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Acute mountain sickness (AMS) commonly plagues people who travel to high altitude and can be life threatening. Clinically, AMS is defined by a constellation of symptoms as outlined in the Lake Louise Criteria. The underlying etiology is thought to be related to a decrease in partial pressure of oxygen leading to tissue hypoxia. Patent foramen ovale (PFO) has been postulated to play a role in AMS through right-to-left shunt, which can worsen hypoxemia. Recent data demonstrate a higher prevalence of PFO in hikers with AMS. Future studies are needed to further elucidate the relationship between PFO and AMS.

Introduction: Acute mountain sickness, high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE) are a spectrum of high-altitude conditions, with HACE being the most life-threatening. Most cases develop at altitudes of greater than 4,000 meters (~13,000 feet) above sea level and after one to five days.Case Report: A previously healthy 46-year-old female presented to the emergency department with ataxia, altered mental status, and vomiting that developed after rapidly ascending to ~2,400 meters (~7,800 feet) above sea level. She was treated for HACE and HAPE with resolution of her symptoms within 24 hours.Conclusion: High-altitude pulmonary edema and HACE can develop rapidly and at moderate altitudes. Expeditious recognition and treatment is imperative to avoid life-threatening complications.

OBJECTIVES: Ascending to altitudes >2500 m may lead to acute mountain sickness (AMS). METHODS: The demographics, height, weight, body mass index (BMI), smoking, and alcohol consumption of 104 healthy controls were collected in Chengdu (500 m). Heart rate (HR), saturation of pulse oxygen (SpO2), and AMS-related symptoms were collected in Hoh Xil (4200 m). A headache with Lake Louise score ≥3 was defined as AMS. RESULTS: The incidence of AMS was 60.58%. AMS group had a lower SpO2 and higher HR than non-AMS group. Alcohol consumption seemed a risk factor for AMS. There was no difference in the BMI, age, height, weight, and smoking between AMS and non-AMS groups. The most common AMS symptom was headache, followed by dyspnea, insomnia, dizziness, lassitude, and anorexia. Women were prone to suffer from dizziness. The value of SpO2 and HR was improved both in AMS and non-AMS groups after hypoxia acclimatization, and the value showed greater improvement in AMS group. Oxygen therapy decreased the AMS-induced tachycardia, which had no any effect on SpO2 and symptom alleviating time. CONCLUSION: Lower SpO2 and higher HR following exposure to high altitude were associated with AMS susceptibility. The anthropometric data changes were larger in AMS group than non-AMS group before and after hypoxia acclimatization. [ABSTRACT FROM AUTHOR]

Background: Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. Methods: This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. Discussion: This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. Trial registration: Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) causes serious illness for many individuals ascending to high altitude (HA), although preventable with appropriate acclimatisation. AMS is a clinical diagnosis, with symptom severity evaluated using the Lake Louise Score (LLS). Reliable methods of predicting which individuals will develop AMS have not been developed. This systematic review evaluates whether a predictive relationship exists between oxygen saturation and subsequent development of AMS. PubMed, PubMed Central, MEDLINE, Semantic Scholar, Cochrane Library, University of Birmingham Library and clinicaltrials.gov databases were systematically searched from inception to 15 June 2023. Human studies involving collection of peripheral blood oxygen saturation (SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) from healthy lowlanders during ascent to HA that evaluated any relationship between SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS severity were considered for eligibility. Risk of bias was assessed using a modified Newcastle–Ottawa Tool for cohort studies (PROPSPERO CRD42023423542). Seven of 980 total identified studies were ultimately included for data extraction. These studies evaluated SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS (via LLS) in 1406 individuals during ascent to HA (3952–6300 m). Risk of bias was ‘low’ for six and ‘moderate’ for one of the included studies. Ascent profiles and SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ measurement methodology varied widely, as did the statistical methods for AMS prediction. Decreasing oxygen saturation measured with pulse oximetry during ascent shows a positive predictive relationship for individuals who develop AMS. Studies have high heterogeneity in ascent profile and oximetry measurement protocols. Further studies with homogeneous methodology are required to enable statistical analysis for more definitive evaluation of AMS predictability by pulse oximetry. [ABSTRACT FROM AUTHOR]

Aims: When entering a mountain plateau, people are at risk of developing acute mountain sickness (AMS), for which there are limited prophylactic medicines available. This study aimed at exploring the effectiveness of ibuprofen, acetazolamide, and methazolamide in preventing AMS and at providing valuable insights for the future development of related drugs. Methods: A total of 137 mountaineers were recruited for this study and divided into six groups: a control group, an ibuprofen group, an acetazolamide group, a methazolamide group, an ibuprofen/methazolamide combination group, and a high‐dose ibuprofen/methazolamide combination group. After the assigned drug was taken for three days at a lower elevation (300 m), the participants ascended to a plateau environment at 5050 m. The Lake Louise AMS Score (LLS) system was used to diagnose and evaluate the AMS rates of the mountaineers in each group, and the results were compared through statistical analysis. Results: The results show that all the medications tested herein were effective in preventing AMS, but their level of effectiveness varied. The prevalence of AMS was 50.00% in the control group, 14.29% in the ibuprofen group, 5.56% in the acetazolamide group, 27.27% in the methazolamide group, 44.8% in the ibuprofen and methazolamide group, and 22.50% in the high‐dose ibuprofen and methazolamide group. Acetazolamide demonstrated a significant prophylactic effect on symptoms related to AMS diagnosis, and ibuprofen showed the best efficacy for preventing headache. Conclusion: Acetazolamide remains an effective medicine for preventing AMS. Ibuprofen combined with methazolamide is less effective than ibuprofen alone to prevent AMS. Trial Registration: ClinicalTrials.gov identifier: ChiCTR-TRC-12002219 [ABSTRACT FROM AUTHOR]

