Oxidative Stress Reaction to Hypobaric-Hyperoxic Civilian Flight Conditions.

BACKGROUND: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude. AIM: We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals. METHODS: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at -21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. RESULTS: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude. CONCLUSION: Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m-4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

Influence of nutrition and food on sleep-is there evidence?

BACKGROUND: The influence of sleep disorders on metabolism, especially concerning obesity and diabetes, as well as obesity and obstructive sleep apnea, has been widely investigated. However, the effect of nutrition and the intake of certain foods on sleep has only recently gained attention. In recent years, there have been publications on intake of certain foods and certain diets regarding their influence on sleep, as well as activity of adipocytes and their effect on production of sleep hormones. METHODS: Following PRISMA guidelines, we performed a PubMed search using the key words "sleep," "sleep disorders," "nutrition," "food," and "food intake" published from 2012 to 2022. We excluded by consensus all articles with diets and exercise programs or bariatric surgery for weight loss to treat sleep apnea, all articles on connections between sleep disorders and metabolic disorders, and articles concerning the influence of drugs on neuroactive substances. RESULTS: Of the 4155 publications revealed, 988 had nutrition, metabolism, and sleep as the primary topic of research. Of these 988 publications, only 26 fulfilled the content requirements concerning the influence of certain food and diets on sleep or sleep disorders, including the influence of the gastrointestinal system and adipocytes on sleep hormones. None of the investigations revealed clear evidence of an effect of a certain diet or food on sleep. Epidemiologic surveys suggest that shortened or fragmented sleep and chronotype in adults influence nutrition and fat metabolism. Additionally, there is evidence that adipocyte signaling influences neuronal mediators and hormones of the sleep-wake cycle. CONCLUSION: There is no evidence of a direct influence of certain nutrition or food intake on sleep. Obesity via adipocyte signaling may influence the sleep-wake cycle, though the molecular research on this topic is based on animal studies.

Weight Loss and Fat Metabolism during Multi-Day High-Altitude Sojourns: A Hypothesis Based on Adipocyte Signaling.

Several publications and random observations have reported weight loss in high-altitude sojourners of both sexes. This could be a result of multiple adaptations, which hypoxia and mountaineering provoke on a cellular and organic level. Several publications have discussed the effect on appetite-regulating hormones to be one of the main contributing factors. We aimed to review the available data and show the current state of knowledge regarding nutritional aspects in high altitude with a special focus on fatty dietary forms. To reach this aim we conducted a literature search via PubMed according to the PRISMA 2020 protocol to identify relevant studies. We found that very few studies cover this field with scientifically satisfying evidence. For final analysis, reviews as well as papers that were not clearly related to the topic were excluded. Six articles were included discussing hormonal influences and the impact of exercise on appetite regulation as well as genetic factors altering metabolic processes at altitude. Leptin expression seems to be the biggest contributor to appetite reduction at altitude with an initial increase followed by a decrease in the course of time at high altitude. Its expression is greatly dependent on the amount of white adipose tissue. Since the expression of leptin is associated with an increased ß-oxidation of fatty acids, a high-fat diet could be advantageous at a certain time point in the course of high-altitude sojourns.

Expiratory Peak Flow and Minute Ventilation Are Significantly Increased at High Altitude versus Simulated Altitude in Normobaria.

