The popularity of using normobaric hypoxia (NH) to prepare for hypobaric hypoxia (HH) experienced during mountaineering activities at real altitude raises the question about the comparability between the effects of NH and HH. The primary condition that differs between NH and HH is the mechanism by which partial pressure of inspired oxygen (P_iO₂) is reduced, with P_iO₂ defined as inspired oxygen fraction (FiO₂) × (P_B-47 mmHg). Reductions in P_iO₂ can be achieved by altering the barometric pressure (P_B) in HH or the inspired fraction of oxygen (F_iO₂) in NH (Conkin and Wessel, 2008). Since seminal work by Paul Bert in 1878, lower P_iO₂ has been assumed to be the primary stimulus for adapting to any hypoxic state (Bert, 1878; Conkin and Wessel, 2008). More recently, a direct relationship between lower arterial partial pressure of carbon dioxide (PaCO₂) and the reduction of P_B was found, proposing a synergistic effect of environmental pressure and F_iO₂ (Saltzman et al., 1971; Savourey et al., 2003). This effect has been used to explain differences regarding the physiological responses in HH compared to NH environments (Tucker et al., 1983; Roach et al., 1996; Loeppky et al., 2005).

Peripheral oxygen saturation (SpO₂) and arterial blood oxygen saturation (SaO₂) have been found to be significantly lower in HH compared to NH. This has been speculated to be due to increased dead space ventilation, provoked by a lower tidal volume (V_t) and a higher breathing frequency (f) (Savourey et al., 2003, 2007). Accordingly, PaCO₂ decreases with alkalemia as a consequence, shifting the oxyhemoglobin dissociation curve to the left (Savourey et al., 2003). A recent review describes the variations in ventilation in NH and HH (Coppel et al., 2015). The heart rate (HR) is increased in HH (Savourey et al., 2007; Self et al., 2011; Faiss et al., 2013). The severity of acute mountain sickness (AMS) as a result of physiological differences in HH appears to be greater as well (Tucker et al., 1983; Roach et al., 1996; Loeppky et al., 2005).

After years of altitude research most differences between NH and HH appear to be sufficiently explored.

However, one aspect that is still debated is the interchangeability of the HH and NH environments regarding their effects on physiological responses. Previous studies often lack standardization or detailed documentation and do not provide comparability of study designs (Millet et al., 2012a,b; Mounier and Brugniaux, 2012; Saugy et al., 2016). Most of the studies conducted used laboratory settings for both NH and HH (Millet et al., 2012a) Since the advent of chamber research on hypoxia, questions have remained regarding the comparability between conditions of the simulated chamber environment and the real-life mountain environment.

According to a recent review, several studies have compared NH and HH but the comparison of laboratory (NH) and field (HH) environments in a single standardized study has not yet been performed (Coppel et al., 2015). To show differences in SpO₂, HR, and AMS between laboratory NH and field HH conditions we conducted measurements of these parameters during a hike in simulated altitude and again in real altitude, standardizing variables as much as possible to allow for maximal comparability over the course of a 7-h exposure time. We hypothesized that we could verify the significant differences in SpO₂, HR, and AMS previously reported by other researchers from laboratory research and research at fixed altitudes by performing a study protocol with continuously increasing altitude in the field.

All participants completed the two exposure trials successfully. During ascent in NH, F_iO₂ was lowered continuously from 14.6% at 2,800 m, 13.2% at 3,500 m to 12.1% at 4,205 m (P_B = 767.3 mmHg). The room air CO₂ concentration was kept relatively constant during the experiment at 884 ppm ± 325 within limits that did not influence ventilation. On the mountain, P_B was measured with a value of 550 mmHg at 2,800 m, 496 mmHg at 3,500 m and 465 mmHg at 4,205 m (Figure 1). Temperature ranged in both conditions (at Mauna Kea between sunrise and sunset) at all altitude levels around 20°C (19–24°C) and humidity was between 50 and 60% (average on Mauna Kea 58%; in the chamber 55%). Wind speed on Mauna Kea was below 5 mph.

An overall statistical difference between NH and HH regarding HR and SpO₂ was detected (p < 0.05; Tables 2, 3). However, AMS scores did not differ significantly between the chamber and the mountain. Self-reported Borg scale values showed no difference (p = 1.00) for rate of perceived exertion in both NH (12.33 ± 2.07) and HH (12.33 ± 1.75).

This is the first study to compare a 7-h simulated high altitude hike in a normobaric hypoxia chamber and a mountain hike at real altitude. This study provides a descriptive comparison of physiological parameters (HR and SpO₂) and AMS scores measured in a chamber (NH) and on the mountain (HH). Our findings do verify previously reported differences for SpO₂ and HR, with SpO₂ values significantly lower and HR values significantly higher in a HH environment compared to NH. However, in contrast to prior reports, AMS severity did not differ significantly between the two settings.

