The following excerpts are from the E-mail discussion of the committee on chronic mountain sickness, prior to
The 3rd World Congress on Mountain Medicine and High Altitude Physiology and  The 18th Japanese Symposium on Mountain Medicine carried out in Matsumoto, Japan (May 20th - 24th, 1998).

Date:         20 Mar 98 16:16:43
Subject:      Re: CMS Symposium
X-mailer:     Pegasus Mail v2.3 (R5).
 To:   "John Reeves" <>
Dear Jack:
Thank you for your E-mail of march 15. We were out of town and
just returned yesterday.
You wrote:
> I have the abstract "Incidence of Disease at High Altitude in La Paz
> Bolivia".  Will that be the subject of your presentation in the CMS session?
Yes, we consider this to be more adequate to our field than in
the high altitude population in the world symposium. In fact we
meant to deal more with CMS in this presentation.
> How long are you planning to talk?
Would 20 minutes be fine?
> Keep in mind that we are hoping for as much
> time as possible for discussion.
> One of the main question that will require discussion is that
> of the definition of CMS, so that we can all play from the same
> sheet music. In your case, do you include or exclude persons with
> chronic lung disease in the CMS group?
Following is the summary of the modest opinion of my father and
myself, from many years of observations in the bowl-shaped city
of La Paz to El Alto (between 3100m and 4100m), with much CMS in
a population above 1.2 million:

1) In our concept, CMS or Monge's disease are adequate
denominations for a disease present only in hypoxic conditions
due mainly to respiratory and ventilatory alterations of
different etiopathogenesis, some complicated by other alterations
such as kidney disease, arterial hypertension, and so on.

2) CMS at high altitude is expressed as cyanosis and low arterial
saturation which gives rise to pulmonary hypertension and
increased polycythemia, as compensatory mechanisms of adaptation
to the disease under hypoxic conditions.

3) CMS is irreversible in diseases like pulmonary fibrosis, and
reversible in chronic bronchitis, for example. If the arterial
blood is completely saturated at 98%, as such is the case when
the subject descends to sea level, there is a regression of the
symptoms and signs. Giving continuous oxygen administration to a
patient with COPD at sea level, will achieve similar results.

4) Respiratory diseases are the same at high altitude, in
etiopathogenesis as those of sea level; but the impaired
respiratory function, with low oxygen saturation, below the
plateau of the saturation curve (in the steep part), shows
us what we know as CMS or Monge's disease.

5) Since CMS is a common denominator of diverse diseases of the
respiratory system, each case should be diagnosed and treated
according to the etiopathogenesis. It seems also evident that
some subjects are more prone to suffer pulmonary diseases.
Similarly, men have a greater tendency to develop pulmonary
disease, than women and consequently are more susceptible to
develop CMS.

So, hoping to answer your question:
The confusion arrives because the classical description of
Monge's disease in 1928, expressed that there is no pulmonary
anatomical or functional alterations, not able to become evident at the time,
due to the lack of modern technology that we have nowadays.
Not all patients with respiratory disease at high altitude
develop CMS. Some pulmonary diseases alter as a sequelae
the pulmonary function, like impaired diffusion, uneven
ventilation, increased shunt, or hypoventilation. These lead to
low saturations in hypoxic conditions and to CMS.
Please read our article New Concepts on Chronic Mountain Sickness
We enjoyed preparing these comments, and if you should have any
doubts, questions or comments please feel free to send us an E-
We were hoping to meet you in Cuzco, and inquired about you but
they said you were in Russia. We were supposed to go the meeting
in Ukraine invited by Beloshitsky. We ran into many problems. We
couldn't get to Ukraine from Moscow. We will tell you more when
we meet in Japan.
Gustavo Sr.      &      Gustavo Jr.
                    Gustavo Zubieta, M.D.
