Tests
in the Evaluation
of Exercise-Induced
Asthma
Gerd J. A. Cropp, M.D., Ph.D., with the technical assistance of I. J. Schmultzler, B.S.
From the Department of Clinical Physiology. National Asthma Center, Denver, Colorado
ABSTRACT. Sixty asthmatic children were exercised on a bicycle ergometer and had pulmonary function tests per-formed before and repeatedly after exercise. Pulmonary function measurements included airway resistance (Raw), specific airway conductance (SG awl’ functional residual capacity (FRC), peak expiratory flow rate (PEFR), maxi-mum mid-expiratory flow (MMEF), forced expiratory volume during first second of expiration (FEy1), and forced vital capacity (FVC). At any one time during the post-exercise observation period decreases in SGaw were greater than changes in any other pulmonary function test, making SGaw the most sensitive test for the detection. of exercise-iflduced airw#{224}yobstrtation in asthmatics. Beyond five mm-utes after exercise PEFR and MMEF were reduced by exercise approximately equally, but somewhat less often and less markedly than SGaw. Exercise-induced reduc-tions in FEy1 were less marked and less frequent than de-creases in PEFR and MMEF, and reductions in FVC were the least severe and least often observed abnormality. Decreases in SGaw were significantly, but not linearly correlated with decreases in PEFR, MMEF, FEy,, FVC, and FEV1/FVC. There were statistically significant linear correlations between exercise-induced increases in FRC and decreases in FVC and between increases in Raw and FRC. If we accept that increases in Raw and FRC indicate increases in large and small airway obstruction respec-tively, exercise-induced decreases in FVC may indirectly suggest acute hyperinflation and thus small airway oh. struction. Although the positive correlation between Raw and FRC indicated that both large and small airway ob-struction developed after exercise in many of our asth-matics, increases in Raw were usually greater than in-creases in FRC, suggesting that large airway obstruction tends to be greater than small airway obstruction in exer-cise-induced asthma. Pediatrics, 56 (suppl): 860-867, 1975.
In asthmatic children strenuous exercise is often followed by clinical signs and symptoms and physio-logical evidence of acute airway obstruction.’’ In the evaluation of asthmatics after exercise, many dif-ferent pulmonary function tests have been used to detect the presence and severity of exercise-induced
asthma (EIA). There is, however, little information on the relative sensitivity of different pulmonary function tests for the detection of EIA and how changes in one test compare with changes in others. We, therefore, evaluated 60 asthmatic children with a battery of pulmonary function tests before and re-peatedly after exercise to determine the frequency of, the severity of, and the relations among various exercise-induced abnormalities in lung functions.
METHODS
Pulmonary function tests were performed before and repeatedly after exercise in 30 boys and 30 girls with perennial asthma. The patients’ ages, heights, and weights, their treatment, and their pre-exercise pulmonary functions were described previously’; they were referred to our laboratory for diagnostic testing to determine whether they would develop airway obstruction after strenuous exercise. Exercise was performed on a bicycle ergometer, starting at low work loads and increasing the loads incremen-tally until exhaustion or near-exhaustion were reached. Details of the exercise protocol were des-cribed in an earlier report.’ All patients were free of acute asthma at the time of testing. The follow-ing pulmonary function tests were performed: (1) Peak expiratory flow rates (PEFR) with a peak flow meter*; (2) forced vital capacities (FVC), forced ex-piratory volumes during first second of expiration (FEy1), FEV1/FVC ratios, and maximum mid-expiratory flow rates (MMEF) on a water-sealed spirometert; and (3) functional residual capacities (FRC) and airway resistances (Raw) in a constant-volume plethysmograph by the methods of DuBois et al.’-’#{176}When Raw was measured, we also deter-mined the thoracic gas volume (TGV) simultaneously sothatthe specific airway conductance (SGaw) could be calculated. Each of the pulmonary function tests
Supported in part by grant HL 16074-01 CVB from the
National Heart and Lung Institute.
