January - March 2004: 
Volume 17, Issue 1

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Clinical cardiopulmonary exercise testing in a greek sedentary population
Selecting the appropriate reference values for maximal oxygen uptake (VO2peak) is of pivotal importance in the differential diagnosis of abnormal findings in cardiopulmonary exercise testing. The currently used reference values proposed by Jones et al, Hansen et al, and Fairbarn et al, which are based on cycle ergometry, present significant interstudy differences and cannot be applied to sedentary subjects, whereas reference values for several other variables have not been assessed at all, making it difficult to deduce valid conclusions. We studied 68 normal male adults, aged 18–48 years, who reported absence of systematic exercise. A progressive incremental exercise of 20 Watts/min up to exhaustion was performed, using a cycle ergometer and a mixing chamber system (EOS Sprint, Jaeger). Maximal oxygen uptake, heart rate, performed work, tidal volume, ventilation, oxygen pulse, lactate threshold and respiratory reserve were measured at peak exercise. The height of the subjects ranged from 166 to 194 cm and the weight from 57 to 95 kg. Smokers and subjects with exertional dyspnea or cough were included in the study, provided that resting spirometry was normal. In overweight subjects, Bruce’s correction for weight was used. Predicted values for VO2 proposed by Fairbarn, Jones and Hansen were found to be systematically higher by 45%, 25% and 6%, respectively. VO2peak varied according to age and height, while maximal heart rate was predicted by age alone. Normal values for respiratory reserve set at >11 Lit/min showed specificity of 99% and for VT/FVC ratio at >30% had a specificity rate of 96%. Lactate threshold appeared at 80% of VO2peak, with a lower limit of 56% (SD 9%). In conclusion, predicted values proposed by Hansen et al are comparatively more representative of the Greek sedentary general population, but still not ideal. The results of the present study are proposed as useful reference values in the evaluation of cardiopulmonary exercise testing in the average Greek population. Pneumon 2004, 17(1):55-63.
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The selection of appropriate normal values is the cornerstone of the differential diagnosis of various pathophysiologic conditions during the assessment of cardiopulmonary exercise testing (CPET). Preliminary analyses of the available data on normal subjects showed that only five studies1-5 meet the minimum criteria for clinical use. Blackie et al3 have covered a short age range (55-80 years), whereas Bruce et al report data obtained from predominantly fit subjects performing cycle ergometric exercise. Final analyses of data proposed for use in the evaluation of maximal oxygen uptake (VO2peak) are limited in three groups of predicted values2,4,6. Hansen et al1,6 provide a complete range of predicted values obtained from a population of seamen of relatively advanced age; VO2max was calculated using Bruce's equations, corrected for ideal weight and for the use of a cycle ergometer (a 10% reduction). Values proposed by Fairbarn et al4 are systematically higher than those suggested by Jones et al and by Hansen et al in both males and females; furthermore, data on other important variables, apart from VO2peak and heart rate, are not provided. These limitations that are associated with the currently available normal values make the interpretation of CPET results difficult, while there are no predicted values for submaximal exercise or for other important variables.7 In order to determine the range of predicted values in a general population predominantly consisting of people who lead sedentary lives, such as white-collar workers who do not report systematic physical exercise, we retrospectively studied the cardiopulmonary exercise testing results of 68 adult males selected from a large group of more than 200 evaluated individuals, which also included professional athletes, amateur athletes, Armed Forces raiders, laborers, military personnel and/or regularly exercising persons. Smokers as well as hypertensive or overweight subjects were included in our study, because these conditions are frequently present and hence should be taken into account in order to have a sample representative of the general population; in addition, the effect of weight in the prediction of VO2peak merits special attention and consideration.

Material and methods

We selected 68 subjects from a large group of people who have visited the Lung Function Laboratory of the Pulmonary Medicine Department for a routine pulmonary function examination in the last 5 years. Clinical examination was followed by radiographic examination and electrocardiogram. Medical history included information about past diseases and general health status, occupation, exercise, symptoms appearing during exercise and smoking habit. Subjects presenting any of the following were excluded from the study: history or signs of cardiovascular disease, peripheral vascular disease, treatment with beta blockers, antiarrhythmic agents or digitalis, pulmonary disease, neuromuscular or skeletal disease, malignancy, diabetes mellitus or metabolic acidosis at rest, as well as poor motivation. Since our intention was to study subjects with a relative lack of physical activity (sedentary population), we enrolled only those who reported absence of regular exercise or just occasional exercise (once a week, "weekend", leisure score=0 according to Jones2). The occupation of the study subjects should not involve walking, standing combined with walking or manual work. Due to the lack of physical exercise, certain subjects were overweight, but not obese (body mass index, BMI, 25-30); in these cases, corrected weight according to Bruce (weight in kg=0,79 x height in cm -60,7) was used in the evaluation of CPET results.

