a multinational andean genetic and health program. viii. lung function changes with migration...

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A Multinational Andean Genetic and Health Program VIII. LUNG FUNCTION CHANGES WITH MIGRATION BETWEEN ALTITUDES ' WILLIAM H. MUELLER,' FANNY YEN,2 PATRICIA SOTO,' VICTORIA N. SCHULL,' FRANCISCO ROTHHAMMER (I AND WILLIAM J. SCHULL 'University of Texas Health Science Center, Center for Demographic and Population Genetics, Houston, Texas 77025; 3Znstitute for Andean Biology, University of San Marcos, Lima, Peru; 'Department of Anthropology, Universidad del Norte. Ariea, ChiEe and Universidad de Chile, Departamento de Biologia Celular y Genetica, Casilla 6556, Santiago 7, Chile KEY WORDS Lung function . Hypoxia . Migration . Developmental adaptation . Altitude . South America ABSTRACT Studies of lung function in high altitude populations have sug- gested the influence of hypoxic environment on the development of this charac- teristic independent of confounding variables such as ethnicity and habitual exercise. However, often the effect of altitude on vital capacity is greater in children than adults, suggesting that more than developmental adaptation is operative. Also selective migration could account for the similarity of migrants and permanent residents at a destination altitude. To explore these problems we studied the lung function (FVC, FEV1,PFR) of 377 individuals who had mi- grated between altitudes in northern Chile. Migrant measurements were adjusted to those of permanent residents of ap- propriate age, sex and height at the altitudes of origin and destination. The measurements were then related to ethnicity (Spanish-Aymara ancestry), oc- cupation and permanence, the latter combining information on both age at mi- gration to and length of stay at a destination altitude. Upward migration was associated with increased chest depth, FVC and FEV,, but not height or other chest measurements. Downward migration had no sig- nificant effect. The flow-dependent test PFR was so sensitive to observer vari- ability and occupation that it was difficult to establish its relationship to per- manence. Unlike the body measurements, lung function measurements (espe- cially PFR) tended to deviate from permanent controls at the origin altitude in a direction suggestive of selective migration, nor was permanence itself inde- pendent of ethnicity and occupation. Because of these difficulties the question of developmental adaptation in lung function may not be answerable in cross- sectional studies like the present and previous efforts, but rather in longitudi- nal investigations in which the control is the individual himiherself. Studies of human pulmonary function in high altitude populations suggest a strong environmental component in the variability of this character (via hypoxia or hypocapnia), based on these general observations: (1) Life- long residents of high altitude regions have larger lung function measurements than sea level controls (Boyce et al., '74; Frisancho, '69; Hurtado, '32; Velasquez, '76), apparently in- dependent of ethnic origin (DeGraff et al., '70; Harrison et al., '69; Mueller et al., '78b) and habitual exercise (Anderson et al., '78). (2) Individuals who migrate to an altitude dif- ferent from that in which they were born tend to have lung functions similar to those of per- manent residents at the destination (Boyce et ' This research was supported by grants HL 15613, HL 05266, GM 19513 and CA 19311 from the National Institutes of Health. AM. J. PHYS. ANTHROP. (1979) 51: 183-196. 183

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Page 1: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

A Multinational Andean Genetic and Health Program VIII. LUNG FUNCTION CHANGES WITH MIGRATION BETWEEN ALTITUDES '

WILLIAM H. MUELLER,' FANNY YEN,2 PATRICIA SOTO,' VICTORIA N. SCHULL,' FRANCISCO ROTHHAMMER (I AND WILLIAM J. SCHULL 'University of Texas Health Science Center, Center for Demographic and Population Genetics, Houston, Texas 77025; 3Znstitute for Andean Biology, University of San Marcos, Lima, Peru; 'Department of Anthropology, Universidad del Norte. Ariea, ChiEe and Universidad de Chile, Departamento de Biologia Celular y Genetica, Casilla 6556, Santiago 7, Chile

KEY WORDS Lung function . Hypoxia . Migration . Developmental adaptation . Altitude . South America

ABSTRACT Studies of lung function in high altitude populations have sug- gested the influence of hypoxic environment on the development of this charac- teristic independent of confounding variables such as ethnicity and habitual exercise. However, often the effect of altitude on vital capacity is greater in children than adults, suggesting that more than developmental adaptation is operative. Also selective migration could account for the similarity of migrants and permanent residents a t a destination altitude. To explore these problems we studied the lung function (FVC, FEV1, PFR) of 377 individuals who had mi- grated between altitudes in northern Chile.

Migrant measurements were adjusted to those of permanent residents of ap- propriate age, sex and height a t the altitudes of origin and destination. The measurements were then related to ethnicity (Spanish-Aymara ancestry), oc- cupation and permanence, the latter combining information on both age a t mi- gration to and length of stay a t a destination altitude.

