John B.West

(加州大學(xué)圣地亞哥分校醫(yī)學(xué)系，美國(guó)，加利福尼亞州 92093-0623)

It is a special pleasure to write this short invited review on the topic of oxygen conditioning at high altitude.One reason for this is that I believe that oxygen conditioning at high altitude is going to become increasingly important over the next 10 or so years.The principles of oxygen conditioning are already well known，but some of the technical problems are challenging.However，as in other areas of research，the technical issues will be overcome if the need is there，and we shall soon see extensive progress in this area.

The second reason why a review is particularly suitable for the new journal Chinese High Altitude Medicine and Biology is that the region of the world where these advances are most likely to be implemented is on the Tibetan plateau.There are only two areas in the world where millions of people live and work at very high altitudes.One is the South American Andes，and the other is the Tibetan plateau.There are other small areas，for example in the Ethiopia highlands.However the Tibetan plateau is the site of very rapid development and many of the newcomers do not tolerate high altitude well.I believe that oxygen conditioning is destined to play a large part in this development.

What is oxygen conditioning?I like to think of it in analogy to air-conditioning.We all know that air-conditioning，that is modifying the temperature and perhaps the humidity of the air that is supplied to buildings，has revolutionized living and working in many hot areas of the world.As an example，I have made many visits to Houston，Texas because of our work in the NASA space program.One short visit in the summer is enough to convince anybody that it would be impossible to live，let alone work，in that environment without air-conditioning. Just as air-conditioning improves working conditions and productivity in a hot climate，I believe that oxygen conditioning has the potential to do the same at high altitudes.

It is interesting to look briefly at the history of raising the oxygen concentration in the air at high altitude to improve working and living conditions.This was first done over 20 years ago for astronomers who were working at the very high altitude of 5 000 m in Chile(West 1995).Another application at about the same time was in high altitude mines where the workers complained of difficulty with sleeping.In these applications，oxygen was injected into the rooms along with the normal ventilation，so that the oxygen concentrations were increased from 21% to as much as 27%.This was so successful that oxygen enrichment of room air as it is called，is now used in many sites at high altitude including dormitories，offices，and the rooms of expensive hotels.The transition from raising the oxygen concentration in rooms，to the air-conditioning of large buildings is a natural progression.

One of the reasons why oxygen enrichment of room air is so powerful is that a very small increase in oxygen concentration can result in a large reduction in the physiological altitude.By physiological attitude，we mean the altitude that has the same inspired PO2.Remarkably，every 1% increase in oxygen concentration of the room air reduces the physiological altitude by about 300 m.In other words somebody working in a room at the actual substantial altitude of 4 000 m but in which the room oxygen concentration has been increased from 21% to 28%，is at a physiological altitude of only 1 800 m.This is only a little above the attitude of Denver，Colorado where most people are unaware of the hypoxia.Thus，major reductions in the physiological altitude can be obtained by relatively small increases in the oxygen concentration of the air.

Figure 1 summarizes the relations between the physiological or equivalent altitude and the actual altitude for different concentrations of oxygen in the air.To use this diagram to check the example given above，move along the horizontal axis to the actual altitude of 4 000 m.Then move vertically up to the sloping line for 28% oxygen.The vertical axis then shows that the equivalent or physiological altitude is about 1 800 m.

For example，at an actual altitude of 4000m，the physiological altitude can be reduced to 1800m by increasing the oxygen concentration to 28%

Figure1Diagramtoshowhowadesiredphysiologicalaltitudecanbeobtainedatanactualaltitudebyraisingtheconcentrationoftheoxygenintheair

A caution here is that if the oxygen concentration is increased too much，there is a fire hazard.This means that common materials such as clothing will burn more rapidly than is the case at sea level.The area under sloping broken line in Figure 1 shows the conditions for a fire hazard.These have been thoroughly worked out in the USA by the National Fire Protection Agency.It may be useful to have an oxygen meter in the room to ensure that the safe level is not exceeded.A carbon dioxide meter can also be added because if the level rises too much，the ventilation flow should be increased.

Occasionally people who hear about oxygen enrichment of room air for the first time question whether leaving an oxygen enriched room by walking outside will have sudden deleterious effects such as causing the subject to faint.This is never seen.One simple way to think about the situation is to imagine that you are on a mountain with a helicopter available.If you rapidly ascend from 1 800 m to 4 000 m，you may well be aware of the increase in altitude，but it is extremely unlikely that you will faint.The same is true of leaving an oxygen-enriched room.Moving in or out of it is the same as moving down or up a mountain.

