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Baseline Oxygen Saturation Predicts Exercise Desaturation Below Prescription Threshold in Patients With Chronic Obstructive Pulmonary Disease
Mark T. Knower, MD;
Donnie P. Dunagan, MD;
Norman E. Adair, MD;
Robert Chin, Jr, MD
Arch Intern Med. 2001;161:732-736.
ABSTRACT
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Background Recent studies of exercise-induced hypoxemia in patients with chronic
obstructive pulmonary disease (COPD) have shown that oxygen supplementation
during exertion increases exercise tolerance and alleviates dyspnea. Although
measurements of forced expiratory volume in 1 second and diffusion capacity
for carbon monoxide (DLCO) are known to predict exercise-induced desaturation
in patients with COPD, baseline oxygen saturation has never been studied as
a predictor of exercise-induced desaturation.
Methods A retrospective analysis was performed of 100 consecutive patients with
forced expiratory volume in 1 second–forced vital capacity ratio of
70% or less who underwent exercise testing for desaturation. Any desaturation
to 88% or less with exercise was considered significant. Nineteen patients
with total lung capacity of 80% or less were excluded to avoid evaluating
those with combined obstructive and restrictive defects; 81 patients remained
available for study.
Results Nineteen (51%) of 37 patients with resting saturation of 95% or less
desaturated with exercise as opposed to 7 (16%) of 44 with resting saturation
of 96% or greater (P = .001). The sensitivity and
the negative predictive value of baseline saturation of 95% or less as a screening
test for exercise desaturation were 73% and 84%, respectively. If all patients
with DLCO of 36% or less were excluded, 40 patients were left for study. Eight
(40%) of 20 patients with baseline saturation of 95% or less compared with
0 of 20 with resting saturation of 96% or greater desaturated with exercise
(P = .006). In this subset, the sensitivity and the
negative predictive value of baseline saturation of 95% or less as a screening
test for exercise desaturation both improved to 100%.
Conclusions In patients with COPD, baseline saturation of 95% or less is a good
screening test for exercise desaturation, especially in patients with DLCO
greater than 36%. This readily available office screening procedure merits
further study in larger prospective patient cohorts.
INTRODUCTION
LONG-TERM oxygen supplementation is valuable therapy in the outpatient
treatment of patients with hypoxemic chronic obstructive pulmonary disease
(COPD). Secondary effects of persistent hypoxemia, including pulmonary hypertension
and erythrocytosis, might be reversed with long-term oxygen administration.1-3 In certain populations,
oxygen supplementation enhances neuropsychiatric performance and results in
improved exercise tolerance.1, 4-6
The Nocturnal Oxygen Therapy Trial and the British Medical Research Council
Trial of the early 1980s established that the use of supplemental oxygen in
patients with chronically hypoxemic COPD reduced mortality at 1 year.7-9
Earlier studies have suggested early mortality in patients with COPD
who are normoxic at rest but experience exercise desaturation.10-11
Oxygen supplementation with exertion can increase peak exercise level, decrease
minute ventilation, improve exercise tolerance, decrease dyspnea, and prevent
transitory increases in pulmonary arterial pressure and pulmonary vascular
resistance at submaximal workloads.12-15
Previous studies have determined that baseline forced expiratory volume in
1 second (FEV1) or diffusion capacity for carbon monoxide (DLCO)
can serve as screening tests to predict which COPD patients will desaturate
with exercise.16-17 These studies
require a trained technician and testing in an approved pulmonary function
laboratory. Baseline oxygen saturation measured by standard pulse oximetry
(SpO2) could represent a simple and readily available office screening
procedure for exercise desaturation in patients with COPD. Therefore, a retrospective
review of 100 consecutive patients with COPD who had undergone exercise testing
was performed to determine the predictive value of resting SpO2
for exercise desaturation.