Upward migration was associated with increased chest depth, FVC and FEV,, but not height or other chest measurements. Downward migration had no sig- nificant effect. The flow-dependent test PFR was so sensitive to observer vari- ability and occupation that it was difficult to establish its relationship to per- manence. Unlike the body measurements, lung function measurements (espe- cially PFR) tended to deviate from permanent controls a t the origin altitude in a direction suggestive of selective migration, nor was permanence itself inde- pendent of ethnicity and occupation. Because of these difficulties the question of developmental adaptation in lung function may not be answerable in cross- sectional studies like the present and previous efforts, but rather in longitudi- nal investigations in which the control is the individual himiherself.

Studies of human pulmonary function in high altitude populations suggest a strong environmental component in the variability of this character (via hypoxia or hypocapnia), based on these general observations: (1) Life- long residents of high altitude regions have larger lung function measurements than sea level controls (Boyce et al., '74; Frisancho, '69; Hurtado, '32; Velasquez, '76), apparently in-

dependent of ethnic origin (DeGraff et al., '70; Harrison et al., '69; Mueller et al., '78b) and habitual exercise (Anderson et al., '78). (2) Individuals who migrate to an altitude dif- ferent from that in which they were born tend to have lung functions similar to those of per- manent residents a t the destination (Boyce et

' This research was supported by grants HL 15613, HL 05266, GM 19513 and CA 19311 from the National Institutes of Health.

AM. J. PHYS. ANTHROP. (1979) 51: 183-196. 183

Page 2: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

MUELLER, YEN, SOTO, SCHULL, ROTHHAMMER AND SCHULL 184

al., '74; Frisancho et al., '73b; Harrison et al., '69). (3) Migration to high altitude during growth (but not in adulthood) is associated with increased physiological efficiency via aerobic and vital capacity (Frisancho, '75; Fri- sancho et al., '73a,b). However, there are some gaps in our knowledge: (a) The altitude effect on a typical functional measurement like vital capacity (FVC) is often greater in children than adults (Anderson e t al., '78; Mueller et al., '78b). Residual volume, not FVC, appeared to differentiate adult highland Peruvians from coastal controls (Hurtado, '64). Were developmental adaptation (changes during growth in response to environment) impor- tant, one would expect to see a greater effect in adults than children. (b) Whether selective migration may be the root of the lung function similarity of migrants and destination perma- nents has not been tested.

Previously we examined lung function (forced vital capacity - FVC, forced expira- tory volumes a t one and three seconds - FEV, and FEV i, and peakflow rate - PFR) in relation to sex, age, body size, altitude (0- 4,000 m), and ethnicity (Spanish-Aymara ancestry) among permanent residents of an altitude gradient in Chile (Mueller et al., '78b). In this paper we turn to the migrants of this population in order to assess the effects of upward and downward migration on physio- logical development and provide insights into the above questions.

MATERIALS AND METHODS

In 1973-1974 a multidisciplinary study sought to assess the health status of the indigenous population (the Aymara) of the Department of Arica in northern Chile and study human adaptability to high altitude (Schull and Rothhammer, '77). A total of 2,096 individuals who claimed Aymara ances- try were studied in (a) two coastal locales, (b) five sierra villages (2,500-3,500 m), and (c) four altiplano hamlets (4,000-4,500 m). In this paper we report on the lung function (FVC, FEV, and PFR) of 377 migrants who had not been excluded from the analysis of lung func- tion measurements because they were less than six years of age, had a respiratory ail- ment, rated poor performance in the test or failed to have either the body measurement or lung function examination. Reasons for these exclusions have been set out in detail else- where (Mueller et al., '78b). The age group

distribution of migrants is as follows: 72 boys (6-18 years old), 40 girls (6-16 years old), 155 men and 110 women (19-60f years old). Veri- fication of most children's ages was possible by reference to the fertility histories supplied by parents. Migrants were classed according to direction of movement. Because of dif- ficulties of classification, only migrants who had moved in one direction (upwards or down- wards but not a combination of the 2) are con- sidered here. The upward group included 172 coast to sierra, 70 coast to altiplano and 6 sier- ra to altiplano migrants; the downward group included 29 sierra to coast, 62 altiplano to coast and 38 altiplano to sierra migrants.

Lung function was assessed with a port- able Hewlett-Packard analyzer (Model No. 47401A), which yields BTPS corrected units. The average of the two best trials (out of 4) was taken as a subject's value for each of the three lung function measurements following recommendations of the National Heart and Lung Institute ('71). A trial run in which the subject was instructed in the test was ex- cluded from the above calculation. Subjects were not permitted to smoke one hour before the test.

