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CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine

2020; Wiley; Volume: 598; Issue: 5 Linguagem: Inglês

10.1113/jp279160

1469-7793

Jean‐Paul Richalet,

Chronic Obstructive Pulmonary Disease (COPD) Research

A debate about a possible specific effect of barometric pressure has been introduced, for various reasons, into the domains of exercise and altitude physiology, as well as sports training. Economic considerations may have promoted normobaric methods since normobaric conditions are less expensive to simulate than hypobaric ones, either natural or simulated, in hypobaric chambers. Countries without mountains may well need to train their athletes in hypoxia without the cost of travelling far from home. A debate then arose because scientists challenged the idea that the two methods were equivalent. Medical aspects may arise, especially in the context of high altitude-related diseases (acute mountain sickness, high altitude pulmonary or cerebral oedema). Is the occurrence of these diseases more or less frequent in normobaric or hypobaric conditions? Is return to normobaric conditions more efficient in treating these diseases than inhaled oxygen? An initial Point/Counterpoint debate was published in 2012 (Millet et al. 2012; Mounier and Brugniaux, 2012); a comprehensive review was published in 2015 (Coppel et al. 2015); and a meta-regression analysis was published in 2017 (McMorris et al. 2017). It is not my purpose here to provide a new review of all publications in favour (e.g. Loepky et al. 1997; Beidleman et al. 2014) or not in favour (e.g. Richard et al. 2014; Bourdillon et al. 2017; Hauser et al. 2017; Woods et al. 2017) of a specific effect of barometric pressure for a given . Since these previous studies, no convincing mechanistic hypothesis has been put forward to explain the possible difference between hypobaric and normobaric hypoxia. Indeed, a well-designed recent study, precisely controlling in each condition, failed to find any difference in markers of physiological stress between normobaric and hypoxia (Woods et al. 2017). Similarly, a meta-analysis on the effect of hypoxia on cognition revealed no difference between normobaric and hypobaric conditions (McMorris et al. 2017). The first important methodological point is to know what are we talking about. Do we need the same ambient (dry) air , the same inspired (, taking into account the water vapour pressure), or the same (which is the real reaching all cells). It is clear that the water vapour pressure should be taken into account in the formula for the calculation of equivalent for a given altitude. Between and , several physiological mechanisms may interfere such as work of breathing depending on air density or the effect of absolute alveolar pressure on O2 diffusion (Levine et al. 1988). Several studies reviewed by Coppel et al. (2015) reported a number of variables (e.g. minute ventilation and NO levels) that were different between the two conditions, lending support to the notion that true physiological differences are present. However, the presence of confounding factors such as time spent in hypoxia, temperature and humidity, and the limited statistical power due to small sample sizes, temper the conclusions that can be drawn. Some authors suggest that reduced air density during exposure to an altitude of 3500 m increases maximal ventilation and extends time to exhaustion but without affecting oxygen consumption or arterial oxygen saturation (Ogawa et al. 2019). Specific effects of barometric pressure have been evoked on various aspects of physiology, such as renal function, catecholamine secretion, sleep, physical performance, cognition and erythropoiesis, but many confounding factors may mitigate the conclusions. Comparative studies are often performed in hypobaric chambers vs. normobaric rooms or tents (e.g. DiPasquale et al. 2016). These two conditions are probably perceived with a different level of stress by the subjects, which represents another important confounding factor. Let us first come back to basic physics in order to have a precise correspondence between hypobaric and normobaric hypoxic conditions. Therefore, the equivalent value using this model is also given in Table 1 (column ‘model atmosphere’). It appears that, as a function of the ambient temperature or the model used, the equivalent used in normobaria may significantly vary for a given target simulated altitude and vice versa. Therefore, the whole debate about the difference between normobaric and hypobaric hypoxia is dependent on the accuracy of the calculation of equivalent altitude and may depend on the location of the experimental site, the ambient temperature or the degree of hygrometry and the official standard used. Very few studies mention the exact formula used to calculate the equivalent . It is frequently not even mentioned whether they took into account water vapour pressure in their calculation. Moreover, the uncertainty of values given by the apparatus delivering the hypoxic gas mixture leads to a great imprecision in the simulated altitude. For example, looking at Table 1, for