Av. Saavedra 2302                       Tel:    591-2-368734
P.O. BOX 2852                           Fax:    591-2-229504
La Paz, Bolivia                         E-mail:
Date: 31 Mar 1998 08:23:27 U
From: "John Reeves" <>
Subject: Re: CMS discussion
To: "Gustavo Zubieta" <>
Cc: "Ingrid Asmus" <>,
        "Linda Curran" <>,
        "Dr. Gerilli" <>,
        "GUSTAVO ZUBIETA, M.D. * IPPA *" <>,
        "Toshio Kobayashi" <>,
        "Fabiola Leon-Velarde" <>,
        "Shigeru Masuyama" <>,
        "Prof. Mirrakhimov" <>,
        "Carlos Monge" <>, "Hideki Ohno" <>,
        "Lorna G. Moore" <>

 3/31/98            8:20 AM

Thank you so much for the thoughtful remarks.  They are extremely useful for
the purpose of initiating discussion.  As a bystander who does not see CMS
patients,  but who is interested in consensus, I do see differences of opinion
that could and should be laid out on the table for friendly discussion, where
everyone benefits.  Getting these diverse opinions in ahead of the meeting
should make people aware of the differences, and allow them to think about the
problems. I hope you agree. Final answers may not come from the meeting, but
the process of discussion will have been initiated.  I am trying to keep Wu
informed by fax of these discussions, but am not sure the faxes are getting
through.  I have taken the liberty of sending your thoughtful comments around,
as I believe they deserve wide distribution. I hope that is O.K.
Date: 3/30/98 4:05 PM
To: John Reeves
          Here goes the homework requested by you, Lorna Moore
and her colleagues.
We feel troubled by the subject of scoring CMS.  As you can read
from our publications, we are confident that there is no "loss of
adaptation of life at altitude", but rather an adaptation of
pulmonary, cardiac, renal or other disease to the hypoxia at high
altitude. (And to tell you the truth, CMS patients do remarkably
well, provided their basic disease is treated or looked after).
In general, patients with CMS are examined while attending a
regular consultation. Most often, after suffering the disease
during many years and only when they and their family become
aware of the change in the color of the skin, particularly in the
face. Also, when the consultation is for another kind of disease
and the routine laboratory tests report increased polycythemia.
At this time, the signs and symptoms can be present in different
degrees and are prominent or more evident in THS.
The score will only be valid for some patients with CMS and
exclude others. Gastrointestinal ulcers, are frequent findings.
Gastro-intestinal bleeding, will change the score. The same
happens with Gout. Several patients with CMS have increased uric
acid, and some with evident signs of Gout by deposits in the ear
helix. Gout can lead to well known pulmonary alterations.
Similarly, hypertension is also present in some of them. This
generally implies kidney disease. Finger clubbing is present in
some, even when they are very young. In broncho-pulmonary lesions
of smokers, for example, there can be severe cyanosis, low
saturation, increased polycythemia and pulmonary hypertension. If
they stop smoking there is significant improvement. This is the
same as at sea level, but in chronic hypoxia they reach lower
saturation. Another example are some patients with asthma. This
shows that CMS patients have a different etiopathogenesis. If all
these examples are not included, are they going to be considered
a different kind of disease? It does not seem so.
At altitude, "cyanotic pulmonary diseases and asymptomatic high
altitude polycythemia" (as defined by Hultgren) are, in our
experience, CMS, and the later approaches more exactly CMS
present at moderate altitude.
If you use a score, you have to be aware that it will apply for
that moment only and it will most probably change even within the
next few days. Also, great differences in scoring will be found,
depending on the degree of compromise of lung or cardiac
function, the type of disease, and of course the altitude.
Why?  Because patients that have CMS are subject to viral
diseases, bronchitis, colds or even seasonal climate changes (we
have a CMS patient with allergies). This we described as triple
hypoxia syndrome (THS), an acute condition overimpossed on CMS
(please see further down and the article in our Web page below).
So, if the score pretends to be used to access the moments'
clinical state of the patient with CMS, that is fine.