Fifteen observers took the lung function measurements of migrants, one of whom was responsible for 60% of all observations, another five for 5-15%, and the rest, a very small percentage of all observations. Most of the extra observers were used in the sierra (in- termediate altitude), hence observer vari- ability could be more critical in upward mi- grants most of whom were found in the sierra. An analysis of variance was performed among observers for whom there were sufficient numbers of observations (the 6 main ob- servers). The rest were combined into a seventh class. Prior to the analysis, lung func- tion measurements were adjusted for sex, age, altitude of origin and body height. TWO ob- servers - among those who took 515% of the measurements - were significantly different (p < 0.01) from the rest in PFR, one higher, the other lower. The observer who measured significantly lower than the rest in PFR, also had significantly lower FVC's. These results are not strictly due to measurement error per se, because each observer measured different subjects, and these were not necessarily assigned a t random. However, the low PFR and FVC suggest a failure to obtain a maximal effort from subjects and hence real technical

Page 3: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

185 LUNG FUNCTION AND MIGRATION IN CHILE

error. Therefore subjects measured by this ob- server (N = 57) were excluded from the analy- sis of mination effects. v

Body measurements were taken by two ob- servers who measured similar numbers of sub- jects a t all altitudes, following standard pro- cedures (Weiner and Lourie, ’69). This aspect of the study is described in detail in another publication (Mueller e t al., ’78a). We include here five measurements of possibly the greatest functional interest (Mueller et al., ’ 7 8 ~ ) : height, chest circumference a t max- imum inspiration, transverse chest, anterior- posterior chest and sternal length.

Permanence The following data were available to deter-

mine an individual’s migrational status or permanence: altitude of birth, altitude of resi- dence, number of years a t the village of resi- dence, subject’s age and location of all other villages in which the subject lived for at least a year. If the subject’s birth and residence al- titude were the same and if other villages the subject might have lived in were a t the same altitude, the subject was classified as a per- manent resident of the altitude in question. If the birth and residence altitude were different or if the subject had lived for a time in villages a t an altitude different from that of hisiher birth, the subject was classified as a migrant. Then the subject’s age a t migration was deter- mined by subtraction of the number of years at the residence village from the subject’s age. Of course, this would yield age a t migration only when there had been one move, since we know length of time only a t the present village. If the subject resided in other villages between birthplace and present residence, we only know the number and location of such villages. This difficulty arose only in a mi- nority of cases. In such cases age a t migra- tion was calculated as follows:

Age at migration = (A-Y) [(No)/(NT)I

where A = subject’s age, Y = number of years a t present village, NT = total number of villages lived in exclusive of present village and No = number of villages lived in a t al- titude of origin.

Obviously when No = NT, age at migration reduces to the simple difference between a subject’s age and number of years a t present village. However, when No is smaller than NT (it can never be larger), in all probability a

greater proportion of time has been spent at the destination altitude and age a t migration will consequently diminish. We believe this calculation to be the conservative one.

If developmental adaptation is important in the variability of a measurement, the effect of migration will be greatest for those who would have migrated early in development and have lived a t the destination altitude for the longest time. Thus, permanence was scored as follows: (a) individuals who migrated as adults ( 2 0 f years of age) or who migrated during childhood but had spent less than five years a t the destination, (b) individuals who moved during late childhood (10-19 years of age) with over five years a t the destination, or individuals who migrated in early childhood (0-9 years of age) and had spent five to nine years a t the destination, and (c) individuals who migrated in early childhood (0-9 years of age) who had been ten or more years at the destination. We have assumed that perma- nence is independent of all other factors, environmental and genetic. To test this as- sumption two variables were considered: ethnicity and occupation.

Ethnicity Individuals were classified as either (a) non-

Aymara (i.e., Spanish), (b) mestizo, or (c) Aymara, based on the maternal and paternal surnames. Details of this classification have been given elsewhere (Schull and Rothham- mer, ’77; Diaz e t al., ’78). The assignment was conservative in the sense that more Aymara were likely misclassified as mestizo than vice versa. Hence “mestizos” are probably closer genetically to Aymara than Spanish (Gold- smith e t al., ’77; Palomino et al., ’78).

Occupation Individuals were classed into one of three

categories: (a) professionals (including ad- ministrative, clerical, employee, semi-skilled worker and military), (b) student, and (c) agri- cultural (including laborers, farmers, herds- men, unemployed, housewives and unknown).

Statistical analysis Two age corrected values were obtained on

body and lung function measurements by subtracting an individual’s value from the ap- propriate agelsex mean of permanent resi- dents of the origin (x - Xo) and destination al- titude (x - ED). Control group means were ob-

