The gold standard measurement of cardiorespiratory fitness has traditionally been an individual's peak oxygen uptake (V˙O2peak), the point at which no further oxygen is used despite an increasing work rate. The ability to attain V˙O2peak is dependent on patient effort and can be influenced by pain, shortness of breath, and fatigue. Such issues may be of particular concern when studying overweight individuals (13,17,29,31). A substantial percentage of overweight individuals fail to achieve V˙O2peak during exercise testing (13,23). We recently have reported that 24% of overweight, versus 12% of normal weight, adolescents did not achieve V˙O2peak during exercise testing (26).
Some investigators have proposed that the mathematically derived, oxygen uptake efficiency slope (OUES) can be used as an objective, submaximal measure of cardiorespiratory fitness in the clinical setting that would be independent of exercise intensity (3,18,35). Baba et al. (3) first defined OUES as the slope of the logarithmic relationship between oxygen uptake and minute ventilation (VE) during incremental exercise. The OUES is thought to be determined by 1) plasma pH, 2) the arterial carbon dioxide (PaCO2) set point, and 3) the dead space:tidal volume ratio (Vd/Vt) (1), all of which may be influenced by obesity (33,38).
It is intuitive that the OUES above and below the lactate inflection point (LI) would be different because of differences in ventilatory drive that accompany metabolic acidosis. However Marinov et al. (21) report no difference in OUES above and below LI and no difference in OUES between moderately overweight and normal-weight children, suggesting that OUES is exercise intensity independent.
The OUES has been found to be reproducible (2) and related to V˙O2max in healthy children (4), moderately overweight children (21), healthy adults, and adults with heart disease (3,5,12,18,35). Others have demonstrated that the OUES is a good predictor of V˙O2max in nonoverweight individuals when data up to 75, 85, or 90% of V˙O2max are included in the analysis (5,18,27). Pichon et al. (27) and Van Laethem et al. (36), using the Bland-Altman method, conclude that interindividual variation in OUES limits its clinical utility. The Bland-Altman method involves plotting the difference between measured and predicted V˙O2peak against the average of measured and predicted V˙O2peak, revealing limits of agreement between measures and the presence or absence of magnitude bias, which can significantly increase error of prediction at high and low values of the predicted variable (i.e., V˙O2peak). To our knowledge, there has been no investigation of the relationship between OUES and fitness in severely overweight adolescents. Therefore, the purpose of this investigation was to determine whether the OUES is a clinically useful submaximal predictor of fitness in severely overweight adolescents.
We studied 141 severely overweight African American and Caucasian adolescents ages 12-17 yr recruited for a weight loss study (22), before they underwent weight loss treatment, and 48 healthy, nonoverweight (body mass index, BMI, between 5th and 94.99th percentiles for age and sex) volunteer adolescents ages 12-17 yr, recruited specifically for exercise studies (Table 1). Overweight subjects were in good general health but were required to have a BMI ≥ 95th percentile for age, sex, and race (24) and at least one obesity-related comorbid condition (primarily hyperinsulinemia and/or dyslipidemia). For both groups, subjects were excluded if they had used any anorexiants within the past 6 months; were pregnant; had major pulmonary, hepatic, or cardiac disorders; or had lost more than 3% of body weight during the past 2 months. All participants were recruited from the greater Washington, DC metropolitan area by newspaper advertisements, flyers posted in local commercial venues, and through physician referrals. No subject had previously performed a cycle test with measurements of gas exchange, and none were familiar with exercising to maximal capacity. Each subject was admitted to the National Institutes of Health Clinical Research Center for a cycle ergometry test. Before exercise testing, each subject was evaluated with a medical history, physical examination, and 12-lead electrocardiogram. All subjects were free of musculoskeletal injury as determined by a physician, and American Heart Association guidelines for exercise testing (37) were observed. Subjects' parents signed consent statements (and adolescents gave their written assent) for all studies under a protocol approved by the institutional review board of the National Institute of Child Health and Human Development, National Institutes of Health.
