Results
Baseline characteristics
Sixty-two asthmatic children and adolescents completed the study. Seven
did not attend on the second day because of transport difficulties and
were excluded. All individuals were able to complete the six-minute EVH
and there was no need to interrupt the 30-minute FEV1 evaluation because
of respiratory symptoms.
No patient was excluded because of a low predicted FEV1level. Twelve were prescribed a low-dose (200mcg/day) continuous-use
corticosteroid inhaler (beclomethasone, which is distributed free of
charge by the government) but none were using it regularly and none had
used it for at least one week before testing. No patient was using
long-acting beta-2 agonists and all had albuterol for recovery. General
data are presented in Table 1.
Mean laboratory temperature was 25.5oC
(+ 2.8oC) and relative humidity 58.7%
(+ 6.2%), with no differences between test days
(p>0.05).
Reproducibility and agreement
Twenty-six of the 62 patients responded positively for EIB after EVH on
both days (i.e., had a FEV1fallmax%> 10%), 17 on one day only (5 on the first day and
12 on the second), and 19 responded negatively on both days. The overall
agreement was 72.5% (95% CI 61.6%, 83.6%) and the positive and
negative agreement proportions were 41.9% and 30.6% respectively.
No difference was observed in mean FEV1fallmax% after
EVH between visits for the group as a whole, with low bias (mean
difference between visits for FEV1fallmax%) but with
wide LOAs. The same was found for the AUC0-30min (Table
2 and Figure 1). Seventeen out of 26 patients with a positive response
on both test days (65.4%) experienced a decrease in
FEV1 > 15%, and, in 10 of these,
the reduction was > 20%. In this sub-group of
individuals, bias was also small and LOAs were wide for both
FEV1falmax% and AUC0-30min (Table 2).
The mean FEV1fallmax% in those individuals testing
positive for EIB on one visit only (divergent group) was 17.7%+ 13.5% on the positive day (either visit one or two) and was
statistically different from that observed in those individuals testing
positive for EIB on both days (p = 0.016 for visit 1 / p = 0.021 for
visit 2).
For the group as a whole, the intra-class correlation coefficient (ICC)
for the FEV1fallmax% between the two visits was 0.854
(95% CI 0.758, 0.912;
p<0.001) and was 0.858 (95% CI 0.764, 0.915;
p<0.001) for AUC0-30min.
There was a significant correlation between
FEV1fallmax% and AUC0-30min for both
visits (visit 1: r = 0.91, p < 0.001 and visit 2: r = 0.89, p
< 0.001).
Confounding factors
Potential differences in baseline FEV1 (as a percentage
of predicted) and achieved ventilation rate (as a percentage of the
calculated target) between visits were considered confounding factors
that could interfere with the FEV1 response after EVH.
As shown in Table 3, no differences between visits were observed in
these two parameters either between groups or within groups. A more
detailed overview of the individual target ventilation rates achieved on
both visits for each group is provided in Figure 2.
Baseline asthma control status measured using the ACT score was also
considered a potentially confounding variable but showed no difference
between groups (Table 3). There were no differences either between
groups in terms of age and BMI (p=0.624 and p=.0957, respectively -
Kruskal-Wallis) or sex (p=.0738 - Chi-square).
Severity of EIB and recovery
During visit one, FEV1 did not return spontaneously to
baseline levels by the thirtieth minute in 15 of the individuals testing
positive on both days (n=26), and, during visit two, in 14. In those
testing positive on one day only, this occurred in 6/17. These
individuals were given 400mcg inhaled albuterol and FEV1returned to baseline values (within 10%) in all of these. Among those
testing positive on both days, the severity of
FEV1fallmax% was graded as mild on Visits 1 and 2 in 16
and 13, respectively, as moderate in 8 and 11, and as severe in the same
two individuals on both days. Fourteen of the individuals testing
positive on one visit only had a mild FEV1fallmax%
response and three had a moderate response. There was no need to
interrupt the FEV1 measurements after EVH due to respiratory complaints
or oxygen desaturation below 94%.