RESPIRATORY PHYSIOLOGY

Spirometry and Respiratory Muscle Function During Ascent toHigher Altitudes

Sat Sharma Æ Bryce Brown

Accepted: 6 November 2006� Springer Science+Business Media, LLC 2007

Abstract Alteration in lung function at high altitude

influences exercise capacity, worsens hypoxia, and may

predispose to high-altitude illness. The effect of high

altitude on lung function and mechanisms responsible

for these alterations remain unclear. Seven adult male

mountaineers were followed prospectively during a

climbing expedition to Mount Everest, Nepal. Mea-

surements of spirometry and respiratory muscle func-

tion were performed for the duration of the expedition,

during changes in altitude between 3450 and 7200

meters (m). Measurements included the forced vital

capacity (FVC), forced expiratory volume in 1 second

(FEV1), maximal voluntary ventilation (MVV) in

12 seconds, maximal inspiratory pressure (MIP), max-

imal expiratory pressure (MEP), and respiratory

muscle endurance (Tlim). At an altitude of 3450 m,

the FVC initially increased (9%) over 24 h, followed by

a significant decline; the FEV1, MVV, MIP, and MEP

showed similar progressive decline. At 5350 m, FVC

increased by 21% over the first 48 h, then decreased.

The FVC, FEV1, MVV, MIP, and MEP initially

increased and then gradually diminished over time.

Respiratory muscle endurance (Tlim) decreased over

the first three days at 3450 m but then remained

unchanged. MVV decreased at lower altitude followed

by a slight increase and then a significant decline.

Compared with baseline, we observed a fluctuating

course for spirometric measurements, respiratory

muscle strength, and endurance at high altitude. Initial

transient increases in parameters occurred on ascent to

each new altitude followed by a gradual decline during

prolonged stay.

Keywords Respiratory muscle endurance �Spirometry � High altitude � Fatigue � Strength

Introduction

Mountain climbing and trekking at high altitude are

becoming increasingly popular recreational activities.

Hypoxia and alterations in lung function play a

significant role in morbidity and mortality related to

high-altitude exposure [1–4]. Lung function changes at

high altitude may worsen the severity of hypoxemia

beyond that expected due to low barometric pressure.

These changes in lung function affect exercise capacity

and predispose to altitude illness. Previous studies

have evaluated impact of altitude on lung function at

high-altitude laboratories or by simulating altitude

in hypobaric chambers [5–7]. However, conditions

encountered during actual climbing expeditions differ

from those in more controlled experiments, and limited

data regarding alterations in spirometric measurements

and respiratory muscle function in an expedition

S. SharmaSections of Pulmonary and Critical Care Medicine,Department of Internal Medicine, University of Manitoba,Winnipeg, Manitoba, Canada

B. BrownSection of Emergency Medicine, Department of FamilyMedicine, University of Manitoba, Winnipeg, Manitoba,Canada

S. Sharma (&)Sections of Pulmonary and Critical Care Medicine,University of Manitoba, St. Boniface General Hospital,BG034, 409 Tache Avenue, Winnipeg, Manitoba R2H 2A6,Canadae-mail: ssharma@sbgh.mb.ca

Lung (2007) 185:113–121

DOI 10.1007/s00408-006-0108-y

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setting are available [8–15]. Compared with altitude

chamber studies, results of terrestrial field studies may

be confounded by factors such as acclimatization,

weight loss, dehydration, sleep deprivation, thermal

stress, exposure to pollutants, and other factors.

At high altitude, forced vital capacity (FVC) has

been shown to decrease, whereas forced expiratory

volume in 1 second (FEV1) and maximal voluntary

ventilation (MVV) have shown conflicting findings [6-

15]. Ascent to higher altitudes affects lung functions by

a variety of mechanisms that have not been completely

delineated; however, a few hypotheses have been

proposed. As density of air gradually lessens on ascent,

expiratory airflows and lung emptying is facilitated [5].

Development of subclinical pulmonary edema was

considered a pivotal factor in reducing FVC [6].

Respiratory muscle strength and endurance are ex-

tremely important for functioning at high altitudes.

However, the effect of high altitude, excessive venti-

latory requirements, and harsh environmental factors

on their role in maintaining respiration and how these

factors may affect these indices are not entirely clear.

