David A. Self

Joseph Mandella

O. Veronika Prinzo

Estrella M. Forster

Robert M. Shaffstall

Civil Aerospace Medical Institute

Federal Aviation Administration

Oklahoma City, OK 73125

December 2010

Final Report

Physiological Equivalence of 

Normobaric and Hypobaric Exposures 

of Humans to 25,000 Feet

DOT/FAA/AM-10/20

Office of Aerospace Medicine

Washington, DC 20591

OK-11-0024-JAH

Federal Aviation

Administration
NOTICE

This document is disseminated under the sponsorship 

of the U.S. Department of Transportation in the interest 

of information exchange. The United States Government 

assumes no liability for the contents thereof.

___________

This publication and all Office of Aerospace Medicine technical reports are 

available in full-text from the Civil Aerospace Medical Institute’s publications 

Web site: 

www.faa.gov/library/reports/medical/oamtechreports
i

Technical Report Documentation Page 

1. Report No. 2. Government Accession No. 3. Recipient's Catalog No. 

DOT/FAA/AM-10/20 

4. Title and Subtitle 5. Report Date 

December 2010 

6. Performing Organization Code 

Physiological Equivalence of Normobaric and Hypobaric Exposures of 

Humans to 25,000 Feet 

 7. Author(s) 8. Performing Organization Report No. 

Self DA, Mandella J, Prinzo OV, Forster EM, Shaffstall RM 

9. Performing Organization Name and Address 10. Work Unit No. (TRAIS) 

FAA Civil Aerospace Medical Institute 

P.O. Box 25082 11. Contract or Grant No. 

Oklahoma City, OK 73125 

12. Sponsoring Agency name and Address 13. Type of Report and Period Covered 

Office of Aerospace Medicine 

Federal Aviation Administration 

800 Independence Ave., S.W. 

Washington, DC 20591 14. Sponsoring Agency Code 

15. Supplemental Notes 

Work was accomplished as an AAM-600 in-house research project. 

16. Abstract 

Introduction. Skepticism exists whether normobaric and hypobaric hypoxic exposures are equivalent. We have 

evaluated if physiological differences between the two environments would translate into actual differences in 

hypoxia symptoms. 

Methods. We exposed 20 subjects to 5-min 25,000 ft (7620 m) equivalent environments in an altitude chamber 

and then in a ground-level portable reduced-oxygen training enclosure (PROTE). Heart rate and hemoglobin 

oxygen saturation (SAO2

) were continuously monitored. Alveolar gas samples were collected at 1-, 3-, and 4-min 

elapsed time. Subjects completed hypoxia symptom questionnaires at the same time points. 

Results. Mean 4th min alveolar oxygen tension (PAO2

), alveolar carbon dioxide tension (PACO2), and respiratory 

quotient (RQ) differed significantly between the chamber and PROTE. Declines in SAO2

 appeared biphasic, 

with steepest declines seen in the first minute. Rates of SAO2 decline over the 5-min exposure were significantly 

different. Heart rate was not different, even when indexed to body surface area. Mean number of hypoxia 

symptoms between hypobaric and normobaric environments after 1 min were significant. However, the temporal 

pattern of symptom frequencies across subjects between the chamber and PROTE were similar. 

Conclusions. Alveolar gas composition, as well as arterial hemoglobin oxygen desaturation patterns, differed 

between a ground-level and hypobaric exposure. Differences in mean number of hypoxia symptoms between 

hypobaric and normobaric environments after 1 min, but not at 3 and 4 min, coupled with similar patterns in 

symptom frequencies, suggest that ground-level hypoxia training may be a sufficiently faithful surrogate for 

altitude chamber training. 