Page 4: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

MUELLER, YEN, SOTO, SCHULL, ROTHHAMMER AND SCHULL

TABLE 1

Distribution ofthe sample by occupationalstatus (1 = professional, 2 = student, 3 =farmer), ethnicity I1 = non-Aymara, 2 = mestizo, 3 = Aymara) andpermanencr (1 = migrated as adult or

short stay, 2 = migrated in childhood with intermediate stay, 3 = migrated in early childhood withprolonged stay). Italicized cells were

not included in subsequent analysis of variance

Occupntion

I !2 3

Ethnicity Ethnicity Ethnicity Permanence

1 2 3 1 2 3 1 2 3

1 0 2 0 3 0

1 0 2 0 3 0

1 14 2 + 3 0

1 1 2 + 3 0

0 0 0

0 0 0

4 6

I 3

1 2 1

0 0 0

2 3

0 1

Downward males (N=63) I 4 2 0 4 4 0 5 3

Downward females (N=49) 0 3 1 0 2 3 0 0 1

Upward males (N= 126) 4 7 7 0 8 8

Upward females (N = 82) 4 4 2 0 12 4

I 11 0 9 0 4

3 12 0 9 0 4

6 5 1 17

5 6 0 14

5 4 2

6 3 2

5 29

0 25

tained in the sample of permanents by com- puting three-year moving averages to dampen somewhat the effect of small samples at each year of age during growth. For adults control means were calculated within three age cat- egories: 19-39, 40-59 and 60+.

An hierarchical analysis of variance of body and lung function measurements was carried out within sex and migrant group (upward or downward) with occupation, ethnicity and permanence as control variables. By “hierar- chical” we mean the effects of occupation are tested first, those of ethnicity next with ef- fects of occupation constant, and those of per- manence last with the effects of both of the preceding variables constant. Given the small samples in the categories occupation = 1 and ethnicity = 1, these were dropped from the analysis of variance in some of the migrant- sex groups to minimize the numer of empty cells. Likewise, it was found necessary to com- bine permanence categories 2 and 3 in upward migrants (table 1).

RESULTS AND DISCUSSION

In table 2 are given means with standard errors of body and lung function measure- ments of the total sample of upward and down- ward migrants compared to those of coastal

and altiplano permanent residents which have been published previously (Mueller et al., ’78a,b). Means were estimated by linear re- gression to age 10 in children and age 40 in adults. The migrants are compared to coastal and altiplano permanents because the latter two altitudes are the places of origin of most migrants.

Generally migrants resemble those a t the destination more than the origin altitude. This occurs more consistently for the lung function measurements, but is not as ap- parent in adult males where both kinds of mi- grants are more similar to coastal perma- nents. Downward migrants tend to have larger body dimensions (particularly chest) but smaller functional measurements as com- pared to altiplano permanents. Upward mi- grants are smaller in size but have larger functional measurements than those on the coast.

Ethnicity appears t o be similarly dis- tributed in downwards migrants (table 1) and permanent residents of the highlands pub- lished previously (Mueller et al., ’78b). How- ever only about 17% of upward migrants are non-Aymara which contrasts to about 50% non-Aymara in coastal permanents (the source altitude of most upward migrants).

Page 5: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

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Page 6: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

188 MUELLER, YEN, SOTO, SCHULL, ROTHHAMMER AND SCHULL

Thus, the upward migrants are more Amerin- dian than are those who remain on the coast all of their lives. Common ancestry could thus contribute to the general similarity of upward migrants to highland permanents. However, it could hardly explain the similarity of down- ward migrants and coastal permanents. The data in table 2 suggest either environmental influences or selective migration with respect to lung function. In order to assess these fac- tors we will examine first occupational and ethnic influences on these measurements before turning to those associated with migra- tion itself (fig. 1).

In figure 1 are shown the effects of occupa- tion, ethnicity and permanence on the body and lung function measurements of migrants. The effects of each of the control variables is illustrated with effects of the other two held constant. The lung function measurements are further adjusted for body height. Shown are the mean differences from the altitude of origin and destination divided by the standard error of the mean difference. A deviation of -+2 in the figure is significant at p < 0.05. The actual means t standard errors are given in tables 3a and 3b, and F-ratios from the analy- sis of variance testing for effects of occupa- tion, ethnicity and permanence are shown in tables 4a and 4b.

Ethnicity and occupation There is a striking association of ethnicity

and body height in upward migrants (fig. 1). Non-Aymara Le., Spanish) are taller than coastal (origin) but especially highland (des- tination) permanents, and Aymara are short- er on the average than coastal permanents. This trend is reflected in the other body - but not lung function - measurements of upward migrants. I t is also reflected across occupa- tional classes suggesting a correlation of oc- cupational status and ethnicity (table 1).

Occupation and ethnicity affect flow-depen- dent tests (FEV,, PFR) more than FVC. More- over, the effects are often in opposite di- rections in the two sexes giving the appear- ance of no general trend across occupation or ethnic classes in figure 1. It may be best to regard this as a byproduct of another striking feature of figure 1. The lung function mea- surements in general deviate uniformly - in opposite directions in upward and downward migrants - across all ethnic/occupation clas- ses. In contrast, this does not usually occur for body measurements. This pattern suggests se-

lective or non-random migration and is par- ticularly evident in the flow-dependent tests (FEV,, PFR): upward migrants are signifi- cantly larger in PFR than origin (coast) per- manents over many occupation/ethnic classes. Likewise, downward migrants generally have smaller flow rates than their origin (highland) population.