Several investigators have described diaphragmatic

fatigue in exercising healthy humans under hypoxic

conditions or at high altitude [16–18]. Measurements of

respiratory muscle pressures and respiratory muscle

endurance have not been previously performed in a

longitudinal fashion at high altitude.

The purpose of this study was to investigate the

effects of acute and prolonged exposure to high

altitudes on lung function and to clarify the role of

respiratory muscle strength and endurance in mediat-

ing these changes.

Methods

Seven healthy mountaineers, who were part of an

expedition to climb Mt. Everest, Nepal, participated in

the study. All subjects were nonsmoking white males

and were experienced mountaineers. None of the

subjects had a history of acute mountain sickness

(AMS) or high-altitude pulmonary edema (HAPE).

The study was performed in accordance with the

ethical standards of the Helsinki Declaration for

experimentation on human subjects, and informed

consent was obtained. These individuals had no prior

experience with the study procedures. Each participant

had a normal physical examination and had no

previous history of a respiratory or other medical

disorder. All subjects were familiarized with the study

protocol and received training in performance of

spirometry and measurement of respiratory muscle

strength and endurance.

The subjects were studied at various elevations

between 3450 and 5350 meters (m) over a two-month

period. During this time the subjects also made

multiple sojourns up to much higher altitudes of

approximately 7200 m. Because of expedition logistics,

baseline measurements could not be performed at

Kathmandu (altitude 1337 m). The subjects arrived at

Namche Bazaar, an altitude of 3450 m, via a 1.5-h

helicopter ride from Kathmandu. The first measure-

ments were performed within 4 h of arrival. All

subjects were periodically evaluated for development

of AMS and HAPE throughout the expedition,

although formal AMS scoring was not done. On arrival

to Namche Bazaar, the subjects were questioned for

symptoms of headache, nausea, fatigue, cough and sore

throat, and a physical examination was performed for

the presence of rales and other abnormalities. The

subjects were also clinically evaluated each test day to

ensure that injuries, concurrent infections, or other

factors did not influence the study procedures. None of

the subjects demonstrated any significant abnormality

at baseline or during subsequent test days. The subjects

were encouraged to provide maximal effort and

received strong verbal encouragement during the

performance of the study procedures.

In regard to altitude, days 0–3 were spent at an

altitude of 3450 m; days 4–13 were spent slowly

ascending from 3450 to 5350 m; and days 13–42 were

spent at the Everest base camp, at an altitude of 5350

m. Between days 15 and 23, the subjects climbed to

Camp 2 at an altitude of approximately 6300 m, and

between days 23 and 42, all subjects ascended to Camp

3 at approximately 7200 m. Measurements were

performed on days 0, 1, and 3 at Namche Bazaar

(3450 m) and on days 13, 15, 23, and 42 at Everest base

camp (5350 m). All measurements were performed in

indoor conditions (lodge or weather port shelter) and

adjusted to body temperature pressure saturated

(BTPS). None of the subjects suffered from AMS or

HAPE during this expedition.

Study Procedures

All measurements were performed at approximately

the same time each test day and were completed

within 30 min for each subject. The same investigator

(Bryce Brown) performed all the measurements. The

subjects were comfortably seated with their trunks at

a 90� angle and wore a noseclip. Measurements were

performed in a tent where the temperature remained

relatively constant at approximately 10�C. Instru-

ments were stored at ambient temperature in a tent

at night. All instruments were allowed to warm to

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114 Lung (2007) 185:113–121

the testing temperature of approximately 10�C before

use.

A battery-powered, hand-held Welch Allyn Pneu-

mocheck (PneumoTach) spirometer (Welch Allyn,

Skaneatles, NY) was used to assess lung function.

Spirometry had previously been shown to be a reliable

method to measure lung function at high altitude [15].

