The Relationship between Acute Mountain Sickness and Pulmonary Ventilation at 2,835 Meters (9,300 ft)

The Relationship between Acute Mountain Sickness and Pulmonary Ventilation at 2,835 Meters (9,300 ft)* James D. Anholm, M.D.;·· Charles S. Houston, M.D.; and Tom M. Hyers, M.D.t

We have demoastrated a smaD bot statistkaIIy siplftcant decrease in forced vital capacity aDd ill ........., low rates amonl 126 persons studied daily for the first three days after arrival at an altitude of 2,835 meten (9,300 ft). Nearly half of these individuals had syaptoms attrlbutable to altitude sidmess, and tIaoIe witII the _ . . tIysp-

A scent to altitudes over 2,413 meters (8,000 ft)

produces in some individuals a variety of signs and symptoms called "altitude sickness," with the type and severity of the symptoms depending both on the rate of ascent and the altitude reached. The mildest and most common syndrome is acute mountain sickness, which is characterized by headache, nausea, and vomiting. This is usually self-limited and requires little treatment. High-altitude pulmonary edema is characterized by an accumulation of fluid and by microthrombi and hyaline membranes in the lungs.' High-altitude pumonary edema can be fatal. The third form, cerebral edema, is characterized by severe headache with a variety of neurologic signs, such as hallucinations, ataxia, and coma; this form also is occasionally fatal. Although the afHictions due to altitude have been known for centuries, Ravenhi1l2 in 1913 was the first to define these three forms of altitude sickness, labeling them "normal puna," "cardiac puna," and "nervous puna," respectively; (puna is the South American term applied to mountain sickness, a term in use where Ravenhill" worked as a physician to a mining camp). Considerable literature on the subject has appeared in the last decade, following descriptions by Houston'[ and by Hultgren et al4 of high-altitude pulmonary edema, which has become the most frequently fatal high-altitude illness. There is a grow·From the Department of Epidemiology and Environmental Health, University of Vermont, Burlington. • °Presently at Mt Sinai Medical Center Milwaukee. tPresentlyat University of Colorado M;hcal Center, Denver. Manuscript received February l~revision accepted June 13. Reprint requests: Dr. Houston, H Ledge ~ Burlinglon, Vermont 05401

CHEST, 75: 1, JANUARY, 1979

nea aDd wont headache alto showed the greatest e. . . . . in pulmonary function studied. We suaest that there is a relationship hetweea the symptolDl of altitude limand pulmonary function consistent with the a"......ee of eaty interstitial or alveolar . . . . .

ing impression that the three forms of altitude sickness are part of a continuum or spectrum of "physiologic disease," any part or all of which may occur in combination or separately.5 There have been several deaths and near deaths at altitudes below 3,050 meters (10,000 ft), and the study reported herein was undertaken to determine whether acute symptoms of altitude sickness might be related to changes in pulmonary function, as reflected in changes demonstrated by spirometric data, in persons going from near sea level to moderate altitude. MATERIAL AND METHODS

During February 1977, a total of 228 individuals visiting a ski resort at 2,835 meters (9,300 ft) were studied and

completed a questionnaire. These individuals represented a nonselected sample of approximately 5,000 individuals registering at this resort during this period. Brochures describing the research project were available at the registration desk, and persons showing interest were invited to participate. Those who had been at 2,835 meters for more than 12 hours were excluded; aD others were accepted. One hundred twenty-six of these underwent spirometric testing and also completed questionnaires, while 102 others completed only the questionnaire. The initial spirogram was obtained after registration, in every case within ten hours or less of arrtval at altitude. AD tests were done at approximately the same time in the afternoon or evening, in order to minimize diurnal variation, and were done by the same individual. Three follow-up measurements were made at 24-hour intervals. At each follow-up, subjects were questioned about new symptoms, and responses were recorded as none, mild, moderate, or severe. Spirometric studies were done with a Stead-Wells spirometer, with the subject standing. At least two tests of forced vital capacity (FVC) were made each time, and the largest FVC was used to calculate the forced expiratory volume in

ACUTE IOUNTAIN SICKNESS AND PULMONARY VEIITILlnON 33

..

one second (FEV1)' the forced expiratory flow during the middle half of the FVC (FEF25-7M), aud the ratio of FEV l/FVC. The temperature of the water in the spirometer was recorded, and aD volumes were corrected to body temperature and pressure, saturated.