Cycle ergometry testing procedure.
Before the test, each subject was familiarized with the cycle ergometer (Ergoline 800, SensorMedics; Yorba Linda, CA) and instructed to maintain pedaling cadence at 60 rpm. Exercise began with a 4-min warm-up with no additional resistance applied to the pedals (unloaded exercise), followed by continuously increasing workloads of 15-20 W·min−1, until the subject could no longer continue to maintain the prescribed pedaling cadence. Subjects were encouraged to exercise to the limit of their tolerance. Workloads were selected to result in total test time of 8-12 min. Expired gas exchange was measured breath by breath during exercise using a metabolic cart (Sensormedics Vmax, Yorba Linda, CA). Before each exercise test, the gas analyzers and flow meter were calibrated using gas mixtures of known concentrations and a 3-L syringe. The gas-transit time delay and analyzer response times, measured during calibration, were used by the metabolic cart software (Sensormedics Vmax, Yorba Linda, CA) to align ventilation and fractional gas-concentration signals. LI was determined using the V-slope method (6). Peak oxygen uptake and respiratory exchange ratio (RER) were defined as the highest 20-s average value achieved during the last minute of exercise. Continuous heart rate was measured by 12-lead electrocardiogram (Cardiosoft, Sensormedics Vmax, Yorba Linda, CA) during exercise, and the highest heart rate achieved during the last minute of exercise was defined as the peak heart rate. Peak exercise rating of perceived exertion (RPE) was measured within the first minute of exercise recovery using the Borg 6-20 rating of perceived exertion scale (8,10). Subjects who met at least two out of the four following criteria during cycle ergometry were considered to have achieved their V˙O2peak: 1) maximal heart rate ≥ 185 bpm; 2) RER ≥ 1.10; 3) RPE = 18-20; and 4) achievement of an oxygen plateau (13,15). Attainment of an oxygen plateau was defined as a change ≤ 2.0 mL O2·kg−1·min−1 in oxygen uptake during the last minute of exercise. We use the term V˙O2peak rather than V˙O2max, even though we applied criteria similar to those used to define V˙O2max, because for most non-cycle-trained subjects, a cycle ergometer test will yield lower values than would be obtained with treadmill testing (28).
Height was recorded as the average of three measurements using a stadiometer (Holtain Ltd., Crymmyck, Wales) calibrated before each height to the nearest 1 mm. Weight was obtained using a calibrated digital scale (Scale-Tronix, Wheaton, IL) to the nearest 0.1 kg. Body composition was assessed after an overnight fast by air-displacement plethysmography (Life Measurement Instruments, Concord, CA) as previously described (25). Subjects wore minimal clothing (either tight-fitting underwear or a tight-fitting bathing suit) and a swim cap during measurements. Thoracic gas volume was measured during tidal breathing and during exhalation against a mechanical obstruction. Percent body fat was determined from body density using the standard two-compartment model calculated from the Siri equation (34).
Data were analyzed using StatView 4.5 software (Abacus Concepts, Inc., Berkeley, CA). The OUES was determined using simple regression of V˙O2 plotted against the semilogarithmic transformation of minute ventilation (3). The OUES slope was determined using data starting 1 min after exercise began and including all data through three defined end points: at LI (OUES LI), at 150% of LI (OUES 150), and at V˙O2peak (OUES PEAK), for those subjects who achieved V˙O2peak.