Wu, Yu, Wenqi Zhao, Bao Liu, Jianyang Zhang, Zhifeng Zhong, Simin Zhou, Jiaxin Xie, Yuqi Gao, Peng Li, and Jian Chen. Assessment of Acute Mountain Sickness: Comparing the Chinese Ams Score to the Lake Louise Score. High Alt Med Biol 25:164–173, 2024. Objective: To compare the ability of the Chinese AMS Score (CAS) to detect acute mountain sickness (AMS) using the 2018 version of the Lake Louise Score (LLS) as reference. Methods: After flying from Chengdu (altitude: 500 m) to Lhasa (3,658 m), 2,486 young men completed a questionnaire. The questionnaire contained LLS and CAS items. An LLS ≥3 and/or a CAS ≥cutoff were used as the criteria for AMS. Hierarchical cluster analysis and two-step cluster analysis were used to investigate relationships between the symptoms. Results: AMS incidence rates were 33.8% (n = 840) with the LLS and 59.3% (n = 1,473) with the CAS (χ2 = 872.5, p < 0.001). The LLS and CAS had a linear relationship (orthogonal regression, Pearson r = 0.91, p < 0.001). With the LLS as the standard, the CAS had high diagnostic accuracy (area under the curve = 0.95, 95% confidence interval: 0.94–0.96). However, with the CAS, 25.5% (n = 633) more participants were labeled as having AMS than with the LLS (false positives). Two clusters were identified: one with headache only (419 participants, 66.2%) and one without headache but with other symptoms (214 participants, 33.8%). Reducing the weight of headache in the CAS allowed to align CAS and LLS. Conclusion: In comparison to the LLS, the CAS has a sensitivity close to 100% but lacks specificity given the high rate of false positives. The different weight of headaches may be the main reason for the discrepancy. [ABSTRACT FROM AUTHOR]

Background: Controversy remains in the association between smoking and the risk of acute mountain sickness (AMS). Therefore, a systematic review of the existing literature may help clarify this association. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library from database inception up to October 19, 2021. Both unadjusted and adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare the risk of AMS in the smoking and nonsmoking groups. Meta-regression was conducted to explore the factors causing heterogeneity of the studies, and subsequent stratified analysis was performed to present the pooled RR in different subgroups. Publication bias was assessed using funnel plots. Results: A total of 28 eligible articles (31 studies) were included. The pooled unadjusted and adjusted RRs were 0.88 (95% CI: 0.78–1.01) and 0.87 (95% CI: 0.77–0.99), respectively, using random-effect models. Publication bias was observed owing to restrictions on the sample size. The ascending altitude and sex composition of the study population were likely sources of heterogeneity according to meta-regression. Studies on participants with an ascending altitude of over 3,500 m or composed of both males and females reported a slight but not significant protective effect of smoking on the risk of AMS, with high heterogeneity. Conclusions: Smoking had no significant effect on AMS risk in this meta-analysis. Current studies showed high heterogeneity and included little information on quantitative exposure to smoking (i.e., dose and frequency); thus, the results require careful explanation. [ABSTRACT FROM AUTHOR]

Abstract Background Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. Methods This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. Discussion This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. Trial registration Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Abstract High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory‐based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end‐tidal carbon dioxide (PETCO2) against peripheral oxygen saturation (SpO2) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self‐administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning PETCO2 and SpO2 measurements were collected on 46 acetazolamide‐free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. Highlights What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide‐free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

Objective To investigate the role of sea-level cerebral blood flow (CBF) in predicting acute mountain sickness (AMS) using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL). Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging (MRI) including 3D-pCASL at sea level. The CBF values of the bilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) territories and the laterality index (LI) of CBF were compared between the AMS and non-AMS groups. Statistical analyses were performed to determine the relationship between CBF and AMS, and the predictive performance was assessed using receiver operating characteristic (ROC) curves. Results The mean cortical CBF in women (81.65 ± 2.69 mL/100 g/min) was higher than that in men (74.35 ± 2.12 mL/100 g/min) (P < 0.05). In men, the cortical CBF values in the bilateral ACA, PCA, PICA, and right MCA were higher in patients with AMS than in those without. Cortical CBF in the right PCA best predicted AMS (AUC = 0.818). In women, the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753. Conclusion Although the mechanism and prediction of AMS are quite complicated, higher cortical CBF at sea level, especially the CBF of the posterior circulatory system, may be used for prediction in male volunteers using non-invasive 3D-pCASL. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in dynamic cerebral autoregulation (CA) during short‐term and long‐term exposure to high altitude with ultrasonography, and also study the sex differences in the response of CA to altitude. Methods: We assessed the differences in dynamic CA and measured with Doppler ultrasound of the bilateral internal carotid artery (ICA), vertebral artery (VA), and middle cerebral artery (MCA) and the values of basic information within 48 hours and at 2 years after arrival at Tibet in 65 healthy Han young Chinese volunteers, meanwhile, we compared the resistance index (RI) and pulsatility index (PI) of the right MCA at inhale oxygen 8 minutes when a newcomer with 2 years after arrival at Tibet. Results: With 2 years of altitude exposure, the SaO2 of all subjects was above 90%, the mean PEF, DAP, and HR values decreased, HGB increased compared within 48 hours in same‐gender groups. Comparisons of cerebral hemodynamics between before 2 years and after 2 years within male and female groups, the mean RI and PI values of bilateral MCA after 2 years were significantly higher than before 2 years, at the same time, the mean RI and PI values of bilateral ICA were significant differences (P <.05) between male groups, with regard to female groups, showed that the mean RI and PI values of bilateral VA were significant differences (P <.05). Comparisons of Right MCA hemodynamics between after oxygen uptake 8 minutes and 2 years, the mean RI and PI values were no significant difference within male and female groups (P >.05). Conclusions: Acute mountain sickness could result from an alteration of dynamic autoregulation of cerebral blood flow, but the impaired autoregulation may be corrected with the extension of time, furthermore, the response of CA to altitude in males and females are different. [ABSTRACT FROM AUTHOR]

