Search Results (20)

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

Wilderness medicine is a rapidly evolving field and has benefited from expanded research efforts. Moreover, with an escalating occurrence of severe and cataclysmic global climatologic events, human illness arising from interaction with wilderness and recreational environments warrants increasing consideration. Within the last decade, the Wilderness Medical Society (WMS) has aggregated research findings and created guidelines on prevention measures and therapeutic options for acute altitude illness, frostbite injuries, and avalanche and non-avalanche snow burials. As new research emerges, some guidelines have been updated to reflect the most current and sound scientific conclusions. In this review, we have synthesized the evidence-based guidelines and have reviewed the quality of the guidelines according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework. Further research efforts can expand the scope of evidence-based practice in travel medicine and ideally standardize the implementation of recommendations within both pre-travel and post-travel medical practices. Full article

The Qinghai–Tibet Plateau, famously known as the “Roof of the World”, has witnessed a surge in individuals traveling or working there. However, a considerable percentage of these individuals may suffer from acute mountain sickness (AMS), with high-altitude pulmonary edema (HAPE) being a severe and potentially life-threatening manifestation. HAPE disrupts the balance of intrapulmonary tissue fluid, resulting in severe lung function impairment. Current therapeutic interventions for HAPE have limitations and are accompanied by significant side effects. Aldose reductase (AR), a crucial enzyme in the polyol metabolic pathway, has been implicated in various diseases. In this study, we sought to explore the role of AR in HAPE. Utilizing both in vivo and in vitro models, we investigated the impact of AR on hypoxia-induced pulmonary edema, vascular pressure, inflammatory factors, and oxidative stress. Our findings revealed that AR knockdown mitigated hypoxia-induced pulmonary edema, decreased the expression of vascular pressure and inflammatory factors, and enhanced the expression related to oxidative stress. These results indicate that AR may serve as a potential therapeutic target for HAPE, offering a plausible pathological basis and novel drug targets for the prevention and treatment of this condition. Full article

High-altitude diseases, including acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE), are closely related to an individual’s ability to adapt to hypoxic environments. However, specific research in this field is relatively limited, and further biomarker research and clinical trials are needed to clarify the exact role and potential therapeutic applications of key genes in high-altitude diseases. This study focuses on the role of the STC1 gene in high-altitude diseases and explores its expression patterns in different types of cancer. By using gene expression data analysis and functional experiments, we identified STC1 as a key gene affecting the development of altitude sickness. In addition, we also conducted expression and mutation analysis on STC1 in various cancer samples and found significant differences in the expression of this gene in 13 types of malignant tumors, which is associated with the hypoxic state in the tumor microenvironment. In addition, STC1 is significantly associated with patient prognosis and influences tumor immunity by mediating six types of immune cells (CD8+T cells, CD4+T cells, neutrophils, macrophages, monocytes, and B cells) in the tumor microenvironment. The expression and diagnostic value of STC1 were confirmed through GEO datasets and qPCR testing, indicating consistency with the results of bioinformatics analysis. These results indicate that STC1 is not only an important factor in the adaptive response to high-altitude diseases but may also play a role in the adaptation of cancer to low-oxygen environments. Our research provides a new perspective and potential targets for the discovery of biomarkers for high-altitude diseases and cancer treatment. Full article

Background: The illnesses associated with changes in barometric pressure can be classified into three types: acute mountain sickness, high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema. HAPE is a rare form of pulmonary edema that occurs in susceptible individuals after arriving at altitudes over 2500 m above sea level (m). Only a few studies have reported classical HAPE among children with underlying cardiopulmonary comorbidities. In this study, we report two pediatric cases of classical HAPE that occurred immediately upon arriving at Abha city (with an average elevation of 2270 m above sea level). Notably, both patients possessed underlying chronic lung diseases, raising crucial questions about susceptibility factors and the early onset manifestations of HAPE. Case: Two pediatric cases of HAPE are presented. The first patient, with a medical history of repaired right congenital diaphragmatic hernia and subsequent right lung hypoplasia, developed HAPE following their ascent to a high altitude. The second patient, diagnosed with diffuse lung disease of unknown etiology, experienced HAPE after a rapid high-altitude ascent. Both patients resided in low-altitude areas prior to ascent. The initial emergency room assessment revealed that both patients had severe hypoxia with respiratory distress that mandated the initiation of respiratory support and 100% oxygen therapy. They required intensive care unit admission, improved after 5 days of hospitalization, and were sent home in good condition. Conclusion: HAPE is a complex, potentially life-threatening high-altitude illness with diverse clinical presentations and variable risk factors. This case report sheds light on a potential predisposition factor—pre-existing lung disease—in children experiencing severe HAPE. While further validation is crucial, this valuable insight opens doors for improved preventative strategies and informed medical decisions for children with pre-existing lung conditions traveling to high altitudes. Full article