Using a two-tailed design, and P of 0.05, unpaired t-tests were used to test for significant differences in V˙O2peak, LI, and OUES (expressed relative to lean body mass) between the overweight and nonoverweight groups. Regression analysis was used to determine the relationships between three independent variables: OUES LI, OUES 150, OUES PEAK and one dependent variable: V˙O2peak. The regression equations were then used to predict V˙O2peak from each subject's OUES values. Predicted V˙O2peak for each subject was calculated from the regression equation of measured V˙O2peak against OUES LI (y = 1098.6 + 0.417x), OUES 150 (y = 749.5 + 0.528x), and OUES PEAK (y = 472.6 + 0.6x). The Bland-Altman procedure (7,19) was used to evaluate the agreement between measured V˙O2peak and V˙O2peak predicted from OUES LI, OUES 150, and OUES PEAK. A priori acceptable limits of agreement for predicted V˙O2peak were set at ± 15% of measured V˙O2peak, which equates to clinically significant changes reported to occur with aerobic training and deconditioning (9). To identify whether OUES was exercise intensity dependent, repeated-measures ANOVA with t-test post hoc analysis was used to test for differences between OUES LI, OUES 150, and OUES PEAK.
The overweight and nonoverweight adolescents who achieved V˙O2peak were of similar height and age but differed significantly in race, total weight, BMI, lean body mass, body fat mass, percent body fat, and BMI Z score (Table 1). Exercise data for the adolescents who reached V˙O2peak are presented in Table 2 and Figure 1. Absolute V˙O2peak (P = 0.33), LI (P = 0.87), and OUES 150 (P = 0.11) were not different between overweight and nonoverweight groups. However, OUES PEAK and OUES LI were both significantly greater in overweight subjects (P ≤ 0.05). When expressed relative to lean body mass (LBM) V˙O2peak, LI, OUES LI, OUES 150, and OUES PEAK were significantly lower in the overweight versus the nonoverweight group (P < 0.001). Maximal heart rate and power at the lactate inflection point were significantly lower in the overweight group (P ≤ 0.05). There was no significant difference in maximal respiratory exchange ratio for the overweight and nonoverweight groups (P = 0.5).
Five of 48 (10%) nonoverweight and 34 of 141 (24%) overweight subjects did not achieve V˙O2peak and were not included in the analysis of OUES. In the normal-weight group, those who did not achieve V˙O2peak did not significantly differ in BMI or lean body mass. However, among the overweight group that did not achieve V˙O2peak, there was a higher percentage of African Americans, and both BMI (P = 0.02) and BMI Z score were significantly greater (P = 0.03).
Relationship between OUES and fitness and exercise intensity.
OUES at all exercise intensities for both groups was significantly related to V˙O2peak (r2 = 0.35-0.83 P < 0.0001; overweight data shown in Figs. 2A, 2C, and 2E). LI was significantly related to V˙O2peak in nonoverweight adolescents (r2 = 0.84, P < 0.0001) and overweight adolescents (r2 = 0.69, P < 0.0001). Bland-Altman plots comparing measured V˙O2peak with V˙O2peak predicted from OUES in the overweight and nonoverweight groups showed large limits of agreement (± 478 to ± 670 mL·min−1) for all exercise intensities (overweight data shown in Figs. 2B, 2D, and 2F). These limits of agreement were as high as 30% of average V˙O2peak in the nonoverweight group and 34% of average V˙O2peak in the overweight group. Significant magnitude bias was found for OUES as a predictor of V˙O2peak for all exercise intensities in the overweight group (P < 0.0001), with OUES overpredicting V˙O2peak at low fitness levels and underpredicting V˙O2peak at high fitness levels (Figs. 2B, 2D, and 2F). Similar results were found for the nonoverweight group, with significant magnitude bias for OUES LI and OUES 150 (P ≤ 0.05). There was a significant increase in OUES with increasing exercise intensity in both overweight and nonoverweight groups (Fig. 1, P < 0.001).
The purpose of this investigation was to determine whether OUES was a useful submaximal estimate of fitness that might substitute for the actual determination of V˙O2peak. The fact that almost one quarter of the present investigation's overweight subjects did not achieve V˙O2peak underscores the need for a suitable submaximal measurement of fitness in such individuals. Our results suggest that, although OUES is related to V˙O2peak, it shows large interindividual variation, magnitude bias, and dependence on exercise intensity.