The spirometer volume was calibrated with a 3-L

syringe at the start of each test day and the observed

values corrected to BTPS units. Barometric pressure

was measured with a Kestrel 400 weather monitor

(Nielsen-Kellerman, Chester, PA). The barometric

pressure varied between 485 and 495 mmHg and

between 380 and 395 mmHg at 3450 and 5350 m,

respectively. Temperature of the air in the calibrating

3-L syringe was the same as that of the ceramic sensor

in the PneumoTach. The FVC and FEV1 were mea-

sured according to the American Thoracic Society

protocol [19]. Each subject performed three good

spirometric efforts, each lasting 6 s, and the spirometric

maneuver with the highest sum of FVC and FEV1 was

accepted. The maximal inspiratory pressure (MIP) and

maximal expiratory pressure (MEP) were determined

with a digital pressure monitor (Porta-Resp, S&M

Instrument Company Inc., Doyelstown, PA) connected

to a mouthpiece. The pressure manometer was cali-

brated with a water manometer over the range of 0–

200 cmH2O. MIP was measured from the residual

volume following maximum inspiration, and the MEP

was determined from the total lung capacity following

maximum inspiration. The maximal pressures were

sustained for more than 1 s; the measurements were

visible to the subjects, thus encouraging maximum

effort. These maneuvers were repeated at least three

times after rest until two similar measurements within

5% variation were obtained. The percutaneous oxyhe-

moglobin saturation (SpO2) was measured by pulse

oximeter (N-10, Nellcor Inc., Hayward, CA) at base-

line and each test day.

Several methods are available to measure respira-

tory muscle endurance [20–25]. One validated method

is by quantifying Tlim, the length of time a subject can

endure an inspiratory load before fatigue develops [24,

25]. Endurance measures have been researched at sea

level hypoxia but have shown contradictory results [26,

27]. We used two indices of respiratory muscle endur-

ance: maximal voluntary ventilation (MVV) in 12 s and

a modified version of the method (Tlim) developed by

Grassino et al. [28]. The subjects were placed in a

sitting position and a plastic flanged mouthpiece was

used. The mouthpiece was joined to a graduated

pressure gauge with 30 cm of noncollapsable plastic

tubing. Each subject was given a target mouth pressure

of 50% of his MIP as the goal for sustained inspiratory

effort. The subject then inspired to this predetermined

pressure from RV and sustained this pressure for as

long as possible. The time elapsed from the beginning

of the task until task failure was recorded as T-limit

(Tlim) in seconds [28]. Verbal encouragements were

provided to ensure that task failure did not occur

prematurely because of insufficient motivation.

Statistical Analysis

All values were averaged on each test day and

compared using analysis of variance (ANOVA) and

the Student-Neuman-Keul multiple comparison test

and Student’s t test. A p value of less than 0.05 was

considered significant. Data in text and table are

presented as mean ± standard deviation (SD).

Results

The seven accomplished mountaineers completed all

study procedures. Their mean age was 44.25 ± 12.03

years (range = 25–69 years). Table 1 and Figures 1, 2,

and 3 summarize changes in spirometry and respiratory

muscle strength measurements that occurred with

changes in altitude.

The mountaineers experienced a transient increase

in mean FVC at 3450 m, from 4.86 ± 0.56 L on day 0

to 5.31 ± 0.17 L on day 1 (9% increase, p < 0.05),

which was followed by a decline to 4.03 ± 1.02 L on

day 3 (17% decrease, p < 0.05). Upon climbing to the

higher altitude of 5350 m, they experienced a second

transient increase in their FVC from 4.16 ± 1.13 L to

5.07 ± 0.29 L (21% increase, p < 0.05). Thereafter,

FVC gradually decreased to 3.99 ± 0.40 L by day 42

(18% decrease, p < 0.05). FEV1, FEV1/FVC ratio,

and MVV decreased from 3.97 ± 0.33 L/s,

81.83 ± 2.43%, 166 ± 24.71 L to 2.74 ± 1.06 L/s

(31%, p < 0.05), 65.29 ± 14.56% (20%, p < 0.05),

and 112.71 ± 25.85 L (32%, p < 0.05), respectively,

at 72 h. On arrival at 5350 m, FEV1, FEV1/FVC ratio,

and MVV initially improved from 3.08 ± 1.06 L/s,

72.71 ± 9.21%, and 120.14 ± 24.48 L to 4.22 ± 0.41 L/s

(37%, p < 0.05), 83.14 ± 4.6% (14%, p < 0.05), and

172.43 ± 34.28 L (43%, p < 0.05), respectively. FEV1

and MVV continued to slowly decrease, whereas

FEV1/FVC ratio stabilized during the rest of the

expedition. The data on the FEV1/FVC ratio show an

initial decrease that occurred at the lower altitude,

whereas a slight but significant increase in the FEV1/

FVC ratio was observed with chronic exposure to the

higher altitude.