Spirometry was performed using a calibrated dry volume Vitalograph type spirometer; forced expiratory volume in one second (FEV1) and forced vital capacity (FEV) were expressed in BTPS with predicted normal values those proposed by Knudson et al.9 The exercise test was performed two hours after the subjects had their last meal. The electromagnetically controlled cycle ergometer (ER900, Jaeger) was calibrated and controlled by the manufacturer, so that Watt indications accurately corresponded to performed work in revolutions per minute (rpm) (between 40 and 60). Measurements of minute ventilation (V^E), oxygen uptake (V^O2) and carbon dioxide output (V^CO2) were obtained every 30 seconds based on exhaled air analysis by the mixing chamber system (EOS Sprint; Jeager, Wurzburg, Germany).10The pneumotachograph, O2 analyzer (paramagnetic) and CO2 analyzer (infrared) were controlled for linearity and accuracy prior to each test. Heart rate and electrocardiogram (V1, II, V5 lead equivalent) were continuously recorded and monitored (Cardiotest, EK53K; Hellige, Freiburg, Germany), and haemoglobin saturation (SaO2) was measured by use of an ear oxymeter (Johnson, Greece); an air cuff was used for blood pressure measurements, which were automatically made at 1-minute intervals using the oscilometric method. After 3 minutes of unloaded cycling, workload was increased by 20 Watts/min (incremental protocol) until maximal tolerated work rate or a drop in revolutions to <40/min, which would not increase despite exhortation. Maximal work was defined as the higher work rate the subject achieved and maintained for 30 seconds, whereas breathing difficulty was titrated at rest and at maximal work rate using the modified Borg scale.11 Maximal values recorded by gas analyzers for V^O2, maximal ventilation (V^E), heart rate (HR), oxygen pulse (O2P) were considered peak exercise values. Recording continued for a further 2-minute period (recovery) after peak exercise. In addition, four subjects repeated the exercise test to provide biological calibration and ensure reproducibility. Anaerobic threshold (AT) was noninvasively defined combining ventilatory and gas exchange thresholds to maximize accuracy and discretion. In particular, AT was assessed based on V^CO2 versus V^O213 and VE/V^CO2 versus VE/V^O214 plots. Respiratory reserve (RR) was defined as minute ventilatory volume (MVV) (indirectly calculated using the formula: FEV1x35) reduced by the amount of maximal ventilation (VEmax) at the end of the exercise test (RR=MVV-VEmax). Continuous measurements of V^O2 and V^CO2 (STPD), HR, VT (tidal volume) and VE (BTPS) were performed every 30 seconds using the mixing chamber system.


Table 1. Anthropometric and spirometry data of 58 normal male adults

N=58                         Mean value                 SD                          Range                P value**

Age (years)                   028.45                  09.18                        18-48                       -

Height (cm)                   177.34                  06.07                      166-194                     -

Weight (kg)                   078.43                  09.32                        57-95                       -

FEV1 (L)                        004.10                  00.50                     3.62-5.02                > 0.05

Maximal ventilation*      141.39                  11.64                   116.2-166.6                  -

FVC                              005.05                  00.42                     4.15-5.95                > 0.05

Haematocrit (%)            043.80                  02.30                     39.5-46.2                    -

* Maximal ventilation (MVV)=FEV1΄35

** vs predicted values as evaluated by the use of paired t-test analysis



Table 2. Peak values of cpet parameters

Parameter                           Units                       Mean peak value                 Standard deviation (SD)

Maximal work                      Watts                               202.77                                       30.75

VO2 peak                             L/min                               002.59                                       00.53

VO2 peak                         mL/min/kg                           033.72                                       08.40

O2P                                   mL/beat                             014.94                                       02.81

VEmax                                   L/min                               086.99                                       21.84

