Discussion
This study shows that histamine and mannitol challenges are equally sensitive tests to demonstrate the effect of ICS on bronchial responsiveness.
To explore the validity of the tests to demonstrate the healing process of asthma by inhaled budes-onide, the correlation between changes in the responsiveness to the tests and the changes in other indexes of asthma severity was analyzed (Table 4). Change in mannitol responsiveness correlated significantly with the changes in sum symptom score and in FEV1. In addition, change in mannitol responsiveness tended to correlate with change in daily use of bronchodilating drugs. Change in cold air respon.
Table 2—Responsiveness to the Challenges at Baseline and After 3 Months and 6 Months of Treatment With Inhaled
Budesonide in 17 Asthmatic Patients*
| Variables | Baseline | 3 Months | 6 Months |
| Mannitol responders, No. of patients with mannitol PD^ < 635 mg | 17 | 7 | 7 |
| Geometric mean of mannitol PD^, mg
Geometric mean fold change in mannitol PD^ from baseline |
168 (84-335) | 512 (262-1,002) 3.0 (1.3-7.3) | 606 (370-991) 3.6 (1.6-8.4) |
| Histamine responders, No. of patients with histamine PD^ < 1.0 mg | 17 | 13 | 10 |
| Geometric mean of histamine PD^, mg
Geometric mean fold change in histamine PD15 from baseline |
0.16 (0.09-0.26) | 0.48 (0.22-1.04) 3.0 (1.5-6.3) | 0.85 (0.46-1.57) 5.4 (2.3-13) |
| Cold air responders, No. of patients with fall in FEV: > 9% after cold air challenge | 7 | 3 | 2 |
| Mean fall in FEV1 after cold air challenge, %
Mean change in fall in FEV1 after cold, % from baseline |
9.5 (5.2-14) | 4.9 (1.5-8.3) 4.6 (0.7-8.4) | 3.9 (1.2-6.6) 5.6(1.0-10) |
*Data are presented with 95% CIs unless otherwise indicated.
Time after start of treatment (months)
Log-transformed mannitol and histamine RDRs before and at 3 months and 6 months of treatment with inhaled budesonide; p values indicate the statistical significance of the changes in the these indexes from baseline (repeated-measures analysis of variance). Budesonide-induced change in RDR values did not differ significantly between the challenges at 3 months or at 6 months of treatment (Student paired t test).
The decrease in bronchial responsiveness to these challenges was statistically significant and of similar magnitude after 3 months and 6 months of treatment with inhaled budesonide. Cold air challenge seems to be less sensitive than mannitol and histamine challenges since the change in responsiveness to it did not reach statistical significance. This study also shows that mannitol and cold air challenges are valid tests to demonstrate the healing of asthma by ICS since the change in responsiveness to them correlated significantly with the change in symptom severity, as well as with changes in lung function parameters. Histamine challenge seems to be less valid than the other two challenges, since the change in responsiveness to it did not correlate significantly with changes in asthmatic symptoms.
Our study could not confirm the findings that suggest that indirect challenges would be more sensitive than direct challenges to demonstrate the effect of ICS on bronchial responsiveness. Of the many types of indirect challenges, adenosine challenge is the one most consistently shown to be more sensitive than direct challenges in this respect.