Funding

AT is formal, publicly funded military training. Participation in AT is ‘an integral aspect of military training that supports the values and standards of the military thus enhances an individual's ability to withstand the rigours of operations’.1 This direct public funding contributed around 50% of the costs for each subject which in turn facilitated the relatively large numbers for a research expedition. Research funding was supported by industry (Reveal LINQ (Medtronic, Dublin, Ireland) devices provided free of charge), public funding through RCDM, funding from Leeds Beckett University, University of Oxford, the Mount Everest Foundation and a grant from the Royal Navy Royal Marines Charity (RNRMC). It is exceptional for the RNRMC to support research in this way but a large fundraising event with the support of the Duke of York enabled the charity to raise sufficient funds to underwrite the research costs. Additional support with kit and equipment was provided by expedition sponsors notably Honda generators and Solarpod equipment to power the research kit described in the protocols.

Environment

For the initial part of the trek of the Dhaulagiri circuit, the terrain was at low altitude (although daily ascent was considerable) and through hot, humid pasture and rainforest. From Italian Base camp (IBC) onwards, the trek followed glaciated terrain around the western and northern aspects of Dhaulagiri. This terrain was dry and hot during the day and cold at night. Temperatures in the Hidden Valley (at 5140 m) were frequently around −10°C by night with considerable wind chill. By day temperatures in the direct sun or inside tents could be as high as +30°C. Above IBC all precipitation fell as snow due to the low temperatures, whereas IBC itself experienced heavy afternoon rain storms during the latter part of the expedition. All research took place in tents as there is no hard accommodation on the circuit above IBC, and frequently early in the morning to take measurements in the starved state. This placed a great strain on the research teams who had to work in extreme temperatures, often clad in one piece down suits!

Research protocols

The pathophysiology of HA illness remains ill-defined but the rate of AMS among military personnel ascending to HA as part of AT is significant, with 34% of those ascending Mount Kenya suffering severe AMS in one report.4 AMS was also a significant cause of disease non-battle injury (DNBI) during the Battle of Taku Ghar in Afghanistan in 2002 with 18 cases of AMS requiring casevac from theatre of operations and treatment by 274th Field Surgical Team.5 The programme of research on the expedition was aimed at enhancing our understanding of the pathophysiology of HA exposure and AMS and answering some of the questions raised previously in this journal.3 The following submissions were made to the Ministry of Defence Research Ethics Committee (MoDREC):

▸ Protocol 578, cardiovascular adaptation and recovery in chronic hypoxia: we have previously assessed various methods of recording HR variability (HRV) at HA6 and this study aimed to collect data on all the trekking teams, investigating changes in a range of physiological variables including HRV, central aortic BPs and pulmonary artery pressures.

▸ Protocol 580, utility of brain natriuretic peptide (BNP) in diagnosing AMS: we have previously published that BNP may have utility in the diagnosis of altitude illness.7–10 This study aims to recruit subjects who become unwell on expeditions at HA over the next few years. This will enable us to establish whether BNP can be used to discriminate between those with AMS or other conditions.

▸ Protocol 608, the effects of progressive HA on the development and burden of significant cardiac arrhythmias using an implantable cardiac monitor (REVEAL study): this study used a small implantable (into the subcutaneous fat of the upper chest) cardiac monitoring device, a ‘Reveal LINQ’. This has the capability to record and store information about HR and rhythm that can then be downloaded to a hard drive for subsequent analysis. The marked hypoxaemia that occurs at altitude could be arrhythmogenic and significant cardiac morbidity is known to occur at HA. This work builds on a smaller study using the predecessor to the current Reveal device that suggested significant arrhythmias do occur at HA.11

▸ Protocol 624, appetite responses during a HA expedition: very little is known about the underlying mechanisms regarding the anorexia and nausea suffered at HA, a topic previously reviewed in this journal.12 Reductions in appetite contribute to the degradation that ultimately impairs performance at HA. This project investigated nutritional changes at HA using food diaries, an assessment of gut hormones involved in appetite regulation and the novel use at HA of wearable technology assessing continuous subcutaneous interstitial glucose levels.