 

17. Key Words 18. Distribution Statement 

 

 

Altitude Chamber, PROTE, Alveolar Gas, Hypoxia 

Training Environments

Document is available to the public through the 

Defense Technical Information Center, Ft. Belvoir, VA 

22060; and the National Technical Information 

Service, Springfield, VA 22161 

19. Security Classif. (of this report) 20. Security Classif. (of this page) 21. No. of Pages 22. Price 

Unclassified Unclassified 16 

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized 

iii

ACKNOWLEDGMENTS

The authors wish to thank Junior R. Brown, Larry M. Boshers, Donald J. DeMuth, Rogers V. Shaw II, 

Eric Simson, and Roger A. Storey of the Civil Aerospace Medical Institute’s Airman Education Program for their 

enthusiasm and competence; and the students who volunteered to participate in this study.

v

Contents

INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

METHODS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Subjects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Training Devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

RESULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Physiological Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Relatedness of Physiological Variables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

DISCUSSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

CONCLUSIONS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

1

Physiological Equivalence of Normobaric and

Hypobaric Exposures of Humans to 25,000 Feet

INTRODUCTION

Hypoxia awareness training is an accepted method 

of demonstrating to aircrew their individual hypoxia 

signature. The symptoms of hypoxia that airmen remember following their hypoxia awareness training appear to reflect accurately the symptoms they experience 

during acute hypoxia (20). Hypobaric (low barometric 

pressure) chamber training has been the traditional 

method of demonstrating hypoxia to aviators. Various training profiles are used by aeromedical training 

centers around the world to demonstrate hypoxia. The 

Federal Aviation Administration (FAA) began altitude 

training for civilian pilots and crewmembers in 1962 

and continues providing physiological training on a 

frequent schedule. 

Advances in technology have yielded a new generation of commercially available training devices capable 

of producing hypoxic environments at ground level 

(normobaric) by altering the fraction of ambient oxygen, 

thus avoiding some of the risk factors associated with 

altitude chamber training. Recently, the U.S. Navy (1) 

and Air Force (2) physiological training programs have 

instituted ground-level hypoxia training.

Respiratory physiologists have been skeptical for 

decades that normobaric and hypobaric hypoxic environments are equivalent (3, 5, 11, 14). These researchers 

argued that alveolar gas composition and respiratory 

quotients (RQ) under hypobaric and normobaric conditions will be quite different at the same level of ventilatory 

response to hypoxia. Additionally, the effectiveness of 

alveolar ventilation and the diffusivity of a gas vary in 

relation to the density of the gas breathed (3). In turn, 

this may differentially influence pulmonary blood flow 

distribution (6), resulting in higher hemoglobin desaturation rates in hypobaric hypoxic exposures. Recent 

work by Wolff and Garner (19) and West (18) suggest 

that because of reduced diffusivity constants of oxygen 

at high altitude, alveolar and end-pulmonary-capillary 

oxygen tensions may not reach equilibrium, leading to 

less oxygen availability than would be seen at the corresponding normobaric ambient oxygen tension. 

The potential for an effect of barometric pressure, 

independent of lowered oxygen tension in hypobaric 

environments, has been addressed. Roach, Loeppky, 

and Icenoglea (13) found an increased severity of acute 

mountain sickness afflicting subjects in a controlled 

hypobaric environment when compared to a normobaric 

environment with identical ambient PO2

. Furthermore, 

Savourey et al. (14) found greater hypoxemia, hypocapnia, blood alkalosis, and lower SAO2

 in subjects under 

hypobaric hypoxic conditions when compared to normobaric ones. They suggested these differences could be 

accounted for by an increase in dead space ventilation 

resulting from lowered air density.

These findings provided a rationale for additional 

study on how hypobaric and ground-level-induced 

hypoxia may differ. We compared the responses of 20 

subjects to 5-min hypobaric and normobaric exposures at 

a simulated altitude of 25,000 ft. Differences in alveolar 

gas composition, rates of hemoglobin desaturation, and 

heart rate responses were studied using a repeated measures design. To see if physiological differences would 

translate into actual differences in hypoxia symptoms, 

we utilized a standardized hypoxia symptom questionnaire (see Appendix A) to compare subjects monitoring 

of their own symptoms during both the normobaric and 

hyperbaric exposures.

METHODS

Subjects

A sample of 20 healthy subjects, 17 men and 3 women 

[mean age, height, and weight: 42.0 yrs (± 10.8); 1.8m 

(±0.09); 85.2 kg (±18.3)], not acclimated to high altitude, participated in the study. None of the subjects 

had previous altitude chamber experience. The study 

protocol was approved in advance by the Civil Aerospace 

Medical Institute (CAMI) Institutional Review Board 

for the Protection of Human Subjects.

Each subject provided written informed consent 

before participating and possessed a current Class II 

Airman Medical Certificate. All were students enrolled 

in the FAA physiological training course. 

