High Altitude Pulmonary Edema

High

Altitude

Epidemiologic Herbert

Pulmonary Observations

N. Hultgren,

Edema* Peru

in

and

Emilio

A. Marticorena,

The incidence of high altitude pulmonary edema was examined by a survey (via questionnaire) of residents living at 3,750 meters (12,303 feet) in the mining cornmunity of La Oroya, Peru. Ninety-seven subjects made a total of 1,157 ascents to high altitude after a stay at sea level of longer than 14 days. Sixty-four subjects experienced at least one episode of high-altitude pulmonary edema. The incidence was higher in subjects aged 13 to 20 years, where 17 percent (15) of 90 ascents resulted in episodes of high-altitude pulmonary edema, than in subjects 21 years or older (3 percent; 18/686 ascents).

H igh

altitude

pulmonary

edema

is now

a sojourn

after features

of

several Little

this

at

comment, sea

see page

level.

syndrome

The have

In addition,

in

information of high-altitude

is available regarding the incidence pulmonary edema. Such data are of importance to at least the following two groups of subjects who are at risk of developing highaltitude pulmonary edema: ( 1 ) sojourners, ie, mountaineers, skiers, hikers, and travelers who rapidly ascend to high altitude and engage in heavy exertion

are

quickly

for

maneuvers

many

instances

soon

after

deployed

from

or

combat

of high

arrival sea

( for

altitude

and

level

troops

to high

example, pulmonary

who altitude

in

1962, edema

were observed in Indian troops who were rapidly moved to the Himalayas for combat ); and (2) residents, ie, individuals and families who live and work at high altitude and make periodic trips to lower elevations, followed by rapid return to high altitude. #{176}From the

Departments of Medicine, Stanford University of Medicine, Stanford, Calif; the Veterans Administration Hospital, Palo Alto, Calif; the Institute of Andean Biology, San Marcos University, Lima, Peru; and the Chulec General Hospital, La Oroya, Peru. Supported in part by research funds from the Veterans Administration. a #{176}Professorof Medicine and Chief, Cardiology Service, Veterans Administration Hospital. tChief, Medical Service, Chulec General Hospital. Manuscript received November 22; revision accepted March 20. Reprint requests: Dr. Hultgren, VA Hospital, Palo Alto, Callfornia 94304 School

372

HULTOREN, MARTICORENA

into

sons, nary

certain

pulmonary important

epidemiologic

edema etiologic

an epidemiologic

may

aspects

provide

mechanisms.

study

of

an For

of high-altitude

high-

insight

these

rea-

pulmo-

was performed in an industrial mining in the Andes Mountains in central Peru.

clinical

described

reports.

physical

altitude

edema community

354

essential been

Young subjects (2 to 12 years old) had more severe episodes of high-altitude pulmonary edema (81 percent; 30/37 episodes) than adults (22 percent; 4/ 18 episodes). No episodes were observed in children under two years old. Five subjects under 21 years of age experienced recurrent episodes. Our estimated incidence of severe episodes of high altitude pulmonary edema per ascent in adults (0.6 percent; 4/686) is similar to that reported by other workers (incidence of 0.15 to 0.57 percent) In various parts of the world.

a well-rec-

ognized cause of acute disability and occasional death in persons ascending to altitudes in excess of 2,500 meters (7,369 feet) either for the first time or For editorial

M.D.f

MATERIALS

AND METHODS

The study was carried out in the city of La Oroya, Peru. La Oroya is the center of the mining and smelting operations of the Centromin-Peru in the Andes Mountains of central Peru ( Fig 1 ).The city is located on the Mantaro River at an elevation of 3,750 meters ( 12,303 feet) above sea level. La Oroya has a total population of 40,000, and approximately 17 percent of the native male population is engaged in mining or refining activities. In addition, about 800 largely white workers and their families live in the vicinity of La Oroya. Most of these employees have previously resided at sea level and have worked in the area for periods ranging from 3 to 15 years. La Oroya is readily accessible from the seacoast by rail or road, with a time for travel of three to five hours. The trip from Lima by rail or automobile requires the crossing of a pass at Ticlio that is 4,694 meters ( 15,400 feet) high. In addition, travel to the lower regions of the jungle to the east by road requires three to six hours. Workers and their families frequently travel to the seacoast or jungle for vacation or business, with varying periods of stay at these lower elevations. High altitude pulmonary edema has been observed in the population of La Oroya for many years, and the early clinical descriptions of the syndrome were based upon studies of patients in the Chulec General Hospital in La Oroya.1 This hospital is the central facility for medical care of the Centromin-Peru. All workers and their families have a complete physical examination, including a chest x-ray film, at the start of their stay in La Oroya. In addition, all workers are given an annual physical examination, including an electrocardiogram. These features of the population in La Oroya suggested that a survey via questionnaire would be an effective method

CHEST, 74: 4, OCTOBER, 1978

Feet 25.OOO

Snow

MorocochaJ ;.

hne

\

Cerro

)5000

I

Oroqa

10,000

Matucana

#{149}.#{149}

;.: .