Subjects came from many parts of the United States. Of the 126 individuals tested with the spirometer, 64 percent were male subjects, and:rr percent were female subjects. Ages ranged from 13 to 62 years, with a mean of 37 years. More than 90 percent lived below 910 meters (3,000 ft), but 79 percent had previously been higher than 3,000 meters. None had been at altitude immediately preceding their arrival at 2,835 meters. Of the 102 persons in the group who only &ned out questionnaires (without spirometric tests), 59 percent were male subjects, and 41 percent were female subjects; the mean age was 38 years (range, 16 to fj'{ years) .

Symptoms Different individuals experienced their worst symptoms on different days, but in general, symptoms tended to be worse on the day after arrival. Symptoms noted in the group with spirometric data were headache (49 percent), insomnia (41 percent), dyspnea (34 percent), cough (20 percent), palpitations (14 percent), and nausea (10 percent). The frequency and distribution of symptoms in this group were similar to those reported by the group who only filled out the questionnaire (no spirometric data), as shown in Table 1, and were also similar to data reported by others.8-10 Spirometric Data Of the 126 subjects undergoing spirometric testing, 48 completed four consecutive daily spirometric

1'''' ........1'''' r ...Spiro-

Table l-lneidenee 01 S1'm"",m. in JneCrie Tau fPIfl SlId

Data

Spirometric Tests

No Spirometric Tests

126

102

20

12 56 54

No. of subjects Incidence of symptom, percentages Cough

Headache Dyspnea Palpitations Nausea Insomnia

34 ANHOLM, HOUSTON, HYERS

49 34 14 10 41

30'

23 58

Table Z-T. .r.,. Anal,..;. of Yarianee lor Two Sa6-

.,.".". of ThoM .,11 Spiromelric Tau·

Subgroup, Data, and Source of Variation

df

Subgroup 1 FVC Subjects 47 Days 3 Residual 141 Total 191 FEV. Subjects 47 Days 3 Residual 141 Total 191 FEF25-75% Subjects 47 Days 3 Residual 141 Total 191 Subgroup 2 FVC Subjects 79 Days 2 Residual 158 Total 239 FEV. Subjects 79 Days 2 Residual 158 Total 239 FEF25-75% Subjects 79 Days 2 Residual 158 Total 239

Sum of Squares

Mean Square

F

P Value

2.094XI0· 4.455XI0· 3.66 P ....0.014 1.516XI0' 5.052XI04 1.948X 10' 1.381XI0 4 2.115XI0· 1.461XI0· 3.109XI0· 4.10 P-0.OO8 3.236XI0· 1.079XI0· 3.707X 10' 2.629XI0 4 1.501X lOS 2.455XI0· 5.223XI0· 2.62 P=0.053 (NS)·· 2.636 X 10' 8.786 X 10' 4.726 X 10' 3.351 XI0' 2.954 X 10'

2.469 X 10' 3.125XI0· 8.57 3.435XI0' 1.717X 10' 3.166XI0' 2.004 X 104 2.503XI0·

P
1.611XI0' 2.040XI0· 9.98 P
·Subgroup 1 was 48 subjects tested on four consecutive days; subgroup 2 was 80 persons tested on three consecutive days. df, Degrees of freedom; and F, variance ratio. ··NS, Not significant.

tests. The others missed one or more spirograms in the first 72 hours at altitude. Two-way analysis of variance of data from the 48 persons who completed all four tests indicated that the mean FVC and the FEVt decreased significantly during the three days after arrival at altitude, with a nadir at the third day, followed by a return toward baseline values. Eighty subjects had three consecutive daily spirograms, and analysis of variance here too indicated that the mean vital capacity and How rates were decreased significantly after 48 hours (Table 2). Mean values for the FVC, FEV 1, and FEF25751 at each 24-hour interval for the 48 persons with complete data are shown in Table 3. The most significant diHerences in the FVC and FEV1 were found between the first day and the third day, and by the fourth day, values had returned nearly to baseline. The spirometric data from those persons with in-