Training Devices

The CAMI altitude training chamber (Figure 1) is 

a computer-controlled, man-rated, low-pressure (hypobaric) chamber. It normally accommodates 20 subjects 

and two inside safety observers. The altitude chamber 

uses a vacuum pump to remove gas/pressure from the 

chamber. As the pressure is removed, it simulates the 

corresponding pressure of a particular altitude according 

to the U.S. 1976 Standard Atmosphere (9). 
2 

Figure 2. The Portable Reduced Oxygen Training Enclosure under test conditions.

Figure 1. The Civil Aerospace Medical Institute low-pressure altitude training chamber in operation with students and an 

instructor inside.
3

The Portable Reduced Oxygen Training Enclosure 

(PROTE, Figure 2) is a commercially available portable 

altitude training system developed by Colorado Altitude 

Training; Louisville, CO. The system’s operational control 

is a microprocessor that monitors two oxygen sensors, 

a carbon dioxide sensor, and an atmospheric pressure 

sensor. It uses this information to calculate the simulated 

altitude and, in turn, to control nitrogen-concentrating air 

units, CO2

 scrubbers, and vents (as needed) to maintain 

the enclosure at the desired simulated altitude setting. 

We monitored barometric pressure (Pb

) in both the 

chamber and PROTE with a NIST-traceable precision 

absolute manometer (model M2O2; Meriam Process 

Technologies; Cleveland, OH). We monitored chamber 

and PROTE oxygen percentage (FiO2

) with a mass spectrometer (PerkinElmer Life and Analytical Sciences, Inc; 

Waltham, MA). Accuracies were ±1% of full scale for O2

, 

and ±2% of full scale for CO2

. Two-point calibrations 

were performed before each experiment using room air 

and a certified calibration gas with a different composition. Real-time equivalent altitude was computed using 

a lookup table that converted calculated ambient PO2

( Pb

 x FiO2) to altitude using values in the U.S. 1976 

Standard Altitude Tables (9). 

Procedure

All subjects were given their hypobaric exposure in the 

morning and their normobaric exposure in the afternoon 

of the same day. Although there were multiple students 

on each chamber flight, only one subject was tested. 

There were always two inside observers on each chamber 

flight, and one inside observer in the PROTE. We did 

not randomize the order of the tests because of concerns 

that, going from a high-nitrogen environment into a 

hypobaric, one would increase the risk of decompression 

sickness (12). We attempted to conduct the morning and 

afternoon tests with subjects in similar prandial states. The 

chamber flight profile depicted in Figure 3 was utilized 

in this study and is the standard training profile flight 

used by the FAA during the physiological training course.

The chamber and PROTE were manually adjusted to 

the 25,000 ft equivalent, with real-time mass spectrometer 

and barometer measurements prior to subjects beginning 

the hypoxia demonstration. In practice, the chamber Pb 

was adjusted by either adding or removing ambient air 

from the chamber, while the PROTE O2 concentration 

was adjusted by altering the composition of the nitrogenrich air inside the enclosure. In the PROTE exposure, 

the subjects simply walked into the enclosure, sat down, 

and then removed their oxygen masks. Subjects in both 

the chamber and PROTE breathed 100% oxygen via an 

aviator’s mask until the beginning of the 5-min exposure 

to 25,000 ft. In both the chamber and PROTE hypoxia 

exposures, the subjects gave alveolar air samples and 

filled out a new hypoxia symptoms questionnaire at 1, 

3, and 4 min. All subjects went back on 100% oxygen 

at the 5-min point. 

A questionnaire (Appendix A) listing the common 

symptoms of hypoxia was presented to the subjects in 

the chamber and PROTE. The subjects were given time 

to become familiar with the document prior to their 

hypoxia exposures. Immediately following the alveolar air 

sampling performed at 1, 3, and 4 min, they were asked 

to circle any symptoms and their severity on the sheets. 

6,000 ft 6,000 ft

8,000 ft 8,000 ft

FL 180

FL 250

3K FEET

PER MINUTE

3K FEET

PER MINUTE

RAPID RAPID 

DECOMPRESSION

HYPOXIA 

DEMONSTRATION

VISUAL ACUITY 

DEMONSTRATION

30 min

Denitrogenation

Period Time (min) not to scale

Figure 3. Altitude Chamber Flight Profile.
4 

An inside observer collected the sheets after each time 

point and presented the subject with a new sheet just 

prior to the next time point. Subjects were given access 

to their questionnaires from previous hypoxia exposures 

once they completed both test conditions.

