Hematological Risk Factors for High-Altitude Headache in Chinese Men Following Acute Exposure at 3,700 m

Huang, He; Bao, Lei; Wu, Gang; Xu, Gang; Sun, Bing‐Da; Gao, Yuqi

doi:10.3389/fphys.2017.00801

Cited by 9 publications

(6 citation statements)

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“…In addition, within hours of exposure to high altitude hypoxia, hypoxic tachypnea may lead to respiratory alkalosis, increased natriuresis and diuresis, promoting fluid shift away from intravascular space, result in blood concentration, even hypovolemia [ 21 ]. Our study observed most hematological parameters (RBC, Hgb, Hct, MCH, PLT, WBC and LYM#) were elevated from sea-level to altitude of 3700 m within a 72 h ascending processes, which also in consistency with previous studies [ 14 ].…”

Section: Discussionsupporting

confidence: 93%

“…Several studies have demonstrated that young age, smoking history, higher body mass index history of migraine, high heart rate (HR) and low pulse oxygen saturation (SpO 2 ) are independent risk factors for HAH [ 1 , 11 – 13 ]. Previously, Huang et al performed the first investigation on the relationship between hematological parameters and HAH before and after rapid ascending at 3700 m with 45 subjects, and found that HAH is associated with sea-level reticulocyte and neutrophil counts [ 14 ]. Because erythrocytes are the principal carrier of oxygen in the circulatory system, the hematological parameters may provide useful information regarding HAH.…”

Section: Introductionmentioning

confidence: 99%

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Physiological, hematological and biochemical factors associated with high-altitude headache in young Chinese males following acute exposure at 3700 m

Wang

Zhang

et al. 2018

J Headache Pain

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BackgroundHigh-altitude headache (HAH) is the most common sickness occurred in healthy people after rapid ascending to high altitude, and its risk factors were still not well understood. To investigate physiological, hematological and biochemical risk factors associated with high-altitude headache (HAH) after acute exposure to 3700 m, we conducted a two-stage, perspective observational study. In 72 h, total 318 young Han Chinese males ascended from sea level (altitude of 50 m) to altitude of 3700 m by train. Demographic data, physiological, hematological and biochemical parameters of all participants were collected within one week prior to the departure, and within 24 h after arrival.ResultsThe incidence of HAH was 74.84%. For parameters measured at sea level, participants with HAH exhibited significantly higher age and lower BUN (p < 0.05). For parameters measured at 3700 m, participants with HAH exhibited significantly lower blood oxygen saturation (SpO2), higher resting heart rate (HR), higher systolic blood pressure at resting (SBP) and lower blood urea nitrogen (BUN) (all p < 0.05). At 3700 m, the severity of HAH associated with SpO2, HR and BUN significantly (all p < 0.05). Multivariate logistic regression revealed that for parameters at sea level, BUN was associated with HAH [BUN (OR:0.77, 95% CI:0.60–0.99)] and for parameters at 3700 m, SpO2, HR and BUN were associated with HAH independently [SpO2 (OR:0.84, 95% CI:0.76–0.93); HR (OR:1.03, 95% CI:1.00–1.07); BUN (OR:0.64, 95% CI:0.46–0.88)]. No association between hematological parameters and HAH was observed.ConclusionWe confirmed that higher HR, lower SpO2 are independent risk factors for HAH. Furthermore, we found that at both 50 m and 3700 m, lower BUN is a novel independent risk factor for HAH, providing new insights for understanding the pathological mechanisms.Electronic supplementary materialThe online version of this article (10.1186/s10194-018-0878-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Physiological, hematological and biochemical factors associated with high-altitude headache in young Chinese males following acute exposure at 3700 m

Wang

Zhang

et al. 2018

J Headache Pain

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“…We calculated the sample number at 95% confidence interval, 80% chance of detection and ratio of wild type to homozygous haplotype carrying individuals being set at 0.2 for high altitude given 80% of the Tibetans carry this haplotype at high altitude and 50% of Tibetans carry this haplotype at sea level [ 10 , 16 ]. Based on available literature [ 34 , 35 ] addressing WBC and monocyte percentage alteration as a result of hypobaric hypoxia exposure we set a difference of 5% between means of the two genotypes and a standard deviation of 5. The calculation was done using CDC's statistics tool ( http://www.openepi.com/Menu/OE_Menu.htm ) The prediction of the sample size calculation was to collect 48 PHD2 D4E;C127S homozygous individuals and 10 PHD2 WT individuals from high altitude and 16 PHD2 D4E;C127S homozygous and 16 PHD2 WT individuals from sea-level.…”