Analysis of variance (tables 4a, 4b) for the most part confirms significant effects of ethnicity and occupation on several of the body measurements and PFR. Variability in height appears more related to ethnicity, and chest measurements and PFR to occupation. Ethnic effects are evident mostly in upward male migrants, the sample with the greatest ethnic heterogeneity. That is, in upward males there were sufficient numbers of Spanish (ethnicity = 1) to be included in the analysis of variance (table 1). In both upward and downward males, professionals have larger PFR than farmers, suggesting an effect of acculturation on flow-dependent tests; those more urbanized might be less intimi- dated by the laboratory procedures. Among female upward migrants ethnicity is signifi- cantly associated with FVC (p < 0.05), Aymara having larger measurements than non- Aymara.

In tables 4a and 4b the majority of F-ratios are of similar magnitude for a given variable with reference to both origin (0) or destina- tion (D). Exceptions are maximum chest cir- cumference and PFR in male downward mi- grants, in which F-ratios are strikingly higher for measurements as deviations from destina- tion means. It is not clear why heterogeneity is greater for D-measurements in these two cases, although this may reflect genetic dif- ferences in the measurement-age relationship as migrants are less likely to resemble the destination altitude in this respect.

Permanence If developmental adaptation is important,

Fig. 1 The effects of occupation, ethnicity and perma- nence on the body and lung function measurements of mi- grants. The effects of each of the control variables is illus- trated with the effects of the other two held constant. Shown are the mean differences from the altitudes of ori- gin and destination divided by the standard error of the mean difference. A deviation of ?2 is significant a t p < 0.05. (occupation: 1 = professional, 2 = student, 3 = agricultural; ethnicity: 1 = non-Aymara, 2 = mestizo, 3 = Aymara; permanence: 1 = migrated as adult or very short stay; 2 = migated as older child with intermediate stay; 3 = migrated in early childhood with prolonged stay)

Page 7: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

189 LUNG FUNCTION AND MIGRATION IN CHILE

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Page 8: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

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Page 9: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

TABLE 3b

Means of body and lung function m

easurements expressed as deuiations from

age and sei specifm m

eans ofpermanent residents at the altitude of origin (Fa and destination E

D) by category of the control

variables (occupation, ethnicity and permanence). B

ody measurem

ent means (in cm

) are shown for a given control variable w

ith the effects of the other two uariables held constant. The sam

e is true for lung function m

eans (in U except that these are further adjusted for body height, Italics indicate that migrants deuiate significantly (p <