Alveolar gas samples were collected by having subjects exhale into flow-through ‘party blowouts’ that had 

sample collecting ports connected directly to a mass 

spectrometer (Model MGA-1100; PerkinElmer Life and 

Analytical Sciences, Inc. Waltham, MA). The inflated 

party blowouts provided a small positive pressure in the 

oropharynx sufficient to prevent air from being drawn 

in through the nose. Exhaled breaths were analyzed for 

percent composition of CO2

, O2, and N2 in real time. 

Alveolar gas samples were collected at the end of the 1st, 

3rd, and 4th minute of the hypoxia exposure by the inside observers using the technique of Rahn (10). Briefly, 

subjects exhaled forcibly into the collection device just 

after a normal inspiratory volume. They were instructed 

to keep the party blowout extended for as long as possible. Fractions of respiratory gases were then obtained 

by averaging values from 4/5ths through the expiratory 

effort, to the end of the breath. Respiratory quotients 

(RQ) for each alveolar air sample were calculated using 

the equation developed by the Subcommittee on Oxygen 

and Anoxia (16): 

 RQ = FiN2

 (PACO2)

 FiO2

 (Pb-47-PACO2)-PAO2

Percent hemoglobin saturation (SAO2

), expressed as 

the ratio of oxyhemoglobin to reduced hemoglobin in 

arterial blood, was measured from a forehead sensor placed 

above the eyebrow that emitted light at 660 and 940 nm. 

Absorption ratios and heart rate were then computed by 

a pulse oximeter (Model RAD-87, Masimo Corp.; Irvine, 

CA) and displayed as percent saturation and beats per 

minute (bpm), respectively. The same sensor was used for 

both conditions in each subject. We attempted to reposition the sensor for the PROTE exposure in exactly the 

same location as in the chamber exposure. To account for 

individual differences in baseline oxygen consumption, 

heart rate (HR) was indexed to body surface area (BSA) 

for each subject by using the Mostellar formula (8, 17).

Signals from the mass spectrometers, barometers, and 

pulse oximeters were digitized at 25 samples-sec-1 and 

recorded with a custom-built LabView data acquisition 

instrument (National Instruments Corp.; Austin, TX). 

Analysis

The analyses were conducted using a one-factor within 

subjects design, with all subjects being exposed to both 

environments (chamber and PROTE). Significance was 

set a priori at alpha ≤ 0.05. All statistical analyses were 

performed using SPSS v. 17.0 software (SPSS, Inc.; 

Chicago, IL).

All physiological data were examined using a Student’s 

two-tailed t-test for paired samples. The probabilities of 

observing chance effects of the dependent variables are 

presented as exact p-values. The dependent variables were 

heart rate, SAO2

, PAO2, PACO2, and heart rate/BSA at 4 

min, rate of hemoglobin saturation decline during the 1st

min, and over the entire exposure. All data are expressed 

as means ± standard deviations (SD). All appropriate pairs 

of dependent variables were examined for relatedness 

using Pearson correlations. The change from baseline 

SAO2

 with time during the 5-min chamber and PROTE 

hypoxia exposures was described by a monoexponential 

curve-fitting routine using the method of least squares.

Alveolar gas samples were collected at the end of 

1, 3, and 4 min. Samples collected at 5 min were not 

included in the dataset because hypoxic incapacitation 

at this point frequently prevented us from obtaining a 

satisfactory alveolar gas sample. Also, between-subjects 

variability for the 1- and 3-min samples was so great as 

to make comparisons difficult. However, this variability 

disappeared to a large extent by 4 min. Thus, the paired 

comparisons were limited to samples obtained at 4 min.

Mean number of hypoxia symptoms at 1, 3, and 4 

min was the dependent variable. Differences in number 

of hypoxia symptoms reported by subjects between the 

chamber and PROTE exposures were tested for significance by a repeated measures two-way analysis of variance. 

RESULTS

Physiological Measures 

Representative traces of HR, SAO2

, and alveolar gas 

composition are shown in Figure 4 for both the chamber 

(top) and PROTE (bottom) exposures for one subject. 