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Lung (2007) 185:113–121 115

Respiratory muscle strength and endurance were

also measured at the lower and the higher altitudes. The

MIP was 103.67 ± 24.17 cmH2O at baseline, decreased

to 67.57 ± 39.13 (47%, p < 0.05) cmH2O on day 3, and

was still lower than baseline on arrival at 5350 m, where

an increase to 95.14 ± 11.26 (49%, p < 0.05) cmH2O

was observed. The MEP was 189 ± 12.01 cmH2O at

baseline, also decreased to 131.57 ± 41.48 (30%,

p < 0.05) cmH2O on day 3, and increased to

156.57 ± 11.25 (12%, p < 0.05) cmH2O on day 15. Both

the MIP and the MEP remained unchanged for the

remainder of the expedition. Tlim was 14.27 ± 4.43 s at

baseline, unchanged at 14.9 ± 10.25 s on day 1, but

decreased to 9.94 ± 6.82 s (30% decrease, p < 0.05) on

day 3. On arrival at higher altitude, Tlim was

12.96 ± 3.39 s (day 13) and was essentially unchanged

at 12.6 ± 1.88 s 10.97 ± 1.72 s and 13.65 ± 3.07 s on days

15, 23, and 42, respectively. Oxyhemoglobin saturation

(SpO2) increased on day 1 to 88.5 ± 3.28% from a

baseline of 85.30 ± 3.58% (p < 0.05) at 3450 m. Similar

changes occurred on arrival at 5350 m where SpO2

increased from 84 ± 7.39% to 86 ± 4.16% [not signif-

icant (NS)] 48 h later.

Table 1 Spirometric measurements and respiratory muscle strength and endurance at lower and higher altitudes

Parameter(units ± SD)

3450 m 5350 meters

Day 0 Day 1 Day 3 Day 13 Day 15 Day 23 Day 42

FVC (L) 4.86 ± 0.56 5.31 ± 0.17* 4.03 ± 1.02* 4.16 ± 1.13* 5.07 ± 0.29*� 4.27 ± 0.65* 3.99 ± 0.40*

Percentpredicted (%)

96.24 105.15 79.80 82.38 100.40 84.55 79.01

FEV1 (L/s) 3.97 ± 0.33 3.94 ± 0.26 2.74 ± 1.06* 3.08 ± 1.06* 4.22 ± 0.41*� 3.46 ± 0.76* 3.23 ± 0.41*

Percentpredicted (%)

97.54 96.80 67.32 75.67 103.69 85.01 79.36

FEV1/FVC (%) 81.83 ± 3.43 74.33 ± 5.82 65.29 ± 14.56* 72.71 ± 9.21* 83.14 ± 4.6� 80.5 ± 6.38� 81.17 ± 4.54�Percentpredicted (%)

101.91 92.56 81.31 90.55 103.54 100.25 101.08

MVV (L) 166 ± 24.71 167.5 ± 12.10 112.71 ± 25.85* 120.14 ± 24.48* 172.43 ± 34.28� 150.83 ± 29.84 134.67 ± 20.43*

MIP(cm/H2O) 103.67 ± 24.17 117 ± 18.16 67.57 ± 39.13* 63.86 ± 28.06* 95.14 ± 11.26*� 111 ± 13.94 90.33 ± 14.10MEP (cm/H2O) 189 ± 12.01 190.67 ± 33.37 131.57 ± 41.48* 140 ± 19.19* 156.57 ± 11.25*� 164.83 ± 14.77 166 ± 21.43Tlim (s) 14.27 ± 4.43 14.9 ± 10.25 9.94 ± 6.82* 12.96 ± 3.39 12.6 ± 1.88 10.97 ± 1.72 13.65 ± 3.07SpO2 (%) 85.3 ± 5.58 88.5 ± 3.28* 87 ± 2.65 84 ± 7.39 86 ± 4.16� 81.3 ± 6.47* 84.2 ± 8.82