High-altitude illnesses, encompassing a spectrumof health threats including Acute Mountain Sickness (AMS), pose significant challenges to individuals exposed to high altitude environments, necessitating effective prophylaxis and immediate management. Given the variability in individual responses to these conditions, accurate prediction of high-altitude illnesses onset is of paramount importance. This review systematically consolidates recent advancements in research on predicting AMS by evaluating existing cohort data, predictive models, and methodologies, while also delving into the application of emerging technologies. Through a thorough analysis of scholarly literature, we discuss traditional prediction methods anchored in physiological parameters (e.g., heart rate, respiratory frequency, blood pressure) and biochemicalmarkers, aswell as the integration and utility of novel technologies such as biosensors, genetic testing, and artificial intelligence within high-altitude prediction research. While conventional pre-diction techniques have been extensively used, they are often constrained by limitations in accuracy, reliability, andmultifactorial influences. The advent of these innovative technologies holds promise formore precise individual risk assessments and personalized preventive and therapeutic strategies across various forms of AMS. Future research endeavors must pivot decisively towards the meticulous identification and stringent validation of innovative predictive biomarkers and models. This strategic re-direction should catalyze intensified interdisciplinary cooperation to significantly deepen our mechanistic insights into the pathogenesis of AMS while refining existing prediction methodologies. These groundbreaking advancements harbor the potential to fundamentally transform preventive and therapeutic frameworks for high-altitude illnesses, ultimately securing augmented safety standards and wellbeing for individuals operating at elevated altitudes with far-reaching global implications. [ABSTRACT FROM AUTHOR]

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory‐based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end‐tidal carbon dioxide (PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$) against peripheral oxygen saturation (SpO2${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self‐administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and SpO2${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide‐free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. Highlights: What is the central question of this study?What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)?What is the main finding and its importance?Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide‐free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments. [ABSTRACT FROM AUTHOR]

Background and objectives: Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Methods: Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. Results: We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1a/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. Conclusion: The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and proinflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies. [ABSTRACT FROM AUTHOR]

BackgroundLeisure, work, and sports activities that involve ascending to high altitudes (HA) are growing in popularity, yet they also pose the risk of developing acute mountain sickness (AMS). Despite the dynamic nature of AMS, its prevalence, clinical manifestations, and associated risks have still not to be comprehensively characterized.MethodsA total of 770 healthy males, ranging in age from 18 to 45 years, were included in this study. The subjects were divided into two cohorts: a fast ascent cohort (n = 424) who ascended to 3,650 m by airplane, and a slow ascent cohort (n = 346) who ascended to the same altitude by bus. Subsequently, they all further ascended to 4,400 m. AMS was diagnosed using the Lake Louise Scoring system (LLS), with either the old or new version were employed.ResultsAs diagnosed by the old LLS and new LLS, the incidence of AMS was 37.9 and 32.4% at 3650 m, respectively, which decreased to 35.7 and 32.4% after further ascending to 4,400 m in the fast ascent cohort; the incidence of AMS was 26.5 and 23.2% at 3650 m, which increased to 44.5 and 42.3% after further ascending to 4,400 m in the slow ascent cohort. Furthermore, there were noticeable disparities in the occurrence and progression of AMS-related symptoms among cohorts adhering to different ascent protocols. Specifically, fast ascent protocol posed a risk during the initial phase of the ascent, but transformed into a protective effect upon further ascent to a higher altitude.ConclusionAscent protocol emerged as the pivotal influence on the prevalence of AMS and associated manifestations, demonstrating a transition from a risk factor during initial ascent to a protective factor following further ascent to higher altitudes. These findings suggest an innovative strategy for high-altitude expeditions and work endeavors, emphasizing the importance of a strategic plan for ascending to higher altitudes.