Although the rate of alveolar gas composition change 

with time was highly variable between subjects, all showed 

the general trend of decreasing PAO2

 and PACO2 as the 

ventilatory and cardiovascular responses to low ambient oxygen tension developed. Table I presents mean 

physiological measures (± SD) taken during the hypoxia 

exposures for all 20 subjects.
5

Chamber

0

20

40

60

80

100

120

140

0 50 100 150 200 250 300

Time (sec)

HR (bpm) and SAO2 (%)

0

10

20

30

40

50

60

70

PAO2 and PACO2 (mm Hg)

PAO2

HR

SAO2

PACO2

PROTE

0

20

40

60

80

100

120

140

0 50 100 150 200 250 300

Time (sec)

HR (bpm) and SAO2 (%)

0

10

20

30

40

50

60

70

PAO2 and PACO2 (mm Hg)

PAO2

HR

SAO2

PACO2

Figure 4. Representative recordings of alveolar gases, SAO2, and HR from a 5-min hypobaric (top) and 

normobaric (bottom) hypoxia exposure to 25,000 ft equivalent in one subject.
6 

Alveolar Gas Composition and RQ

The results of the paired comparisons show that 

PAO2

 , [t (19) = 3.30; p = 0.004], PACO2, [t (19) = -8.56; 

p = ≤ 0.005], and RQ, [t (19) = 10.51; p ≤ 0.005] differed significantly between the chamber and PROTE. 

Table I shows that PAO2

 was higher and PACO2 lower in 

the chamber. This is reflected in the mean RQ values of 

2.37 (± 0.53) and 1.41 (± 0.15) for the chamber and 

PROTE, respectively.

Hemoglobin Oxygen Saturation

Figure 5 presents scatter plots of all 20 subjects’ SAO2

recordings during the 5-min exposures in the chamber and 

PROTE, along with a mean value line overlay. Both chamber and PROTE lines were fit to monoexponential decay 

functions with R values of 0.934 and 0.889, respectively. 

Declines in SAO2

 were biphasic, with steepest declines 

seen in the first minute. Mean initial rates of oxygen 

desaturation were not significantly different between the 

chamber and PROTE [t (19) = 1.17]. However, differences in rate of decline of SAO2

 over the entire 5-min 

exposure were significantly different [t (19) = 2.72; p = 

0.013). Mean SAO2

 at 4 min also differed significantly 

between the hypobaric and normobaric exposures [t (19) 

= -4.76; p ≤ 0.005].

Heart Rate Responses

Beginning mean heart rate was 104.9 (±14.3) bpm 

in the chamber and 96.6 (±14.6) bpm in the PROTE 

and differed significantly [t (19) = 2.37; p = 0.029;]. 

When HR was indexed to BSA, the significant difference 

persisted [t (19) = 2.83; p = 0.011]. These differences in 

HR [t (19) = 2.04] and HR/BSA [t (19) = 2.06] were 

not present at the 4-min point.

Relatedness of Physiological Variables

All appropriate pairs of dependent variables were examined for relatedness using Pearson correlations. Significant 

pairs are presented in Table II along with their r values. As 

expected, Alveolar PO2

 and PCO2 at 4 min were highly 

related in both the chamber and the PROTE, showing 

a significant negative correlation. Interestingly, RQ at 4 

min was significantly related to PAO2

 but not PACO2in both 

normobaric and hypobaric hypoxic exposures. Mean SAO2

at the 4 min point was significantly correlated with PAO2 and PACO2

 in the chamber but not the PROTE. However, 

the mean overall SAO2

 rate of decline in the PROTE was 

significantly correlated with the 4-min PAO2

.

Subjective Hypoxia Symptoms

A two-way repeated measures analysis of variance was 

conducted on hypoxia environment (chamber, PROTE) 

and time of exposure (1 min, 3 min, and 4 min). The 

analysis revealed a statistically significant main effect of 

exposure time [F (2,38) = 8.99; p ≤ 0.001] but not hypoxia 

environment [F (1,19) = 0.003; p = 0.959]. However, there 

was a significant hypoxia environment • time of exposure 

interaction [F (2, 38) = 5.92; p = 0.006]. Figure 6 presents the average number (± SD) of symptoms identified 

by the subjects during their two hypoxia exposures. The 

subjects’ number of reported hypoxia symptoms differed 

between the chamber and PROTE exposure by an average 

of 2.36, 3.4, and 4.89 at 1, 3, and 4 min, respectively. 