.oo0 l.tn a Ca level

.......:............................... . I Mites

0 FIGURE

1. Cross-section

.

)OO of Peruvian

Andes

.

.

200 at Lima,

Peru,

showing

303

antiplano

where

La Oroya

is

located. of assessing some of the epidemiologic features of highaltitude pulmonary edema. The questionnaire consisted of 20 questions using simple terms; it was sent to 100 families through the company’s personnel office. The families were selected on the basis of their residence in two communities adjacent to the Chulec General Hospital. Approximately 120 families live in these communities. Twenty families could not be contacted to answer the questionnaire because of their temporary absence from the area. The racial composition of the group of families was approximately 50 percent white and 50 percent Peruvian. About half of the Peruvian families were of native ( Quechua ) stock. A summary sample of questions related to high-altitude pulmonary edema is as follows : ( 1 ) list the members of your family by name, age, and sex; (2 ) list the number of times that any member of your family spent more than 14 days at sea level or at an altitude of less than 1,500 meters (4,921 feet) and then returned to high altitude; ( 3) list the members of your family and the approximate dates that highaltitude pulmonary edema occurred which was severe enough to require hospitalization or a physician’s attention; (4 ) list the members of your family and the approximate dates that high-altitude pulmonary edema occurred but a physician was not called nor was hospitalization needed; (5) have any members of your family had high-altitude pulmonary edema upon return to high altitude after staying at sea level or below 1,500 meters for less than 14 days; and (6) have you used any precautions to prevent high-altitude pulmonary edema from occurring upon return to high altitudes ( if so, please describe). The completed questionnaire was returned to the Department of Medicine of the Chulec General Hospital. Analysis of the results of the questionnaire was performed independently by two physicians, with essentially identical results. One hundred questionnaires were distributed, and 60 ( 60 percent) were completed and returned. A total of 97 individuals had made at least one ascent from sea level to high altitude during the preceding two years with a stay at sea level exceeding 14 days. Of the 97 subjects, 36 ( 37 percent) were 2 to 12 years old, ten ( 10 percent) were 13 to 20 years old, and 51 ( 52 percent ) were 21 years of age or older. Infants under two years old were not included in the analysis, since none of the 20 infants under two years of age experienced

CHEST, 74: 4, OCTOBER, 1978

high altitude pulmonary edema. A trace was made of mdividuals who did not return the questionnaire. Reasons for not returning the questionnaire were as follows : ( 1 ) forgot to fill it out; ( 2 ) new employee who had just arrived; and (3) employee who had left the company. There was no evidence that failure to return the questionnaire was motivated by a desire to conceal symptoms of high altitude pulmonary edema. The incidence of high altitude pulmonary edema is expressed in terms of rapid exposures to high altitude. An exposure is defined as either an initial ascent or reascent to high altitude after two weeks or more at an altitude of less than 1,500 meters. This interval of time was selected because previous studies have shown that high-altitude pulmonary edema was unlikely to occur upon reascent if the subject spent less than two weeks at a lower elevation. An episode of high altitude pulmonary edema was defined by the appearance of the usual symptoms ( cough, dyspnea, weakness, and fatigue ) that were of sufficient severity to require either admission to a hospital or a physician’s supervision of medical treatment ( including bed rest and therapy with supplemental oxygen at home ) . The diagnosis of highaltitude pulmonary edema was based upon the following additional criteria: ( 1 ) onset of typical symptoms, including cough and dyspnea at rest, after arrival at high altitude ( subjects who had symptoms prior to arrival were not included ) ; ( 2 ) absence of signs of infection, such as nasal discharge, sore throat, or fever; ( 3 ) presence of pulmonary rales and cyanosis; ( 4 ) prompt disappearance of symptoms and signs after three days of treatment by bed rest and therapy with supplemental oxygen; and (5) verification of the diagnosis during the acute phase of illness by an interview and a physical examination performed by a physician who is experienced in the recognition of high-altitude pulmonary edema. In addition, all medical records were reviewed by two investigators to verify the accuracy of the diagnosis. Chest x-ray films were available in 83 percent (81 ) of the 97 subjects and confirmed the clinical diagnosis in each instance. Episodes of high altitude pulmonary edema were classified as mild if symptoms were not incapacitating and if treatment required only bed rest and therapy with supplemental oxygen at home or a stay in the hospital of one to two days. Episodes were classified as severe if symptoms were incapacitating and if more than two days of hospitalization were required.

