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.

Driving habits and risk factors for traffic accidents among sleep apnea patients--a European multi-centre cohort study.

Obstructive sleep apnea is associated with increased motor vehicle accident risk, and improved detection of patients at risk is of importance. The present study addresses potential risk factors in the European Sleep Apnea Database and includes patients with suspected obstructive sleep apnea [n = 8476, age 51.5 (12.5) years, body mass index 31.0 (6.6) kg m(-2) , 82.4% driver's licence holders]. Driving distance (km year(-1) ), driver's licence type, sleep apnea severity, sleepiness and comorbidities were assessed. Previously validated risk factors for accident history: Epworth Sleepiness Scale ≥16; habitual sleep time ≤5 h; use of hypnotics; and driving ≥15 000 km year(-1) were analysed across European regions. At least one risk factor was identified in male and female drivers, 68.75 and 51.3%, respectively. The occurrence of the risk factors was similar across Europe, with only a lower rate in the eastern region (P = 0.001). The mean number of risk factors increased across classes of sleep apnea severity. Frequent driving was prevalent [14.0 (interquartile range 8.0-20.0) × 10(3)  km year(-1) ] and 32.7% of drivers had severe obstructive sleep apnea [apnea-hypopnea index 50.3 (38.8-66.0) n h(-1) ]. Obesity, shorter sleep time and younger age were associated with increased traffic exposure (P ≤ 0.03). In conclusion, the risk factors associated with accident history were common among European patients with suspected obstructive sleep apnea, but varied between geographical regions. There was a weak covariation between occurrence of risk factors and clinically determined apnea severity but frequent driving, a strong risk factor for accidents, was over-represented. Systematic evaluation of accident-related risk factors is important to detect sleep apnea patients at risk for motor vehicle accidents.

Changes in cognitive function and daytime sleepiness in patients with chronic heart failure and Cheyne-Stokes respiration with adaptive servo ventilation treatment.

STUDY OBJECTIVES: Cheyne - Stokes respiration (CSR) is prevalent in patients with chronic heart failure (CHF). Adaptive Servo Ventilation (ASV) alleviates CSR and improves objective sleep quality. We investigated the effects of ASV on neurocognitive function in the symptomatic phenotype of patients with CSR and CHF. METHODS: This case series included patients diagnosed with stable CHF (NYHA ≥ II) and CSR (N = 8). Sleep and neurocognitive function were assessed at baseline and after 1- and 6-months following initiation of ASV treatment. RESULTS: In CHF patients (n = 8, median age 78.0[64.5-80.8] years and BMI 30.0[27.0-31.5] kg/m2, median ejection fraction 30[24-45]%, Epworth Sleepiness Scale (ESS) score 11.5[9.0-15.0]), ASV markedly improved respiration during sleep (Apnea-Hypopnea Index (AHI) 44.1[39.0-51.5]n/h at baseline, 6.3[2.4-9.7]n/h at 6 months treatment, respectively, p < 0.01). The 6-min-walk test distance increased by treatment from (295.0[178.8-385.0] m to 356.0[203.8-495.0] m (p = 0.05)). Sleep structure was modified, and Stage 3 increased markedly from 6.4[1.7-20.1] % to 20.8[14.2-25.3] %, p < 0.02). Sleep latency in the Maintenance of Wakefulness Test increased from 12.0[6.0-30.0] min to 26.3[12.0-30.0] min, (p = 0.04). In the Attention Network Test, evaluating neurocognition, the number of lapses decreased from 6.0[1.0-44.0] to 2.0[0.3-8.0], (p = 0.05) and the overall number of responses to a preset stimulus increased after treatment (p = 0.04). CONCLUSIONS: ASV treatment in CHF patients with CSR may improve sleep quality, neurocognition and daytime performance.

Sleep apnea-related risk of motor vehicle accidents is reduced by continuous positive airway pressure: Swedish Traffic Accident Registry data.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle accidents (MVAs). The rate of MVAs in patients suspected of having OSA was determined and the effect of continuous positive airway pressure (CPAP) was investigated. DESIGN: MVA rate in patients referred for OSA was compared to the rate in the general population using data from the Swedish Traffic Accident Registry (STRADA), stratified for age and calendar year. The risk factors for MVAs, using demographic and polygraphy data, and MVA rate before and after CPAP were evaluated in the patient group. SETTING: Clinical sleep laboratory and population based control (n = 635,786). PATIENTS: There were 1,478 patients, male sex 70.4%, mean age 53.6 (12.8) y. INTERVENTIONS: CPAP. MEASUREMENTS AND RESULTS: The number of accidents (n = 74) among patients was compared with the expected number (n = 30) from a control population (STRADA). An increased MVA risk ratio of 2.45 was found among patients compared with controls (P < 0.001). Estimated excess accident risk was most prominent in the elderly patients (65-80 y, seven versus two MVAs). In patients, driving distance (km/y), EDS (Epworth Sleepiness score ≥ 16), short habitual sleep time (≤5 h/night), and use of hypnotics were associated with increased MVA risk (odds ratios 1.2, 2.1, 2.7 and 2.1, all P ≤ 0.03). CPAP use ≥ 4 h/night was associated with a reduction of MVA incidence (7.6 to 2.5 accidents/1,000 drivers/y). CONCLUSIONS: The MVA risk in this large cohort of unselected patients with OSA suggests a need for accurate tools to identify individuals at risk. Sleep apnea severity (e.g., apnea-hypopnea index) failed to identify patients at risk.

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

OBJECTIVES: Sleep 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). METHODS: Overnight 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. RESULTS: At 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. CONCLUSIONS: PTOs 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.

Increased neck soft tissue mass and worsening of obstructive sleep apnea after growth hormone treatment in men with abdominal obesity.

BACKGROUND: Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion. AIM: To study the effect of GH treatment on OSA in abdominally obese men with impaired glucose tolerance. PATIENTS AND METHODS: Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumference. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. RESULTS: GH treatment increased insulin-like growth-factor-1i from (mean [SD]) 168 (72) to 292 (117) microg/L, the apnea-hypopnea index from (n/h) 31 (20) to 43 (25) and oxygen-desaturation index from (n/h) 18 (14) to 29 (21) (p = 0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross-sectional area (p = 0.007, 0.01, 0.02) increased, while abdominal visceral adipose tissue (p = 0.007) was reduced. No between-group differences in total sleep time, REM sleep, NREM sleep, and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. CONCLUSIONS: GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be reflected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in abdominally obese men.