PATIENTS AND METHODS
PATIENT SELECTION
A review of the database of the pulmonary function laboratory at Wake
Forest University Baptist Medical Center, Winston-Salem, NC, was performed
retrospectively from December 1, 1997, to October 31, 1999. Patients who had
undergone exercise testing for desaturation and had spirometry with FEV1/forced vital capacity (FVC) of 70% or less were considered eligible
for inclusion in this study. If lung volume measurements had also been performed,
patients were excluded if total lung capacity (TLC) was 80% or less to avoid
evaluating those with combined obstructive and restrictive defects. If the
TLC maneuver was not done, the single-breath alveolar volume taken during
DLCO measurement was used as a surrogate value for TLC. Spirometry, helium
dilution lung volume, and DLCO measurements were all performed using the Collins
DSPLUS system (WE Collins, Braintree, Mass). Diffusion capacity for carbon
monoxide, TLC, and residual volume measurements were recorded if they had
been performed, but they were not required for enrollment. The number of days
between exercise testing and spirometry, lung volumes, or DLCO measurements
were recorded and are presented as mean ± SEM. The predicted normal
values for spirometry and lung volumes are taken from Crapo et al18; predicted values for DLCO are taken from Miller
et al.19 Patient demographics and pulmonary
function measurements are presented as mean ± SD.
EXERCISE FOR DESATURATION
Baseline SpO2 was documented using a handheld pulse oximeter
(model N-20; Nellcor Inc, Hayward, Calif) with a finger clip. All exercise
testing consisted of a 6-minute walk at a moderate pace on a flat surface
performed under the supervision of a respiratory therapist while the pulse
oximeter was worn by the patient. Estimated walking distance for men was calculated
using the following formula: [7.57 x height (cm)] - [5.02 x
age] - [1.76 x weight (kg)] - 309 m.20
Estimated walking distance for women was calculated using the following formula:
[2.11 x height (cm)] - [5.78 x age] - [2.29 x
weight (kg)] - 667 m.20 Maximum saturation,
minimum saturation, and 6-minute walking distance were recorded. Patients
were encouraged to walk at their own pace for 6 minutes or until limited by
shortness of breath or fatigue. Clinically significant desaturation was considered
to be any SpO2 decrease of 4% or more to a nadir of 88% or less
during exercise regardless of the baseline SpO2, according to current
oxygen prescription guidelines.21
STATISTICAL ANALYSIS
Population data were analyzed using the t test.
Statistical analysis of experimental data was performed using  2 or Fisher exact testing. Discriminating cutoff values for baseline
SpO2 and DLCO were estimated by visual inspection of the data and
subsequently confirmed by statistical analysis. Comparisons were made between
incidence of exercise desaturation in all patients with baseline SpO2 of 96% or greater and 95% or less. The sensitivity and the negative
predictive value of baseline SpO2 of 95% or less as a clinical
screening test for exercise desaturation were calculated by standard methods.
If DLCO measurements were also available, subgroup analysis was performed
on patients with DLCO greater than 36%. The sensitivity and the negative predictive
value of baseline SpO2 of 95% or less as a screening test for exercise
desaturation in patients with DLCO greater than 36% were also calculated.
Any P .05 was considered statistically significant.
RESULTS
One hundred patients with FEV1/FVC of 70% or less who had
undergone exercise testing were considered eligible for study. Ninety-two
(92%) of these patients had lung volumes previously recorded (92 patients
with TLC or single-breath alveolar volume and 89 with residual volume). Nineteen
patients with TLC of 80% or less were excluded, leaving 81 patients available
for analysis. Four of these 19 patients were excluded because of single-breath
alveolar volume of 80% or less. Of the remaining 81 patients, DLCO measurements
were documented for 70 (86%). The study population consisted of 42 men and
39 women with a mean age of 64.2 ± 11.0 years (range, 42-84 years). Table 1 lists patient demographics and
pulmonary function data for the entire study population and for the 2 groups
with baseline SpO2 of 96% or greater and 95% or less. Patients
with resting SpO2 of 95% or less had more severe obstructive lung
disease, as documented by lower mean FEV1/FVC (P = .04), with a trend toward lower mean percentage of predicted FEV1 and FVC (P = .13 and P = .32, respectively). There were no significant differences in TLC
or resting DLCO. The group with baseline SpO2 of 95% or less also
exhibited lower exercise tolerance, with a mean walking distance of 297.9
± 148.8 m compared with 374.2 ± 131.2 m in the group with baseline
SpO2 of 96% or greater (P = .02). All
pulmonary function testing was performed within a mean of 1 year of the exercise
test.