V˙O2peak and LI were significantly lower in the overweight group when expressed relative to lean body mass (Table 2). In contrast, others have found no differences in V˙O2peak values between nonoverweight and moderately overweight adolescents and children when scaled to lean body mass (16,20). Rowland et al. (28) suggest that moderately obese children have normal cardiorespiratory function, although a significant decline in physical performance may exist because of differences in body composition. Indeed, several investigations have found that body composition is a major determinant of performance (11,14,26). In the present study of severely overweight individuals, we found that once V˙O2peak and LI were adjusted for LBM, these measures were lower in the overweight group, suggesting that some degree of cardiorespiratory impairment or deconditioning exists. This was also further substantiated by the significant differences in the lactate inflection point expressed in watts per minute. Mean V˙O2peak (scaled to LBM) was 25% less in the overweight group compared with the nonoverweight group. This degree of decline in V˙O2peak has been reported with bed rest-related deconditioning (9). It is possible that overweight subjects similarly spend more time in a physically inactive state, contributing to deconditioning. However, we cannot rule out that other factors unique to obesity may have contributed to the decrease in V˙O2peak observed in this study. Absolute values for OUES PEAK and OUES LI were actually greater in the overweight group, which might suggest that overweight adolescents were aerobically fitter. However, when scaled to lean body mass, OUES at all exercise intensities was significantly lower in the overweight group.
Similar to results of previous studies (3-5,12,18,21,27,35), we found that OUES at all intensities for both groups was significantly related to V˙O2peak. However, there was large interindividual variation in V˙O2peak predicted by OUES, with limits of agreement as high as 30% of average V˙O2peak in the nonoverweight group and 34% of average V˙O2peak in the overweight group. Meaningful clinical changes in V˙O2peak can be much smaller than the interindividual variation in V˙O2peak predicted by OUES in our study. Typical changes in V˙O2max with training or deconditioning are on the order of 10-15% (30,32). In addition, a significant magnitude bias in OUES was identified for the overweight group, indicating that OUES may increasingly underpredict V˙O2peak at higher fitness levels and overpredict V˙O2peak at lower fitness levels. It is likely that the large variability in OUES predictions of V˙O2peak and the magnitude biases make it of limited value for predicting fitness for individuals.
In contrast to some previous studies (5,18,35) Pichon et al. (27) found a significant difference in OUES at different exercise intensities in nonoverweight and overweight adolescents. Similarly, we found a significant increase in OUES with increasing exercise intensity in nonoverweight and overweight adolescents. These differences were not confined to slopes below the LI; they included differences in OUES above the LI as well. This indicates that the V˙O2 (y-axis variable in the OUES slope calculation) increased in a disproportionate manner, relative to VE, with increasing exercise intensity. Typically, at exercise intensities above LI, there is hyperventilation with respect to V˙O2. When plotting OUES, VE is logarithmically transformed to produce a linear slope. Because V˙O2 continues to rise with increasing exercise intensity, and the change in VE is mathematically altered, the OUES seems to increase with increasing exercise intensity. However, because a primary requisite for a submaximal determinant of fitness would be exercise intensity independence, this finding again suggests that the OUES may not be a valid submaximal predictor of V˙O2peak.
In conclusion, OUES adjusted for lean body mass was shown to be lower in overweight adolescents. In addition, the wide interindividual variation, the magnitude bias, and the intensity dependence of the OUES impede its clinical utility for assessing the fitness level of severely overweight adolescents.
This research was supported by the Intramural Research Program of the NICHD/NIH, grant ZO1-HD-00641 to J. A. Yanovski. The authors have no conflicts of interest to disclose.
B. Drinkard and M. Roberts contributed equally to this article as first coauthors. J. A. Yanovski, B. Drinkard, J. C. Han, and D. P. Merke are commissioned officers in the U. S. Public Health Service, Department of Health and Human Services.
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