* p < 0.05 compared with baseline

�p < 0.05 compared with initial measurement at 5350 m

Fig. 1 FVC, FEV1, and MVV at altitudes of 3450 and 5350 mare shown. FVC and FEV1 decreased significantly on days 3 and13, followed by an increase on day 15, and then subsequentlydeclined. In addition, FVC increased significantly on day 1compared with the baseline measurement. FVC and FEV1 at3450 and 5350 m are shown. FVC and FEV1 decreasedsignificantly between days 2 and 4, followed by an increasebetween days 14 and 16, and then subsequent decline on days 16to 43. MVV, as a measure of respiratory muscle endurance,decreased on day 4, increased on day 16, and then decreasedagain by day 43

Fig. 2 Respiratory muscle pressures (MIP and MEP) showedinitial decrease on day 4, both increased on day 16, and thenremained unchanged

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116 Lung (2007) 185:113–121

Discussion

Review of Literature (Table 2)

Pulmonary physiology at altitude has been extensively

reviewed by several authors in the past [1, 3, 4, 8].

Severe oxygen deprivation at extreme altitudes can be

tolerated only because of an enormous increase in

ventilation that protects the alveolar PO2 against the

markedly reduced inspired oxygen concentration. Nev-

ertheless, the arterial PO2 on the Everest summit is less

than 30 mmHg. Hyperventilation results in a very low

arterial PCO2, which causes severe respiratory alkalo-

sis. Respiratory alkalosis increases hemoglobin’s oxy-

gen affinity and enhances oxygen loading at the

pulmonary capillaries under diffusion-limited condi-

tions [29]. Schoene [4] investigated limits of the

response and adaptation of the lungs to this hypoxic

stress, both at rest and during exercise. They noted that

at high altitudes the driving pressure for movement of

oxygen from the air to the blood is lower and the

transit of blood across the pulmonary capillaries more

rapid, allowing less time for equilibration of oxygen.

These two altitude-related phenomena limit the diffu-

sion of oxygen across the alveolar-capillary membrane,

thereby accentuating hypoxemia.

Welsh et al. [6] studied alterations in spirometric

measurements in eight normal human male subjects

during prolonged graded altitude exposure in a hypo-

baric chamber to as high as 8848 m above sea level

(SL). They found a significant and progressive drop in

FVC, which slowly resolved within 48 h after descent.

Pollard et al. [9, 10] investigated the effect of altitude

on spirometric data in members of the 1994 British

Mount Everest Medical Expedition. Lung volumes

were measured with a pocket turbine spirometer at SL

and at Mount Everest base camp. The mean FVC fell

by 5% during this period [9] and lower oxygen

saturations at 5300 m were associated with lower

FEV1 and FVC [10]. In a study by Mason et al. [11],

subjects were evaluated twice daily during an ascent

from 2800 to 5300 m over a period of 10-16 days.

Measurements of FVC, FEV1, peak expiratory flow

(PEF), SpO2, and acute mountain sickness (AMS)

were recorded. Compared with values at SL, the mean

FVC at 2800 m was decreased by 4% and the mean

FVC at 5300 m was decreased by 8.6%; the FEV1 did

not change with increasing altitude. These changes

were not significantly related to SpO2 or AMS scores.

Thus, while some other studies have shown altitude-

related decreases in the FVC and/or FEV1 over time,

they have not shown the initial increases in these

parameters observed in our study.

Cogo et al. [8] studied effects of altitude in 17 healthy

subjects at both Capanna Regina Margherita (Italian

Alps, 4559 m) and the Pyramid Laboratory in Nepal

(5050 m). Peak expiratory flow rates significantly

increased with altitude. The mean increase in PEF was

15% at both 3200 and 3600 m and 26% at 4559 m. FVC

values significantly decreased during the first few days

above 3500 m (p < 0.005) but improved after several

days at this altitude. Wolfe et al. [1] evaluated the FVC,

FEV1, FEV1/FVC ratio, mean expiratory flows at 75%,

50%, and 25% of FVC (MEF75, MEF50, MEF25), and

PEF at altitudes of 171 m and 1580 m above SL. The

MEF75 and MEF50 values positively correlated with

the altitude, with mean rises of 15% and 11%, respec-

tively; in contrast, the other parameters did not signif-

icantly change with altitude. Basu et al. [13] studied 16

healthy males at SL and at high altitudes (HA) of 3110,

3445, and 4177 m. Identical studies also were performed

in acclimatized lowlanders, who remained at 3110m and

Table 2 Alteration in lung function at higher altitudes as reported in literature