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Patient Demographics and Pulmonary Function Data*
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Twenty-six (32%) of 81 patients desaturated to 88% or less with walking.
All 26 patients desaturated 4% or more from baseline values. Nineteen (51%)
of 37 patients with resting saturations of 95% or less as opposed to 7 (16%)
of 44 with resting saturations of 96% or greater desaturated with exercise
(P = .001) (Figure
1). The sensitivity and the negative predictive value of a resting
saturation of 95% or less as a screening test for exercise desaturation were
73% and 84%, respectively. Receiver operating characteristic curve analysis
was used to confirm that the best combination of sensitivity and specificity
occurred at a baseline SpO2 cutoff value of 95% (Figure 2).
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Figure 1. Baseline oxygen saturation by
pulse oximetry (SpO2) vs maximum desaturation with exercise. Any
desaturation of 88% or less was considered significant.
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Figure 2. Receiver operating characteristic
curve for baseline oxygen saturation via pulse oximetry as a screening test
for exercise-induced desaturation.
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No patients with DLCO greater than 36% predicted and baseline saturation
of 96% or greater desaturated with walking. If all patients with DLCO of 36%
predicted or less were excluded, 40 patients remained for subgroup analysis.
Eight (20%) of these 40 patients desaturated to 88% or less with walking.
Eight (40%) of 20 patients with resting saturation of 95% or less compared
with 0 of 20 patients with resting saturation of 96% or greater desaturated
with exercise (P = .006) (Figure 3). The sensitivity and the negative predictive value of
baseline saturation of 95% or less as a screening test for exercise desaturation
in patients with DLCO greater than 36% both improved to 100%.
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Figure 3. Baseline oxygen saturation by
pulse oximetry (SpO2) vs resting diffusion capacity for carbon
monoxide (DLCO). No patients with DLCO greater than 36% and SpO2
of 96% or greater desaturated with exercise.
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COMMENT
Chronic obstructive pulmonary disease is a worldwide health issue, affecting
up to 15 million people in the United States in 1995, and is responsible for
as many as 18.6 deaths per 100 000 persons.22-23
Over the past 3 decades, the role of long-term oxygen therapy in the outpatient
setting also has become widely applied for resting hypoxemia and exercise
desaturation.8-9,12-15
However, no screening test has emerged as a completely reliable predictor
of which patients with COPD will desaturate during exercise and subsequently
require oxygen supplementation.
Pulse oximetry is a simple, readily available office procedure that
provides an accurate measure of arterial saturation at rest. However, use
of pulse oximetry during exercise has been challenged as a poor measure of
true arterial desaturation.24 Although transcutaneous
oximetry might poorly correlate with co-oximetry or direct measurement of
arterial oxygen tension during exercise, oximetry trends noted during exercise
have been proven reliable and are used for prescription of oxygen therapy.21, 25 Earlier studies evaluating other
physiologic variables as predictors of exercise desaturation used a decrease
in SpO2 of 2% to 4% or greater from baseline as significant.16-17 Although such levels of desaturation
might be physiologically significant and represent a poor prognostic sign,
only desaturations to SpO2 of 88% or less are of interest clinically.
It is this lower value that allows the physician to prescribe oxygen therapy
as part of outpatient management of the patient with COPD.10-11,21
Our retrospective cohort of 81 patients included those with documented
obstructive disease. Among these patients, we found that oxygen desaturation
to 88% or less with exercise tended not to occur when the patient's baseline
SpO2 was 96% or higher. This cutoff value provided sensitivity
of 73% and negative predictive value of 84%. If previous DLCO measurements
are known at the time of baseline SpO2 recording, patients with
DLCO greater than 36% and SpO2 of 96% or greater should not require
subsequent exercise testing because of the excellent sensitivity of this combination
of screening variables (100%). This new screening test would allow the physician
to determine which patients might need exercise testing by performing a simple
office oximetry, with better sensitivity and negative predictive value than
formal pulmonary function tests. When available, previous DLCO measurements
will add to the sensitivity of a baseline screening oxygen saturation.