About scoring CMS:
In the score used by Dr. Wu in CMS, the signs are present
particularly in AMS and the triple hypoxia syndrome, that we also
call "sorojche (AMS) in bed".  With the exception of hyperaemia
in conjunctivae and mucosae, which are chronic.
The scores 0, 1, 2 and 3 for none, mild, moderate and severe,
seem adequate.
We think that everybody agrees that the disorder regresses on
descent to sea level, in around one month. Patients who reascend
to high altitude, and are exposed again to hypoxia, develop CMS
once more. This is a mechanism of adaptation, to supply the
necessary oxygen to the tissues. The patients from low lands with
chronic pulmonary diseases commonly unnoticed at sea level,
develop CMS at altitude. Are we going to consider these cases as
a loss of adaptation?. Certainly not, it is hard to think in such
a way.
We agree that the most appropriate approach to score the disease,
are the laboratory findings: hemoglobin or hematocrit and oxygen
saturation, with or without carbon dioxide retention, depending
of the severity of the case. For over 15 years now, we have been
using a classification by number of red blood cells ("El mal de
monta$a cr"nico y los mineros", published in the magazine of the
Academia Nacional de Ciencias de Bolivia,1985;4:109-116), and it
has proved to be a good guide in our medical practice.
Originally, diagnosis was based on clinical examination, chest x-
rays film and hemogram only, due to the lack of equipment.
It is as follows:
moderate  6.5 to 7.5 million RBC/mm3
severe    7.5 to 8.5 million RBC/mm3
grave     > 8.5 million RBC/mm3
For 3600 m. of altitude only.
We feel now that it would have been better to name them as mild,
moderate and severe and to use the hematocrit or hemoglobin,
which amount to the same thing.
With respect to your 7th question, (a very good one, indeed);
yes, there is an altitude at which everyone gets CMS.  Please see
the abstract "Pulmonary disease, CMS and gender differences at
high altitude" that we plan to present as a poster.  When the
respiratory frequency and ventilatory capacity are unable to
compensate the extreme hypoxia, the last resort for the human
being is to develop severe pulmonary hypertension (right heart
hypertrophy) and increase the number of the red cells. All
permanent residents will be sick with CMS at 5500 m, for example
at the mine of Chorolque located at 5562 m. Since not everyone
has equal capacity of adaptation, the CMS will be more severe in
some than in others, and still they will survive. Of course, in
miserable conditions.
In terms of genetic predisposition, CMS is most probable for some
individuals, over 40 years old, who have a tendency to gain
weight, but this is due to the predisposition to get sick from
respiratory disorders.
Also, about impairment of intelligence in these patients, and
intelligence itself in chronic hypoxia, we drop the subject for
the moment.
It is important to mention that chest X-rays films as a test of
diagnosis of CMS is mandatory, (and now CAT scan or NMR)  as is
the clinical history of pulmonary diseases, and the pulmonary
function tests.
In summary, to answer the first question about Chronic Mountain
Sickness, "What is it?".
We feel that the most simple description of CMS, is going to be
the most adequate for the moment. In that respect we are closer
to John Weil's definition.
Our definition is:
"CMS or Monge's disease is found in residents at high altitude
with some abnormal pulmonary function (increased shunt, impaired
diffusion, uneven ventilation and/or hypoventilation), sequelae
of diseases of diverse etiopathogenesis. These lead to a
sustained (and variable) low oxygen saturation and cyanosis,
giving rise to pulmonary hypertension and increased polycythemia
as compensatory mechanisms of adaptation to the disease under
chronic hypoxic conditions. The symptoms and signs are reversible
by descent to sea level or by increasing the PIO2."
Both of us (Gustavo Sr. and Jr.) discuss this subject profoundly
and we only write down the subjects in which we are in full
We are expectant of the discussion on the scoring system.
Gustavo Sr and Gustavo Jr.
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          id 3382 ; Mon, 30 Mar 98 18:10:51
To: "John Reeves" <>
Date:         30 Mar 98 18:10:51
Subject:      CMS discussion
Priority: normal
X-mailer:     Pegasus Mail v2.3 (R5).
