Evidence map›Paper›PMID 26064476›Full record

ArticleF1000Research2015

Design and conduct of Xtreme Everest 2: An observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia.

Edward Gilbert-Kawai, Adam Sheperdigian, Thomas Adams, Kay Mitchell, Martin Feelisch, Andrew Murray, Mark Peters, Grace Gilbert-Kawai, Hugh Montgomery, Denny Levett and 4 more

Abstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in F1000Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it

0cells of the map it votes in

10citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

Placental mitochondria in high-altitude pregnancy: metabolic adaptations and a toolkit for respiratory assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
Review
Determining Candidate Hypobaric Hypoxia Profiles for Humane Killing of Laboratory Mice.Frontiers in veterinary science · 2022
Article
Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.Physiological reports · 2021
Article
Enhanced flow-motion complexity of skin microvascular perfusion in Sherpas and lowlanders during ascent to high altitude.Scientific reports · 2019
Article
Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?Redox biology · 2019
Article
Population History and Altitude-Related Adaptation in the Sherpa.Frontiers in physiology · 2019
Review
The Smell of Hypoxia: using an electronic nose at altitude and proof of concept of its role in the prediction and diagnosis of acute mountain sickness.Physiological reports · 2018
Article
Near infrared spectroscopy with a vascular occlusion test as a biomarker in children with mitochondrial and other neuro-genetic disorders.PloS one · 2018
Observational
Metabolic basis to Sherpa altitude adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2017
Article
Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude.Journal of applied physiology (Bethesda, Md. : 1985) · 2017
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Edward Gilbert-KawaiUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Adam SheperdigianUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Thomas AdamsUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Kay MitchellUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK ; Integrative Physiology and Critical Illness Group, Faculty of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK ; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK ; NIHR Southampton Respiratory Biomedical Research Unit, Southampton, CB2 3EG, UK.

Martin FeelischIntegrative Physiology and Critical Illness Group, Faculty of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK ; NIHR Southampton Respiratory Biomedical Research Unit, Southampton, CB2 3EG, UK.

Andrew MurrayUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK ; Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.

Mark PetersUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK ; Critical Care Group Portex Unit, UCL, Institute of Child Health, London, WC1N 1EH, UK.

Grace Gilbert-KawaiUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Hugh MontgomeryUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Denny LevettUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Rajendra KumarUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK ; Nepal Health Research Council, Kathmandu, Nepal.

Michael MythenUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Michael GrocottUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK ; Integrative Physiology and Critical Illness Group, Faculty of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK ; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK ; NIHR Southampton Respiratory Biomedical Research Unit, Southampton, CB2 3EG, UK.

Daniel MartinUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, W1T 7HA, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveOxygen availability falls with ascent to altitude and also as a consequence of critical illness. Because cellular sequelae and adaptive processes may be shared in both circumstances, high altitude exposure ('physiological hypoxia') assists in the exploration of the response to pathological hypoxia. We therefore studied the response of healthy participants to progressive hypobaric hypoxia at altitude. The primary objective of the study was to identify differences between high altitude inhabitants (Sherpas) and lowland comparators.

methodsWe performed an observational cohort study of human responses to progressive hypobaric hypoxia (during ascent) and subsequent normoxia (following descent) comparing Sherpas with lowlanders. Studies were conducted in London (35m), Kathmandu (1300m), Namche Bazaar (3500m) and Everest Base Camp (5300m). Of 180 healthy volunteers departing from Kathmandu, 64 were Sherpas and 116 were lowlanders. Physiological, biochemical, genetic and epigenetic data were collected. Core studies focused on nitric oxide metabolism, microcirculatory blood flow and exercise performance. Additional studies performed in nested subgroups examined mitochondrial and metabolic function, and ventilatory and cardiac variables. Of the 180 healthy participants who left Kathmandu, 178 (99%) completed the planned trek. Overall, more than 90% of planned testing was completed. Forty-four study protocols were successfully completed at altitudes up to and including 5300m. A subgroup of identical twins (all lowlanders) was also studied in detail.

conclusionThis programme of study (Xtreme Everest 2) will provide a rich dataset relating to human adaptation to hypoxia, and the responses seen on re-exposure to normoxia. It is the largest comprehensive high altitude study of Sherpas yet performed. Translational data generated from this study will be of relevance to diseases in which oxygenation is a major factor.

Indexed as

Critical careHigh altitudeHypoxiaMicrocirculationMitochondriaNitric OxideSherpa

Identifiers

PMID26064476

DOI10.12688/f1000research.6297.1

PMCPMC4448741

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LicenceCC BY

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.