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* From the University of Arizona (Drs. Hadeli, Sherrill, and Enright, and Ms. Siegel), Tucson, AZ; and the Mayo Clinic (Dr. Beck), Rochester, MN.
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Abstract |
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Design and setting: This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center.
Patients and
measurements: All patients 
35 years old who underwent
spirometry, diffusing capacity of the lung for carbon monoxide
(DLCO), lung volumes, and pulse oximetry during 3-min
submaximal step-test exercise during 1996 were included (4,545 men and
3,472 women). Logistic regression models, correcting for gender, age,
and weight, determined the odds ratios (ORs) for oxygen desaturation of
4% during exercise for each category of lung function abnormality
(compared to those with entirely normal lung function).
Results: Approximately 74% of the patients had airways obstruction, while only 5.6% had restriction of lung volumes. One third of those with obstruction had a low DLCO, compared to 56% with restriction, while 2.7% had a low DLCO without obstruction or restriction. The risk of oxygen desaturation during submaximal exercise was very high (OR, 34) in patients with restriction and low DLCO (as in interstitial lung disease) and in patients with obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in 75% sensitivity and specificity for exercise desaturation. No untoward cardiac events occurred in any patients during or following the submaximal exercise tests.
Conclusions: The risk of oxygen desaturation during submaximal exercise is very high in patients with a low DLCO. Submaximal exercise tests are safe, even in elderly patients with heart and lung diseases.
Key Words: asthma • chronic bronchitis • emphysema • interstitial lung diseases • oximetry • oxygen desaturation • pulmonary function tests • submaximal exercise
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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A maximal exercise test using a treadmill or bicycle ergometer, as used by previous studies, is time-consuming, expensive, risky, and often not easily available. Therefore, we used a simple 3-min submaximal exercise test that is easily and quickly done with minimal equipment (a step, a metronome, and a pulse oximeter) in the outpatient setting.
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Materials and Methods |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Oxygen saturation was estimated at rest and during submaximal exercise using the finger probe of a pulse oximeter (Bio; model 3740; Boulder, CO). The unit was configured to display the average pulse oximetric saturation (SpO2) and pulse rate from the average during the previous 10 s. SpO2 and pulse rate were recorded from the display after 1 min of rest. The patient was then instructed to step up and down for 3 min to the beat of a metronome (set at 60 beats/min). The finger probe was attached to the index finger of the left hand, using a strain relief loop attached with adhesive tape to the forearm. The patient avoided undue motion or fist clenching of the left hand during the exercise, in order to minimize oximeter motion artifact. A 9-inch-high step with a handrail on the right side was used. SpO2 and pulse rate were again recorded immediately before the end of the exercise period.
Spirometry, lung volumes, and DLCO were measured using a system (models 1070 and 1085; Medical Graphics; St Paul, MN) with a body plethysmograph to measure static lung volumes,13 according to methods that met or exceeded American Thoracic Society recommendations.14 15 Mean reference values (predicted values based on gender, age, and height) and lower limits of the normal range (LLNs) for FEV1, FVC, total lung capacity (TLC), and DLCO were all obtained from the same population-based sample of healthy adult, never-smoking residents from the state of Michigan.16 17 18 We defined (interpreted) common patterns of lung function abnormalities as recommended by the American Thoracic Society19 : obstruction was defined as FEV1/FVC and FEV1 both below LLN, and restriction was defined as TLC below the LLN (without obstruction). Subcategories of obstruction and restriction had low DLCO vs DLCO above the LLN. Another category was isolated low DLCO (without obstruction or restriction). The "normal" lung function comparison group included patients without any of the above abnormality patterns. If the patient had anemia, the DLCO was corrected for the most recently measured hemoglobin level.
Analysis
We chose to define oxygen desaturation during exercise as a
decrease in SpO2 of 4% (exercise
minus resting), and used this categorical desaturation variable as the
dependent (outcome) variable. Multiple logistic regression was used to
determine the odds ratio (OR) for the association of oxygen
desaturation with each category of lung function abnormality. These
models also included the factors known to influence desaturation: age,
gender, weight, and height. Log-likelihood ratio tests were used to
determine the significance of interaction terms. The final model was
determined by stepwise logistic regression, beginning with all main
effect variables, then the interaction terms of obstruction and low
DLCO, restriction and low DLCO, and gender
interactions. Determination of the combined effect of obstruction and
low DLCO, and restriction and low DLCO was done
by linear combination and verified by manual calculation or the
unadjusted OR in each specific subgroup of the population. The fit of
these logistic models was determined by the Hosmer-Lemeshow
goodness-of-fit test, and logistic regression models were then done
using software (Stata Statistical Software, release 6.0; College
Station, TX).20
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Results |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Gender Differences
In the preliminary gender-specific models (controlling for age,
weight, and height), the ORs for exercise desaturation were similar for
men and women in those with airways obstruction (within both categories
of normal and low DLCO). However, for patients with an
isolated low DLCO, the ORs for men to have desaturation was
higher than for women (OR, 10.2 vs 8.5, respectively). The
gender-interaction term was statistically significant in the combined
model, showing that men in this category were about 1.4 times more
likely to experience desaturation than women (95% confidence interval
[CI], 1.1 to 1.8). Men with restriction but a normal DLCO
(usually a chest-wall abnormality) were about twice as likely as women
in this category to have desaturation in gender-specific models, but
the gender-interaction term in the combined model was not significant.