Date: 10 Apr 1998 16:47:23 +0100
From: "John Reeves" <>
Subject: FWD>Comments, please
To: "Inder Anand" <>,
        "Ingrid Asmus" <>,
        "Peter Bartsch" <>,
        "Buddha Basnyat" <>,
        "Linda Curran" <>,
        "Marlowe Eldridge" <>,
        "Bob Grover" <>,
        "Peter Hackett" <>,
        "Toshio Kobayashi" <>,
        "Fabiola Leon-Velarde" <>,
        "Shigeru Masuyama" <>,
        "Professor Mirrakhimov" <>,
        "Carlos Monge" <>,
        "Susan Niermeyer" <>,
        "Hideki Ohno" <>,
        "Akio Sakai" <>,
        "Tatiana Serebrovskaya" <>,
        "Peter Wagner" <>,
        "Gustavo Zubieta" <>,
        "Lorna G. Moore" <>
Mail*Link(r) SMTP               FWD>Comments, please
Very interesting and important comments from the Zubieta's.  Dr. Leon-Velarde
and myself, the Zubieta's  and others would like to hear some comments on
these points.
Jack Reeves
Date: 4/10/98 8:59 AM
Dear Jack:
We completely agree  with you, that we should be aware of the
differences in opinions and also of the similarity in the
approach to clarify some aspects in CMS.
The paramount point of this forthcoming congress, I am sure
(Gustavo Sr.), is that the assistants, while enjoying the
friendship, try to find out some clues that will benefit
thousands of people, who live, get sick and are treated at high
altitude, all around the world. We are sure that everything you
are doing is OK and please feel free and confident to make us
notice any illogical digression of our part.
Regarding the difficulty in making sure lungs are normal in CMS,
because severe polycythemia itself alters gas exchange, Dr. West
points out:
"I would like to add a small point. Jack Reeves stated that
'severe polycythemia itself alters [pulmonary] gas exchange'. I
do not think this issue is settled. We induced severe
normovolemic polycythemia in dogs (hematocrits up to 76%) and
found no broadening of the distribution of ventilation perfusion
ratios (J. Appl Physiol. 65:1686-1692, 1988). In the introduction
to that article we reviewed the published studies on whether
polycythemia impairs pulmonary gas exchange and no clear message
These interesting remarks, show us that many people think that
polycythemia (of unknown etiopathogenesis), affects pulmonary
function in CMS. According to Dr. West's research, this would not
be so.
 Gustavo Sr, believes that those experiments resemble more what
would happen in polycythemia Vera (Vaquez-Osler disease), where,
according to the scarce bibliography, he has, there are no
cardio-pulmonary alterations. If these experiments were repeated
at high altitude, probably the results would be the same: No
broadening of the distribution of ventilation-perfusion ratios.
Some authors found that in polycythemia Vera, the pulmonary
diffusing capacity was greater than in normals, attributed to
increased hemoglobin concentrations (Journal of Clinical
Investigation, Vol 4, NO. 7, 1963). Polycythemia increases the
total surface of red blood cells exposed to oxygen, which is
another advantage.
In Monge Medrano's original paper, he thought that he found
polycythemia Vera of high altitude (1928). Then he realized that
it was not exactly the same so he changed his point of view to
"loss of adaptation" and CMS (1937 & 1943). The clinical
description and observation of increased polycythemia was an
important contribution to high altitude pathology, made 70 years
ago. We look forward to the presentation by Carlos Monge and
Fabiola Leon Velarde, our distinguished friends, on the history
of how CMS was discovered .
If the disease exists at high altitude, with the original
description, Gustavo Sr. has not been able to see it in over 40
years of medical practice (and we were always looking for it). As
you know there are thousands of people with increased
polycythemia, in the Bolivian high plateau (abnormal), that can
be easily diagnosed by simple observation in the streets, when
there is the experience.