An impressive example of the application of oxygen enrichment of room air is in the Chinese train that runs from Golmud in Qinghai province to Lhasa.This passes through an altitude of 5 072 m，which is high enough to cause serious hypoxemia in passengers who are completely unacclimatized.Of course the fact that the passengers are seated at rest，and not involved in physical work，lessens the risk.Nevertheless the hypoxemia constitutes a definite risk for people who are traveling from near sea level，for example from Beijing.

The ingenious solution is to provide an oxygen generator in every passenger car，and effectively isolate the air that the passengers breathe from the outside.This includes sophisticated airtight but flexible walkways between adjacent passenger cars.In this instance，the added oxygen is obtained from the air using a molecular sieve.This is not the most efficient method of generating oxygen from air but it is adequate for this particular application.The oxygen concentration of the air is raised to about 24-25% that，as indicated earlier，reduces the equivalent altitude by about 900 to 1 200 m.There are also outlets in each car for delivering oxygen by nasal cannulas if necessary，and each train has a nurse with special equipment.The route mainly passes through sparsely inhabited regions，and the train makes very few stops.When it does stop，the number of doors that are opened to the outside is restricted.This is a very ingenious solution to a challenging problem.Note that it does not use a large central oxygen generator，which would be the case for oxygen conditioning in a building，but instead it uses a series of small oxygen generators analogous to window air conditioners in an apartment block.A typical train has 16 passenger cars with a total of over 900 passengers，so this is oxygen enrichment on a large scale.

Sometimes people question whether it is feasible to generate the large amounts of oxygen that are needed for oxygen conditioning a large building.These people are surprised to learn that many industries use enormous amounts of oxygen.One example is the paper pulp industry where，in the past，chlorine was used as an oxidant to produce high quality paper.This practice is now unacceptable because of the environmental pollution attributable to the chlorine，and instead large amounts of oxygen are used.Other industries that need extensive quantities of oxygen include those devoted to the treatment of wastewater，metallurgical factories where oxidation of some products is needed on a large scale，and also fish farming where the tanks containing large numbers of fish develop oxygen depletion unless large quantities of the gas are supplied.

The commonest way of generating large amounts of oxygen from the air is to use synthetic zeolites.These substances distinguish between the oxygen and nitrogen molecules，and they adsorb nitrogen under appropriate pressure conditions，allowing oxygen-enriched gas to be collected.Then when the pressure is changed，the nitrogen is liberated.Small examples of these devices are used in homes by the thousands by patients who are hypoxic because of lung disease.These machines can provide up to 5 L per minute of 90% oxygen which is usually delivered to the patient by nasal cannulas.The devices contain two columns of zeolite.Air is pumped through one of these columns at high pressure，with the result that the nitrogen is preferentially adsorbed and the effluent gas has a high oxygen concentration.Then the zeolite is unable to adsorb the nitrogen after a short time，and the incoming gas is then switched to the other tube，while the first tube is flushed with air at normal pressure.These devices run off the house electricity and are used extensively in homes.

The same principle is used on an industrial scale where very large amounts of oxygen are generated from the air.Various pressure swing patterns can be used.Examples that are presently available include the models DOCS 1 500 and 5 000 from PCI Gases，Riverside CA.These can produce 1 500 and 5 000 liters per minute of nearly 100% oxygen per minute respectively.Similar machines are available in China，which is a world leader in the field of oxygen generating equipment.

In the context of oxygen conditioning at high-altitude，it is useful to divide people into three groups.The first group is visitors to high altitude.These people typically spend a few days or a few weeks at altitude.Everybody who has done this is aware of the deleterious effects of the hypoxia if the altitude is high enough.These include a reduction in maximal exercise capacity，shortness of breath and sometimes neuropsychological changes.It is common knowledge that walking rapidly at high altitude leaves one panting for breath，while little increased breathlessness occurs at sea level.Apart from these physiological effects，symptoms of mild acute mountain sickness are very common.These include headache，change of mood，and loss of appetite.Some visitors are aware of neuropsychological changes.For example they find it difficult to concentrate，and memory is impaired.A common serious problem is sleep，which is typically fitful，and may be accompanied by unpleasant dreams.

All these features are reversed if oxygen conditioning is used and the physiological altitude is reduced enough.This can be very important under some conditions，for example if someone is attending an important scientific meeting where critical decisions are being made.Another example is a businessman who is planning a large project and needs to have all his wits about him.Clearly such a person will prefer to have the meeting at low altitude，but if this is not possible，an oxygen-enriched facility at high altitude would be valuable with the physiological altitude being reduced to near sea level.