CHEST, 75: 1, JANUARY, 1979

Table 3-Mean Yalua (± SE) for &he 4B Subjeea..11I Four ComeeulitJe Daily Spirornelrie Tau FEF25-75%,

Day

FVC, ml*

FEV., ml**

Day 1

4,697±157

3,946±131

4,554±180

Day 2

4,665±149

3,885±130

4,409±201

Day 3

4,618±153

3,820±123

4,270±164

Day 4

4,651 ±154

3,862±127

4,321 ±175

ml/sec

Pulmonary Mechanics and Symptoms

*p <0.001 for day 1 vs 2; and P <0.0005 for days 1 vs 3, 1 vs 4, 2 VB 3, and 3 VB 4. **P <0.0005 for day 1 VB 3.

complete data are similar to the findings in the 48 with complete data, and when these additional incomplete data are included, the FEF25-75';, as well as the FVC and FEVt, decreased significantly by the third day. These findings also agree with the observations of others. 11- 14 Symptoms es Spirometric Data

Dyspnea and headache were significantly more frequent in individuals showing the greatest decrease in spirometric data and also in those with the most physical activity. Nausea, insomnia, palpitations, and cough were not significantly related to spirometric changes. Age, Sex, and Smoking There was no significant relation between sex or age and the severity of symptoms or the changes in pulmonary mechanics. No significant diHerence was found between smokers and nonsmokers at 24 and 48 hours after arrival, although at 72 hours, more smokers complained of dyspnea than did nonsmokers (P < 0.01). Both smokers and nonsmokers had similar spirograms, Respiratory Infection

Some investigators" have suggested that infection of the upper or lower respiratory tract may increase susceptibility to high-altitude pulmonary edema. In this study, persons who acknowledged a recent respiratory infection also reported more cough at altitude than did those without any recent infection (P = 0.002), but other symptoms and pulmonary functions were no diHerent. DISCUSSION

Population

Seventy-nine percent of the individuals tested with the spirometer had previously been to 3,050 meters or higher, but in general, they were not

CHEST, 75: 1, JANUARY, 1979

aware of the problems which may occur at altitude and so were unlikely to be biased by previous experience. Experimental error was reduced by having spirograms performed by the same individual, in the same way, and during the same period of each day.

Others have shown decreases in vital capacity after going rapidly to high altitude. 1t.14-18 As early as 1875, Hewett described a decrease in vital capacity following exposure to high altitude; however, in 1952, Rahn and Hammond'" reviewed the literature and found wide variation in the various reports of a reduction in vital capacity at altitude, attributing the diHerences to the failure of various investigators to correct for pressure and temperature. Our data confirm the finding of a decreased FVC at altitude. No previous workers have reported efforts to correlate symptoms with changes in pulmonary function at altitude. Gray et al 19 have shown an increase in the slope of phase 3 of the single-breath nitrogen-washout curve but did not relate that change to symptoms. Sutton et al20 found that those subjects with the highest carbon dioxide tension on arrival at 5,360 meters (17,586 ft) subsequently became the sickest. Alveolar-arterial oxygen pressure gradients were also greater in the sicker subjects. In the present study, we have demonstrated a relationship between dyspnea and headache and a decrease in FVC and . FEV1• No other symptoms were related to those spirometric changes. Hypoxia produces a rise in the pulmonary arterial pressure," which may increase the volume of extravascular Huid and progress in some cases to acute pulmonary edema." Staub22 has shown that in the development of pulmonary edema in dogs, Huid first appears in the interstitial spaces, although by using pulmonary closing volumes, Gray et al23 were unable to demonstrate increased interstitial fluid upon exposure to altitude; however, Gray et al 23 only measured closing volumes after seven days at altitude and may have missed the period of maximal increase in fluid in the pulmonary extravascular space. It is possible that fluid accumulates and then dissipates without or before Hooding the alveoli, thus causing the decrease in FVC at 48 hours followed by a return to baseline by 72 hours which we found. Alternatively, it might be that the acute hypoxic pressor response directly decreases vital capacity and Howrates, although transiently. ACKNOWLEDGMENT: We wish to express special thanks to the staff and administration of Keystone Inc. for their encouragement and assistance in this study.