The number of symptoms the subjects experienced in 

the PROTE went from being less than those during the 

chamber at 1 min to increasingly more at 3 and 4 min.

Table I. Physiological Measures During 5-Minute Exposures to a Hypobaric (Chamber) and 

Normobaric (PROTE) PO2 of 58.9 mm Hg, simulating a 25,000-ft altitude. 

Measure Chamber PROTE 

Beginning HR (bpm) 104.9 ± 14.3 96.6 ± 14.6 * 

HR at 4 min (bpm) 113.3 ± 12.3 102.2 ± 26.9 

Beginning HR/BSA (bpm/m2) 52.3 ± 8.7 47.8 ± 10.8 * 

HR/BSA at 4 min (bpm/m2) 56.4 ± 9.8 53.9 ± 10.6 

Fall in SAO2 at 1 min (% SAT) 20.56 ± 3.8 19.6 ± 3.1 

SAO2 at 4 min (% SAT) 62.3 ± 8.4 69.5 ± 4.9 * 

SAO2 rate of decline over 5 min (%SAT/sec) 0.156 ± 0.032 0.135 ± 0.031 * 

PAO2 at 4 min (mm Hg) 33.5 ± 2.4 31.4 ± 3.6 * 

PACO2 at 4 min (mm Hg) 28.2 ± 3.1 32.1 ± 2.6 * 

RQ at 4 min 2.37 ± 0.53 1.41 ± 0.149 * 

Values are mean ± SD, * p< 0.05. All physiological data were examined using a student’s two-tailed t-test for 

paired samples. 
7

CHAMBER

0

20

40

60

80

100

120

0 50 100 150 200 250

Time (sec)

Percent Saturation

PROTE

0

20

40

60

80

100

120

0 50 100 150 200 250

Time (sec)

Percent Saturation

Figure 5. Scatter plots of percent hemoglobin saturation during a 5-min exposure to simulated 25,000 ft 

altitude. Shown are the raw traces with the mean at each time point (overlay).
8 

Table II. Significant Pearson Correlations of Pairs of Dependent Variables. 

Pair R value Two-tailed significance 

Chamber SAO2 and PAO2 at 4 min 0.470 0.037 

Chamber SAO2 and PACO2 at 4 min 0.616 0.004 

Chamber PAO2 and PACO2 at 4 min -0.726 < 0.005 

PROTE PAO2 and PACO2 at 4 min -0.720 < 0.005 

PROTE PAO2 at 4 min and SAO2

rate of decline 0.533 0.016 

Chamber RQ and PAO2 0.647 0.002 

PROTE RQ and PAO2 0.837 < 0.005 

3

4

5

6

7

8

9

10

11

12

1 min 3 min 4 min

Number of Symptoms

Chamber

PROTE

Figure 6. Mean number (± SD) of hypoxia symptoms of 20 subjects exposed to chamber and PROTE environments.
9

Tukey post-hoc comparisons showed that participants reported more hypoxia symptoms at 1 min in 

the chamber than in the PROTE (p < 0.05). Also, 

participants reported more symptoms in the PROTE 

at 3 min than at 1 min (p < 0.05). This was not the 

case in the chamber, where no statistically reliable 

difference occurred between the 3rd and 4th min and 

the 1-min point.

To see if a qualitative pattern of symptoms differed 

between the two hypoxia environments, we compared 

the number of subjects reporting each symptom at 

each time point. Figure 7 presents graphs of symptoms at 1, 3, and 4 min, along with their frequencies, 

showing their patterns of occurrence in the chamber 

and PROTE. It can be seen that the frequencies of 

symptoms reported in the hypobaric and normobaric 

environments were in very close agreement. In general, 

the frequencies were closest at 1 min, and least close at 

4 min. Also, the most- and least-reported symptoms 

in one environment exhibited the same pattern in the 

other environment.

In summary, although the physiological variables 

differed between normobaric and hypobaric exposures, 

these differences did not result in meaningful differences in either the number of symptoms experienced 

by subjects or their pattern of occurrence. Table III 

summarizes our findings.