HRmax                                beats/min                           174.60                                       08.38

RR                                      L/min                               060.78                                       24.52

VTmax                                      L                                  002.48                                       00.63

VTmax/FVC                           (%)                                  49.00                                       13.00



Table 3. Proposed equations for the estimation of cpet parameters

Parameter Height Age  Weight  FVC   Watts  VEmax    VO2   VO2/kg Constant  multiple r  P-value   SEE

Wmax              -          -         -       4.80       -         -      42.56      -       067.26       0.81        <10-4        18.21

VO2 peak  0.004  -0.019     -          -         -         -          -          -       002.43       0.34       0.030   00.51

VO2 peak -0.3400 -0.330     -          -         -         -          -          -       103.72       0.40       0.007   07.81

HRmax            -      -0.300     -          -         -         -          -          -       183.18       0.33       0.010   07.98

O2P          0.033  -0.078     -          -         -         -          -          -       011.16       0.28       0.100   02.74

VTmax        0.007      -         -          -         -     0.021      -          -        0-0.71       0.74        <10-4        00.43

HRmax        4.010      -         -          -         -         -          -          -       164.24       0.27       0.050   08.17

VO2 peak      -          -         -          -     0.015      -          -          -      00-0.51*      0.81        <10-4        00.34

Wmax              -      -0.820 0.047      -         -         -          -          -       218.64       0.21       0.400   34.62

AT/kg       0.003  -0.090                                                                    028.45       0.19       0.700   05.93

AT/kg           -          -         -          -         -         -          -      0.668   004.33       0.83         10-5          00.11

*constant P value = 0.17



Statistical analysis

Statistical analysis was performed using the statistical software package SPSS for Windows (version 6.0). Paired t-test analysis was used for comparisons between measured and predicted FEV1 and FVC values. Analysis of variance (ANOVA) was used for multiple comparisons according to Scheffe to evaluate differences in various parameters. Multiple linear regression analysis was employed to assess the statistical significance of dependent variables.14 Two-tailed P values of less than 0.05 were considered statistically significant.


As shown in Table 1, the age of the study subjects ranged from 18 to 48 years, height from 166 to 194 cm, weight from 57 to 97 kg, whereas spirometry was considered normal since no significant deviation from predicted values was documented. Work rate at maximal exercise (Wmax) showed a weak correlation with age (A, yr) and corrected weight (W, kg), but no correlation with height: Wmax=218.64 - 0.82A + 0.047W (multiple r=0.21; P=0.4; SEE=34.62; SEE denotes standard error of the estimate or bias). As regards the effect of the rest of the assessed variables, FVC showed the smaller variation and influenced the Wmax-VO2 relationship as an indirect indicator of anthropometric parameters (improvement in r2=5%): Wmax=67.26 + 4.80FVC + 42.56VO2 (r=0.81; P=10-4; SEE=18.21). Maximal oxygen uptake (VO2 peak) was found to correlate with age and height according to the following equation: VO2 peak = 2.43 - 0.019A + 0.004H (r=0.34; P=0.03; SEE=0.51; H denotes height in cm). The function V^O2peak/kg of true body weight revealed an inconsistent inverse relationship with height, which is attributed to the reduction of VO2 peak/kg in overweight persons: VO2 peak/kg = 103.72 - 0.33A - 0.34H (r=0.40; P=0.007; SEE=7.81) (Table 3). Maximal heart rate (HRmax) showed a linear reduction with age, which was unaffected by other variables: HRmax=183.18 - 0.30A (r=0.33; P=0.01; SEE=7.98). Maximal oxygen pulse (O2Pmax) varied with age and height: O2Pmax=11.16 - 0.078A + 0.033H (r=0.28; P=0.1; SEE=2.74). The slope of the VO2-WR (work rate) curve, which is an indicator of work efficiency, was approximately 30% (10 mLxmin-1xW-1) and was not related to age, height or overweight, suggesting that the rate of VO2 increase is not related to anthropometric parameters. AT appeared at a VO2 peak level of 80% (confidence intervals 56-90%; SD 9%) and showed a weak correlation with age and height: AT/kg=28.45 - 0.09A + 0.003H (r=0.19; P=0.7; SEE=5.93). However, there was a statistically significant positive relationship of AT with VO2 (the positive constant is expressed in mL/min/kg): AT/kg = 0.668 (VO2/kg) + 4.33 (r=0.83; P=10-5; SEE=0.11). At maximal exercise, tidal volume (VTmax) varied with maximal ventilation (VEmax), whereas for a given VEmax value, VTmax was found to be positively related to height, but not to FVC (forced vital capacity), as shown in the following equation: VTmax= -0.71 + 0.021VEmax + 0.007H (r=0.74; P<10-4; SEE=0.43). VTmax/FVC ratio was 49±13% (SD); only three subjects had a ratio of less than 30% (specificity 96%). Respiratory reserve (MVV-VEmax) was 54.25±24.41 L/min (SD), with only one subject having respiratory reserve lower than 11 L/min (specificity 99%). Maximal values recorded during the exercise test are shown in Table 2. The equation that describes maximal heart rate as a function of V^O2, as well as the relationship between VO2 and performed work (in Watts) are presented in Table 3. Provided that no difference in the HR-VO2 relationship was noted between the 18-30 and 31-48 age groups, the same equation applies to all study subjects irrespective of their age. Predicted values of VO2 according to the equations proposed by Fairbarn et al, Jones et al and Hansen et al were systematically higher by (mean value±standard deviation; percentage of VO2max [L/min] in our study) 1.16±0.55 (45%), 0.66±0.57 (25%) and 0.16±0.56 (6%), respectively. Both one-way analysis of variance (ANOVA) and post hoc multiple comparisons Scheffe test indicated that statistical difference was established only in relation to the predicted values proposed by Fairbarn et al (P=0.05). The highest respiratory exchange ratio (RER) at peak exercise was 1.20±0.13, whereas after a 2-minute recovery period this ratio increased to 1.49±0.21 due to hyperventilation. The coefficient of variation that was derived from four subjects who repeated the exercise test for the purpose of biologic calibration was 4.0±1% for HR, 8.5±5% for VO2, and 8.0±6% for VEmax.