Reference FVC FEV1 FEV1/FVC FEF25–75 MVV MIP MEP

Wolfe et al. [1] M M NA NA › NA NAWelsh et al. [6] fl M NA › NA NA NACogo et al. [8] fl M NA fl NA NA NAPollard et al. [9] fl fl NA NA NA NA NAPollard et al. [10] fl fl NA NA NA NA NAMason et al. [11] fl M NA NA NA NA NABasu et al. [13] fl fl NA › fl NA NAForte et al. [14] fl › NA NA › M M

Hashimoto et al. [15] fl fl NA NA fl NA NACurrent study › M M NA M M M

› Increased compared to baseline

fl Decreased compared to baseline

M No change compared to baseline

NA not available

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Lung (2007) 185:113–121 117

at 4177 m for two years. They found increases in the

minute ventilation, tidal volume, and respiratory rate on

arrival at HA, which remained elevated during the

entire period of observation [13]. FVC and FEV1 did not

change on the first day of arrival at HA but significantly

decreased (p < 0.001) on the second day of exposure to

3110 m. Although FVC and FEV1 had returned to SL

values by day 3, they declined further with exposure to

altitudes of 3445 and 4177 m. The MVV declined on

arrival at HA. The PEF also seemed to decline during

the initial days but had increased by day 3 and remained

elevated during the subsequent exposure to HA. Some

of these findings (e.g., decrease in FVC and FEV1 upon

arrival at HA) resemble our findings, although the time

courses of the changes differ.

Forte et al. [14] studied 18 healthy men at SL, HA

(Pikes Peak, 4300 m), or in a hypobaric chamber (PB

approximately 460 mmHg). They found that the mean

MVV increased by 20% with exposure to HA but that

HA had no effect on maximum inspiratory and

expiratory muscle pressures. Hashimoto et al. [15]

studied pulmonary ventilatory function, including

responses to bronchodilation, during a two-week trek

in the Himalayas. Study participants were evaluated at

baseline (1624 m) and at various altitudes (3404–4896

m) and were subjected to interventions at altitudes of

1624–5265 m; the bronchodilator effect was measured

after administration of albuterol via rotahaler. These

investigators found that the FVC decreased by an

average of 3.8% per 1000-m altitude increment, while

the FEV1 decreased by 3.7% per 1000-m altitude

increment. The maximal midexpiratory flow rate

(FEF25–75) also decreased by 3.6 for each 1000-m

altitude increment. Thus, changes in some pulmonary

ventilatory parameters (FVC, FEV1, and FEF25–75)

were proportional to the magnitude of the altitude

encountered during the trek. A significant bronchod-

ilator response was not demonstrated, thus suggesting

that hyperventilating cool dry air did not cause

bronchial hyperresponsiveness.

At high altitude, the decreased gas density could

substantially reduce the resistive load of breathing,

particularly during exercise. Because of lower baro-

metric pressure at altitude, marked increase in venti-

lation has to occur to supply the same amount of

oxygen for any given rate of work at sea level.

Hypoxemic stimulation of carotid bodies and subse-

quent hypoxic ventilatory response further increase the

ventilatory demands. Despite the lower resistive load

that occurs secondary to lower gas density, excessive

ventilation and consequent augmentation in work of

breathing lead to greater energy expenditure at high

altitude during exercise [30]. The finite amount of

energy is carefully distributed to optimize balance

between energy used to produce work and the work

output. The respiratory muscles require a substantial

portion of oxygen consumption while exercising at high

altitude. Investigators have described a phenomenon

of ‘‘cardiac steal’’ where a considerable fraction of all

cardiac output was dedicated to the muscles of respi-

ration, at the expense of limiting blood flow to the

exercising muscles [17, 30, 31, 32]. Cibella et al. [30]

estimated that oxygen cost of breathing at HA and SL

amounted to 26% and 5.5% of VO2 max, respectively.

