleep disorders and associated impacts on daytime function in public transport drivers.

Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study

Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27–35 kg·m−2 were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean±sd 33±39% and oxygen desaturation index by 28±31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7±3.0 kg versus 2.3±2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP. The carbonic anhydrase inhibitor zonisamide reduces sleep apnoea, but the effect is inferior to CPAP treatment http://ow.ly/tnmQ1

Attention deficits detected in cognitive tests differentiate between sleep apnea patients with or without a motor vehicle accident

OBJECTIVESnObstructive sleep apnea (OSA) is associated with an increased motor vehicle accident (MVA) risk. Conventional measures of OSA severity do not predict individual risk. Cognitive function tests have failed to incorporate outcomes in risk prediction. We aimed to identify markers of cognitive function for MVA risk prediction in OSA.nnnMETHODSnOSA patients [nu2009=u2009114, 75% male, median age 51 (43-61) years, body mass index (BMI) 30 (27-33) kg/m2, apnea-hypopnea index 25 (6-49) n/h, and Epworth Sleepiness (ESS) score 11 (8-16)] were recruited from a sleep laboratory. Two cognitive function tests, the Attention Network Test (ANT) and a modified Oxford Sleep Resistance Test (OSLER) test (GOSLING), were assessed.nnnRESULTSnOSA patients with (nu2009=u200911) or without (nu2009=u2009103) a MVA record in the Swedish traffic accident registry were identified. In patients with a MVA, 64% were commercial drivers. In patients with a MVA history, more lapses [42 (5-121) vs. 5 (1-25), Pu2009=u20090.02] and fewer responses [238 (158-272) vs. 271 (256-277), Pu2009=u20090.03] to stimuli in the ANT were found. In the GOSLING, the number of lapses was higher (29 (10-97) vs. 7 (2-19), Pu2009=u20090.01) and the reaction time was longer [462 (393-551) vs. 407 (361-449) ms, Pu2009=u20090.05]. OSA severity and ESS score poorly predicted MVAs (Pu2009>u20090.2).nnnCONCLUSIONSnWe have demonstrated that deficit in sustained attention, assessed by daytime neurocognitive function tests, was associated with MVA risk in OSA patients. We were unable to detect an association between MVA history and severity of OSA or the ESS score. The findings provide a rationale for further development of objective MVA risk assessment tools in OSA.

Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia

STUDY OBJECTIVESnThe catalytic function of the enzyme carbonic anhydrase (CA) plays a fundamental role in carbon dioxide (CO2), proton (H(+)), and bicarbonate (HCO3(-)) homeostasis. Hypoxia and tissue acidosis have been proposed to increase physiological CA activity in various compartments of the body. We hypothesized that CA activity in blood is upregulated in patients with obstructive sleep apnea (OSA).nnnDESIGNnCross-sectional analysis of a sleep clinic cohort.nnnSETTINGSnSleep laboratory at a university hospital.nnnPARTICIPANTSnSeventy referred patients with suspected OSA (48 males, age 54 ± 13 y, apnea-hypopnea index (AHI) median [interquartile range] 21 [8-41] n/h).nnnINTERVENTIONSnN/A.nnnMEASUREMENTS AND RESULTSnIn-laboratory cardiorespiratory polygraphy was used to assess OSA. CA activity was determined by an in vitro assay that quantifies the pH change reflecting the conversion of CO2 and H2O to HCO3(-) and H(+). CA activity was positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity versus logAHI and CA versus logODI4) were independent of sex, age, body mass index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension status, and use of diuretic medication in two generalized linear models (P = 0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated with CA activity after adjustment of sex, age, body mass index, mean oxygen saturation, and AHI (P = 0.046).nnnCONCLUSIONSnCarbonic anhydrase (CA) activity increased with apnea-hypopnea index and related nocturnal hypoxemia measures in patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a component that modulates respiratory control and hemodynamic regulation in patients with OSA.