The Lake Louise Score (LLS) is a common tool for diagnosing acute mountain sickness (AMS) after a recent gain in altitude. Required symptoms (headache, dizziness, fatigue or gastrointestinal symptoms) are unspecific, subjective and not detectable by physiological parameters. (Talks et al., 2022; Boos et al., 2018) This study aimed to enhance present knowledge concerning the impact of mental health on LLS. In a cross-sectional questionnaire study, we assessed 3 groups: 100 inpatients (Ward for psychosomatic medicine – Innsbruck, PSY), 73 mentally healthy individuals (Innsbruck, Austria at an altitude of 570 m, CO) and 223 mountaineers in Nepal (Pheriche 4,371 m and Dingboche 4,410 m, NEPAL). Beside social demographics and LLS 2018 (cutoff for LLS-positivity: LLS ≥ 3 including at least 1 point for headache), we examined symptoms of anxiety (Zung Self-Rating Anxiety Scale [SAS], General Anxiety Disorder Questionnaire 7 [GAD-7]), affective states (International Positive and Negative Affect Schedule Short form [I-PANAS-SF]) and sleep (Insomnia Severity Index [ISI]). In this preliminary analysis, the average age was 39 ± 16 years in PSY, 34 ± 16 years in CO and 40 ± 14 years in NEPAL. Gender distribution showed greater portion of women in PSY and CO (PSY: 72% female 24% male 3% non-binary, CO: 64% female 36% male) contrary to NEPAL (36% female 64% male). At sea level, 67% scored LLS-positive in PSY and 12% in CO (Fishers exact test, p < 0.001). In NEPAL 25% met AMS-criteria by LLS. CO and NEPAL score significantly lower in LLS than PSY (ANOVA: diff = -3.70, p < 0.0001; diff = -3.68, p < 0.0001, respectively). PSY and CO showed significant weak to moderate correlations (Spearman-Rho, p < 0.001) of anxiety (SAS, GAD), affective states (I-PANAS-SF) and sleep impairment (ISI) with LLS-sum. NEPAL showed significant very-weak to weak correlations of insomnia, anxiety and negative affect with LLS-sum. Using logistic regression analysis (Figure 1), higher odds of LLS-positivity are significantly associated with insomnia and anxiety (ISI, SAS) in PSY, with anxiety in CO (SAS) and insomnia and negative affect in NEPAL. While of course a recent gain in altitude is a prerequisite for the diagnosis of AMS this study shows that patients with pre-existing mental illness at low altitude score more frequently false-positive on the LLS than a mentally healthy cohort. Symptoms of anxiety, negative affect and sleep disturbance can affect the AMS-defining questionnaire of LLS both at sea level and at high altitude. There is still uncertainty on a possible common pathophysiological pathway of psychiatric diseases and AMS since there is no Gold Standard in diagnosing AMS. Concerning (well-)established risk-factors for AMS like speed of ascent (Berger et al., 2023) and female sex (Hou et al., 2019), we see no evident data. The data presented here suggest that strength of expression of negative affect can cause positive LLS scoring. Acute mountain sickness and psychiatric disorders show overlapping symptoms at sea level. At high altitudes, negative affect seems to be a possible cause for the development of AMS. Further research focus should be placed on mountaineers in high altitude with psychiatric disorders and their mental state. References Berger, M. M., Hüsing, A., Niessen, N., Schiefer, L. M., Schneider, M., Bärtsch, P., & Jöckel, K. H. (2023). Prevalence and knowledge about acute mountain sickness in the Western Alps. PLoS ONE, 18(9), Article e0291060. https://doi.org/10.1371/journal.pone.0291060 Boos, C. J., Bass, M., O’Hara, J. P., Vincent, E., Mellor, A., Sevier, L., Abdul-Razakq, H., Cooke, M., Barlow, M., & Woods, D. R. (2018). The relationship between anxiety and acute mountain sickness. PLoS ONE, 13(6), Article e0197147. https://doi.org/10.1371/journal.pone.0197147 Hou, Y. P., Wu, J. L., Tan, C., Chen, Y., Guo, R., & Luo, Y. J. (2019). Sex-based differences in the prevalence of acute mountain sickness: A meta-analysis. Military Medical Research, 6, Article 38. https://doi.org/10.1186/s40779-019-0228-3 Talks, B. J., Campbell, C., Larcombe, S. J., Marlow, L., Finnegan, S. L., Lewis, C. T., Lucas, S. J. E., Harrison, O. K., & Pattinson, K. T. S. (2022). Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Altitude Medicine & Biology, 23(1), 69–77. https://doi.org/10.1089/ham.2021.0073

This article explores the effects of altitude on exercise tolerance and the development of acute mountain sickness (AMS) in young men. The study found that exercise tolerance was similar at high altitude and under simulated hypobaric hypoxia conditions (SHHC), but higher at sea level. The researchers also identified physiological variables that could predict the development of AMS, including exercise intensity and blood pressure. However, it is important to note that this article has been retracted and should be approached with caution. [Extracted from the article]

Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders. Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes. Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5- day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p < 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively). Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity. [ABSTRACT FROM AUTHOR]

Background: Optic nerve sheath diameter (ONSD) increases significantly at high altitudes, and is associated with the presence and severity of acute mountain sickness (AMS). Exposure to hypobaria, hypoxia, and coldness when hiking also impacts intraocular pressure (IOP). To date, little is known about ocular physiological responses in trekkers with myopia at high altitudes. This study aimed to determine changes in the ONSD and IOP between participants with and without high myopia (HM) during hiking and to test whether these changes could predict symptoms of AMS. Methods: Nine participants with HM and 18 without HM participated in a 3-day trek of Xue Mountain. The ONSD, IOP, and questionnaires were examined before and during the trek of Xue Mountain. Results: The ONSD values increased significantly in bothHM(p = 0.005) and non-HMtrekkers (p = 0.018) at an altitude of 1,700 m. In theHMgroup, IOP levels were greater than those in the non-HM group (p = 0.034) on the first day of trekking (altitude: 3,150 m). No statistically significant difference was observed between the two groups for the values of ONSD. Fractional changes in ONSD at an altitude of 1,700m were related to the development of AMS (rpb = 0.448, p = 0.019) and the presence of headache symptoms (rpb = 0.542, p = 0.004). The area under the ROC curve for the diagnostic performance of ONSD fractional changes at an altitude of 1,700m was 0.859 for predicting the development of AMS and 0.803 for predicting the presence of headache symptoms. Conclusion: Analysis of changes in ONSD at moderate altitude could predict AMS symptoms before an ascent to high altitude. Myopia may impact physiological accommodation at high altitudes, and HM trekkers potentially demonstrate suboptimal regulation of aqueous humor in such environments. [ABSTRACT FROM AUTHOR]

In high-altitude environments, the oxygen and air density are decreased, and the temperature and humidity are low. When individuals enter high-altitude areas, they are prone to suffering from acute mountain sickness (AMS) because they cannot tolerate hypoxia. Headache, fatigue, dizziness, and gastrointestinal reactions are the main symptoms of AMS. When these symptoms cannot be effectively alleviated, they can progress to life-threatening high-altitude pulmonary edema or high-altitude cerebral edema. If the risk of AMS can be effectively assessed before people enter high-altitude areas, then the high-risk population can be promptly discouraged from entering the area, or drug intervention can be established in advance to prevent AMS occurrence and avoid serious outcomes. This article reviews recent studies related to the early-warning biological indicators of AMS to provide a new perspective on the prevention of AMS. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). Methods This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. Results The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07–0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3 − 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. Conclusions The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. Trial registration ClinicalTrials.gov NCT05023941.