0.05) from origin or destination perm

anents

Maxim

um chest

Tr8

IlSW

rnC

A

nterior-posterior Sternal

Control

Height

circumference

cheat chest

length FV

C

FEV

, PFR

varisbles

~~~~

N LO

*SE E

D+SE

iO

2SE

~

D*

SE

jiO

?SE

ED

-SE

ioeS

E

in2

SE

io?S

E

ID?SE

fo&

SE

E

D~

SE

EO

*SE ~

D+

SE

*O

*SE ED*=

Occupation 1

29

2 34

3 63

1

25 2

47 3

54 Perm

anence 1

54

2+

3

72

Ethnicity

Occupation 1

-

2 26

3 50

I 9

2 36

3 31

Permanence

1

21 2

+3

55

Ethnicity

Upw

ard males (N =

126)

1.0-tl.8 2.3.tO

.6 0.721.6

1.621.6 -0.221.0

0.820.6 -0.220.4 -0.620.5

-0.4rt0.5 -0.720.7

0.320.2 0.120.1

0.220.1 0.320.1

1.1eO.5

1.320.5 -0.121.7

1.421.3 0.721.3

0.221.0 -0.1fO

.9 0.1f0.3

0.4f0.3 -0.120.7

-0.lkO.3

-0.120.3 0.120.1

-0.020.3 0.3fO

.l 0.120.1

1.3f0.4 0.2k0.3

-0.9fl.O

1.7Z0.9 -1.221.0

0.6f0.8 -0.820.4

0.420.3 0.4-0.3

-0.120.2 --0.420.2

-0.420.2 0.220.1

5.221.8 - 1.7'1.2 -2.5 *I. 1

-0.52 1.2 - 0.820.9

- - 0.32 1.9 -0.821.2

5.223.0

- 1.5e 1.4 -- 1.22 1.3

7.5

~1

.8 2.221.8

3.5

21.5

0.220.1

Z.lrt0.5

1.220.5 0.620.4

-0.320.5 -0.220.4

0.821.0 0.0f1.5

0.6e1.0 -0.3e1.1

0.420.4 0.450.3

-0.2rt0.4 -0.5e0.3

4.6

f0.3

-0.122.0

-1.621.1 -0.5e1.0

-0.820.4 0.1e0.4 -0.220.3

-0.6'0.3 -0.320.4

-0.320.3

1.821.2 - 1.121.1 -0.121.7 -0.420.4

0.6C0.4 -0.520.3

4.7

20

.3

-0.6-1-0.3 -0.720.3

1.720.8 0.420.9

1.320.8 -0.520.4

0.3k0.3 0.820.2

0.220.2 -0.1C

0.2 -0.2rtO

.2

Upw

ard females (N =

76)

- -

-

-

- -

- -

- 2.221.7

0.421.8 -0.721.6 -0.220.8

-0.2

k0

.5

-0.520.4 -0.1f0.6

-0.120.6 -0.620.5

- 1.4~

t1.0 1.521.3 -1

.1f1

.1

0.220.6 -0.620.4

0.4-tO.3

-0.520.3 0.720.4

-0.220.4

6.7-3.0 3.3e2.8 -1.422.4

0.821.0 -0.521.0 0.8-0.8

-0.620.6 0.920.9

-0.420.9 1

.6~

1.3

1.721.6 -0.721.5 0.2rt0.7

-0.420.5 0.720.4

-0.2-0.3 0.520.4

-0.3f0.4 0

.3~

1.4

--0.222.2 -1.2e1.4

-0.3'0.6 -0.620.5

0.120.4 -0.320.3

0.120.3 -0.320.4

0.2 2 0.2

0.2s0.1 O

.lfO.1

O.lfO

.l 0.2 20. 1

-

-0.020.1 0.220.1

0.1*0.1 0.020.1 0.220.1

0.521.1 0.120.1

0.2

20

.1

0.2-0.3 0.420.3

0.020.3 0.220.2

0.220.1 0.720.6

0.720.5 0.120.1

0.2r0.2 0.220.1

0.750.4 0.620.4

O.O

e1.4 0.220.1

0.220.1 0.720.3

0.520.3

0.020.1 0.220.1

0.2-tO.1

1.120.4 l.le

0.3

O

.lfO.l

0.220.1 0.220.1

0.5-CO

.3 0.220.8

-

- -

- -

O.OkO.l 0.120.1

0.120.1 0.6&

0.3 0.120.3

0.120.2 0.2*0.1

0.1*0.1 0.820.2

0.4f0.3

0.120.4 0.3k0.2

0.2202 1.4e0.5

0.820.6 0

.0~

0.5

0.120.1 0.1-cO

.l 0.820.3

0.520.3 O

.lrtO.1

0.1?0.1 O

.OkO

.l 0.520.3

-0.120.3

-2.7e2.0 0.322.1

0.123.3 -1.421.7

-0.3rt0.5 -0.620.7

0.420.6 -0.220.5

0.420.6 0.120.9

0.020.1 0.221.0

2.2.tl.O

1.521.2 -0.821.1

0.220.4 -0.520.4 0.520.4

-0.420.3 0.4e0.3

-0.4rt0.3 0.220.1

0.0+0.2 -0.1%

0.2 O

.Ok0.1

0.120.3 0.120.5

0.1

~0

.1 0.220.1

0.1*0.1 1

.0-~

0.2

0.420.2

Page 10: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

192 MUELLER, YEN, SOTO, SCHULL, ROTHHAMMER AND SCHULL

TABLE 4a

F-ratios from an hierarchical analysis of variance of body and lung function measurements testingfor the effects of occupation, ethnicity (with occupation constant) andpermanence (with occupation and ethnicity

constant) for males. 0 = measurement as deviation from age-sex specific mean ofpermanent residents at the altitude of origin, D = measurement as deviation from age-sex

specific mean ofpermanent residents at the altitude of destination

Main effects Two-way interactions Dependent variable

Occupation Ethnicity Permanence Occ x eth Occ x perm Eth x Derm

df =

Height

Maximum cheat circumference

Transverse chest

Anterior-posterior chest

Sternal length

FVC

FEV I

PFR

df =

Height

Maximum chest circumference

Transverse chest

Anterior-posterior chest

Sternal length

FVC

FEV,

PFR

0 D 0 D 0 D 0 D 0 D 0 D 0 D 0 D

0 D 0 D 0 D 0 D 0 D 0 D 0 D 0 D

Downward migrants (N=57) (1,47) (1,471 (2,47) 2.13 0.21 0.73 1.88 0.03 1.05 1.87 0.35 0.08

11.31 0.17 0.35 0.17 0.97 0.27 0.85 0.80 0.83 7.71 0.72 1.30 4.98 0.14 1.94 3.29 1.23 1.76 2.45 0.96 1.85 1.26 0.36 1.82 0.08 0.69 1.75 2.13 0.00 2.95 1.37 0.46 2.10 0.01 0.00 1.01 6.68 ' 0.18 0.59 Upward migrants (N= 126)

(2,112) 2.80 4.64 ' 3.70 2.67 4.99 2

Ufl.fifl ' 2.78 1.01 0.29 1.72 0.72 0.44 1.96 1.68 9.09 2

6.60

(2,112) 16.20 14.70 2.96 3.50 3.02 I

3.56 2.45 1.86 0.54 0.63 0.66 0.61 0.01 0.30 0.31 1.59

(1,112) 0.06 0.00 2.41 1.89 0.10 0.41

20.93 11.23 2.29 2.10 0.64 0.10 0.07 0.27 2.88 6.34