▸ Protocol 623, biomechanical changes in walking gait and balance at altitude: changes in balance may occur at HA and it has been suggested that changes in balance and walking style may be related to the development of AMS and to the incidence of falls and accidents on expeditions. This research examined joint position sense, balance and coordination through a series of assessments including video assessment of gait and balance using a force platform.

▸ Protocol 663, effects of iron status, manipulated using intravenous iron, on cardiopulmonary physiology during ascent to very HA, assessed using echocardiography and self-reported functional performance scores: exposure to the hypoxia of altitude leads to many physiological changes and a key feature is hypoxic pulmonary vasoconstriction (HPV). HPV increases pulmonary artery systolic pressure (PASP) and contributes to right ventricular strain and exaggerated HPV is a feature of HA Pulmonary Oedema (HAPE). This study used an intravenous iron infusion to optimise iron stores which at sea level is known to attenuate the HPV response to hypoxia.13 There has been one previous trial that has also shown a reduction in AMS following intravenous iron.14 Participants were randomised to receive iron or placebo and echocardiography used to assess their PASP in the field, while Lake Louise scores collected allow researchers to assess any difference in AMS rates.

▸ Protocol 586, acclimation and acclimatisation: the effects of exercise under normobaric (normal pressure) hypoxic (reduced FiO₂) conditions: we have been investigating the utility of ‘pre-acclimatisation’ in a hypoxic chamber in order to establish if such exposure can improve performance on deployment to HA and reduce HA illness. This protocol compared the effects of 5 days in a normobaric hypoxic chamber at simulated altitudes of between 4300 and 4800 m with a control group. Echocardiographic variables, biochemical and endocrine markers of physiological stress and indices of respiratory variables representing acclimatisation were assessed prehypoxic and posthypoxic exposure as well as during the expedition in order to elucidate any benefit. Additionally, rates of AMS have been assessed in the field to see if prior acclimation can reduce the threat from HA illness.

▸ Protocol 625, application of apnoeic training and physiological adaptations to altitude: free-divers expose themselves to periods of apnoea and prepare for this by a relatively simple method of ‘breath-holding’. Apnoea training induces changes that could potentially be of benefit at HA, including an increase in haematocrit, haemoglobin, erythropoietin and oxygen saturation.15 This protocol will employ a 6-week breath-hold training programme and compared this with a control group. Variables were assessed in the normobaric hypoxic chamber predeparture at a simulated 4800 m and while on the trek. These assessments included spleen volume, oxygen saturation, haemoglobin, haematocrit, erythropoietin and rates of AMS. Both protocols 586 and 625 benefit from access to the fixed normobaric chamber at Leeds Beckett University and a portable hypoxic chamber purchased with a grant from Joint Medical Command via the Defence Medical Services Research Steering Group.

Protocols were submitted to the Royal Air Force Scientific Advisory Committee (SAC) and subsequently MoDREC during 2014 to ensure plenty of lead in time and that projects could be in place prior to recruiting participants for the AT activity. The researchers acknowledge the efforts and diligence of both the SAC and MoDREC, whose input significantly enhanced the scientific work proposed. Working with sports science specialists at Leeds Beckett University allowed civilian colleagues to make use of an exceptional opportunity for research of this nature and the military researchers to gain from their expertise and equipment. A recce to the area and limited research conducted during February 2015 were hugely useful in finalising research plans and resulted in some limited amendments to protocols.

Participants were all members of Her Majesty's Forces taking part in an AT exercise and on duty. Selection for this expedition was via Defence Instructions and Notices advertising the event, advertisement through military climbing clubs and via word of mouth. Trekking teams were selected by individual leaders and not by the overall expedition leadership or principal investigators. Climbing teams were selected on the basis of previous climbing experience. The climbers were split onto a main team of 12 experienced mountaineers to climb Dhaulagiri and a HA development team (HADT), of 12 less experienced HA mountaineers to climb Tukuche peak and gain experience. Once involved in the expedition, participants were invited to take part in specific research studies. Participants were invited to participate in studies depending on time availability and geographical location before written informed consent was obtained. Where teams were used as controls for an intervention group, every effort was made to match military backgrounds of individuals to ensure similar levels of fitness.