DISCUSSION

Ground-level hypoxia training has become an 

attractive pedagogy for use with aviators assigned to 

military fighter aircraft partly because of the realism 

in training advantages associated with breathing a 

hypoxic gas mixture through an aviator’s mask in a 

flight simulator. However, to be an effective strategy, the 

hypoxia symptoms acquired under these normobaric 

conditions must mirror those experienced at altitude. 

The aim of this study was to compare differences in 

physiological responses between ground-level and 

hypobaric 5-min exposures to a simulated altitude 

of 25,000 ft. We utilized a repeated-measures design 

such that each subject was exposed to both conditions. 

Furthermore, we investigated whether physiological 

differences were sufficient to result in a difference in 

the symptoms of hypoxia the subjects reported during 

the exposures.

0

2

4

6

8

10

12

14

16

18

TINGLING

HOT FLASHES

COLD FLASHES

DIZZINESS

TUNNEL VISION

TROUBLE CONCENTRATING

LIGHT DIMMING

EUPHORIA

SHORT OF BREATH

BLURRED VISION

NAUSEA

APPREHENSION

PRESSURE IN EYES

FTAIGUE

LACK OF COORDINATION

HEADACHE

Number of Subjects Reporting Symptom

CHAMBER 1 min

PROTE 1 min

0

2

4

6

8

10

12

14

16

18

20

TINGLING

HOT FLASHES

COLD FLASHES

DIZZINESS

TUNNEL VISION

TROUBLE CONCENTRATING

LIGHT DIMMING

EUPHORIA

SHORT OF BREATH

BLURRED VISION

NAUSEA

APPREHENSION

PRESSURE IN EYES

FTAIGUE

LACK OF COORDINATION

HEADACHE

Number of Subjects Reporting Symptom

CHAMBER 3 min

PROTE 3 min

0

2

4

6

8

10

12

14

16

18

TINGLING

HOT FLASHES

COLD FLASHES

DIZZINESS

TUNNEL VISION

TROUBLE CONCENTRATING

LIGHT DIMMING

EUPHORIA

SHORT OF BREATH

BLURRED VISION

NAUSEA

APPREHENSION

PRESSURE IN EYES

FTAIGUE

LACK OF COORDINATION

HEADACHE

Number of Subjects Reporting Symptom

CHAMBER 4 min

PROTE 4 min

Figure 7. Patterns of symptoms in 20 subjects undergoing hypoxia 

exposures in normobaric and hypobaric environments.
10 

Our results agree with the predictions of Rahn & 

Fenn (11) that alveolar gas composition differs between 

hypobaric and normobaric exposures at the same ambient PO2

. This finding may reflect that RQ values are 

affected by both Pb

 and FiN2 and dictate what PAO2 and 

PACO2

 values are possible. Alternatively, if ventilation were 

higher during the chamber hypoxia episodes, it would be 

reflected in lower PACO2

 than those obtained in normobaric 

exposures. Although we did not measure ventilation, other 

researchers have presented convincing results showing 

that this is the case (4). We observed lower PACO2

 values 

in the chamber than in the PROTE (28.2 vs. 32.1 mm 

Hg, respectively). This finding is consistent with a higher 

ventilatory response in our subjects in the hypobaric 

exposure. Other researchers have concluded that higher 

ventilation may reflect reduced work of breathing resulting 

from lower ambient air density (3). We measured actual 

alveolar gases rather than end-tidal gases. Previous work 

comparing normobaric and hypobaric hypoxia has made 

use of end-tidal CO2

, in particular, as an easily-obtained 

substitute for true alveolar gases (4, 14). This approach 

may have resulted in obtaining PCO2 values that were 

lower than alveolar CO2

 tensions (7). 

Hemoglobin saturation declined faster and to lower levels in the chamber than in the PROTE, although declines 

during the first minute were not statistically different. In 

Figure 3, it can be seen that variability in desaturation 

rates among subjects was higher in the chamber than in 

the PROTE, as evidenced by the greater scatter of the 

raw data points. This may have been due to the anxietyproducing aspects of the altitude chamber experience. 