Using a study design similar to our protocol, Savourey et al. also found SpO₂ to be significantly lower in a hypobaric chamber (HH) compared to NH with a simulated altitude exposure to 4,500 m (Savourey et al., 2003). The Savourey study was performed at a fixed altitude for a limited time only. However, ventilation was measured and revealed increased dead space ventilation in HH due to a lower tidal volume (V_t) and a higher frequency of breathing (f). This breathing pattern caused a lower PaCO₂, alkalemia, and a lower SpO₂ than in NH (Savourey et al., 2003). Other studies reported a direct relationship between a lower PaCO₂ and the reduction of P_B (Saltzman et al., 1971). To explain the findings of significantly lower SaO₂ values in HH compared to NH at a simulated altitude of 7,620 m a synergistic effect of hypoxia and hypobaria was proposed (Levine et al., 1988; Self et al., 2011).

The studies cited above were characterized by a short exposure time to hypoxia (<1 h) at fixed altitudes. The importance of exposure time was emphasized in a review of five long-term hypoxia exposure studies (>1 h) which did not show any differences in SpO₂ between NH and HH,(Tucker et al., 1983; Roach et al., 1996; Loeppky et al., 1997, 2005; Faiss et al., 2013) possibly due to acclimatization to hypoxia (Coppel et al., 2015). What sets our study apart from prior research is that the study design incorporated a long exposure time at increasing altitudes with movement and exercise performance utilizing actual mountaineering conditions.

Subjects 1 and 3 reacted with values ranging from 90 to 93% in HH compared to 88 and 91% in NH around the 3,500 m break. Because both participants were women, a likely explanation of this finding may be increased respiratory drive due to higher progesterone levels in these participants.

In previous short-term as well as in long-term exposure studies, heart rate values tended to be higher in HH, but showed inconsistent results compared to NH (Savourey et al., 1997). In their first study, Savourey et al. recorded HR values that were significantly higher in HH, whereas in their second study no significant differences in HR were found, despite using a very similar protocol (Savourey et al., 2003, 2007). While the subjects of Savourey et al. were exposed to altitude for only 40 min, Faiss et al. conducted a 24-h exposure study at 3,000 m and did not find any significant differences in HR at rest or during moderate physical activity between conditions of NH and HH (Faiss et al., 2013). In our study HR was significantly higher in HH for the duration of 7 h. The increased HR values may be explained by a need for higher cardiac output due to a lower minute ventilation (V_E) from faster and shallower breathing in HH as has often reported in studies (Savourey et al., 2007; Self et al., 2011; Faiss et al., 2013).

There are other possible explanations for the increased HR we demonstrated during the mountain trail hike: (a) the ground surface on the Humu'ula trail is uneven compared to a treadmill and could have elicited higher exercise performance, (b) ultraviolet light radiation of the sun could have led increased fluid loss on the mountain trail compared to the chamber conditions. With restrictions on fluid intake to maintain comparability of intake between study settings, volume depletion with consequent tachycardia may have occurred, and (c) participants reported marked differences in group dynamics between the settings with more group pressure on Mauna Kea.

Our finding regarding the lack of difference in severity of AMS symptoms between NH and HH agrees with previous research (Richard et al., 2014). There are two factors that affect the generalizability of this finding. First, there was high inter-subject variability with the LLS probably due to the subjective nature of this questionnaire. Second, AMS becomes fully manifest after 6–96 h of hypoxic exposure at moderate to high altitudes (Debevec and Millet, 2014) Therefore, the 7-h exposure duration used in our study design may have had an impact on the participants' experiences of AMS during NH and HH. Limited exposure duration may explain the discrepancies between our observations and those studies reporting the opposite finding with exposure durations longer than 8 h (Debevec and Millet, 2014).

As is true of all studies with high altitude field observations, our study has limitations. Due to logistical problems, it was not possible to randomize assignments to the different study stages. It was also not possible to blind subjects to the experimental conditions in this crossover trial comparing NH in a chamber with natural HH on a mountain. However, due to the fact that the study results are based predominantly on objective parameters as SpO₂ and heart rate the likelihood of influencing results with personal bias is low. A minor limitation is the potential confounding effect of hypobaric acclimatization during the flights to Hawaii (10 and 5 h with 14 h lay-over between flights) as well as the jetlag effect on circadian rhythms. However, 4 days of rest at sea level on Hawaii with extended sleep times and time for sun exposure on the beach diminished these potential cofounding effects (Reilly and Edwards, 2007). Another minor limitation is that we did not measure urine concentrations after the hikes such that we cannot determine the possible contribution of a greater degree of volume depletion during the mountain hike.

In conclusion, our study describes physiological differences in HR and S_pO₂ during a mountain hike at altitudes from 2,800 to 4,200 m compared to a simulated hike in a normobaric hypoxia chamber. These differences must receive consideration when high altitude studies are performed or when mountaineers train for hikes at high altitude using normobaric chambers. The results of our trial also provide important data for aviation medicine and intensive care medicine, environments that confront the critical issue of hypoxia.

NN: designing research study, conducting experiment, providing material, writing manuscript LR: conducting experiment, writing manuscript, acquiring data, analyzing data Manuscript AE, Writing final version of manuscript; HG, analyzing data, writing manuscript; MF, conducting experiment, acquiring data; MB, writing manuscript, analyzing data; SP, designing research study, conducting experiment, analyzing data, acquiring data, writing.