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FIG. 1. Relation between exercise-induced changes in specific airway conductance and peak expiratory flow rates. Note that reductions in specific airway conductance tended to be greater and more frequent than reductions in peak expiratory flow
rates. Results are expressed in percentage of resting values.
were performed before and 5 to 10, 11 to 20, 21 to 30, and 31 to 40 minutes after the completion of the ergometer test. Each pulmonary function measurement was performed often enough to as-sure that an optimum effort had been made and that the results were reproducible. Any one set of pulmonary function tests was completed within four to five minutes. Post-exertional lung functions were expressed in percentage of resting (pre-exercise) values.
The post-exertional measurements of SGaw were compared with nearly simultaneously performed post-exertional measurements of PEFR, MMEF, FEV, FEVI/FVC, and FVC. The relations between paired measurements were approximated by regres-sion functions. Linear, power, exponential, loga-rithmic, and parabolic regressions were calculated for each relation, and the best-fit regression equa-tions were then selected. Correlation coefficients (r) were derived from linear transforms of the nonlinear regression functions. We also evaluated the correlations between post-exercise values of
*wright Peak Flow Meter, Airmed, Harlow, England.
tStead-Wells Spirometer, WE. Colling Inc., Braintree, Massachussetts.
FRC and FVC, and between Raw and FRC and calcu-lated linear regression equations for these relations.
RESU
LTS
There were 240 paired measurements of SGaw (independent variable) and PEFR, MMEF, FEV1, FEV,/FVC, and FVC (dependent variables.) Figures I to 4 show the relations between paired measure-ments, and Table I lists the best-fit regression equa-tions. Four of the regression lines are shown in Fig-ure 5. Table I indicates that high but nonlinear correlations existed between exercise-induced de-creases in SGaw and decreases in PEFR (r=.84), MMEF (r=.86), and FEV1 (r=.93); the correlations between decreases in SGaw and decreases in FEV1/ FVC were also significant but low in comparison to the above three relations. Table II shows the fre-quency with which reductions in pulmonary func-tions occurred between 5 and 40 minutes after ex-ercise. Table II indicates that the total number of significant exercise-induced reductions in SGaw were highest, those of PEFR and MMEF were inter-mediate, those of FEV1 were next in frequency, and those of FVC were least. Reductions to 20% to 75% of resting values were approximately equally
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FIG. 2. Relation between exercise-induced changes in specific airway conductance and maximum mid-expiratory flow rates. Note that reductions in specific airway conductance tended to be greater and more frequent than reductions in maximum
mid-expiratory flow rates. The relation between the two variables is very similar to that depicted in Figure 1.
quent for SGaw, PEFR, and MMEF; however, re-ductions to less than 25% of resting values were much more common for SGaw measurements than for PEFR and MMEF, and they were least common for FEy1 and FVC. Mild reductions, which we do not consider diagnostic of ELA (76% to 100% of baseline), were most frequent for measurements of FVC and FEy1, intermediate for PEFR and MMEF, and least frequent for SGaw. It may be seen in Figures 1 and 2 that small decreases in SGaw were frequently not well indicated by decreases in PEFR and MMEF. Reductions in SGaw had to be even more marked before they were consistently reflected by decreases
in FEV1 or FVC. Figure 4 indicates that decreases in FVC did not occur regularly until SGaw had de-creased to less than 50% of resting values. Figure 5 indicates that a given exercise-induced reduction in SGaw results in sequentially smaller reductions in PEFR, MMEF, FEV1, and FVC. We have listed in Table III the percentage of resting values for PEFR, MMEF, FEV1, and FVC which are predicted from the best-fit regression equations at 75%, 50%, and 25% of post-exercise SGaw values.
Figure 6 shows the observed relation between in-creases in FRC and decreases in FVC. Although there is considerable scatter of the data points, there was a significant negative correlation between the two variables. The linear regression equation predicts that an exercise-induced increase in FRC to 300% of resting values resulted in a reduction in FVC to 60% of pre-exercise values; variations from this average response were, however, often considerable.
