Dataset Information

Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide.

ABSTRACT:

Introduction

Acetazolamide, a carbonic anhydrase inhibitor, remains the only FDA approved pharmaceutical prophylaxis for acute mountain sickness (AMS) though its effectiveness after rapid transport in real world conditions is less clear.

Methods

Over 2 years, 248 healthy adults traveled by airplane from sea level (SL) to the South Pole (ALT, ~3200m) and 226 participants provided Lake Louise Symptom Scores (LLSS) on a daily basis for 1 week; vital signs, blood samples, and urine samples were collected at SL and at ALT. Acetazolamide was available to any participant desiring prophylaxis. Comparisons were made between the acetazolamide with AMS (ACZ/AMS) (n = 42), acetazolamide without AMS (ACZ/No AMS)(n = 49), no acetazolamide with AMS (No ACZ/AMS) (n = 56), and the no acetazolamide without AMS (No ACZ/No AMS) (n = 79) groups. Statistical analysis included Chi-squared and one-way ANOVA with Bonferroni post-hoc tests. Significance was p?0.05.

Results

No significant differences were found for between-group characteristics or incidence of AMS between ACZ and No ACZ groups. ACZ/AMS reported greater LLSS, BMI, and red cell distribution width. ACZ/No AMS had the highest oxygen saturation (O2Sat) at ALT. No significant differences were found in serum electrolyte concentrations or PFT results.

Discussion

Acetazolamide during rapid ascent provided no apparent protection from AMS based on LLSS. However, it is unclear if this lack of effect was directly associated with the drug or if perhaps there was some selection bias with individuals taking ACZ more likely to have symptoms or if there may have been more of perceptual phenomenon related to a constellation of side effects.

SUBMITTER: Harrison MF

PROVIDER: S-EPMC4744068 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide.

Harrison Michael F MF Anderson Paul J PJ Johnson Jacob B JB Richert Maile M Miller Andrew D AD Johnson Bruce D BD

PloS one 20160205 2

<h4>Introduction</h4>Acetazolamide, a carbonic anhydrase inhibitor, remains the only FDA approved pharmaceutical prophylaxis for acute mountain sickness (AMS) though its effectiveness after rapid transport in real world conditions is less clear.<h4>Methods</h4>Over 2 years, 248 healthy adults traveled by airplane from sea level (SL) to the South Pole (ALT, ~3200m) and 226 participants provided Lake Louise Symptom Scores (LLSS) on a daily basis for 1 week; vital signs, blood samples, and urine sa ...[more]

PMID: 26848757

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Project description:Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

Project description:BackgroundWe 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).MethodsThis 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.ResultsThe 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.ConclusionsThe 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 registrationClinicalTrials.gov NCT05023941.

Project description:BackgroundAcute 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.MethodsGSE103927 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.ResultNo 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.ConclusionAZU1 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.

Dataset Information

Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide.

Introduction

Methods

Results

Discussion

Publications

Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide.

Similar Datasets

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