Simulated altitude (normobaric hypoxia, NH) is used to study physiologic hypoxia responses of altitude. However, several publications show differences in physiological responses between NH and hypobaric conditions at altitude (hypobaric hypoxia, HH). The causality for these differences is controversially discussed. One theory is that the lower air density and environmental pressure in HH compared to NH lead to lower alveolar pressure and therefore lower oxygen diffusion in the lung. We hypothesized that, if this theory is correct, due to physical laws (Hagen-Poiseuille, Boyle), resistance respectively air compression (Boyle) at expiration should be lower, expiratory flow higher, and therefore peak flow and maximum expiratory flow (MEF) 75-50 increased in hypobaric hypoxia (HH) vs. normobaric hypoxia (NH). To prove the hypothesis of differences in respiratory flow as a result of lower alveolar pressure between HH and NH, we performed spirography in NH at different simulated altitudes and the corresponding altitudes in HH. In a cross over study, 6 healthy subjects (2 f/4 m, 28.3 ± 8.2 years, BMI: 23.2 ± 1.9) performed spirography as part of spiroergometry in a normobaric hypoxic room at a simulated altitude of 2800 m and after a seven-hour hike on a treadmill (average incline 14%, average walking speed 1.6 km/h) to the simulated summit of Mauna Kea at 4200 m. After a two-month washout, we repeated the spirometry in HH on the start and top of the Mauna Kea hiking trail, HI/USA. Comparison of NH (simulated 4200 m) and HH at 4200 m resulted in increased pulmonary ventilation during exercise (VE) (11.5%, p < 0.01), breathing-frequency (7.8%, p < 0.01), peak expiratory flow PEF (13.4%, p = 0.028), and MEF50 (15.9%, p = 0.028) in HH compared to NH, whereas VO2max decreased by 2%. At 2800 m, differences were only trendy, and at no altitude were differences in volume parameters. Spirography expresses higher mid expiratory flows and peak flows in HH vs. NH. This supports the theory of lower alveolar and small airway pressure due to a lower air density resulting in a lower resistance.

Extreme sports performance for more than a week with severely fractured sleep.

PURPOSE: Severely fractured sleep is mostly portrayed negatively, but investigations in extreme sports show that humans can maintain performance with a minimum of sleep. With two cases of long-lasting extreme sports performances, we demonstrate that severely fragmented sleep does not necessarily lead to a deterioration of physical and cognitive performance. METHODS: We performed continuous polysomnography on a 34 year-old skier for 11 days and nights during a world record attempt in long-term downhill skiing and monitored a 32 year-old cyclist during the Race Across America for 8.5 days via sleep and activity logs. RESULTS: The skier slept fractured fashion in 15-16 naps with a daily average of 6 h consisting of 77% in sleep stage 1 and 2, 11% in stage 3, and 13% in stage REM. The cyclist slept a total of 7 h and 52 min in 8.5 days, split up into 11 short naps and 6 sleep periods. The average duration of napping was 8.8 min and of sleep 64.2 min. CONCLUSIONS: These two cases demonstrate that outstanding performances are possible with severely fractured sleep and/or sleep deprivation. In well-trained athletes, breaking new recordsis possible despite extreme sleep habits.

Periodic breathing in healthy young adults in normobaric hypoxia equivalent to 3500 m, 4500 m, and 5500 m altitude.

PURPOSE: The occurrence of periodic breathing (PB) at high altitude during sleep and the quality of sleep are individually different and influenced by multiple factors including sex. Although poor sleep quality at high altitude might not be directly linked to oxygen desaturations, the PB upsurge at high altitude leads to significant oscillations in oxygen saturation. METHODS: Thirty-three students were recruited. Participants were randomly assigned to three groups (A, B, C) sleeping one full night in a dormitory with normobaric hypoxia at a FIO2 of 14.29% (A), a FIO2 of 12.47% (B), or a FIO2 of 10.82% (C). Full polysomnography was performed in each participant. RESULTS: Mean total sleeping time decreased significantly with increasing hypoxia (p < 0.001). Respiratory events changed from central hypopneas to central apneas (CA) with increasing hypoxia: CA = 17.8%, 50.0%, 92.2% of AHI (37.96 events per hour (n/h), 68.55 n/h, 93.44 n/h). AHI (p = 0.014) and time duration of respiratory events (p = 0.003) were significantly different between sexes, both greater in men. REM sleep was reduced. CONCLUSIONS: Men tend to be more prone to PB in normobaric hypoxia. Further research should implicate a longer acclimatization period around simulated 4500 m in order to find out if the exponential increase in PB between 4500 m and 5500 m could be shifted to lower hypoxic levels, i.e., higher altitudes.

Adiponectin, Leptin and Visfatin in Hypoxia and its Effect for Weight Loss in Obesity.