The present study is an attempt to provide the data necessary for the evaluation of the results of the standard cardiopulmonary exercise test (CPET) using an electromagnetic cycle ergometer. The selected population differs from the populations of maximal exercise studies conducted till now, which enrolled university students, systematically exercising persons and athletes, or laborers, who volunteered to participate in these studies. The study subjects reported lack of systematic physical exercise; furthermore, many of them were overweight. Both lack of exercise (sedentary lifestyle) and overweight are considered features representative of the general population. Compared to previous studies, the size of the study population may seem relatively small; nevertheless, it does not differ greatly from the number of subjects studied by Hansen et al,6 and represents an accepted compromise between a population-based study and the maximal number of subjects with complete data on the primary study variables. In addition, age and height were relatively evenly distributed in the study subjects; as regards spirometry, measured values did not differ from the predicted normal values that are already established for the general population. Some authors have used a continuous incremental or a non-continuous overmaximal work test on a treadmill for the determination of the maximal oxygen uptake plateau,15 but this technique is not clinically feasible and its results are not representative of the average population (although they were not significantly different from the results of the present study, allowing for a 10% reduction for the conversion of the treadmill to a cycle ergometer).

Corrected weight was shown to provide better predictions of maximal work in Watts, as contrasted with height, which has been proposed by Jones et al, indicating that, as an indirect crude indicator of total body mass, weight is superior to height in providing estimates of work performance. In addition, the error provided by our study is lower than that of the afore mentioned investigators (212.39 kpm/min vs. 216 kpm/min). Many years ago, Buskirt and Tailor had already noted that VO2 had a stronger correlation with fat-free mass or metabolically active tissue volume parameters than with total body weight; in addition, they pointed out that VO2max should be evaluated in conjunction with fat-free mass, otherwise overweight persons may be mistakenly identified as unhealthy.16 The results of our study are consistent with the above described considerations; this consistency is further emphasized by the inconsistent and paradoxical inverse relationship between VO2peak/kg of true body weight and height. Moreover, the same investigators, as well as others that followed6 pinpoint that the rate of the VO2 increase is not related to weight, whereas the observed association with VO2peak is attributed to the higher baseline VO2 during unloaded cycling (0 Watts), which is proportional to the subject's weight. Our findings confirm this view, since mechanical efficiency, i.e. the rate of VO2 increase per unit of work increment, was not found to be related to anthropometric variables. In our study, the correlation coefficient of VO2peak with dependent variables was lower than in previous studies;2,4,6 however, VO2peak had approximately the same standard error, which is important for determining the range of normal values in the population. Thus, according to our study, the predicted value of VO2peak for a 40-year-old, 170 cm tall male is 2.35 L/min, whereas the equations of Hansen and Jones provide a predicted value of 2.37 L/min and 2.67 L/min, respectively.