Some of the participants in the CMS discussion affirm that they
have found people with CMS but with no anatomical or functional
alterations. It seems to us that we are observing a different
kind of pathology. By the way, we have neither seen one case of
Polycythemia Vera. When one of us was in USA, nobody gave an
adequate explanation about this last disease. The only thing I
know for sure is that polycythemia vera is accompanied by
leucocytosis, increased platelet count and can evolve to a very
severe hematological disease.
As we previously pointed out, AFTER PROVING THAT THESE PEOPLE
For this reason, our point of view is that pulmonary diseases,
that leave sequelae, give rise to low saturation and consequently
Lets suppose that 3 individuals, apparently normal, one 20 years
old, and two 40 years old, move from the lower part of the city
of La Paz, at 3000 m. They remain 3 months at 3500 m, and 3
months at 4100 m (in the city of El Alto, the highest part). The
blood tests will show that the 20 years old and one of the 40
years old have their hemoglobin and hematocrit normal, for each
 altitude. The other has increased his hemoglobin to around 20
gm%. Can we say that this last one has "lost his adaptation"? and
that the other two have adapted?. The last one has developed
chronic mountain sickness. Do we call this: "adaptation"  or
"loss of adaptation" ?. This is not a hypothesis, it is a fact of
common observation. Furthermore, if he has "lost his adaptation",
is he unable to live there any longer ?.
Here, we are in the most critical point, in health problems.
Should this man go to the lowlands, even though he feels well in
the intellectual and physical conditions? When he becomes aware
that he has CMS, it turns into a big economical and social
problem. Of course, he will, from time to time, suffer from colds
with headaches, lassitude, sleep disturbance and so on (as any
healthy subject with a cold) that will be diagnosed by physicians
as the CMS alteration, but in reality it is the triple hypoxia
syndrome in CMS, that is transitory and treatable.
Since the participants are unable to go to discuss the cases in
the different hospitals, clinics or laboratories, of each
country, may we suggest that you ask each participant in the
liberal discussion on CMS (if feasible), bring a color photograph
of the patient, the clinical history, the laboratory findings,
the cardio-pulmonary function tests or any additional data, to
the meeting so that we can all see the differences and discuss
them, in a friendly way. These results will show us more than a
thousand words.
Gustavo Zubieta Sr.   &    Gustavo Zubieta Jr.
To: "John Reeves" <>
Date:         10 Apr 98 10:12:34
Subject:      CMS discussion
Priority: normal
X-mailer:     Pegasus Mail v2.3 (R5).
Date: 20 Apr 1998 08:47:15 -0600
From: "Lorna G. Moore" <>
Subject: Re: Lorna's questions on "adaptation"
        Reply to:   RE>Lorna's questions on "adaptation"
Thank you for your interesting reply.  If I interpret your remarks correctly,
you are asking if the effects of CMS on life expectancy (mortality) are
similiar to those of COPD at sea level (or at altitude).  That might be an
interesting way to get at the seeming confusion over the uniqueness of CMS as
a high-altitude condition.  Looking forward to seeing you in Japan!
Date: 4/19/98 7:28 PM
To: Lorna G. Moore
Dear Lorna:
Your fundamental points regarding the term "adaptation",
stimulated and gave an electrifying boost to everyone's thoughts.
Thank you for letting us know the interesting definition of
"adaptation" by Theodosious Dobzhansky. We had not heard it
First of all, I (Gustavo Sr) am compelled to explain the
importance of the term "adaptation", which concerns me very
strongly. Any term in medicine implies a concept (knowledge) of
the diseases  which will set the rules for prevention and
treatment (CMS in this case). I include in CMS many kinds of
pulmonary disease in chronic hypoxia.
 By associating CMS with the term "loss of adaptation", attention
has been focused only in the increase of the number of red blood
cells. This, mislead many studies. With such a concept, many
people with pulmonary disorders have been sent to the lowlands in
order to reduce their hematocrit and they die very soon. Due to
the hot, humid and oxygen rich environment (an optimum medium for
bacteria) there is worsening of infectious diseases
(tuberculosis, for example). Some remain living their life as
anyone in the lowlands in any part of the world, with unnoticed
mild respiratory or ventilatory impairment.