Rationale: Hypoxia induces leptin gene expression in human adipocytes via hypoxia-inducible factors (HIF-α/ß). Under ambient moderate hypoxia, leptin in adipocytes is elevated for at least 14 days. Leptin is supposedly involved in the reduced food intake, increased utilization of fatty acids for energy production and possible weight loss observed at high altitudes. Literature on adiponectin and visfatin in high altitude is inconsistent with reports of elevated levels and non-elevated levels. Exercise in hypoxia studies in obese subjects have shown a significant weight loss after up to 3 weeks, but it is unclear if this effect holds up for longer time periods. Therefore, we aimed to investigate 32 obese subjects completing 52 exercise and rest sessions within 8 months at either moderate or sham hypoxia and to analyze leptin, adiponectin, and visfatin mRNA-expression at different time points of exposure. Methods: Abdominal subcutaneous fat biopsies were taken from 32 obese subjects before, after 3 months and after 8 months of intervention. Subjects were randomly divided into two groups and exercised at moderate intensity at two different study sites twice a week. The IG was exposed to normobaric hypoxia (FiO2: 14.0 ± 0.2%,) at exercise and at rest (FiO2: 12.0 ± 0.2%) and the CG to sham hypoxia. Quantitative real-time polymerase chain reaction (qPCR) was used in order to determine mRNA-levels of leptin, adiponectin, and visfatin. Results: No differences in leptin levels after 3 and 8 months compared to baseline and between groups were found. There was no significant difference regarding adiponectin or visfatin at any time point compared to baseline in the hypoxia group, but an increase after 3 months was seen in the control group at normoxia compared to the hypoxia group (adiponectin: p = 0.029 and visfatin: p = 0.014). Conclusion: In this first several months' duration randomized sham controlled hypoxia exercise and rest study with obese subjects, we found no time extended leptin mRNA-expression in subjects under hypoxia after 3 and 8 months compared to baseline levels. Moderate exercise in normoxia not in hypoxia leads to elevated adiponectin and visfatin levels after 3 months.

The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue.

OBJECTIVE: The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue. METHODS: A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion. RESULTS: Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the microenvironment in breast cancer tissue and has proven to affect tumor growth positively as covered in two articles. CONCLUSION: This review indicates that the development of breast cancer is influenced by hypoxia. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α.

Endurance Training in Normobaric Hypoxia Imposes Less Physical Stress for Geriatric Rehabilitation.

Rationale: Evidence suggests that training in hypoxia can be very effective even while requiring less physical effort. We therefore aimed to measure the effect of endurance training under hypoxic conditions on pulmonary and cardiovascular parameters in an elderly population undergoing inpatient rehabilitation. Methods: Forty patients over age 65 years with multiple co-morbid conditions were recruited during a 3-week stay in a geriatric rehabilitation center. Using a randomized, single-blinded, placebo-controlled design, patients were assigned to a hypoxic (HG) or normoxic (NG) group. HG patients completed seven training sessions of 30 min duration on a treadmill in a normobaric chamber with inspired oxygen fraction (FiO2) of 15.27%, with 10-30 min active training. Training was conducted with target heart rate at 80% of peak oxygen consumption (VO2-peak). NG group performed similar training in sham hypoxia (room air or FiO2 = 20.94%). At pre- and post-test completion, measures included: (1) cycle ergometry with ECG monitoring and measurement of VO2-peak, and (2) echocardiography for ejection fraction. Results: The physical effort required of patients to reach target heart rate was reduced significantly (-28%, p = 0.043) in the HG compared to NG. Cardiopulmonary parameters showed no differences between groups. Conclusion: Endurance training at 3,000 meters elevation imposes less stress on the locomotor systems while resulting in a similar physiological strain (i.e., heart rate). Hypoxic training holds promise for successful geriatric rehabilitation by being more accommodating to physical limitations in geriatric patients. Trial registration: Registration at DRKS. (Approval No. 359/12, Trial No. DRKS00005241).

SpO2 and Heart Rate During a Real Hike at Altitude Are Significantly Different than at Its Simulation in Normobaric Hypoxia.