The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training. Full article

Background: Improvement of oxygenation is the aim in the therapy of high-altitude pulmonary edema (HAPE). However, descent is often difficult and hyperbaric chambers, as well as bottled oxygen, are often not available. We compare Auto-PEEP (AP-Pat), a special kind of pursed lips breathing, against the application of bottled oxygen (O₂-Pat) in two patients suffering from HAPE. Methods: We compare the effect of these two different therapies on oxygen saturation measured by pulse oximetry (SpO₂) over time. Result: In both patients SpO₂ increased significantly from 65–70% to 95%. Above 80% this increase was slower in AP-Pat compared with O₂-Pat. Therapy started immediately in AP-Pat but was delayed in O₂-Pat because of organizational and logistic reasons. Conclusions: The well-established therapies of HAPE are always the option of choice, if available, and should be started as soon as possible. The advantage of Auto-PEEP is its all-time availability. It improves SpO₂ nearly as well as 3 L/min oxygen and furthermore has a positive effect on oxygenation lasting for approximately 120 min after stopping. Auto-PEEP treatment does not appear inferior to oxygen treatment, at least in this cross-case comparison. Its immediate application after diagnosis probably plays an important role here. Full article

High altitude hypoxia stress is the key cause of high-altitude pulmonary edema and spleen contraction. The molecular mechanism of immune response of various tissue systems to hypoxia stress remains lacking. In this study, we applied proteomics combined with metabolomics to explore the key molecular profilings involved in high altitude hypoxia response in the spleen of mice. The results showed that 166 proteins were significantly up-regulated, and only 39 proteins were down-regulated. Bioinformatics analysis showed that mineral absorption, neuroactive ligand–receptor interaction, arachidonic acid metabolism, IL-17 signaling pathway and NOD-like preceptor signaling pathway were significantly enriched in the list of 166 upregulated differentially expressed proteins (DEPs). Among these metabolic pathways, the former three pathways were co-identified in KEGG terms from LC-MS/MS based metabolic analysis. We further found that both arachidonate 15-lipoxygenase and hematopoietic prostaglandin D synthase were upregulated by around 30% and 80% for their protein levels and mRNA levels, respectively. Most downstream metabolites were upregulated accordingly, such as prostaglandin A2 and D2. This study provides important evidence that arachidonic acid metabolism potentially promotes spleen hypoxia response through a combined analysis of proteomics and metabolism, which could bring new insights for the spleen targeted rational design upon arachidonic acid metabolism of new therapies. Full article

Background: At altitudes above 2500 m, the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20–65 years en route to the Solu Khumbu region of Nepal were assessed. Echocardiograph measurements were performed at Lukla (2860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5675 m). The altitude profile and the participants’ characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase in SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the respective initial measurements at Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox^® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation, and heart rate. Conclusions: The echocardiograph results indicated that older people are an at-risk group for developing HAPE. A conservative interpretation of the basic tactical rules for altitudes should be followed for older trekkers or trekkers with known problems of altitude acclimatization (“slow acclimatizer”) as SPAP elevates with age. The prophylactic use of Acetazolamide (Diamox^®) should be avoided where not necessary for acute medical reasons. Acetazolamide leads to an increase of SPAP, and this may potentially enhance the risk of developing HAPE. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and a rule of thumb for the altitude profile, but does not replace a HAPE diagnosis. Backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p ≤ 0.05). Full article

Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic alterations in an organism. In the lung, one of the principal responses to hypoxia is the development of hypoxic pulmonary vasoconstriction (HPV), which improves gas exchange. However, when HPV is exacerbated, it induces high-altitude pulmonary hypertension (HAPH). Another important illness in hypobaric hypoxia is high-altitude pulmonary edema (HAPE), which occurs under acute exposure. Several studies have shown that inflammatory processes are activated in high-altitude illnesses, highlighting the importance of the crosstalk between hypoxia and inflammation. The aim of this review is to determine the inflammatory pathways involved in hypobaric hypoxia, to investigate the key role of inflammation in lung pathologies, such as HAPH and HAPE, and to summarize different anti-inflammatory treatment approaches for these high-altitude illnesses. In conclusion, both HAPE and HAPH show an increase in inflammatory cell infiltration (macrophages and neutrophils), cytokine levels (IL-6, TNF-α and IL-1β), chemokine levels (MCP-1), and cell adhesion molecule levels (ICAM-1 and VCAM-1), and anti-inflammatory treatments (decreasing all inflammatory components mentioned above) seem to be promising mitigation strategies for treating lung pathologies associated with high-altitude exposure. Full article