Another form of treatment was targeted to decrease the
hematocrit, by using radioactive compounds (such as phosphorous)
or cytolytic drugs (such as fenilhidrazine). Nowadays, the
pharmaceutical market is full of "medicines" announcing that they
can "reduce" the number of red blood cells. Phlebotomy has to be
revised, in lieu of the advance of knowledge in hypoxia, but we
will not deal with this subject in this letter.
In relation to impaired fertility:
We don't know of any specific studies, however it is a common
observation that the fastest growing city (over 600,000
inhabitants) in Bolivia happens to be El Alto "the high plateau"
(4100 m). There, according to a presentation we will give in
Matsumoto, about 52% of the males and 28 % of females that
receive medical attention in all diseases,  have a hematocrit
 above 58 %.
 The people of the city of El Alto, reproduce even in the most
disadvantageous conditions of poverty, lack of adequate housing,
lack of hygiene and so on.
On the other hand, I (Gustavo Sr.) have studied sick miners of
high altitude mining centers in Bolivia, who had increased
polycythemia with pulmonary diseases and several of them had over
8 children. Many of the children died, because of bad sanitary,
nutritional and infectious conditions in the mines. They only
stopped having children when the women reached menopause.
Incidentally, it is well known that human fetuses live in hypoxic
conditions (and that they are polycythemic! ). That is probably
why they don't die, and can tolerate very long apneas and extreme
hypoxia during delivery. At high altitude, it surprises us more.
By the way, breath-holding in CMS is one of our subjects of
presentation in Matsumoto.
In dealing with hypoxia, environmental factors should never be
overlooked. For example, impotence that has to do with fertility,
is not a common complaint at high altitude, as it happens in
developed countries (paradoxical?)
About life expectancy:
 There are no great differences between disease at sea level and
at high altitude, in the course of life. Again, we know of no
studies on life expectancy in respiratory disease at high
altitude. For example, at sea level, chronic obstructive
pulmonary disease (COPD) and emphysema affect 20-30 % of the
adult population, with more than 60,000 deaths/year. The
predominant age is over 40 and the predominant sex is male. This
is strongly similar to our clinical observations here (except the
death incidence per year, that is not quantified).
If patients with CMS, have reduced life expectancies, it will
probably be due to a reduced life expectancy of chronic lung
disease, just as at sea level. Depending on the severity of the
cases, naturally.
We have followed patients with CMS, for over 14 years,  into
their 80's and we have never looked after one, the moment he
died. No one has reported, up to date, an autopsy of CMS.
Probably, because when the pathological alterations were
discovered, they were classified as cardio-pulmonary disease.
By the way, malnutrition, cor-pulmonale, hypercapnia and a pulse
> 100 are all poor prognostic indicators in COPD at sea level.
The same happens at high altitude. Furthermore, cor-pulmonale in
patients with CMS is probably an advanced and untreated
consequence of respiratory disease. Increased polycythemia can't
be absent in many cases.
At sea level, supplemental oxygen, has been shown to increase
survival. This is conflictive for us. It would imply that there
is a shorter life expectancy for high altitude residents, but
that does not seem to be so. Ever since the use of penicillin,
life expectancy has expanded also at high altitude. Previously,
many people died of pneumonia in their forties. With better
nutrition, improved health care, and more hygiene, we are seeing
people, more and more, that live well into their nineties. We are
not saying that altitude is the best place to live in, but just
that we live here.
We are aware of how easy it is to make a mistake or fall into
speculation, but what you just read comes from our on-site
experience, a lot of hypoxia and its interpretation....
Gustavo Sr. &  Gustavo Jr.
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          id 8078 ; Sun, 19 Apr 98 20:37:23
To: "Lorna G. Moore" <>
Date:         19 Apr 98 20:37:22
Subject:      Lorna's questions on "adaptation"
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