Background: The effect of sleeping positions during acclimatization to high altitude on Acute Mountain Sickness (AMS) and High Altitude Pulmonary Edema (HAPE) is unknown. We tested whether sleeping with the upper body raised by 5° reduces prevalence and severity of symptoms of AMS as well as of elevated pulmonary artery systolic pressure (PASP) values as a risk factor of HAPE. Methods: Randomly assigning trekking tourist volunteers n = 44 (25 m, 19 f; mean age 42.9 yr) sleeping at 4280 m or 5170 m to the experimental group (upper body elevated by 5°), or to the control group. After exclusion of other reasons for AMS-like symptoms those assumed to be related to AMS were rated by Lake Louise Score questionnaire in the evening and the following morning of the study. Transthoracic echocardiography was performed on both occasions to estimate PASP. Results: In the study group, symptoms of AMS were significantly reduced in younger subjects (p = 0.021), prevalence of AMS was reduced in women (p = 0.156), and PASP values were significantly reduced in older subjects and men (p = 0.032; p = 0.031 respectively). Conclusion: Results suggest that sleeping with the upper body in elevated position during a high altitude ascent may benefit those suffering from AMS or at risk of HAPE due to elevated PASP values.

Background: We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). Methods: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. Results: The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07–0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3− 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. Conclusions: The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. Trial registration: ClinicalTrials.gov NCT05023941. [ABSTRACT FROM AUTHOR]

Horakova, Lenka, Peter Paal, Jacqueline Pichler Hefti, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, David Hillebrandt, Dominique Jean, Kastė Mateikaitė-Pipirienė, Alison J. Rosier, Susi Kriemler, and Linda E. Keyes. Women's health at high altitude: An introduction to a 7-part series by the International Climbing and Mountaineering Federation Medical Commission. High Alt Med Biol. 24:243–246, 2023. Background: Women have been traveling to high altitude since the inception of modern mountaineering. Although there are distinct female-specific features such as menstruation and menopause relevant to adaptation to and performance at high altitude, very little data exist on women's high-altitude health. To summarize what is known to date, the Medical Commission of the International Climbing and Mountaineering Federation (UIAA) has created a series of articles on women's health, high altitude illness, and performance at high altitude. Methods: Assembling an international author team, two types of manuscripts were developed: (1) reviews on female-specific topics such as pregnancy; (2) reviews on sex differences in high-altitude related illnesses, nutrition, cold injuries, and mortality. Results: The literature search yielded 7,165 articles, with 482 studies meeting the inclusion criteria for full-text review. The authors of individual chapters reviewed these articles and performed additional hand searches. Conclusions: Some important questions on women sojourning and exercising at high altitude have been studied, but many are still awaiting a qualified and evidence-based response. Our seven reviews, to be published in future issues of this journal, summarize what is known about lowland women sojourning at high altitude, provide recommendations, and highlight knowledge gaps in high altitude women's medicine. [ABSTRACT FROM AUTHOR]

Barclay, Holly, Saptarshi Mukerji, Bengt Kayser, and Jui-Lin Fan. Appetite, hypoxia and acute mountain sickness: A 10-hour normobaric hypoxic chamber study. High Alt Med Biol. 24:329–335, 2023. Background: The effects of hypoxia and acute mountain sickness (AMS) on appetite and food preferences are moot, especially during the early phase of hypoxic exposure. We examined the effects of a 10-hour hypoxic exposure on appetite and food preference. Methods: We assessed appetite (hunger, satisfaction, fullness, perceived appetite, and lost appetite), food preferences (sweet, salty, savory, and fatty), and AMS (Lake Louise score) with questionnaires in 27 healthy individuals (13 women) across 10-hour exposures to normobaric normoxia (fraction of inspired O2 [FiO2]: 0.21) and normobaric hypoxia (FiO2: 0.12, equivalent of 5,000 m) in a randomized, single-blinded manner. Results and Conclusions: Compared with normoxia, hypoxia decreased hunger and appetite (p = 0.040 and <0.001, respectively), which was mediated by a decreased desire for sweet, salty, and fatty foods (p < 0.05 for all). AMS was associated with a decreased desire for sweet (R = −0.438, p = 0.032) and salty foods (R = −0.460, p = 0.024) and greater loss of appetite (R = −0.619, p = 0.018). Our findings suggest that acute hypoxia rapidly suppresses appetite and that AMS development further amplifies anorexia. Clinical Trial Registration Number: ACTRN12618000548235 [ABSTRACT FROM AUTHOR]

Background: The diagnosis and evaluation of the severity of acute mountain sickness (AMS) continue to be problematic due to a lack of consensus on the inclusion of symptoms in a scoring system. Recent investigations highlight the significance of gastrointestinal symptoms in identifying this condition. However, the specific gastrointestinal symptoms associated with AMS have not been thoroughly elucidated in previous studies, and the underlying risk factors remain inadequately comprehended. Methods: This study aimed to investigate the characteristics, trends, and risk factors related to gastrointestinal symptoms encountered during train travel to high altitude. A total of 69 passengers, specifically all with medical backgrounds, were surveyed 6 times over a period of 14 days. Results: The daily incidence of abdominal discomfort was higher than non-gastrointestinal symptoms within 14 days. Gastrointestinal symptoms demonstrated a greater prevalence, longer duration, and increased risk compared to non-gastrointestinal symptoms, such as headaches. The symptoms of abdominal distension and bowel sound hyperaction were found to be prevalent and persistent among patients diagnosed with AMS, exhibiting a high incidence rate. Gender, age, body mass index (BMI), smoking habits, and alcohol consumption were identified as risk factors associated with the occurrence and duration of gastrointestinal symptoms. Conclusion: This study suggests that gastrointestinal symptoms are more common and persistent when traveling to the plateau by train. These symptoms should be taken into consideration in the further diagnosis and prevention of AMS. Therefore, this study provides a significant theoretical foundation for the prevention and treatment of AMS.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Xugang Tang,1,2 Xiuchuan Li,1 Qian Xin,3 Qiang Wang,1 Shuang Li,1 Yongjian Yang1 1Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 2Department of Cardiology, The No. 37 Hospital of Chinese PLA, Ya’an, Sichuan, People’s Republic of China; 3Department of Cardiology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongjian Yang, Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China, Tel +86 28 8657 1255, Fax +86 28 8657 1255, Email yyjcdzyy@sina.comPurpose: We aimed to explore whether anxiety is a risk factor for acute mountain sickness [AMS] in a young Chinese male population.Patients and Methods: A total of 143 young Chinese men with a median age of 23 years (IQR, 21– 25) were employed in the present study, and they were divided into the AMS+ and AMS- groups according to the Lake Louise AMS score [AMS-S] after exposure at 3800 m for two days. Participants’ pulse oximeter saturation [SpO2] and heart rate [HR] were measured. AMS was evaluated using the AMS-S. The anxiety and sleep quality of the subjects were assessed using the Zung Self-Rating Anxiety Scale [SAS] and the Athens Insomnia Scale [AIS], respectively. Outcomes were analysed using Spearman’s partial correlation and logistic regression analysis.Results: After two days of exposure at 3800 m, the overall prevalence of AMS was 54% in the whole group. The HR was significantly higher in the AMS+ group than in the AMS- group, as well as the SAS score and AIS score. A converse pattern was observed for SpO2. A significant difference was observed for the change in SAS and AIS score between the AMS+ and AMS- groups. Correlation analysis showed that AMS-S was positively correlated with SAS score, AIS score, HR, ΔSAS score, ΔAIS score, and ΔHR but negatively correlated with SpO2. AIS score was positively correlated with SAS score. After logistic regression analysis was adjusted for HR, SpO2, ΔAIS and ΔHR, SAS score (OR=1.446, 95% CI 1.200– 1.744, p< 0.001), AIS score (OR=1.216, 95% CI 1.033– 1.432) and ΔSAS score (OR=1.158, 95% CI 1.012– 1.327) were identified as independent risk factors for AMS.Conclusion: The present study suggests that anxiety is a risk factor for AMS among young Chinese men, and poor sleep quality may partially mediate the association.Keywords: anxiety, acute mountain sickness, high altitude, sleep