Owens et al17 first looked at various
aspects of pulmonary function testing to determine whether certain variables
reliably predict the development of desaturation with exercise on a cycle
ergometer in patients with COPD. These data revealed that only DLCO and FEV1 were reliable predictors of exercise desaturation, with a sensitivity
of 68% for a DLCO less than 55% predicted and a sensitivity of 46% for an
FEV1 less than 55% predicted. In our cohort, a baseline SpO2 of 95% or less had a sensitivity of 73% as a predictor of exercise
desaturation, higher than for either variable in the study by Owens et al.17 Desaturation of 4% or more with exercise was considered
significant in the study by Owens et al17;
therefore, the published sensitivity values might have been higher if only
desaturations to 88% or less were considered important. Although there was
no difference in mean baseline SpO2 between the group of patients
who desaturated and those who did not, a specific SpO2 cutoff value
was not evaluated as a predictor for arterial desaturation with exercise in
this previous cohort.
Kelley et al16 studied DLCO as a predictor
of oxygen desaturation during treadmill exercise in patients with COPD as
well as idiopathic pulmonary fibrosis and other restrictive disorders. This
study observed that a DLCO of less than 50% predicted is highly suggestive
of exercise desaturation, with a sensitivity of 89%. Desaturation was more
closely associated with reduced DLCO than with reduced resting oxygen saturation.16 However, these authors considered desaturation of
2% or higher from initial baseline SpO2 as significant. Using this
cutoff value for exercise desaturation, a baseline SpO2 of 95%
or less was not a good screening value for a decrease in arterial saturation
with exercise. Reevaluation of these data, considering only desaturation values
of 4% or greater as significant, reveals that 9 (12%) of 78 patients with
baseline SpO2 of 96% or greater as opposed to 16 (64%) of 25 with
baseline SpO2 of 95% or less desaturated with exercise (P = .001). The sensitivity and the negative predictive value of a baseline
SpO2 of 95% or less as a screening test for exercise desaturation
in this reevaluation are then 64% and 89%, respectively, comparable to the
sensitivity values for DLCO and FEV1 from the study by Owens et
al.17 The sensitivity value of 89% for DLCO
derived by Kelley et al16 might be overestimated
as the inclusion of patients with restrictive pulmonary diseases in the study
group favored an increase in the sensitivity of DLCO as a screening test because
many patients with some restrictive disorders exhibit low resting DLCO and
severe exercise desaturation despite high SpO2 at rest. Data from
the trial by Kelley et al16 did not allow post
hoc subgroup analysis of patients with COPD alone.
In conclusion, our retrospective data suggest that routine baseline
SpO2 measurement may be a good screening test for the likelihood
of exercise desaturation in patients with COPD. All patients in our study
had documented obstructive disease alone, with FEV1/FVC of 70%
or less and TLC greater than 80%. When only desaturation to 88% or less is
considered significant, baseline SpO2 of 96% or greater provides
similar screening sensitivity as previously studied measures of pulmonary
function such as DLCO and FEV1. Baseline SpO2 of 96%
or greater may provide sufficient sensitivity to forgo exercise testing in
patients with COPD, especially in those who have previously documented DLCO
greater than 36%. These results merit further study in a larger prospective
patient cohort.
AUTHOR INFORMATION
Accepted for publication September 21, 2000.
Presented at the American Thoracic Society International Conference,
Toronto, Ontario, May 7, 2000.
We thank David Bowton, MD, for his suggestions on statistical analysis
and the employees of the pulmonary function laboratory at Wake Forest University
Baptist Medical Center for their assistance in acquisition of patient data.
Corresponding author: Mark T. Knower, MD, Section on Pulmonary and
Critical Care, Wake Forest University School of Medicine, Medical Center Boulevard,
Winston-Salem, NC 27157-1054 (e-mail: mknower{at}wfubmc.edu).
From the Section on Pulmonary and Critical Care, Department of Internal
Medicine, Wake Forest University Baptist Medical Center, Winston-Salem, NC.
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