HIGH ALTITUDE PULMONARY EDEMA

313

In the younger group (2 to 20 years old), there were 16 male and 29 female subjects. In the group aged 21 years or older, there were 24 men and 26 women.

ly used heavy

exertion

exposures

to high

of high

altitude,

altitude

70

pulmonary

( 125 episodes high-altitude

years

or older

epi-

preventive

sodes More

were observed of the episodes

old.

cent).

dren 30/37

aged 2 to episodes),

(four)

of the

marized

in

Preventive The edema five

(3 percent;

18 episodes Table

1.

There sexes

No

two

years

edema

severe to only

in adults.

the

Data

was in any

in chil-

(81 22

percent; percent

are

no

difference

age

group.

measures

taken

at 4,300

the

Common

when

meters

use of therapy

of high altitude might be ascribed by

of complete upon arrival,

oxygen

1-High-Altitude Made 1,l57Ascents

adults

in

pulmonary to preven-

and

not

precautionary

rest use

(including of therapy

crossing

the

[14,108

with

feet]),

and

the

rest) in supple-

(starting

the

No.

2-12 yr

of exposures

exposures subject

Mean

along

with

*Ascents sojourn ‘5Numbers

were

Total

10

51

97

381

90

686

1,157

to

9

37 (10)

15 (17)

30 (8)

8 (9)

7 (2)

7 (8)

between

3,750

and

7

12

18 (3)

70 (6)

4 (0.6) 42 (3.6) 14 (2) 4,300

28 (2.4)

meters

after

of more than 14 days (or initial ascent). parentheses are percents of exposures

HULTGREN, MARTICORENA

(P

<

0.005).

not oc10 per-

were

part

of

lower

edema measures.

tude An

analysis

of

two

groups

did

employed

of

subjects that

perhigh-

could

be

some

chil-

episodes of high-altiother children do not.

preventive

measures

not

that

more

in

( 11

in two

in La Oroya

between

preventive

frequently

high-altitude

observed

incidence

in older

reveal

of 21

in 18 episodes of in older subjects,

observed

the

recognized

were

while edema

have frequent recurrent pulmonary edema while

dren

the 52 episodes in subjects under

measures

measures

altitude pulmonary due to preventive

Of

edema

(6 percent), pulmonary

Thus,

in children

pulmonary

these

measures did

who

edema.

Reascent In subjects

nary

edema

level

preceding

Recurrent

who

developed

during

reascent,

return

high

the

to high

altitude

shortest

altitude

pulmo-

stay was

at sea

ten

days.

Episodes

Five subjects had more than one episode of highaltitude pulmonary edema. Four had two episodes, and one had three episodes. All five subjects were below 21 years of age. These episodes are included in Table 1. Racial No

subjects

Difference difference

and Time

at High

in incidence

was

Altitude observed

of Peruvian native ancestry The length of the previous stay

jects. or birth

at high

altitude

protection

any

in group.

374

21 yr

36

11

at sea level within

13-20 yr

per

High-altitude pulmonary edema Total episodes (percent)** Severe episodes (percent)** Mild episodes (percent)**

1 to 20 years

edema did taken in only

occasional

oxygen

Pulmonary Edema in 97 Subjects from Sea Level to High Altitude

No. of subjects

arrival.

aged

preventive

three instances high-altitude

measures bed with

summit

supplemental

by

Age Group Data

old,

)

not develop

subjects.

mental

years

were

lower incidence in older subjects

after

in patients

pulmonary

It is well

sum-

Measures

consisted children

Who

ascents). under

of pulmonary

younger

Table

18/686

in children

12 years were compared

between

12 to 24 hours

cent (28 exposures ). In 456 exposures in older subjects where high-altitude pulmonary edema did not occur, preventive measures were taken in 30 percent

Of the 97 subjects the mean number of exposures to high altitude was 12. The mcidence of high-altitude pulmonary edema was highest in the group aged 13 to 20 years ( 17 percent; 15/90 ascents) and was lowest in the group aged 21

occurred.

incidence

for

where high-altitude pulmonary cur, preventive measures were

Incidence

edema

after arrival. The most commonmeasure in adults was to avoid

In 396 exposures

REsui

In a total of 1,157 episodes (6. 1 percent)

in children preventive

rest

bed

did

against

not

between

and white subat high altitude

appear

high-altitude

to provide pulmonary

edema.