A second group of lowlanders who can be found at high altitude are the sojourners.This is a large population.It consists of people who originally lived at low attitude and did their training there，but now find themselves in high altitude situations where their special expertise is needed.There are a many situations where this occurs.One is in mines at high altitude where the local people can certainly carry out simple operations，but complex tasks such as using very sophisticated equipment need highly trained people.Examples include the enormous trucks and loading equipment that are used in some open cut mines，In addition there are many complicated operational decisions that have to be made，and these require people who have a high educational level that is unlikely to be found in the local population.

A pertinent question is whether people who have moved to high altitude for say two or three years are completely acclimatized and they can work as efficiently as they could at sea level.All the evidence is against this.Of course these people have hypoxemia，and the hypoxic tissues are not able to function as well as they do under normoxic conditions.Large numbers of these people work in，hospitals，schools，banks，embassies and large corporations.Oxygen conditioning will be particularly useful in this context.

An interesting and perhaps provocative feature of the effects of hypoxia on exercise capacity is shown in figure 2.These data collected by Cerretelli(1980)show that acute hypoxia and chronic hypoxia reduce the maximal oxygen uptake(measured as a percentage of the sea level value)by the same amount as is seen in permanent residents of high altitude.The implication is that the reduced PO2in the exercising muscles and elsewhere in the body has the same inhibiting effect irrespective of other factors.

Open symbols，acute hypoxia；solid symbols，chronic hypoxia；crosses，permanent residents of high altitude. Note how all the points from these different populations lie close to the same line.Data from Cerretelli，1980

Figure2Graphshowinghowthemaximumoxygenuptake(asapercentageofthesealevelvalue)isreducedasindividualsareexposedtohypoxia

The third group of people who live at high altitude is the permanent residents.Many of these have been at high altitude for generations.Whether oxygen conditioning will be useful in this group is intriguing and somewhat controversial.Many people argue that permanent residents of high altitude are completely acclimatized to their hypoxic environment.By “completely acclimatized” here，we mean that the adaptation is so effective that they can function as well as if they were at sea level.However there is increasing evidence that this is not the case.For example，it has been shown that permanent residents can often improve their maximal oxygen uptake if they move to a lower altitude(Elsner et al，1964).This is hardly surprising because the increased PO2in the air will raise the PO2in the arterial blood，and other things being equal，will raise the PO2in the exercising muscles.Therefore these observations indicate that permanent residents of high altitude are not fully acclimatized to the hypoxia，because if the inspired oxygen level is increased，their exercise capacity improves.Figure 2 shows the relationship between altitude and work capacity.These studies imply that all three groups that we have discussed here，that is visitors，sojourners，and permanent residents lie on the same line when oxygen up take is plotted against barometric pressure.

A more controversial area is neuropsychological function.Some recent studies have shown that if you compare two populations matched for ethnic background，age，and educational status，the low altitude group performs better than the high altitude group(Yan，2014).These are difficult studies to do and involve sophisticated neuropsychological tests，some of which have only recently been developed.However it will not be particularly surprising if these results are confirmed.The low altitude group will have a higher arterial PO2，and therefore，other things being equal，a higher PO2in the tissues of the central nervous system.As noted earlier，people from sea level who go to high altitude always show some impairment of neuropsychological activity if careful measurements are made and the altitude is high enough.Therefore it is not particularly surprising that high altitude residents who have a low arterial PO2values in their brain，show improvement in neuropsychological function if the PO2of the central nervous system is raised.

One area where oxygen conditioning may be particularly important is in schools at high altitude.There are studies that show that if a group of school age children is either taken abruptly to high altitude，or spend an extensive period at high altitude，their neuropsychological function is statistically impaired compared with a matched group at low altitude(Rimold et al，2016).This finding，which needs to be confirmed，certainly suggests that oxygen conditioning might be valuable in schools at high altitude.

In the context of oxygen conditioning for permanent residents of high altitude，it should be added that much of this population has a low socio-economic status，and oxygen conditioning is likely to be expensive.Therefore the new technique will probably not be used on a large scale but only in specialized facilities such as hospitals and schools.

In summary，oxygen conditioning of buildings is a new concept that shows great promise in facilities such as hospitals，schools，corporation headquarters，banks and embassies at high altitude.It is analogous to air-conditioning，which has revolutionized living and working conditions in hot areas of the world.It is particularly appropriate for the Tibetan plateau where extensive development is taking place，the altitudes are high，and many of the visitors involved do not tolerate high altitude well.I expect major changes to occur over the next 10 years.