All participants received a brief on mountain health including AMS and the military policy of not using prophylactic acetazolamide (Diamox) in this setting. Baseline data were collected in the UK by a suitably qualified researcher before any pre-acclimatisation training took place.

On the expedition, data were collected by the subjects (daily diaries) and then at three research camps established for the duration of the expedition at 3600 m (IBC), 4600 m (Dhaulagiri BC) and 5140 m in the Hidden Valley. These camps had resident staff of two trained researchers with at least one medically qualified in each location; additional researchers (military or Leeds Beckett staff) accompanied specific trekking teams to collect specialist data (continuous glucose measurements, cardiac echo, spleen ultrasound and conduct balance testing).

Climbing teams had background data collected at the time of Reveal LINQ device insertion or when enrolled in the iron study. Any potential subject who could not comply with these timings (usually for service reasons) were not included in these studies, although data were collected for non-intervention studies. All participants were low-altitude dwellers, no trekking team members had exposure to >1500 m terrestrial altitude in the 4 weeks prior to the studies.

Research protocols undertaken by the climbers were developed mindful of minimising the impact of research data collection when in country. All team members flew to Kathmandu via long haul international flights and baseline data were collected the day after arrival or after 4 days in Kathmandu in the case of the advance party. This involved recording symptoms, SpO₂ (Nonin Onyx, Nonin Medical, Plymouth, Minnesota), haemoglobin (Haemocue, Haemocue AB, Angelholm, Sweden), cardiac function and pulmonary artery pressures (Vivid I, GE Healthcare, Amersham, UK) and was completed by one experienced cardiologist blinded to the intervention (in the case of the iron study). The team then moved to 2750 m by road, where a further data collection period took place (day 4). After day 4, all altitude changes where accomplished on foot carrying moderate loads (5–10 kg). Further altitude changes are given in Table 1. Climbers completed an individual itinerary depending on self-declared fitness to continue with the ascent profile and rest days taken as required. Subjects recorded daily Lake Louise self-reported scores (LLS), AMSc scores, anxiety questionnaires (Satet/trait anxiety inventory (STAI)), SpO₂, HR and HRV via iThlete app. The iThlete app records HRV over a 1 min period of timed ventilation (20 breaths) to give a number indicating HRV. The HR is recorded onto a smart phone using the microphone of phones and a finger probe. This number is based on root mean squares of successive differences of HRV and we have recently published the validity of the iThlete app versus conventional HRV measurement.6 HRV recordings were not blinded and were taken by the individual first thing in the morning, in a seated position, before food or caffeine wherever possible. Decisions regarding individual fitness to continue with the itinerary or climb higher were made regardless of HRV reading (after consultation with a medical officer who was also unaware of HRV reading where necessary). Borg Rating of Perceived Exertion for the ‘sessional exertion’ each day was recorded each evening and subjects asked to record their perception as to how hard the hardest bout of exercise that day had been (on a scale of 6–20). Reveal LINQ cardiac rhythm monitors were inserted into members of the climbing team by a consultant cardiologist (CB) at Poole Hospital during January 2016. The device automatically records any tachycardia, bradycardia or arrhythmia. Baseline data were collected automatically via the Carelink system in the UK and downloaded every few days using a larger programmer device in Nepal.

Trekking teams were invited to take part in studies 580, 578, 586, 623, 624 and 625. Recruitment and interest in the studies was high.

All trekkers arrived in Kathmandu by long-haul air travel and travelled by road to 1123 m before attempting a trek of the Dhaulagiri circuit. Each team was accompanied by a medical officer who advised on any changes in itinerary based on team or individual acclimatisation. Further medical support was available at 3600, 4650 and 5140 m. The itinerary (Table 2) and altitude profile (Figure 1) are below. Changes of itinerary were made as necessary when trekkers showed signs of AMS. Trekkers completed a daily recording of LLS, AMS scores, STAI, SpO₂, HR. At 3600, 4650 and 5140 m, HRV was recorded via a Checkmyheart Heart rate monitor device (Daily Care Medical, Neihu, Taiwan). This was a conventional single-lead ECG and data were downloaded to a laptop to be analysed offline by a cardiologist who was blinded to the individuals' performance and LLS.

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Figure 1

Altitude profile for trekking teams.