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Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia

Citation

Levett, DZ and Martin, DS and Wilson, MH and Mitchell, K and Dhillon, S and Rigat, F and Montgomery, HE and Mythen, MG and Grocott, MP and Ahuja, V and Aref-Adib, G and Burnham, R and Chisholm, A and Clarke, K and Coates, D and Coates, M and Cook, D and Cox, M and Dougall, C and Doyle, P and Duncan, P and Edsell, M and Edwards, LM and Evans, L and Gardiner, P and Gunning, P and Hart, N and Harrington, J and Harvey, J and Holloway, C and Howard, D and Hurlbut, D and Imray, C and Ince, C and Jonas, M and van der Kaaij, J and Khosravi, M and Kolfschoten, N and Luery, H and Luks, A and McMorrow, R and Meale, P and Morgan, G and Morgan, J and Murray, A and Newman, S and O'Dwyer, M and Pate, J and Plant, T and Pun, M and Richards, P and Richardson, A and Rodway, G and Simpson, J and Stroud, C and Stroud, M and Stygal, J and Symons, B and Szawarski, P and Van Tulleken, A and Van Tulleken, C and Vercueil, A and Wandrag, L and Windsor, J and Basnyat, B and Clarke, C and Hornbein, T and Milledge, J and West, J, Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia, BMC Medical Research Methodology, 10, (98) pp. 98-111. ISSN 1471-2288 (2010) [Refereed Article]

DOI: doi:10.1186/1471-2288-10-98

Abstract

Background. The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses. Methods. Design. Observational cohort study of progressive incremental exposure to EHH. Setting. University human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m. Participants. 198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest. Main outcome measures. Exercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry. Results. Of 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood flow velocity and microvascular blood flow at 7950 m and arterial blood gas measurement at 8400 m. Conclusions. This study demonstrates the feasibility and safety of conducting a large healthy volunteer cohort study of human adaptation to hypoxia in this difficult environment. Systematic measurements of a large set of variables were achieved in 222 subjects and at altitudes up to 8400 m. The resulting dataset is a unique resource for the study of genotype:phenotype interactions in relation to hypoxic adaptation. © 2010 Levett et al; licensee BioMed Central Ltd.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Medical Physiology
Research Field:Systems Physiology
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Edwards, LM (Dr Lindsay Edwards)
ID Code:68812
Year Published:2010
Web of Science® Times Cited:31
Deposited By:Medicine (Discipline)
Deposited On:2011-03-24
Last Modified:2011-07-27
Downloads:0

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