However, Harms et al. [32] demonstrated that at

maximum exercise, as the work of breathing increases,

both the blood flow to the legs and the rate of oxygen

consumption of the legs decrease, while an increase in

respiratory blood flow was observed. It is difficult to

know which muscle bed, respiratory or legs, is paying

the bigger price from the ‘‘cardiac steal’’ or whether

both are suffering. These pathophysiologic mecha-

nisms played a significant role in the decline of

respiratory muscle function and lung mechanics in

our subjects at HA.

Relevance of Our Study

Several of the above studies have demonstrated a

decrease in lung function on ascent to HA and have

identified several physiologic mechanisms to explain

the decline in lung function [6, 33]. These mechanisms

include an increase in the pulmonary blood volume

due to redistribution of perfusion, recruitment of

capillaries in the upper lung zones, and increased

filling of the heart chambers, all of which may reduce

lung volumes. These alterations may occur because of

hypoxia, although there are no good data to support

this hypothesis. Welsh et al. [6] demonstrated the

development of interstitial pulmonary edema on a

chest radiograph immediately following descent from

HA. Respiratory muscle fatigue produced by submax-

imal neural drive reduces muscle strength and, hence,

the FVC, because muscle strength is an important

determinant of all lung capacities [34]. Early airway

closure may contribute to altitude-related declines in

lung volumes [15, 33, 34], although one study showed

no enhanced effect of bronchodilators at HA [15].

No prior study has shown the acute increases in

FVC, FEV1, and MVV as were observed in our study.

The FVC increased by 9%–21% within 24–48 h on

arrival to each new altitude, and subsequently de-

clined. This is a novel finding that has not been

observed in previous studies, although the significance

and mechanisms underlying these findings are un-

known. It is unclear why previous studies failed to

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118 Lung (2007) 185:113–121

show this observation; it is possible that our subjects

were flown in to a high altitude and subsequently made

short sojourns to even higher altitudes. Either lack of

acclimatization or lack of serial measurements soon

after arrival at a new altitude is the likely explanation.

Lower density of air encountered on ascent to high

altitude lessens airway resistance that facilitates expi-

ratory airflow and efficient emptying of the lungs, thus

increasing the FVC by a reduction in the RV. On

ascending to each altitude, subclinical interstitial pul-

monary edema possibly developed and then cleared up

following rest for 24–48 h [6, 34]. Our data also show

that FVC improvement correlated with an increase in

SpO2 and MIP, thus providing evidence for the

hypothesis described above. Initial decline in FVC in

our study is a consequence of development of veno-

constriction, interstitial pulmonary edema, and respi-

ratory muscle weakness [6, 8, 9, 11, 13, 14, 32, 33].

Simultaneous reduction of respiratory muscle pres-

sures (MIP and MEP) as a result of of fatigue and

subsequent recovery likely contributed to the observed

FVC changes [12, 30–32]. Reduction in FVC over the

prolonged stay at HA as measured on days 23 and 42

was associated with a decline in FEV1 and MVV but

there was no change in MIP, MEP, and Tlim. The most

plausible explanation for these findings appears to be

the development of air flow obstruction and air

trapping, which may occur with prolonged stay at

HA [15, 33, 34]. Development of late-onset interstitial

pulmonary edema that may have occurred after a

prolonged stay at HA, particularly following excur-

sions to much higher altitudes, remains another possi-

bility in our study and needs to be investigated further.

Higher closing volumes at HA, and thus development

of obstructive ventilatory defect described by Cremona

et al. [34], may have resulted in air trapping and

reduction in FVC and FEV1. Our data show evidence

of airflow obstruction on days 1, 3, and 13 according to

the ERS/ATS guidelines for interpretation of lung

function test. An obstructive ventilatory defect is

defined by a reduced FEV1/VC ratio below the 5th

percentile of the predicted value for healthy subjects

[35]. This obstructive defect seems to have appeared

subsequently during the prolonged stay. Hyperventi-

lating cold dry air at HA can lead to airflow obstruc-

tion, possibly secondary to airway inflammation, a

hypothesis put forward by Hashimoto et al. [15] but not

proven.