Detection of cardiovascular risk from a photoplethysmographic signal using a matching pursuit algorithm

AbstractnCardiovascular disease is the main cause of death in Europe, and early detection of increased cardiovascular risk (CR) is of clinical importance. Pulse wave analysis based on pulse oximetry has proven useful for the recognition of increased CR. The current study provides a detailed description of the pulse wave analysis technology and its clinical application. A novel matching pursuit-based feature extraction algorithm was applied for signal decomposition of the overnight photoplethysmographic pulse wave signals obtained by a single-pulse oximeter sensor. The algorithm computes nine parameters (pulse index, SpO2 index, pulse wave amplitude index, respiratory-related pulse oscillations, pulse propagation time, periodic and symmetric desaturations, time under 90xa0% SpO2, difference between pulse and SpO2 index, and arrhythmia). The technology was applied in 631 patients referred for a sleep study with suspected sleep apnea. The technical failure rate was 1.4xa0%. Anthropometric data like age and BMI correlated significantly with measures of vascular stiffness and pulse rate variability (PPT and age rxa0=xa0−0.54, pxa0<xa00.001, PR and age rxa0=xa0−0.36, pxa0<xa00.01). The composite biosignal risk score showed a dose–response relationship with the number of CR factors (pxa0<xa00.001) and was further elevated in patients with sleep apnea (AHIxa0≥xa015n/h; pxa0<xa00.001). The developed algorithm extracts meaningful parameters indicative of cardiorespiratory and autonomic nervous system function and dysfunction in patients suspected of SDB.

Self-Reported Features of Sleep, Utilization of Medical Resources, and Socioeconomic Position: A Swedish Population Survey

This study examined aspects of self reported qualities of sleep and daytime functioning attributed to sleep, including the utilization of physician consultations and prescription medications, and their relationships with age, gender, and educational attainment in the Swedish population using telephone interviews of 1,000 random households. Women were twice as likely to use hypnotics and experienced more poor quality sleep and excessive daytime sleepiness (EDS). Lower educational attainment was associated with twofold increased hypnotic use, life impacts of sleep problems, and EDS, but not dimensions reflecting poor quality sleep. This study demonstrates that educational attainment, gender, and age combine to shape both the attributions of the effects of sleep on wakeful functioning and patterns of using medical resources.

Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial

STUDY OBJECTIVESnThe carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA.nnnMETHODSnIn a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m2, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared.nnnRESULTSnAZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013).nnnCONCLUSIONSnAZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension.nnnCLINICAL TRIAL REGISTRATIONnRegistry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://clinicaltrials.gov/ct2/show/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.

Change in weight and central obesity by positive airway pressure treatment in obstructive sleep apnea patients: longitudinal data from the ESADA cohort

The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n = 1,415, 77% male, age 54 ± 11 [mean ± SD] years, body mass index 31.7 ± 6.4 kg/m2, apnea–hypopnea index 37 ± 24 n per hr, Epworth Sleepiness Scale 10.2 ± 5.0) were selected. Changes in body mass index and neck/waist/hip circumferences at baseline and at follow‐up visit were analysed. Overall, body mass index (0.0 [95% confidence interval, −0.1 to 0.2] kg/m2) and neck circumference (0.0 (95% confidence interval, −0.1 to 0.1] cm) were unchanged after positive airway pressure treatment compared with baseline (follow‐up duration 1.1 ± 1.0 years and compliance 5.2 ± 2.1 hr per day). However, in non‐obese (body mass index <30 kg/m2) patients, positive airway pressure treatment was associated with an increased body mass index and waist circumference (0.4 [0.3–0.5] kg/m2 and 0.8 [0.4–1.2] cm, respectively, all p < 0.05), and weight gain was significantly associated with higher positive airway pressure compliance and longer positive airway pressure treatment duration. In the obese subgroup, body mass index was reduced after positive airway pressure treatment (−0.3 [−0.5 to −0.1] kg/m2, p < 0.05) mainly in patients with a strong reduction in Epworth Sleepiness Scale. In conclusion, positive airway pressure therapy was not found to systematically change body mass index in the European Sleep Apnea Database cohort, but the response was heterogeneous. Our findings suggest that weight gain may be restricted to an obstructive sleep apnea phenotype without established obesity. Lifestyle intervention needs to be considered in both lean and obese patients with obstructive sleep apnea receiving positive airway pressure treatment.