Dexamethasone can be taken prophylactically to prevent hypobaric hypoxia-associated disorders of high-altitude. While dexamethasone-mediated protection against high-altitude disorders has been clinically evaluated, detailed sex-based mechanistic insights have not been explored. As part of our India-Leh-Dexamethasone-expedition-2020 (INDEX 2020) programme, we examined the phenotype of control (n = 14) and dexamethasone (n = 13) groups, which were airlifted from Delhi (∼225 m elevation) to Leh, Ladakh (∼3,500 m), India, for 3 days. Dexamethasone 4 mg twice daily significantly attenuated the rise in blood pressure, heart rate, pulmonary pressure, and drop in SaO2 resulting from high-altitude exposure compared to control-treated subjects. Of note, the effect of dexamethasone was substantially greater in women than in men, in whom the drug had relatively little effect. Thus, for the first time, this study shows a sex-biased regulation by dexamethasone of physiologic parameters resulting from the hypoxic environment of high-altitude, which impacts the development of high-altitude pulmonary hypertension and acute mountain sickness. Future studies of cellular contributions toward sex-specific regulation may provide further insights and preventive measures in managing sex-specific, high-altitude-related disorders.

Introduction and purpose: Acute mountain sickness is caused by hypoxia, of which the brain is the most sensitive. The frequency of occurrence at altitudes above 2500 m above sea level may reach up to 75% of travelers. Prevention of altitude sickness mainly concerns the travel plan and pharmacology. Our study aimed to assess the current literature on altitude sickness, and discuss the possible pathophysiology, epidemiology, and symptoms. Moreover, we underline new guidelines for the treatment, prevention, and diagnosis of altitude sickness in the context of the last guidelines and research. We conducted a PubMed literature review using keywords like "mountaineering sickness" and "altitude sickness". All article types were taken into account: clinical trial, meta-analysis, case report, case series, systematic review, randomized controlled trial, observational study, clinical study, books, and documents in the last 5 years.A brief description of the state of knowledge: In recent years, there has been a surge in the accessibility and popularity of high-altitude tourism, emphasizing the need to disseminate information about altitude sickness among travelers. This heightened accessibility has sparked a push for comprehensive research and viable solutions, aiming to address the ramifications of the increased risk associated with such endeavors. Furthermore, there's a growing call for additional research focusing on the unique medical demands posed by tourist excursions and extreme expeditions. Conclusions:It underscores the necessity for healthcare professionals equipped with specialized knowledge and expertise in both preventing and treating medical conditions arising in exceptional circumstances.

Background: Ascending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive. Methods: A total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMSsusceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS. Results: The occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p<0.05), as well as in the validation cohort. Comparison of plasma protein profiles using GO analysis revealed that DEPs were primarily enriched in granulocyte activation, neutrophil mediated immunity, and humoral immune response. The comparison of potential biomarkers between the sAMS group and non-AMS group at low altitude revealed statistically higher levels of AAT, SAP and LTF in sAMS group (p=0.01), with a combined area under the curve(AUC) of 0.965. Compared to the mAMS group at low altitude, both SAP and LTF were found to be significantly elevated in the sAMS group, with a combined AUC of 0.887. HSP90-a and SAP exhibited statistically higher levels in the mAMS group compared to the non-AMS group at low altitude, with a combined AUC of 0.874. Conclusion: Inflammatory and immune related biological processes were significantly different between AMS-susceptible and AMS-resistant groups at low altitude and middle high-altitude. SAP, AAT, LTF and HSP90-a were considered as potential biomarkers at low altitude for the prediction of AMS. [ABSTRACT FROM AUTHOR]