(1,471 (2,47) (2,471 0.01 0.77 0.24 0.25 2.12 0.51 0.07 0.11 0.36 0.04 0.40 0.11 0.60 0.07 0.03 0.31 0.59 0.28 0.07 0.51 0.01 0.10 0.86 0.00 0.04 1.30 0.04 0.27 0.30 0.09 1.65 0.08 0.04 0.25 0.37 0.26 0.01 0.20 0.19 0.09 0.19 0.33 0.44 0.26 0.65 0.27 0.14 0.80

(4,112) 3.71 3.86 0.60 0.36 0.32 0.21 1.42 2.10 0.64 1.05 0.86 0.36 0.51 0.49 0.99 1.59

(2,112) (2,112) 0.77 0.89 1.14 0.47 0.20 3.66 0.11 2.68 0.70 1.18 0.67 0.66 0.56 2.01 0.02 0.53 0.27 2.48 0.66 4.21 ' 0.69 2.86 0.00 0.09 0.35 0.49 0.07 0.73 1.32 0.43 1.20 1.41

' p < 0.05. ? p < 0.01.

measurements of individuals who migrated as adults or who have been only a short time a t the destination (permanence = 1) might dif- fer significantly from the destination but not the origin mean in figure 1. Contrarily, per- sons who had migrated as young children and had spent the longest time at the destination (permanence = 31, should differ least from the destination and most from the origin. The following measurements seem to conform to

this pattern in upward migrants: male anteri- or-posterior chest and FVC, and all female lung function variables. All of these measure- ments increase with early migration and pro- longed stay in the highlands. Downward mi- gration appears to have little effect.

By analysis of variance the means of anteri- or-posterior chest (p < 0.01) (upward males) and FEV, and PFR of upward females (p < 0.05) differ significantly among permanence

Page 11: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

193 LUNG FUNCI"IW AND MIGRATION IN CHILE

TABLE 4b

F-ratios from an hierarch.ica1 analysis o f variance of body and lung function measurements testing for the effects of occupation, ethnicity (with occupation constant) and permanence (with occupation and ethnicity

constant) for females. 0 = measurement as deviation from age-sex specific mean ofpermanent residents at the altitude of origin, D = measurement as deviation from age-sex

specific mean ofpermanent residents at the altitude of destination

Main effects Two-way interactions Dependent variable

Occupation Ethnicity Permanence Occ x eth Occ X perm Eth X perm

df =

Height

Maximum chest circumference

Transverse chest

Anterior-posterior chest

Sternal length

FVC

FEV , PFR

d f = Height

Maximum chest circumference

Transverse chest

Anterior-posterior chest

Sternal length

FVC

FEV,

PFR

0 D 0 D 0 D 0 D 0 D 0 D 0

0 D

n

0 D 0 D 0 D 0 D 0 D 0 D 0 D 0 D

Downward migrants (N=46) (1,361 (1,361 (2,361 0.25 0.12 0.08 0.38 0.00 0.37 1.24 0.01 0.13 0.49 0.11 0.03 1.32 0.00 0.02 0.14 0.19 0.00 0.83 0.26 1.03 1.92 1.41 1.66 0.24 0.32 0.64 0.11 0.00 1.00 0.70 0.40 0.62 0.01 0.54 0.76 0.03 0.81 0.16 0.69 0.61 0.04 0.14 0.49 0.13 0.71 1.61 0.02

Upward migrants (N=76) (1,67) (2,671 (1,671 0.14 2.99 3.15 0.93 2.81 1.29 0.37 0.81 0.66 0.16 0.18 0.09 0.37 0.49 0.86 1.22 0.07 0.02 0.46 1.07 0.00 1.65 0.14 0.21 2.56 0.73 0.00 0.74 0.07 0.36 3.78 3.14 I 2.39 0.50 1.34 0.76 0.77 0.29 3.96 ' 0.03 0.06 1.44 0.57 0.18 5.41 ' 0.23 1.38 1.57

(1,361 (2,36) 3.57 0.52 3.93 0.60 0.31 0.62 0.25 0.33 0.04 0.02 0.01 0.32 0.13 0.34 0.16 0.10 1.45 0.49 2.37 0.18 0.47 0.40 0.52 0.70 8.10 0.29 3.47 0.46 2.10 0.24 0.32 0.75

(2,36) 1.96 1.22 0.07 0.14 0.12 0.64 1.06 0.32 1.45 2.32 0.14 0.01 0.30 0.13 0.52 0.05

(2,67) (1,671 (1,671 0.47 0.24 1.73 0.97 0.02 0.15 0.08 1.56 0.34 0.24 1.39 0.49 0.00 3.31 0.26 0.46 2.40 0.75 0.69 0.14 0.04 0.06 0.26 0.10 2.48 0.04 0.33 1.07 0.38 0.70 0.02 0.67 0.04 0.01 0.25 0.21 0.34 2.42 0.00 0.04 1.62 0.00 0.66 3.22 1.04 0.15 2.51 1.08

: p < 0.05 * p < 0.01.

classes. PFR of upward males is also signifi- cantly related (p < 0.05) to permanence but in a direction contrary to that expected on the thesis of developmental adaptation (fig. 1). It seems likely that this is an artifact of an even stronger occupational effect on PFR in this group, where professionals and students with highest PFR's are more likely to be recent arrivals in the highlands (table 1).

Permanence is not significantly associated

with FVC in any of the migranthex groups by analysis of variance. Nor does downward mi- gration register significant effects on any of the measurements. However, when sexes were combined (analysis not shown here), the effect of permanence on lung function outweighed that of ethnicity and occupation and was in the expected direction in downward migrants (i.e., diminished FVC with early migration to low altitude), but it did not reach statistical

Page 12: A Multinational Andean Genetic and Health Program. VIII. Lung function changes with migration between altitudes

