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; Rajendra Kumar; Michael Mythen; Michael Grocott; Daniel Martin

doi:10.12688/f1000research.6297.1

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

F1000Res. 2015 Apr 10:4:90. doi: 10.12688/f1000research.6297.1. eCollection 2015.

Affiliations

¹ University 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.
² University 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.
³ Integrative 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.
⁴ University 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.
⁵ University 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.
⁶ University 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.

Abstract

Objective: Oxygen 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.

Methods: We 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.

Conclusion: This 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.

Keywords: Critical care; High altitude; Hypoxia; Microcirculation; Mitochondria; Nitric Oxide; Sherpa.

Grants and funding

No grant funding supported this work; financial contributions were provided by the following organisations: Xtreme Everest 2 was supported by the Royal Free Hospital NHS Trust Charity, the Special Trustees of University College London Hospital NHS Foundation Trust, the Southampton University Hospital Charity, the UCL Institute of Sports Exercise and Health, The London Clinic, University College London, University of Southampton, Duke University Medical School, the United Kingdom Intensive Care Society, the National Institute of Academic Anaesthesia, the Rhinology and Laryngology Research Fund, The Physiological Society, Smiths Medical, Deltex Medical, Atlantic Customer Solutions and the Xtreme Everest 2 volunteer participants who trekked to Everest Base Camp.