In addition, women with restriction and a low DLCO (usually
due to an interstitial lung disease) were about twice as likely as men
in this category to experience desaturation, but the gender-interaction
term in the combined model was not significant.
Predictive Power of DLCO
The power of DLCO to predict exercise-induced oxygen
desaturation was determined by calculating the receiver-operator
characteristic. The DLCO was corrected for age, gender, and
height by expressing DLCO as a percentage of the predicted
value, using the reference equations of Miller et al.16
Maximal sensitivity and specificity were determined for all patients
(n = 8,017), for those with obstruction (n = 5,926), and for those
with restriction (n = 450). The optimal cut points for these three
groups were 61.6%, 59.7%, and 54.3% predicted DLCO,
respectively. Both sensitivity and specificity for predicting
exercise-induced desaturation, using these cut points, were about 75%
for each group of patients.
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Discussion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Patients with normal pulmonary function were unlikely to have oxygen desaturation during submaximal exercise (only 7%). In our 3-min submaximal exercise tests, a low DLCO was a strong predictor of oxygen desaturation, both in those patients with airways obstruction and those with restriction of lung volumes. The ability of all of the preexercise test factors to predict oxygen desaturation during submaximal exercise in any category of abnormal lung function was moderate. The best threshold for predicting oxygen desaturation during exercise without regard to type of lung disease in our study was a DLCO < 62% of predicted, resulting in both a sensitivity and a specificity of about 75%. In a study of patients with interstitial lung diseases, Risk and coworkers8 found that 74 of 79 patients whose DLCO was < 50% predicted experienced a moderate-to-severe increase in alveolar-arterial oxygen pressure gradient during exercise (> 35 mm Hg), compared to 26 of 94 patients with a DLCO > 70% predicted. However, Kelley and coworkers3 found that patients with interstitial lung diseases whose DLCO was > 60% of predicted never experienced exercise-induced oxygen desaturation.
In a study of 48 patients with moderate-to-severe COPD, Owens and coworkers9 found that a cut point of > 55% predicted DLCO had 82% specificity and 100% specificity for excluding exercise-induced desaturation. Therefore, if a patient’s DLCO is below approximately 70% of predicted (using modern DLCO techniques and reference equations) and knowledge of oxygen desaturation during submaximal exercise (of the type and duration often encountered by the patient) would affect their therapy, then a submaximal exercise test (6-min walk or shuttle walking test with pulse oximetry) or a maximal exercise test should be done.
Safety
There were no worrisome complications (side effects) of these
3-min step tests, despite half of the patients being elderly, with a
relatively high prevalence of cardiovascular disease. No patients have
had syncope or cardiovascular collapse related to > 100,000 such
tests done at this location during the 1980s and 1990s. Although
physicians and equipment for cardiopulmonary resuscitation are
available in the pulmonary function laboratory, they have not been
needed to treat complications from this submaximal exercise test. Our
rationale for not performing ECG monitoring during this test is that
all of the patients who perform this test ambulate to the testing area,
often using the stairs, without ECG monitoring. If we were to perform
ECG monitoring, we would be obliged to train the technicians to
recognize and respond to changes in the ECG during the test, and the
testing time would be more than doubled, due to the need to place and
remove the monitoring electrodes.
Type of Lung Disease
The pulmonary function abnormality categories are strongly
associated with types of lung disease. The obstruction category with
low DLCO is usually associated with COPD (specifically
emphysema) due to cigarette smoking. Obstruction with a normal
DLCO may be due to asthma or chronic bronchitis.
Restriction with a low DLCO (and without obstruction) is
often associated with an interstitial type of lung disease. Restriction
with a normal DLCO is usually due to one of many types of
extrapulmonary disorders that limit the depth of inhalation. An
isolated low DLCO (without obstruction or restriction, and
after correcting for anemia) is often associated with a pulmonary
vascular disease, or an early interstitial lung disease (which has not
yet lowered the TLC to below the LLN for that patient).
Study Limitations
A limitation of our classification scheme is that the PFT
abnormality classification groups include more than one type of lung
disease. Many of the patients were undergoing diagnostic workups when
their PFTs were ordered; they were merely asked if they knew their
diagnosis at the time of testing, and we did not use this information.
Also, we did not ask permission to later take data from their medical
charts, so we lack an International Classification of Diseases-type of
discharge diagnosis. Although the sample is very large and all patients
tested during a 12-month period were included, this group of patients
may not be representative of patients seen by physicians seen in other
settings and geographic areas. As demonstrated by their 7% rate of
exercise-induced desaturation, our reference group includes a few
patients with diseases that cause oxygen desaturation during exercise,
such as cardiovascular diseases or circulatory shunts. Therefore, they
are not the ideal reference group. However, some of the falls in
SpO2 during exercise in this group
were probably due to both measurement errors and the choice of a 4%
cut point used to define desaturation.
Many first-generation and second-generation pulse oximeters are known to be relatively sensitive to motion artifact during exercise, often leading to underestimation of SpO2 during exercise.21 22 23 The technicians in our study noted the SpO2 display at the end of the exercise period and recorded the value that seemed stable for about 5 s. It is unlikely that they were biased by knowledge of the patients’ working diagnosis or spirometry results when they estimated the end-of-exercise SpO2, so the ORs that we report were probably not altered by inaccuracy of the pulse oximeters.
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Footnotes |
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Corrrespondence to: Paul Enright, MD, 4460 East Ina Rd, Tucson, AZ 85724; e-mail: lungguy@aol.com
Received for publication July 20, 2000. Accepted for publication February 1, 2001.
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References |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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