Hypoxia induced intestinal barrier injury, microbial translocation, and local/systemic inflammation may contribute to high-altitude associated gastrointestinal complications or symptoms of acute mountain sickness (AMS). Therefore, we tested the hypothesis that six-hours of hypobaric hypoxia increases circulating markers of intestinal barrier injury and inflammation. A secondary aim was to determine if the changes in these markers were different between those with and without AMS. Thirteen participants were exposed to six hours of hypobaric hypoxia, simulating an altitude of 4572 m. Participants completed two 30-minute bouts of exercise during the early hours of hypoxic exposure to mimic typical activity required by those at high altitude. Pre- and post-exposure blood samples were assessed for circulating markers of intestinal barrier injury and inflammation. Data below are presented as mean ± standard deviation or median [interquartile range]. Intestinal fatty acid binding protein (Δ251 [103-410] pg•mL−1; p = 0.002, d = 0.32), lipopolysaccharide binding protein (Δ2 ± 2.4 μg•mL−1; p = 0.011; d = 0.48), tumor necrosis factor-α (Δ10.2 [3-42.2] pg•mL−1; p = 0.005; d = 0.25), interleukin-1β (Δ1.5 [0-6.7] pg•mL−1p = 0.042; d = 0.18), and interleukin-1 receptor agonist (Δ3.4 [0.4-5.2] pg•mL−1p = 0.002; d = 0.23) increased from pre- to post-hypoxia. Six of the 13 participants developed AMS; however, the pre- to post-hypoxia changes for each marker were not different between those with and without AMS (p > 0.05 for all indices). These data provide evidence that high altitude exposures can lead to intestinal barrier injury, which may be an important consideration for mountaineers, military personnel, wildland firefighters, and athletes who travel to high altitudes to perform physical work or exercise. [ABSTRACT FROM AUTHOR]

Small, Elan, Caleb Phillips, William Bunzel, Lakota Cleaver, Nishant Joshi, Laurel Gardner, Rony Maharjan, and James Marvel. Prior ambulatory mild coronavirus disease 2019 does not increase risk of acute mountain sickness. High Alt Med Biol. 24:201–208, 2023. Background: Given its long-term morbidity, understanding how prior coronavirus disease 2019 (COVID-19) may affect acute mountain sickness (AMS) susceptibility is important for preascent risk stratification. The objective of this study was to examine if prior COVID-19 impacts risk of AMS. Materials and Methods: This was a prospective observational study conducted in Lobuje (4,940 m) and Manang (3,519 m), Nepal, from April to May 2022. AMS was defined by the 2018 Lake Louise Questionnaire criteria. COVID-19 severity was defined using the World Health Organization-developed criteria. Results: In the Lobuje cohort of 2,027, 46.2% of surveyed individuals reported history of COVID-19, with 25.7% AMS point-prevalence. There was no significant relationship between prior ambulatory mild COVID-19 and AMS (p = 0.6) or moderate AMS (p = 1.0). In the Manang cohort of 908, 42.8% reported history of COVID-19, with 14.7% AMS point-prevalence. There was no significant relationship between prior ambulatory mild COVID-19 and AMS (p = 0.3) or moderate AMS (p = 0.4). Average months since COVID-19 was 7.4 (interquartile range [IQR] 3–10) for Lobuje, 6.2 (IQR 3–6) for Manang. Both cohorts rarely exhibited moderate COVID-19 history. Conclusions: Prior ambulatory mild COVID-19 was not associated with increased risk of AMS and should not preclude high-altitude travel. [ABSTRACT FROM AUTHOR]

Psychosis is a psychopathological syndrome that can be triggered or caused by exposure to high altitude (HA). Psychosis can occur alone as isolated HA psychosis or can be associated with other mental and often also somatic symptoms as a feature of delirium. Psychosis can also occur as a symptom of high altitude cerebral edema (HACE), a life-threatening condition. It is unclear how psychotic symptoms at HA should be classified into existing diagnostic categories of the most widely used classification systems of mental disorders, including the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and the International Statistical Classification of Diseases and Related Health Problems (ICD-11). We provide a diagnostic framework for classifying symptoms using the existing diagnostic categories: psychotic condition due to a general medical condition, brief psychotic disorder, delirium, and HACE. We also discuss the potential classification of isolated HA psychosis into those categories. A valid and reproducible classification of symptoms is essential for communication among professionals, ensuring that patients receive optimal treatment, planning further trips to HA for individuals who have experienced psychosis at HA, and advancing research in the field. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) causes a number of symptoms within the human body, associated with staying at altitudes higher than 2,500 meters above sea level without prior acclimatization. The human body begins to adapt its functioning to the conditions of hypobaric hypoxia in order to maintain homeostasis. Its disturbance can lead to respiratory failure, pulmonary, or cerebral oedema, and, consequently, death. The best method of AMS prevention is slow acclimatization. A high-carbohydrate diet, thermal protection, and pharmacological agents could be listed as additional prevention measures. The development of AMS is influenced by many factors such as ambient temperature, wind speed, altitude, physical preparation of participants, and appropriate protection against adverse effects of these factors. Nevertheless, both dehydration and overhydration may worsen the AMS symptoms. The body's exposure to altitude and dehydration alone reduces aerobic performance. Appropriate hydration throughout a climb is necessary due to both intense physical exercise and a hypoxic environment. [ABSTRACT FROM AUTHOR]

Anderson, Paul J., Christina M. Wood-Wentz, Kent R. Bailey, and Bruce D. Johnson. Objective versus self-reported sleep quality at high altitude. High Alt Med Biol. 24:144–148, 2023. Background: Previous studies have found little relationship between polysomnography and a diagnosis of acute mountain sickness (AMS) using the Lake Louise Symptom Questionnaire (LLSQ). The correlation between sleep question responses on the LLSQ and polysomnography results has not been explored. We compared LLSQ sleep responses and polysomnography data from our previous study of workers rapidly transported to the South Pole. Methods: Sixty-three subjects completed a 3-hour flight from sea level to the South Pole (3200 m, 9800 ft). Participants completed limited overnight polysomnography on their first night and completed LLSQ upon awakening. We compared polysomnography results at the South Pole with sleep question responses on the LLSQ to assess their degree of correspondence. Results: Twenty-two (30%) individuals reported no sleep problems whereas 20 (32%) reported some problems and 20 (33%) individuals reported poor sleep and 1 reported no sleep (n = 1). Median sleep efficiency was (94%) among response groups and mean overnight oxygen saturation was 81%. Median apnea hypopnea index (AHI; events/hour) was 10.2 in those who reported no problems sleeping, 5.1 in those reporting some problems sleeping, and 13.7 in those who reported poor sleep. These differences were not statistically significant. Conclusion: Self-reported sleep quality varied but there were no associated significant differences in sleep efficiency, overnight oxygen saturation, nor AHI. Studies that explore the role of objective sleep quality in the development of AMS should remove the sleep question on the LLSQ from AMS scoring algorithms. [ABSTRACT FROM AUTHOR]

Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema, which is the leading hypothesis of acute mountain sickness (AMS). However, studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature. This study aimed to investigate ocular microcirculation alterations, the only visualized capillaries in the central neural system (CNS), during early-stage AMS using a hypobaric chamber. This study found that after high altitude simulation, the optic nerve showed retinal nerve fiber layer thickening (P=0.004–0.018) in some locations, and the area of the optic nerve subarachnoid space (P=0.004) enlarged. Optical coherence tomography angiography (OCTA) showed increased retinal radial peripapillary capillary (RPC) flow density (P=0.003–0.046), particularly on the nasal side of the nerve. The AMS-positive group had the largest increases in RPC flow density in the nasal sector (AMS-positive, Δ3.21±2.37; AMS-negative, Δ0.01±2.16, P=0.004). Among multiple ocular changes, OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms (beta=0.222, 95%CI, 0.009–0.435, P=0.042). The area under the receiver operating characteristics curve (AUC) for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882 (95%CI, 0.746–0.998). The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS. RPC OCTA endpoints may serve as a rapid, noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes. [ABSTRACT FROM AUTHOR]

Abstract Background Acute Mountain Sickness (AMS) is one of the diseases that predispose to sudden ascent to high altitudes above 2500 m. Among the many studies on the occurrence and development of AMS, there are few studies on the severity of AMS. Some unidentified phenotypes or genes that determine the severity of AMS may be vital to elucidating the mechanisms of AMS. This study aims to explore the underlying genes or phenotypes associated with AMS severity and to provide evidence for a better understanding of the mechanisms of AMS. Methods GSE103927 dataset was downloaded from the Gene Expression Omnibus database, and a total of 19 subjects were enrolled in the study. Subjects were divided into a moderate to severe AMS (MS-AMS, 9 subjects) group and a no or mild AMS (NM-AMS, 10 subjects) group based on the Lake Louise score (LLS). Various bioinformatics analyses were used to compare the differences between the two groups. Another dataset, Real-time quantitative PCR (RT-qPCR), and another grouping method were used to validate the analysis results. Result No statistically significant differences in phenotypic and clinical data existed between the MS-AMS and NM-AMS groups. Eight differential expression genes are associated with LLS, and their biological functions are related regulating of the apoptotic process and programmed cell death. The ROC curves showed that AZU1 and PRKCG had a better predictive performance for MS-AMS. AZU1 and PRKCG were significantly associated with the severity of AMS. The expression of AZU1 and PRKCG were significantly higher in the MS-AMS group compared to the NM-AMS group. The hypoxic environment promotes the expression of AZU1 and PRKCG. The results of these analyses were validated by an alternative grouping method and RT-qPCR results. AZU1 and PRKCG were enriched in the Neutrophil extracellular trap formation pathway, suggesting the importance of this pathway in influencing the severity of AMS. Conclusion AZU1 and PRKCG may be key genes influencing the severity of acute mountain sickness, and can be used as good diagnostic or predictive indicators of the severity of AMS. Our study provides a new perspective to explore the molecular mechanism of AMS.

Acute mountain sickness (AMS) refers to the impact of the environment on body health at high elevations. It is classified into three based on the onset condition, namely, AMS, high-altitude cerebral edema, and high-altitude pulmonary edema. This type of sickness is a signal that tells the human body to adapt to the environment at 2500 m or above elevation, wherein low air pressure and oxygen will impair bodily functions. The Lake Louise AMS scale was created to assess the condition in adults. It was first developed in 1991 and remains a useful scale to help diagnose the severity of AMS. It was updated in 2018, in which sleep disturbance was removed as an indicating symptom.

Objective: To evaluate the efficacy of traditional Chinese medicine (TCM) for preventing acute mountain sickness (AMS). Methods: We included randomized controlled trials (RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6 major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals (CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0 (RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation (GRADE) approach. Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies (15/20) was of some concerns. In terms of the AMS incidence, Rhodiola rosea (R. rosea, Hong Jing Tian) and Ginkgo biloba (G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR (95% CI): 0.66 (0.43–1.01), 0.82 (0.63–1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR (95% CI): 2.92 (1.69–5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD (95% CI): -0.98 (-1.71, -0.25), -2.05 (-3.14, -0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude. Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

Abstract Background Acute Mountain Sickness (AMS) is typically triggered by hypoxia under high altitude conditions. Currently, rule of time among AMS inpatients was not clear. Thus, this study aimed to analyze the time distribution of AMS inpatients in the past ten years and construct a prediction model of AMS hospitalized cases. Methods We retrospectively collected medical records of AMS inpatients admitted to the military hospitals from January 2009 to December 2018 and analyzed the time series characteristics. Seasonal Auto-Regressive Integrated Moving Average (SARIMA) was established through training data to finally forecast in the test data set. Results A total of 22 663 inpatients were included in this study and recorded monthly, with predominant peak annually, early spring (March) and mid-to-late summer (July to August), respectively. Using the training data from January 2009 to December 2017, the model SARIMA (1, 1, 1) (1, 0, 1) 12 was employed to predict the test data from January 2018 to December 2018. In 2018, the total predicted value after adjustment was 9.24%, less than the actual value. Conclusion AMS inpatients have obvious periodicity and seasonality. The SARIMA model has good fitting ability and high short-term prediction accuracy. It can help explore the characteristics of AMS disease and provide decision-making basis for allocation of relevant medical resources for AMS inpatients.