There was a positive correlation between post-exertional increases in Raw and FRC (Fig. 7). The prediction equation indicates that an increase in Raw to 400% of resting values will on the average be associated with an increase in FRC to 211% of resting values. The correlation was significant, but not high.
DISCUSSION
This study has shown that exercise elicited many changes in pulmonary functions of asthmatic chil-dren. These changes could be detected by measure-ments of SGaw, forced expiration, Raw, or FRC.
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Fic. 3. Relation between exercise-induced changes in specific airway conductance and FEy1. Note that decreases in specific conductance to values between 50% and 75% of resting values were frequently not indicated by reductions in FEy1.
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Ftc. 4. Relation between exercised-induced changes in specific airway inductance and forced vital capacity. Note that the
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REGRESSION EQUATIONS OF RELATIONS BETWEEN EXERCISE-INDUCED CHANGES IN
SPECIFIC AIRWAY CONDUCTANCE AND OTHER PULMONARY FUNCTION TESTS
x vs. y
Best-Type
Fit Regression Equations
Equation
r*
SGawvs PEFR Power y = 5.2460 x 0.6372 .84
SGawvs MMEF Power y = 9.0813 x 0.5310 .86
SGawvs FEy1 Log y = 30.0812 ln x -339945 .93
SGawvs FEV,/FVC Log y = 8.8503 ln x -40.2499 .68
SGawvs FVC Log y 16.0793 ln x +28.0319 .68
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FIG. 5. Best-fit regression equations which describe the relations between exercise-induced reductions in specific airway conductance and peak expiratory flow rates, maximum mid-expiratory flow rates, FEVI, and forced vital capacities. Reduc-tions in peak and maximum mid-expiratory flow rates indicated best reductions in specific airway conductance. Exercise-induced reductions in specific airway conductance were marked before they were consistently predicted by reductions in
FEy, or forced vital capacity.
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FIG. 6. Relation between exercise-induced increases in functional residual capacity and decreases in forced vital capacity. The correlation was not high, but large increases in functional residual capacity were usually associated with reductions
in the vital capacity.
During the time interval from 5 to 40 minutes after exercise, decreases in SGaw were more marked and occurred more often than any other abnorm-ality, making reductions in SGaw the most sensi-tive indicator of exercise-induced airway obstruc-tion. Since SGaw may be reduced by increases in either Raw or TGV, or both, exercise-induced decreases in SGaw indicate that the total cross-sectional area of large airways was no longer appro-priate for the lung volume at which Raw was measured.
Measurements of forced expiratory flow rates were frequently decreased in asthmatics after ex-ercise. The results of this study suggest that mea-sures of PEFR and MMEF were reduced almost as often as quasi-simultaneously measured SGaw. It has been our experience that SGaw, PEFR, and MMEF measurements frequently showed mild re-ductions in lung function (50% to 75% of resting values) when FEV1 measurements had not changed significantly. Most patients in whom SGaw, PEFR, and MMEF had decreased to 50% to 75% of resting values were not dyspneic, although they usually had wheezing or an increase in the mild wheezing
which they exhibited before exercise. Decreases in FEV, were quite regularly present when patients became dyspneic so that decreases in FEV1 may be considered indicative of symptomatic ELA.
Reductions in FVC were noted only when EIA was severe and when the FRC had increased. Since hyperinflation is usually the result of small airway obstruction, exercise-induced decreases in FVC may provide indirect evidence of exercise-induced ob-struction in peripheral airways.
Figure 7 indicates that hyperinflation was loosely correlated with increases in Raw. The increases in Raw tended to be much greater than increases in FRC. Since increases in Raw and FRC indicate pri-manly large and small airway obstruction respec-tively, large airway obstruction seemed to be the predominant post-exertional abnormality in our patients. Although small airway obstruction was as common as large airway obstruction, small airway obstruction was generally of lesser severity than large airway obstruction.’ There were a few mea-surements of marked exercise-induced increases in FRC without concomitant increases in Raw, suggest-ing that small airway obstruction may have been
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FREQUENCY OF EXERCISE-INDUCED CHANGES IN PULMONARY FUNCTIONS
Test % of Resting Values Total
Measurements (No.)