Susceptible It

is

Subjects evident

that

all

subjects

develop high altitude pulmonary subjects, 33 never experienced nary edema.

exposed edema. high-altitude

did Of

not

the 97 pulmo-

CHEST, 74: 4, OCTOBER, 1978

DiscussioN

There are several First, a prospective Constraints of time approach. epidemiologic random

the company one

if the was

This

ent study. The only of the questionnaire least

limitations to the present study. evaluation was not performed. and facilities did not permit this

Retrospective surveys process.

who year.

be due

studies group

the

criterion

have value in is selected by a

in the

situation for

selecting

pres-

recipients

limitation

of this

study

is

that each subject made several ascents to high altibide. A study of the incidence of high-altitude pulmonary edema during initial ascents to high altitude was not possible because of the small number of initial ascents. Data on this problem are currently being

collected.

A third

that

episodes

were (over

less frequent and 21 years), which

use

of

high

of precautionary

limitation

altitude

of high

since that

of the

many either

enough ical have

actual

subjects were

days.

seeing

of patchy

Signs

Another high-altitude

that

had or

and

symptoms not

Mild

severe

subclin-

pulmonary Bolivia.

exudate

which

edema Subjects

disappears

in a few

or pneumonitis

factor which pulmonary

reduces edema

the is the

measures.

If a child

has

are

absent.

incidence employment one

episode

altitude

pulmonary

of of

The higher incidence of high altitude pulmonary edema in younger subjects is a well-known phenomenon in Peru and has been previously reported.8

It

is

well

The

tude.

high

data

at sea

adults

than children observed precautions to prevent highaltitude pulmonary edema. The difference could also

CHEST, 74: 4, OCTOBER, 1978

common

in

level

Little ing

from

the

return

present

study

edema

is rare

is less

than

ten

to those

from

previous

published

the

then

days.

of high

altitude to high

who alti-

indicate

that

if the sojourn

These

data

is available

altitude

regard-

pulmonary

edema.

The

incidence in Indian troops transported an altitude of 3,500 meters ( 11,463 feet)

15.5 percent.

If travel

was

was less. About half years of age.4 Menon5 percent

for

by

truck,

by air to was

the

of the patients were reported an incidence

high-altitude

pulmonary

2.3

troops

was

going

0.44

eight

20 to 29 of 0.57

edema

in

edema

Hackett

( 1.5

in 522

percent)

and

in the

mci-

7,500 feetl)

Rennie#{176} observed

of high

trekkers

In-

level com-

to

percent.

cases

to

incidence

high altitude from sea (largely by air). C. S. Houston, M.D. (written munication, June, 1976 ) has estimated that the dence of high altitude pulmonary edema in climbers on Mt. Kenya (5,300 meters [17,388 dian

are

studies.3

information

incidence

a

become pulmonary

of high

and

pulmonary

comparable

141

viewed

Rainier

climbers

ly 15 percent after

the

had

altitude

pulmonary

Himalayas

and

of clinical

at

pulmonary

deaths

rales

percent

edema

an

alti-

ascending

was

on

in

(1

percent)

this

group

estimated

ett

and

dence

Rennie.6

of high reported

These

of 0.15

to 0.57 percent, of 3 percent ( 18/686 however, investigators

the

pulmonary

Menon5 reported

compared exposures) data

probably

sodes of high-altitude pulmonary ent study the incidence of severe

or Hackan

inci-

to our inciobserved in

reported refer

Two Wilson,

1976). a substan-

altitude by

workers

to

altitude

occurred.

( Rodman

incidence than

to be 0.5

of high

tially

in adults

one

attempted

communication, January, the present study indicates

higher

least

sickness. All The incidence

M.D., written Data from edema

auscultation at

people

episodes

Mt.

Approximate-

).

had

of 587

Ten

edema occurred

basal 10

a total

McKinley.

pulmonary

after

feet]

of acute mountain prior to the climb.

In 1976, Mt.

and

[14,436

moist

climb,

severe symptom were free of rales

climb

before

meters

(4,400

previous

More

altitude

altitude

arrival

do adults.

be

high-altitude

in residents

occur

go to a lower

dence the Andes;

than

may

that

known

may

The explanation is not clear. Some of the difference may be due to younger subjects carrying out more vigorous physical activity without precautions after altitudes

edema

inch-

residents while high-

given individual during childhood, episodes rare as the individual becomes older.

percent.7

high-altitude pulmonary edema, it is likely that during future reascents, preventive measures will be employed by the family, and these measures will minimize the occurrence of future episodes.