Rationale: Exposures to simulated altitude (normobaric hypoxia, NH) are frequently used in preparation for mountaineering activities at real altitude (hypobaric hypoxia, HH). However, physiological responses to exercise in NH and HH may differ. Unfortunately clinically useful information on such differences is largely lacking. This study therefore compared exercise responses between a simulated hike on a treadmill in NH and a similar field hike in HH. Methods: Six subjects (four men) participated in two trials, one in a NH chamber and a second in HH at an altitude of 4,205 m on the mountain Mauna Kea. Subjects hiked in each setting for 7 h including breaks. In NH, hiking was simulated by walking on a treadmill. To achieve maximal similarity between hikes, subjects used the same nutrition, clothes, and gear weight. Measurements of peripheral oxygen saturation (SpO2), heart rate (HR) and barometrical pressure (PB)/inspired oxygen fraction (FiO2) were taken every 15 min. Acute mountain sickness (AMS) symptoms were assessed using the Lake-Louise-Score at altitudes of 2,800, 3,500, and 4,200 m. Results: Mean SpO2 values of 85.8% in NH were significantly higher compared to those of 80.2% in HH (p = 0.027). Mean HR values of 103 bpm in NH were significantly lower than those of 121 bpm in HH (p = 0.029). AMS scores did not differ significantly between the two conditions. Conclusion: Physiological responses to exercise recorded in NH are different from those provoked by HH. These findings are of clinical importance for subjects using simulated altitude to prepare for activity at real altitude. Trial registration: Registration at DRKS. (Approval No. 359/12, Trial No. DRKS00005241).

Principles of practice parameters for the treatment of sleep disordered breathing in the elderly and frail elderly: the consensus of the International Geriatric Sleep Medicine Task Force.

Sleep disordered breathing (SDB) is a leading cause of morbidity worldwide. Its prevalence increases with age. Due to the demographic changes in industrial societies, pulmonologists and sleep physicians are confronted with a rapidly growing number of elderly SDB patients. For many physicians, it remains unclear how current guidelines for SDB management apply to elderly and frail elderly patients. The goal of this consensus statement is to provide guidance based on published evidence for SDB treatment in this specific patient group.Clinicians and researchers with expertise in geriatric sleep medicine representing several countries were invited to participate in a task force. A literature search of PubMed from the past 12 years and a systematic review of evidence of studies deemed relevant was performed.Recommendations for treatment management of elderly and frail elderly SDB patients based on published evidence were formulated via discussion and consensus.In the last 12 years, there have been surprisingly few studies examining treatment of SDB in older adults and even fewer in frail older adults. Studies that have been conducted on the management of SDB in the older patient population were rarely stratified for age. Studies in SDB treatment that did include age stratification mainly focused on middle-aged and younger patient groups. Based on the evidence that is available, this consensus statement highlights the treatment forms that can be recommended for elderly SDB patients and encourages treatment of SDB in this large patient group.

Normobaric Intermittent Hypoxia over 8 Months Does Not Reduce Body Weight and Metabolic Risk Factors--a Randomized, Single Blind, Placebo-Controlled Study in Normobaric Hypoxia and Normobaric Sham Hypoxia.

OBJECTIVE: Both a 1- to 4-week continuous or intermittent stay and moderate exercise in hypoxia versus normoxia can lead to weight loss. We examined the reproducibility and durability of added hypoxic exposure in a feasible health program of several months. METHODS: 32 obese persons, randomly assigned to either a hypoxia (age 50.3 ± 10.3 years, BMI 37.9 ± 8.1 kg/m(²)) or a normoxia (age 52.4 ± 7.9 years, BMI 36.3 ± 4.0 kg/m(²)) group, completed 52 exercise sessions within 8 months. Participants exercised for 90 min (65-70% HR(peak)) either at a simulated altitude of 3,500 m or in normoxia, and rested for further 90 min at 4,500 m or normoxia. Before, after 5 weeks, after 3 months, and after the intervention, body composition and exercise capacity were determined. Risk markers (e.g., blood pressure, cholesterol) were measured before, after 3 months, and after the intervention period. RESULTS: Body weight, BMI, waist and hip circumference, P(peak) and BP(sys) improved over time (p < 0.05) but without group difference. Fat mass reductions correlated with HDL changes (r = -0.427; p < 0.05) in the entire group. CONCLUSION: Long-term, moderate intensity exercise and rest in hypoxia does not lead to higher reductions in body weight than normoxia alone. Therefore, for weight loss and metabolic markers hypoxic exposure does not add effects at least when stimuli (i.e., hypoxia dose, exercise intensity/duration) are unaltered throughout the intervention.