a given altitude it appears that a difference of 0.5% in could mimic the same altitude conditions, depending on the ambient temperature or the model used (e.g. 3000 m altitude could be simulated by a of 13.85–14.38, depending of the standard used and the temperature conditions). Most studies do not specify the formula they used to calculate the values of to simulate a given altitude. For example, Heinzer and Rupp use a of 13.6% to simulate an altitude of 3450 m, which is too high (Table 1) and may perfectly explain why they found a greater effect of hypobaric than of normobaric hypoxia (Heinzer et al. 2016; Rupp et al. 2019). Therefore, no formal conclusion can be drawn for most studies that have addressed this question. It is difficult to propose a solid conclusion, since we have no assurance that the level of hypoxaemia was really similar in normobaric and hypobaric conditions. The proper way to evaluate the actual physiological role of pressure would be to equalize the value of inspired in both conditions. Then if we want to evaluate the potential specific influence of respiratory factors (as compared to circulatory or metabolic ones), the same arterial should be controlled in both normobaric and hypobaric conditions. What would be the rationale for a specific effect of pressure on physiological processes, being maintained equal in both conditions? What matters for the human body is the difference between external and internal pressure, since the equilibration of pressures in liquids occurs rapidly when exposed to hypobaria, excluding of course rapid decompression that may induce specific adverse effects (decompression sickness), but this is not the case with real altitude exposure. Only cavities containing gas may dilate when exposed to rapid hypobaria so that specific symptoms may appear such as intestinal bloating, pain due to air dental cavities or impermeable Eustechian tube and blast of closed air bubbles in lung emphysema. No effect of hypobaria can be expected on liquid compartments: for example, mean systemic arterial blood pressure remains at 100 mmHg, whether you stay at sea level or are at the top of Mount Everest, because the reference value is the ambient pressure. A specific effect of descent when compared with O2 breathing has been evoked for the treatment of high altitude cerebral oedema (Hackett and Roach, 2004), but no control study has ever proved this effect since many confounding factors may interfere (descent inducing a rise in ambient temperature or alleviating the stress of an individual, being evacuated to a more comfortable place). Psychological or placebo effects cannot be ruled out since double blind field studies are not practically available. A correct double-blind protocol would be to use hypobaric chambers either in hypobaric hypoxic or in normobaric hypoxic conditions (by reducing inside the chamber). A specific effect of barometric pressure within the body is highly improbable since there is no barometric sensor. The only baroreceptors are involved in the regulation of blood pressure, and blood pressure is not influenced by barometric pressure. On the contrary, all physiological responses to hypoxia are driven by chemoreceptors sensitive to or intracellular mechanisms involving stabilization of hypoxia inducible factors, depending on the intracellular oxygen concentration, independently of barometric pressure. In conclusion, much energy has been expended to detect any physiological difference between hypobaric and normobaric hypoxia. This effort would now be better used to ascertain the level of using proper equations. The ultimate method should be to adjust the level of in order to obtain the same level of or measured in hypobaric conditions. As a recommendation, I would suggest that people doing studies in hypobaric conditions (chambers or real altitude) give the exact barometric pressure measured during the experiments, and that those who are performing normobaric studies give the used and the exact barometric pressure of the location where the experiments are performed. Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief (250 word) comment. Comments may be submitted up to 6 weeks after publication of the article, at which point the discussion will close and the CrossTalk authors will be invited to submit a ‘LastWord’. Please email your comment, including a title and a declaration of interest, to jphysiol@physoc.org. Comments will be moderated and accepted comments will be published online only as ‘supporting information’ to the original debate articles once discussion has closed. Jean-Paul Richalet has dedicated his scientific career to studying the mechanisms of adaptation to altitude hypoxia. He has led scientific expeditions at high altitude (Numbur, Nepal; Annapurna IV, Nepal; Sajama, Bolivia). He has organized numerous studies at the Observatoire Vallot (4350 m) on Mont-Blanc and a study on acclimatization to extreme altitude at COMEX facilities (Operation Everest III). He developed a ‘Hypoxia Exercise test’ to evaluate the risk of severe high altitude illnesses. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. None declared. Sole author. None.