at high

of younger

among long-term indicates that

tude between 2,800 meters (9,186 feet) and 5,500 meters ( 18,045 feet) . All had flown into Lukia (2,800 meters) from lower altitudes. About 60 percent of the trekkers fly into this area, while the remainder walk. Houston7 examined and inter-

dyspnea, cough, and fatigue. Modtachypnea, and a few basal rales Chest x-ray films may show a small

of infection

of preventive

altiesti-

occurred,

mild were

a physician.

episodes of high altitude been observed in Peru

may have mild erate tachycardia, may be present. area

have

edema

to high a lower

of episodes

may

adults to the

pulmonary

unrecognized

to warrant

edema

with the edema, and a probeen living at high and all had made

altitude

number

is

familiarity

in 6.1 percent (70) of 1,157 exposures tude in 97 subjects probably represents mate

study

pulmonary

measures,

occurrence

this

less severe in young could be due in part

risk of high-altitude pulmonary cess of selection (since all had altitude for at least one year frequent trips to lower altitude). The

of

susceptibility

The experience area of La Oroya

edema

was that they be employees of had lived at high altitude for at

A second

to a biologic

viduals. in the

by

these

to severe

epi-

edema. In the presepisodes in adults

HIGH ALTITUDE PULMONARY EDEMA

315

was 0.6 percent (4/686), these previous reports. It is clearly the

evident

incidence

Young

that

high

of

subjects

which

are

is comparable

several

factors

altitude

clearly

reports

more

attained,

the

more

the physical altitude, the

that

indicate

rapid

effort greater

to

likely

the

the

affect edema.

will

pulmonary

high altitude pulmonary edema severe episodes more commonly Previous

to

develop

than occur

adults, and in children.

higher

the

altitude

the

greater

ascent,

and

expended upon arrival at high will be the incidence and sever-

ity of high altitude pulmonary edema. These observations have practical importance to families who travel to high altitudes or who live at high altitude. Children aged 2 to 12 years may develop high altitude pulmonary edema that is more severe than in adults. Symptoms and signs may be atypical

and

consist

sea, vomiting, and the prompt gen

will

the two

and headache.3 administration

result

measures

of lassitude,

in

rapid

consisting

avoidance days

in

possibility

or nau-

Immediate of supplemental

descent oxy-

improvement.

of gradual

of heavy

somnolence

and

activity

for the

first

reduce

the

physical

susceptible

subjects

of this serious

Preventive

acclimatization may

high-altitude

illness.8

ADDENDUM

Since lication,

this communication a report of high

in children been

altitude

young

This

published.9

pulmonary

high

and edema

dwellers

was

altitude adults

report

for pub-

pulmonary

in Leadville, identifies

as a serious

in North

376 HULTGREN, MARTICORENA

submitted

health

America.

edema Col,

high

has

altitude

problem The

for inci-

dence change

was higher in altitude

in was

children

than

less severe than study, ie, a descent from 3,100 meters to less than 2,200 meters (7,235 feet), the

Peruvian

sea level.

change

The

sojourn

seven days in half is at variance with

in altitude

from

at lower

altitude

in adults. The in the present

( 10,171

feet) to to

compared 3,750 meters

was

less than

of the patients in Leadville, studies in Peru.”8

which

ACKNOWLEDGMENT: The assistance of the administrafive personnel of the Germ de Pasco Coip. and the Centromin-Peru in making this study possible is gratefully acknowledged. REFEREN4 ES

1 Lizarraga

38:244-274,

L: Edema

agudo

del pulmon.

An Fac Med

Lima

1955

2 Houston C: Acute pulmonary edema of high altitude. N Engl J Med 263:478-480, 1960 3 Hultgren H, Spickard W, Hellriegel K, et al: High altitude pulmonary edema. Medicine 40:289-313, 1961 4 Singh I, Roy S: High altitude pulmonary edema: Clinical, hemodynamic and pathological studies. In Hegnauer E (ed) : Biomedicine Problems of High Terrestrial Elevaflora. US Army Research and Development Command, 1969 5 Menon N: High altitude pulmonary edema. N Engi J Med 273:66-73, 1965 6 Hackett P, Rennie D: The incidence, importance and prophylaxis of acute mountain sickness. Lancet 2:11491155, 1976 7 Houston C: High altitude illness: Disease with protean manifestations. JAMA 236:2193-2195, 1976 8 Hultgren H: HAPE: High altitude pulmonary edema. Off Belay, April 1976, pp 7-10 9 Scoggin C, Hyers T, Reeves J, et al: High-altitude pulmonary edema in the children and young adults of Leadville, Colorado. N Engl J Med 297: 1269-1272, 1977

CHEST, 74: 4, OCTOBER, 1978