,->100 76 to 100 50 to 75 25 to 49 25
-‘
Total Below 75%
No. %
SGa 41 55 50 55 39 144 60 240
PEFR 50 84 41 53 12 106 44 240
MMEF 63 76 64 34 3 101 42 240
FEVI 66 119 37 17 1 55 23 240
FVC 84 123 24 8 1 33 14 240
the major fiinct lanaI abnormality of EIA occasionally. We conclude from these observations that EIA can be detected by spirometric and plethysmographic tests. The general availability, the low cost, the speed, and the little training required to do peak flow and spirometric measurements make these tests ideal for detecting exercise-induced pulmonary functional alterations in asthmatic children. Spirometric tests
400
will yield as many positive results as plethysmo-graphic tests when they are performed during the first five minutes after exercise, a time when pleth-ysmographic measurements are technically dif-ficult.’ Spirometric tests do not indicate acute hyperinflation; however, reductions in FVC to less than 80% of resting values suggest that exercise-induced hyperinflation and small airway obstruction
FIc. 7. Relation between exercise-induced increases in airway resistance and functional residual capacity. The correlation
was not high, but large increases in airway resistance were usually associated with hyperinflation.
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SUPPLEMENT
867TABLE III
PREDICTED VALUES FOR EXERCISE-INDUCED REDUCTIONS IN SPIROMETRIC MEASUREMENTS AT THREE ARBITRARY VALUES OF SPECIFIC AIRWAY CONDUCTANCE
Test % of Resting Values*
p.-
-\
At75% At50% At 25%
PEFR 82 63 41
MMEF 90 72 50
FEy1 96 84 63
FVC 97 91 80
*Values calculated from regression equations listed in Table I and shown in Figure 6.
probably have developed. When patients develop bronchospasm after forced expiratory maneuvers, it will be necessary to restrict diagnostic tests to qual-itative clinical evaluations or to plethysmographic measurements.
REFERENCES
1. Jones RS, Buston MH, Wharton MJ: The effects of ex-ercise on ventilatory function in the child with
asthma. Br J Dis Chest 56:78, 1962.
2. Jones RS: Assessment of respiratory function in the
asthmatic child. Br Med J 2:972, 1966.
3. McNeill RS, Nairn JR Millar JS, Ingram CG:Exercise-induced asthma.
Q
J Med 35:55, 1966.4. Fisher HK, Holton P, Buxton RSJ, Nadel JA: Re-sistance to breathing during exercise-induced
asthma attacks. Am Rev Respir Dis 101:885, 1970.
5. Sly RM: Exercise-related changes in airway
obstruc-tion: Frequency and clinical correlates in asthma-tic children. Ann Allergy 28:1, 1970.
6. Chan-Yeung MMW, Vyas MN, Grzbowski S: Exercise-induced asthma. Am Rev Respir Dis 104:915, 1971.
7. Anderson SD, McEvoy JDS, Bianco S: Changes in
lung volumes and airway resistance after exercise in asthmatic subjects. Am Rev Respir Dis 106:30,
1972.
8. Cropp CJA: Grading, time course, and incidence of exercise-induced airway obstruction and hyperin-flation in asthmatic children. Pediatrics 56
(suppl): 868, 1975.
9. DuBois AB, Botelho SY, Bedell GN, et al: A rapid plethysmographic method for measuring thoracic
gas volume: A comparison with a nitrogen
wash-out method for measuring functional residual capacity in normal subjects. J Clin Invest 35:322, 1956.
10. DuBois AB, Botelho SY, Comroe JH Jr: A new method
for measuring airway resistance in man, using a body plethysmograph: Values in normal subjects
and in patients with respiratory distress. J Clin Invest 35:327, 1956.
ACKNOWLEDGMENT
I would like to thank Mrs. S. Sirotak, Mrs. S. Fisher, and
Miss J. Megonigle for their help in the preparation of this manuscript.