194 MUELLER, YEN. SOTO, SCHVLL, ROTHHAMMER AND SCHULL

significance (p < 0.07). For those variables significantly affected by permanence there are no significant two-way interactions. Vari- ances were homogeneous by the F-max test (Sokal and Rohlf, ’69).

As stated earlier we tried to exclude from our analysis of variance, cells with small num- bers or zeros by combining classes as shown in table 1. Nevertheless, some of the cells in table 1 are small or contain zeros. Several reasons suggest that this is not a factor in our failure to demonstrate unequivocally developmental adaptation in lung function. First, Nie e t al., (’75) state that the SPSS ANOVA program used in our calculations can “cope with un- equal cell sizes and can usually cope with emp- l y cells” (p. 398). Second, among downward male migrants all cells were adequately filled, but downward females had one zero cell and two cells with only one individual. Neverthe- less, results were similar for both sexes. Third, for upward migrants the prevalence of cells with one or no individuals is somewhat greater (table 1). Therefore, we recomputed the analysis of variance combining categories further as follows: occupation category 1 (pro- fessionals) was dropped - to make the analy- sis for males and females similar - and ethnicities 1 and 2 (Non-Aymara and Mestizo) were combined. This left upward males with adequate numbers in all cells and females with only one zero cell. Results (not shown here) were essentially the same as those already given in tables 4a and 4b, except that male PFR was no longer significantly related to permanence in a way unexpected on the hy- pothesis of developmental adaptation.

Lung function and developmental adaptation

We have investigated the effects of migra- tion on human pulmonary function measure- ments in two ways: (1) by examining trends in mean deviations of migrants from permanents a t the altitude of origin and destination over all permanence categories, and (2) by testing the effects of permanence by analysis of vari- ance. In each procedure we have held constant the effects of other variables of possible importance (ethnicity, occupation) which in- deed, as is evident in table 1, are not them- selves independent of permanence. The effects of permanence were greater for measure- ments of pulmonary function and chest depth than for other measurements.

Not all of the effects of permanence on lung

function can be considered independent of ethnicity or occupation. Larger FVC’s of upward females who have migrated when young may reflect a correlation of ethnicity and permanence (the Aymara are more likely to have migrated upward as youngsters). How- ever, larger FVC and anterior-posterior chest in males and FEV, in females with greater permanence a t high altitude occur in the ab- sence of correlations with ethnicity and oc- cupation. Thus, our results concur with others in suggesting the importance of hypoxia on the development of lung function. In light of the correlation of permanence with ethnicity and occupation, and the suggestion of se- lective migration with respect to the physio- logical measurements, the results of our study have to be interpreted with considerable cau- tion. The question of developmental adapta- tion may not be answerable in cross-sectional studies like the present and previous ones, but rather in investigations in which each subject serves as hisiher own control (longitudinal).

ACKNOWLEDGMENTS

We are indebted to the Junta de Adelanto de Arica and its president, Luis Beretta, the members of the Departamento de Desarrollo Comunal y Plan Andino, particularly Carlos Solari, its chief, without whose support this study would not have been possible. We also owe much to the Servicio Nacional de Salud, the Carabineros de Chile and numerous teach- ers who made our examinations a success. We thank Doctor Frederick Sargent for helpful discussions on the subject of Lung function. We thank Ms. Susan Seybold, Mr. Richard Al- len, Ms. Paula Carlock and especially Doctor Merry Makela and Ms. Sara Barton without whose help these data would not be available. Finally, to the Ariquenos, of the coast, the sierra and the altiplano, we express our grat- itude.

LITERATURE CITED

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Boyce, A. J., ,J. S. J. Haight, D. B. Rimmer and G. A. Har- rison 1974 Respiratory function in Peruvian Quechua Indians. Ann. Hum. Biol., 1: 137-148.

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