ACUTE MOUNTAIN SICKNESS AND PULMONARY YENTlLAnON 35

REFERENCE'S 1 Arias-SteIla J, Kruger H: Pathology of high altitude pulmonary edema. Arch PathoI76:147-157, 1963 2 Ravenhill TH: Some experiences of mountain siclcness in the Andes. J Trap Med Hgy 16:313-320, 1913 3 Houston CS: Acute pulmonary edema of high altitude. N Engl J Med 263:478-480,1960 4 Hultgren HN, Spickard WB, HeDriegel KO, et al: High altitude pulmonary edema. Medicine 40:289-313, 1961 5 Houston CS: High altitude illness: Disease with protean manifestations. JAMA 236:2193-2195, 1976 6 Hackett PH, Rennie lOB, Levine HD: The incidence, importance, and prophylaxis of acute mountain sidcness. Lancet 2: 1149-1155, 1976 7 Singh I, Khanna PIC, Srivastava MC, et at: Acute mountain sickness. N Engl J Med 280:175-183, 1969 8 Forwand SA, Landowne M, Follansbee IN, et al: Effect of acetazolamide on acute mountain sickness. N Eng} J

Moo279:839-845, 1968

9 Evans WO, Robinson SM, Horstman DH, et a1: Amelioration of the symptoms of acute mountain sickness staging and acetazolamide. Av Space Environ Med 47 :512-516, 1976 10 Houston CS: Proceedings of the Mountain Medicine Symposium, Yosemite Institute, Yosemite, Cal, 1976 11 Tenney SM, Rahn H, Stroud RC, et a1: Adaptation to high altitude: Changes in lung volumes during the 6rst seven days at Mt. Evans, Colorado. J Appl PhysioI5:607613, 1953 12 Horrobin DF, Cholmondeley HG: High altitude pulmonary oedema: Pathogenesis and recommendations for

38 AIIHOUt, HOUSTON, HYERS

13 14 15 16 17 18

19 20 21 22 23

treatment and prevention. East AIr Med J 49:327-331, 1972 Hultgren HN: Biomedicine Problems of High Terresbial Elevations (AH Hegnauer, 00). US Anny Medical Research and Development Command, 1969 Rahn H, Hammond D: Vital capacity at reduced barometric pressure. J Appl PhysioI4:715-724, 1952 Kellogg RH, Mines AH, Gourlay SJ, et a1: Pulmonary mechanics during acclimatization. Fed Proc 24:215, 1965 Ross BB, Buist AS: Changes in lung volumes on acute exposure to high altitude. Fed Proc 32:361, 1973 Jaeger JJ, Maher ]T, Denniston JC, et al: Changes in closing capacity and lung volumes during three days of physical activity at high altitude. Fed Proc 36:533, 1977 Dramise JC, Consolazio F, Johnson HL: Changes in pulmonary volumes with relocation to 1,600 m following acute translocation to 4,300 m. Av Space Environ Med 47 :261-264, 1976 Gray GW, McFadden OM, Houston CS, et al: Changes in the single-breath nitrogen wash-out curve on exposure to 17,600 feet. J Appl PhysioI39:652-656, 1975 Sutton JR, Bryan AC, Gray GW, et al: Pulmonary gas exchange in acute mountain sickness. Av Space Environ Med 47: 1032-1037, 1976 Reeves]T: Pulmonary vascular response to high altitude. Cardiovasc Clin 5:81-95, 1973 Staub NC: Pathogenesis of pulmonary edema. Am Rev Respir Dis 109:358-372, 1974 Gray CW, Rennie lOB, Houston CS, et al: Phase IV volume of the single-breath nitrogen wash-out curve on exposure to high altitude. J Appl Physiol 35:227-230, 1973

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