MVV, a surrogate for respiratory muscle endurance,

generally followed alterations in FVC and MIP. MVV

declined with declining FVC and MVV but improved

with FVC recovery on day 15. There was additional

evidence of decrement in respiratory muscle endur-

ance (Tlim) on day 3 at lower altitude; this value

remained unaltered for the remainder of the expedi-

tion. FEV1 and FEV1/FVC ratio decreased markedly

on day 3, and initially stayed lower but then recovered,

although FEV1 declined again on days 23 and 42.

Before these measurements the subjects had climbed

to much higher altitudes, up to 7200 m, and thus

possibly acquiring worsening of restrictive and/or

obstructive defect.

Our study provides good evidence to support the

hypothesis that a decrease in respiratory muscle

strength and endurance contributes to the decrement

in lung capacities during the initial stay at HA. A

reduction in respiratory muscle strength and endurance

is likely the result of the hypoxia, increased ventilation

due to the hypoxic ventilatory response, and higher

workload of breathing observed at HA. After the

initial decline, respiratory muscle function is main-

tained as the expedition progresses because of the

compensatory responses to hypoxia, which become

more effective with acclimatization. Respiratory mus-

cles are known to receive increased blood flow at HA,

because the diaphragm can greatly boost its blood flow

when work of breathing increases and hypoxic vasodi-

latation ensues [30–32]. In addition, the diaphragmatic

capillary density is known to increase in rats with

prolonged exposure to altitude [12]. Recently, Pelleg-

rino et al. [36] tested the hypothesis that hypoxia

decreases respiratory muscle strength to explain pre-

viously reported hypoxia-associated decrease in FVC.

They found a progressive decline in FVC, MIP, MEP,

and sniff nasal inspiratory pressure (SNIP) at 6 and 12

h of exposure to an equivalent altitude of 4267 m in a

hypobaric chamber. MIP, MEP, and SNIP strongly

correlated with FVC reduction [36]. These data may

explain some of the results of our study; our study,

however, was more complex. In the ‘‘real world,’’

climbers experience acute and chronic altitude expo-

sure, where not only the hypoxia but other environ-

mental factors such as extreme cold, fatigue, and

weight loss may alter lung mechanics.

Our study has several limitations because it was

performed over the course of a climbing expedition.

The most obvious limitation is the lack of true baseline

data. Because of expedition logistics, it was impossible

to obtain measurements before ascent to altitude or on

return to sea level. However, the first measurements

occurred within hours of initial ascent. Previous studies

have demonstrated that there are no significant

changes in spirometry on the first day of arrival at

altitude; therefore, baseline measurements in our study

should not be significantly different from those at

Kathmandu [6, 9, 13]. This is also supported by our

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Lung (2007) 185:113–121 119

later data between 3450 and 5350 m, with which we do

not find a change in spirometry until 48 h after change

in altitude.

Another study limitation is the field setting, where

temperature, wind, and precipitation may have af-

fected subjects or the measurements. In addition,

internal factors such as a subject’s general physical

condition, hydration level, and tolerance to the cold

can inhibit performance. Our study demonstrated

different patterns of lung function between acute

exposure to HA without acclimatization and prolonged

exposure with acclimatization. Our data show that

while respiratory muscle strength and endurance fluc-

tuates with changes in altitude and acclimatization,

over a prolonged stay their function appears to be

protected via compensatory mechanisms that improve

with acclimatization. Thus, our data reinforce the

notion that acclimatization is an essential part of a

climbing or trekking expedition. This would be an

interesting area for a larger study with more frequent

measurements, which should also include measures of

acclimatization (e.g., AMS scores) to correlate with

lung function.

Conclusion

Our study of experienced mountaineers during their

ascent of Mount Everest demonstrated a transient

increase in spirometric measurements at lower altitude,

followed by a decline. This short-term increase in lung

volumes was also seen after slow ascent to a higher

altitude but again diminished over time. Respiratory

muscle strength (MIP and MEP) also decreased with

time at the lower altitude; upon arrival at the higher

altitude, these initially increased (at 48 h) before

stabilizing. In addition to the consequences of hypoxia

on pulmonary hemodynamics, alterations in spiromet-

ric variables denote the effects of respiratory muscle

strength and endurance on lung mechanics that remain

to be fully explored. In this study we presented data

that are unlike any previously reported in the litera-

ture.

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