This possibility is supported by a difference in heart 

rates at the beginning of the hypoxia exposure between 

the chamber and the PROTE. SAO2

 values at 4 min in 

the chamber and SAO2 rate of decline in the PROTE 

were correlated with PAO2

 but not HR or HR/BSA. It is 

interesting to note that SAO2

 fell to lower levels in the 

chamber but did so in the face of higher PAO2

 values. We 

applied the Severinghaus equation (15) to predict what 

hemoglobin saturation should have been at a given PAO2,

. 

In the chamber, mean PAO2

 fell to 33.5 mm Hg at 4 min. 

The predicted SAO2

 is 64.6%, but we measured a mean 

value of 62.3%. In the PROTE, the mean 4 min PAO2

was 31.4 mm Hg and should have produced an SAO2

value of 60.4%. Instead, it had a value of 69%. Hence, 

the SAO2

 was lower than predicted in the chamber and 

higher than predicted in the PROTE. Several mechanisms may partially explain this finding. The diffusivity 

constant for oxygen is affected by density such that the 

flux of oxygen should be greater in a hypobaric environment at the same PO2

. However, gas transfer from the 

alveoli to the blood under both normobaric and hypobaric 

conditions may be diffusion-limited by the combination 

of faster capillary transit times resulting from increased 

cardiac output and a drastically reduced concentration 

gradient (19). This may differentially affect subjects exposed to low Pb

 if dead space ventilation is increased as a 

result of lower air density. Previous work has shown that 

at the same ambient PO2

, hypobaric environments will 

induce lower PACO2

 values, blood alkalosis, and a greater 

hypoxemia reflected in lower SAO2

 than normobaric 

(14). Our results are in agreement with these findings.

In general, all subjects reported increasing severity of 

their hypoxia symptoms with increasing time of exposure. During a follow-up interview, all but two subjects 

reported that their symptoms seemed more intense and 

quicker in onset in the chamber but that the individual 

symptoms were the same during both the hypobaric 

Table III. Summary Comparison of Dependent Variables Between 

the Chamber and PROTE. 

MEASURED VARIABLE SAME DIFFERENT 

Alveolar gas at 4 min X 

SAO2 at 4 min X 

SAO2 rate of decline 

 at 1 min X 

 at 5 min X 

Heart rate 

 at 1 min X 

 at 4 min X 

Hypoxia symptoms 

 at 1 min X 

 at 3 min X 

 at 4 min X 
11

and normobaric exposures. This latter statement was 

supported by an examination of the frequencies of each 

reported symptom at the same time point in the chamber 

and PROTE environments, where there was remarkable 

similarity in their patterns of occurrence. We did, however, 

observe a significant difference in the mean number of 

hypoxia symptoms identified by subjects after 1 min (but 

not after 3 and 4 min) between the chamber and PROTE 

hypoxia exposure, with the chamber producing a greater 

number of symptoms. This difference may reflect the 

subjects’ perception that their symptoms were slower in 

onset in the PROTE. Although we collected symptom 

severity data, we chose not to include it in this analysis 

because these data did little to clarify the answer to the 

basic experimental question of whether the two environments were equivalent.

Possible weaknesses in our experimental design may 

have resulted from both clinical concerns regarding decompression sickness and the necessity of using students 

enrolled in the FAA physiological training classes. Reliability of the subjects’ responses to the hypoxia symptom 

questionnaires may have been affected by an ordering effect 

resulting from a lack of randomization in presentation 

order and the inability to “blind” the subjects to experimental condition. However, the pattern of identifying 

a greater number of symptoms in the chamber than the 

PROTE, initially, followed by a reversal of this relationship 

as the time of exposure increased, was manifested across 

all subjects (Figure 7). Furthermore, the disparity between 

the post-hypoxia interview responses of the subjects and 

the questionnaire responses during the hypoxia exposure 

limits our certainty in using the subjective data as a basis 

to argue for or against environmental equivalence. Accordingly, further investigation is warranted in which 

performance on a cognitive task is objectively measured. 

CONCLUSIONS

The results of this study revealed that alveolar gas 

composition, as well as arterial hemoglobin oxygen 

desaturation patterns, differed between a ground-level 

and hypobaric exposure to a simulated altitude of 25,000 

ft. Differences in mean number of hypoxia symptoms 

between hypobaric and normobaric environments after 

1 min, but not at 3 and 4 min, coupled with similar patterns in symptom occurrence, suggest that ground-level 

hypoxia training may be a sufficiently faithful surrogate 

for altitude chamber training.

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