Perceived sleep deficit is a strong predictor of RLS in multisite pain – A population based study in middle aged females

Abstract Background Chronic pain conditions as well as Restless Legs Syndrome (RLS) are known to be associated with subjectively and objectively disturbed sleep. RLS has been recently described as highly prevalent in multisite pain and the role of sleep as a modifying factor in this RLS phenotype is unknown. This study aimed to investigate if perceived sleep deficit and other sleep related parameters predict RLS in subjects with multisite pain. Current knowledge/study rationale We have recently demonstrated a strong association between Restless Legs Syndrome (RLS) and number of pain locations. In the current analysis we hypothesized that impaired sleep predicts RLS in subjects with multisite pain. Method Questionnaire-based data from 2727 randomly selected women aged 18-64 years were used to analyze RLS symptoms, self-reported sleep quality, and the degree of daytime sleepiness (Epworth Sleepiness Scale (ESS)) in relation to type, degree and localization of body pain. Potential confounders including anthropometrics, pain localization, co-morbidities, and medication were adjusted for in the Generalized Linear Models (GLM). Results Perceived sleep deficit ≥90 min (OR 2.4 (1.5-3.8), p < 0.001) and frequent nocturnal awakenings (OR 2.3 (1.4-3.6), p <0.001) were the strongest sleep related predictors for RLS in subjects with multisite pain. Additional factors include prolonged sleep latency (≥30 min, OR 1.8 (1.1-2.8), p = 0.01) and daytime symptoms like elevated daytime sleepiness (ESS score ≥9, OR 1.8 (1.2-2.7), p = 0.005). Accordingly, RLS diagnosis was associated with impaired sleep quality (TST (Total Sleep Time) -8.2 min, sleep latency +8.0 min, and number of awakenings from sleep +0.4, p <0.01). ESS score increased with RLS diagnosis (+0.74, p <0.01) and number of pain locations (0.5, 1.7, and 1.8 for 1, 3, and 5 pain areas, p <0.001). In addition, confounders like pain severity, the history of psychiatric disease, and current smoking were associated with impaired sleep quality in this group of females. Conclusions Perceived sleep deficit and sleep fragmentation are the strongest sleep related predictors of RLS in multisite pain. Potential implication of our results are that clinical management programmes of RLS in subjects with multisite pain need to consider both sleep quality and sleep quantity for individually tailored treatment regimes. Study impact RLS, pain, and sleep disorders are highly interrelated. Our study strongly suggests that clinical management of RLS in patients with multisite pain needs to consider sleep quality as an independent risk factor.

Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea

BackgroundObstructive sleep apnea is characterized by intermittent hypoxia and hypercapnia. CO2 production, transport and elimination are influenced by the carbonic anhydrase enzyme. We hypothesized that elevated standard bicarbonate, a proxy for increased carbonic anhydrase activity, is associated with apnea severity and higher blood pressure in patients with obstructive sleep apnea.MethodsA retrospective analysis of a sleep apnea cohort (nu2009=u2009830) studied by ambulatory polygraphy. Office systolic/diastolic blood pressure, lung function, and arterial blood gases were assessed during daytime.ResultsArterial standard bicarbonate was increased with apnea severity (mild/moderate/severe 24.1u2009±u20091.8, 24.4u2009±u20091.7 and 24.9u2009±u20092.9xa0mmol/l, respectively, Kruskal-Wallis test pu2009<u20090.001). Standard bicarbonate was independently associated with apnea hypopnea index after adjustment for sex, age, body mass index, smoking, alcohol, hypertension, pO2 and pCO2 (standard bicarbonate quartile 1 vs. quartile 4, βu2009=u200910.6, pu2009<u20090.001). Log-transformed standard bicarbonate was associated with a diagnosis of hypertension or diastolic blood pressure but not systolic blood pressure adjusting for cofounders (pu2009=u20090.007, 0.048 and 0.45, respectively).ConclusionsThere was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.