Actigraphy of Wrist and Ankle for Measuring Sleep Duration in Altitude Travelers.

Latshang, Tsogyal Daniela, Daniela Juliana Mueller, Christian Maurizio Lo Cascio, Anne-Christin Stöwhas, Katrin Stadelmann, Noemi Tesler, Peter Achermann, Reto Huber, Malcolm Kohler, and Konrad Ernst Bloch. Actigraphy of wrist and ankle for measuring sleep duration in altitude travelers. High Alt Med Biol. 17:194-202, 2016-Aims: Actigraphy might be convenient to assess sleep disturbances in altitude field studies. Therefore, we evaluated whether actigraphy accurately measures sleep duration in healthy subjects traveling to altitude. METHODS: Fifty-one healthy men, aged mean ± standard deviation (SD) 27 ± 9 years, were studied during one night at Zurich (490 m), two nights at Davos Wolfgang (1630 m), and two nights at Jakobshorn (2590 m), in randomized order. Sleep duration measured by actigraphy, using a one-axis device at the wrist (n = 51), a three-axis device at the other wrist, and a three-axis device at the ankle (n = 22), was compared with corresponding total sleep time (TST) measured by polysomnography. RESULTS: During 255 polysomnographic overnight studies, 449 paired actigraphic recordings were obtained. The median polysomnographic-derived TST ranged from 397 to 408 minutes. Actigraphic mean TST from wrists with one-axis and three-axis devices, and from ankle agreed well with polysomnographic values with a bias of +1, -7, +6 minutes, respectively. Corresponding limits of agreement (±2 SD of bias) were ±51, ±60, and ±59 minutes. Limits of agreement of mean TST over five nights by actigraphy and polysomnography were similar to the coefficient of repeatability (2 SD of mean) of polysomnographic TST, that is, ±31, ±38, and ±36 minutes versus ±34 minutes. CONCLUSIONS: Actigraphy of the wrist or ankle by a one-axis or a three-axis device accurately estimates mean TST in groups of subjects and mean TST over several nights in individuals traveling to altitude. Therefore, actigraphy is valuable for assessing effects of altitude and other environmental influences on sleep duration during field studies over extended periods.

Impaired postural control in healthy men at moderate altitude (1630 m and 2590 m): data from a randomized trial.

OBJECTIVES: Intact postural control is essential for safe performance of mountain sports, operation of machinery at altitude, and for piloting airplanes. We tested whether exposure to hypobaric hypoxia at moderate altitude impairs the static postural control of healthy subjects. METHODS: In 51 healthy men, median age 24 y (quartiles 20;28), static control was evaluated on a balance platform in Zurich, 490 m, and during a 4-day sojourn in Swiss mountain villages at 1630 m and 2590 m, 2 days each. The order of altitude exposure was randomized. Total center of pressure path length (COPL) and sway amplitude measured in two directions by a balance platform, and pulse oximetry were recorded. Data were compared between altitudes. RESULTS: Median (quartiles) COPL during standing on both legs with eyes open at 490 m and in the evenings on the first and second days at 1630 and 2590 m, respectively were: 50 (45;57), 55 (48;62), 56 (49;61), 53 (47;59), 54 (48;60) cm, P<0.001 ANOVA. Corresponding arterial oxygen saturation was 97% (96;97), 95% (94;96), 95%(94;96), 92%(90;93), 93%(91;93), P<0.001. Anterior-posterior sway amplitudes were larger at 1630 and 2590 m compared to 490 m, P<0.001. Multiple logistic regression analysis confirmed that higher altitudes (1630 and 2590m) were independently associated with increased COPL when controlled for the order of altitude exposure and age (P=0.001). CONCLUSIONS: Exposure to 1630 and 2590m was associated with impaired static postural control even when visual references were available. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

Ascent to moderate altitude impairs overnight memory improvements.

Several studies showed beneficial effects of sleep on memory performance. Slow waves, the electroencephalographic characteristic of deep sleep, reflected on the neuronal level by synchronous slow oscillations, seem crucial for these benefits. Traveling to moderate altitudes decreases deep sleep. In a randomized cross-over design healthy male subjects performed a visuo-motor learning task in Zurich (490 m) and at Davos Jakobshorn (2590 m) in random order. Memory performance was assessed immediately after learning, before sleep, and in the morning after a night of sleep. Sleep EEG recordings were performed during the nights. Our findings show an altitude induced reduction of sleep dependent memory performance. Moreover, this impaired sleep dependent memory performance was associated with reduced slow wave derived measures of neuronal synchronization. Our results are consistent with a critical role of slow waves for the beneficial effects of sleep on memory that is susceptible to natural environmental influences.

Impact of acetazolamide and CPAP on cortical activity in obstructive sleep apnea patients.

STUDY OBJECTIVES: 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy. DESIGN: Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed. SETTING: Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m. PATIENTS: Study 1: 39 OSAS patients. Study 2: 41 OSAS patients. INTERVENTIONS: Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500-750 mg) or placebo at moderate altitudes. MEASUREMENTS AND RESULTS: An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5-10%) and increase in beta activity (approximately 25%). CONCLUSIONS: The higher evening dose of 500 mg acetazolamide showed the "spectral fingerprint" of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.

Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

PURPOSE: Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. METHODS: Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. RESULTS: Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/µl 95 % CI -370.8/-119.0, lactadherin+ -202/µl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/µl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 µl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. CONCLUSIONS: In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

Sleep respiratory disturbances and arousals at moderate altitude have overlapping electroencephalogram spectral signatures.

An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.

Are nocturnal breathing, sleep, and cognitive performance impaired at moderate altitude (1,630-2,590 m)?

STUDY OBJECTIVES: Newcomers at high altitude (> 3,000 m) experience periodic breathing, sleep disturbances, and impaired cognitive performance. Whether similar adverse effects occur at lower elevations is uncertain, although numerous lowlanders travel to moderate altitude for professional or recreational activities. We evaluated the hypothesis that nocturnal breathing, sleep, and cognitive performance of lowlanders are impaired at moderate altitude. DESIGN: Randomized crossover trial. SETTING: University hospital at 490 m, Swiss mountain villages at 1,630 m and 2,590 m. PARTICIPANTS: Fifty-one healthy men, median (quartiles) age 24 y (20-28 y), living below 800 m. INTERVENTIONS: Studies at Zurich (490 m) and during 4 consecutive days at 1,630 m and 2,590 m, respectively, 2 days each. The order of altitude exposure was randomized. Polysomnography, psychomotor vigilance tests (PVT), the number back test, several other tests of cognitive performance, and questionnaires were evaluated. MEASUREMENTS AND RESULTS: The median (quartiles) apnea-hypopnea index at 490 m was 4.6/h (2.3; 7.9), values at 1,630 and 2,590 m, day 1 and 2, respectively, were 7.0/h (4.1; 12.6), 5.4/h (3.5; 10.5), 13.1/h (6.7; 32.1), and 8.0/h (4.4; 23.1); corresponding values of mean nocturnal oxygen saturation were 96% (95; 96), 94% (93; 95), 94% (93; 95), 90% (89; 91), 91% (90; 92), P < 0.05 versus 490 m, all instances. Slow wave sleep on the first night at 2,590 m was 21% (18; 25) versus 24% (20; 27) at 490 m (P < 0.05). Psychomotor vigilance and various other measures of cognitive performance did not change significantly. CONCLUSIONS: Healthy men acutely exposed during 4 days to hypoxemia at 1,630 m and 2,590 m reveal a considerable amount of periodic breathing and sleep disturbances. However, no significant effects on psychomotor reaction speed or cognitive performance were observed. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov: NCT01130948.

Quantitative changes in the sleep EEG at moderate altitude (1630 m and 2590 m).

BACKGROUND: Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep. METHODS: Fourty-four healthy men (mean age 25.0 ± 5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design. RESULTS: Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8-4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (~4% at 1630 m and 15% at 2590 m), while theta activity (4.6-8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4-8 Hz and 13-14.4 Hz) and breathing variables (AHI, ODI; 0.8-4.6 Hz). CONCLUSIONS: The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.

Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

BACKGROUND: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. OBJECTIVES: To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. METHODS: In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. RESULTS: Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001), LDL particle size increased (median difference +0.45 nm, p=0.048) and hsCRP decreased (median difference -0.18 mg/l, p=0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. CONCLUSIONS: Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

Respiratory symptoms and bronchial responsiveness in competitive swimmers.

PURPOSE: A high prevalence of bronchial hyperresponsiveness (BHR) and respiratory symptoms has been reported among competitive swimmers. From the 2002 Winter Olympics, BHR measurements or bronchodilator reversibility have been required for approved use of ß2-agonists in sports. The first aim of this study was to evaluate the relationship among respiratory symptoms in young elite swimmers, eucapnic voluntary hyperpnea (EVH), and the inhaled dose of methacholine, causing a 20% decrease in forced expiratory volume in 1 s (FEV1; PD(20 methacholine)). The second aim of this study was to assess the repeatability of the EVH test. METHODS: For this study, 15 male and 9 female adolescent elite swimmers, aged 15 to 25 yr, performed one PD(20 methacholine) test and two EVH tests in a randomized order. Dry air containing 5% CO2 was inhaled for 6 min with a target ventilation of ≥85% of maximum voluntary ventilation (minimum = 65%). PD(20 methacholine) ≤2 µmol and EVH with FEV1 reduction ≥10% were considered positive. Respiratory symptoms and medication were reported in the modified AQUA2008 questionnaire. RESULTS: Twenty swimmers (83%) reported respiratory symptoms, 13 (65%) of them had a positive provocation test. Fourteen (58%) had at least one positive test to either EVH or PD(20 methacholine); three had only one positive EVH test. One athlete had BHR without symptoms. The sensitivity of PD(20 methacholine) ≤2 µmol for respiratory symptoms was 50% versus 60% and 47.37% for the two EVH tests, respectively, and 75% for PD(20 methacholine) ≤4 µmol. The Bland-Altman plot of the two EVH tests showed a consistent distribution, with only one subject outside the limits of agreement. CONCLUSIONS: BHR was frequently found among adolescent competitive swimmers. PD(20 methacholine) ≤2 µmol and EVH ≥ 10% compared well, but PD(20 methacholine) ≤4 µmol had the highest sensitivity for respiratory symptoms. The EVH test has high repeatability but is very expensive and uncomfortable to perform.