Validación colombiana del cuestionario de Berlín / Colombian validation of the Berlin questionnaire

Resumen Antecedentes. El síndrome de apnea hipopnea obstructiva del sueño es un cuadro clínico con múltiples comorbilidades y complicaciones. Habitualmente no se diagnostica, por lo cual se debe contar con herramientas que permitan identificar a los pacientes con alto riesgo; entre ellas se encuentra el cuestionario de Berlín. Objetivo. Validar el cuestionario de Berlín en Colombia. Materiales y métodos. Se tomaron individuos que acudieron a centros de sueño en Bogotá y estudiantes universitarios. Seis fases: traducción y retrotraducción del cuestionario de Berlín original, validación de apariencia (expertos, n=14), consistencia interna (n=212), validez de criterio y discriminante (n=212) con polisomnografía paralela, reproducibilidad (n=74). Resultados. El cuestionario de Berlín validado localmente tiene una sensibilidad del 87%, especificidad del 70%, valor predictivo positivo del 98%, valor predictivo negativo del 21%, LR+ 2,9, LR- de 18 y un área bajo la curva de 0,7856. La consistencia interna obtuvo un coeficiente alfa de Cronbach de 0,7257. La reproducibilidad encontró un kappa de 0,8150 (Prob>Z=0,0000). Conclusiones. El cuestionario de Berlín está adaptado a las condiciones de vida urbana de la población adulta colombiana, es sensible, específico y tiene una alta reproducibilidad y consistencia interna, de tal manera que es confiable, válido y se correlaciona con la polisomnografía, en forma clínica y estadísticamente significativa.

Summary Background. Obstructive sleep apnea hypopnea syndrome is a clinical picture with multiple comorbidities and complications. Usually it is not diagnosed,therefore there must be tools that can identify patients at high risk. Among them the Berlin Questionnaire. Objective. Validate Berlin questionnaire in Colombia. Materials and methods. Individuals who attended sleep centers in Bogotá and college students were studied. Six phases: translation and back translation of the original Berlin Questionnaire, validating appearance (experts, n=14), internal consistency (n=212), and discriminant validity criteria (n=212) with parallel polysomnography, reproducibility (n=74). Results. Berlin Questionnaire has a sensitivity of 87%, specificity 70%, positive predictive value 98 %, negative predictive value 21 %, LR+ 2.9, LR- 18 and an area under the curve of 0,7856. Internal consistency was a Cronbach's alpha coefficient 0,7257. The reproducibility found at kappa of 0.8150 (Prob>Z=0,0000). Conclusions. Berlin Questionnaire is now adapted to urban living conditions in the Colombian adult population, it is sensitive, specific and has a high reproducibility and internal consistency, so that is reliable, valid and correlates with polysomnography in the form clinically and statistically significant.

The actual role of sodium cromoglycate in the treatment of asthma--a critical review.

INTRODUCTION: Despite international consensus and clearly written guidelines urging wider use of corticosteroids or combinations of inhaled short- and long-acting ß-agonists (SABA and LABA) and corticosteroids in persistent asthma, prescribing patterns and compliance rates fall far short of recommendations. OBJECTIVES: The failure to use steroids more aggressively is due, in part, to their side effects, even with inhaled forms of the drug. There is a role for expanded use of sodium cromolyn in asthma. Its potent anti-inflammatory effects, lack of side effects, and acceptable dosing and method of delivery, as well as its special role in exercise-induced asthma, make it a very suitable choice in the initial therapy for control of asthma. CONCLUSION: Compared to SABA and LABA, cromoglycates alone are unsuspicious of being used to enhance physical performance.

¿Necesitamos polisomnografías repetidas para cambiar la presión en los pacientes con CPAP? / Do We Need Repeated PSGs to Change Pressure in CPAP Patients?

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