Climbers and aviators are exposed to severe hypoxia at high altitudes, whereas divers are exposed to hyperoxia at depth. The aim of this study was to report changes in the adenosinergic system induced by exposure to extreme oxygen partial pressures. At high altitudes, the increased adenosine concentration contributes to brain protection against hypoxia through various mechanisms such as stimulation of glycogenolysis for ATP production, reduction in neuronal energy requirements, enhancement in 2,3-bisphosphoglycerate production, and increase in cerebral blood flow secondary to vasodilation of cerebral arteries. In the context of mountain illness, the increased level of A_2AR expression leads to glial dysfunction through neuroinflammation and is involved in the pathogenesis of neurological disorders. Nonetheless, a high level of adenosine concentration can protect against high-altitude pulmonary edema via a decrease in pulmonary arterial pressure. The adenosinergic system is also involved in the acclimatization phenomenon induced by prolonged exposure to altitude hypoxia. During hyperoxic exposure, decreased extracellular adenosine and low A_2A receptor expression contribute to vasoconstriction. The resulting decrease in cerebral blood flow is considered a preventive phenomenon against cerebral oxygen toxicity through the decrease in oxygen delivery to the brain. With regard to lung oxygen toxicity, hyperoxia leads to an increase in extracellular adenosine, which acts to preserve pulmonary barrier function. Changes in the adenosinergic system induced by exposure to extreme oxygen partial pressures frequently have a benefit in decreasing the risk of adverse effects. Full article

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors. Full article

Several diseases associated with high-altitude exposure affect unacclimated individuals. These diseases include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), chronic mountain sickness (CMS), and, notably, high-altitude pulmonary hypertension (HAPH), which can eventually lead to right ventricle hypertrophy and heart failure. The development of these pathologies involves different molecules and molecular pathways that might be related to oxidative stress. Studies have shown that acute, intermittent, and chronic exposure to hypobaric hypoxia induce oxidative stress, causing alterations to molecular pathways and cellular components (lipids, proteins, and DNA). Therefore, the aim of this review is to discuss the oxidative molecules and pathways involved in the development of high-altitude diseases. In summary, all high-altitude pathologies are related to oxidative stress, as indicated by increases in the malondialdehyde (MDA) biomarker and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant activity. In addition, in CMS, the levels of 8-iso-PGF2α and H₂O₂ are increased, and evidence strongly indicates an increase in Nox4 activity in HAPH. Therefore, antioxidant treatments seem to be a promising approach to mitigating high-altitude pathologies. Full article

Background: Despite a potential high risk of acute mountain sickness (AMS) in the Swiss Alps, there is a lack of analyses concerning its relevance over longer periods. In consequence, the aim of this study is to analyze the prevalence of AMS in comparison to other causes of mountain emergencies in recent years in Switzerland. Material and Methods: Based on the central registry of mountain emergencies of the Swiss Alpine Club (SAC), all cases in the period between 2009 and 2020 were analyzed for AMS including the most severe forms of high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Emergencies were assessed for the severity of the event with a National Advisory Committee for Aeronautics (NACA) score. Results: From a total of 4596 high-altitude mountaineering emergencies identified in the observational period, a total number of 352 cases of illnesses were detected. Detailed analysis revealed 85 cases of AMS, 5 cases of HAPE, and 1 case of HACE. The average altitude was 3845 ± 540 m. Most cases were in the canton of Valais, especially in the Monte Rosa region and the mountains of the Mischabel group (Täschhorn, Dom, Südlenz, Nadelhorn, Hohberghorn). There were only three deaths related to high-altitude illnesses; all the other events could be identified as moderate to severe but not life-threatening. Discussion: An emergency due to AMS that requires rescue is unlikely in the Swiss Alps. This does not imply that AMS is not a concern. However, the facts that the maximal altitude is relatively low and that fast self-descents often seem possible probably minimize the likelihood that mountaineers with symptoms contact emergency services. Full article

Decreased oxygen saturation (SO₂) at high altitude is associated with potentially life-threatening diseases, e.g., high-altitude pulmonary edema. Wearable devices that allow continuous monitoring of peripheral oxygen saturation (SpO₂), such as the Garmin Fēnix^® 5X Plus (GAR), might provide early detection to prevent hypoxia-induced diseases. We therefore aimed to validate GAR-derived SpO₂ readings at 4559 m. SpO₂ was measured with GAR and the medically certified Covidien Nellcor SpO₂ monitor (COV) at six time points in 13 healthy lowlanders after a rapid ascent from 1130 m to 4559 m. Arterial blood gas (ABG) analysis served as the criterion measure and was conducted at four of the six time points with the Radiometer ABL 90 Flex. Validity was assessed by intraclass correlation coefficients (ICCs), mean absolute percentage error (MAPE), and Bland–Altman plots. Mean (±SD) SO₂, including all time points at 4559 m, was 85.2 ± 6.2% with GAR, 81.0 ± 9.4% with COV, and 75.0 ± 9.5% with ABG. Validity of GAR was low, as indicated by the ICC (0.549), the MAPE (9.77%), the mean SO₂ difference (7.0%), and the wide limits of agreement (−6.5; 20.5%) vs. ABG. Validity of COV was good, as indicated by the ICC (0.883), the MAPE (6.15%), and the mean SO₂ difference (0.1%) vs. ABG. The GAR device demonstrated poor validity and cannot be recommended for monitoring SpO₂ at high altitude. Full article