As regards the rest of the variables assessed at maximal exercise, maximal heart rate was found to vary with age, which is consistent with other reports. The relationship between heart rate and VO2 provides information about stroke volume due to the strong linear relationship between cardiac output and VO2; hence, pulse oxygen at maximal exercise reflects maximal stroke volume. The equations proposed by the present study predict oxygen pulse as a function of age and height, whereas a single reference by Jones2 suggests gender and height, but not age, as predictors of oxygen pulse. However, the standard error of the estimates (SEE) of HRmax and O2Pmax provided by the equations suggested by the present study is clearly lower than those reported by Fairbarn4 and Jones2, whereas Hansen6 does not report a standard error value at all. In our study, in particular, SEE for HRmax and O2Pmax is 7.98 beats/min and 2.74 mL/beat versus 10.3 beats/min and 2.8 mL/beat in the study by Jones et al, respectively.

Measurements of anaerobic threshold (AT), introduced by Wassermann et al,17 provide accurate indications of functional capacity and work efficiency. Although normal AT variation expressed as percentage of VO2peak was originally found to be small,18 later studies showed that this variation was greater in the general population. In addition, it is known that the AT/VO2peak ratio decreases with increasing VO2peak.6 We found a higher AT/VO2peak ratio (mean value 80%) with a lower standard deviation (9%). AT was weakly related to anthropometric parameters, as indicated by the respective low correlation coefficients. However, VO2peakk correlated strongly with AT, with anthropometric parameters having practically no effect on this correlation, as earlier noted by Jones et al as well.2 Wasserman et al had already reported that the AT variation in normal subjects depends on age and fitness. Although a number of physiological mechanisms make the interpretation of the variation difficult and unclear,19 we speculate that the characteristics of the study population account for the weak correlation of AT with anthropometic parameters. Moreover, Hoshida et al20 as well as Sue and Hansen21 report AT variation values of 20% and 18%, respectively, which are higher than both those reported by Davis et al18 and our findings. Weitman and Katch22 report higher AT values, but their subjects were young and exercised regularly. Reinhard et al23 state that since the slope of the VO2peak-age curve is greater than the slope of the AT-age curve, the AT/VO2peak ratio increases due to decreasing VO2peak, which is consistent with the findings of the present study. In the present study, VO2peak decreased by 0.019 L/min per year of age (0.021 L/min in the studies conducted by Jones2 and Reinhard23) with AT appearing at 0.0063 L/min (for a person with a body weight of 70 kg, since AT is expressed per kg). The corresponding values reported by the above-mentioned authors are 0.0068 and 0.0070 L/min, respectively. Accordingly, and taking into account the positive constant in the AT-VO2peak relationship, AT predicted values should be based on predicted VO2 rather than on a standard percentage of measured VO2.

Previous studies24 have shown that the increase in tidal volume during exercise is not linear; rather, it tends to increase at a lower rate as exercise becomes more strenuous, thus producing a curvilinear VT-VEmax curve. Thus, some investigators have divided the VT response in two straight lines; a lower, representing the VT increase to a maximal value, and an upper, representing an increase in ventilation effected by increasing respiratory rate, with VT remaining relatively constant.25 We found that the VT-VEmax relationship could be described by a linear model, only slightly different from the exponential model (change in r2=2%), primarily due to the lower exercise and ventilation level observed in our study population.

In conclusion, we have presented data that can be useful in the evaluation of the results of clinical cardiopulmonary exercise testing in relatively unfit populations. Provided that the dispersion of the values shows a relative proportionality, it is suggested that the level of 80% of the value predicted by the study equations be the lower limit of the normal range, as already applied to predicted normal values in pediatric spirometry.26 Although not significantly different from the data reported by Hansen and Jones, our data are associated with a lower standard error in most of the assessed variables; thus, we believe that these data are more appropriate for use in studies of the general Greek population.



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