Section: Methodsmentioning

confidence: 99%

Gain-of-function Tibetan PHD2D4E;C127S variant suppresses monocyte function: A lesson in inflammatory response to inspired hypoxia

et al. 2021

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Background We have previously described an evolutionarily selected Tibetan prolyl hydroxylase-2 (PHD2 D4E;C127S ) variant that degrades the hypoxia-inducible factor (HIFα) more efficiently and protects these highlanders from hypoxia-triggered elevation in haemoglobin concentration. High altitude is known to cause acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) in a section of rapidly ascending non-acclimatised lowlanders. These morbidities are often accompanied by inflammatory response and exposure to hypobaric hypoxia is presumed to be the principal causative agent. We have investigated whether PHD2 D4E;C127S variant is associated with prevention of hypoxia-mediated inflammatory milieu in Tibetan highlanders and therefore identify a potential target to regulate inflammation. Methods We genotyped the Tibetans using DNA isolated from whole blood. Thereafter immunophenotying was performed on PBMCs from homozygous PHD2 D4E;C127S and PHD2 WT individuals using flow cytometry. RNA isolated from these individuals was used to evaluate the peripheral level of important transcripts associated with immune as well as hypoxia response employing the nCounter technology. The ex-vivo findings were validated by generating monocytic cell lines (U937 cell line) expressing PHD2 D4E;C127S and PHD2 WT variants post depletion of endogenous PHD2. We had also collected whole blood samples from healthy travellers and travellers afflicted with AMS and HAPE to evaluate the significance of our ex-vivo and in vitro findings. Hereafter, we also attempted to resolve hypoxia-triggered inflammation in vitro as well as in vivo by augmenting the function of PHD2 using alpha-ketoglutarate (αKG), a co-factor of PHD2. Findings We report that homozygous PHD2 D4E;C127S highlanders harbour less inflammatory and patrolling monocytes in circulation as compared to Tibetan PHD2 WT highlanders. In response to in vitro hypoxia, secretion of IL6 and IL1β from PHD2 D4E;C127S monocytes, and their chemotactic response compared to the PHD2 WT are compromised, corresponding to the down-modulated expression of related signalling molecules RELA, JUN, STAT1, ATF2 and CXCR4 . We verified these functional outcomes in monocytic U937 cell line engineered to express PHD2 D4E;C127S and confirmed the down-modulation of the signalling molecules at protein level under hypoxia. In contrast, non-Tibetan sojourners with AMS and HAPE at high altitude (3,600 m above sea level) displayed significant increase in these inflammatory parameters. Our data henceforth underline the role of gain-of-function of PHD2 as the rate limiting factor to har...

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“…The CIBERSORT predictions also suggested that the expression profile of white blood cells exhibited inconsistencies. This result committed to the study at 3700 m demonstrated an increase in neutrophils and a slight decrease in lymphocytes [ 29 ] and exposure to acute hypoxia marginally raised the neutrophils [ 30 ]. However, several investigations revealed contradictory results.…”

Section: Discussionmentioning

confidence: 87%

Microarray-Based Prediction of Polycythemia after Exposure to High Altitudes

Wang

Liu

Song

et al. 2022

Genes

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In high-altitude environments, the prevalence of high-altitude polycythemia (HAPC) ranges between 5 and 18 percent. However, there is currently no effective treatment for this condition. Therefore, disease prevention has emerged as a critical strategy against this disease. Here, we looked into the microarray profiles of GSE135109 and GSE29977, linked to either short- or long-term exposure to the Qinghai Tibet Plateau (QTP). The results revealed inhibition in the adaptive immune response during 30 days of exposure to QTP. Following a gene set enrichment analysis (GSEA) discovered that genes associated with HAPC were enriched in Cluster1, which showed a dramatic upregulation on the third day after arriving at the QTP. We then used GeneLogit to construct a logistic prediction model, which allowed us to identify 50 genes that classify HAPC patients. In these genes, LRRC18 and HCAR3 were also significantly altered following early QTP exposure, suggesting that they may serve as hub genes for HAPC development. The in-depth study of a combination of the datasets of transcriptomic changes during exposure to a high altitude and whether diseases occur after long-term exposure in Hans can give us some inspiration about genes associated with HAPC development during adaption to high altitudes.

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Hematological Risk Factors for High-Altitude Headache in Chinese Men Following Acute Exposure at 3,700 m

Cited by 9 publications

References 46 publications

Physiological, hematological and biochemical factors associated with high-altitude headache in young Chinese males following acute exposure at 3700 m

Physiological, hematological and biochemical factors associated with high-altitude headache in young Chinese males following acute exposure at 3700 m

Gain-of-function Tibetan PHD2D4E;C127S variant suppresses monocyte function: A lesson in inflammatory response to inspired hypoxia

Microarray-Based Prediction of Polycythemia after Exposure to High Altitudes

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