The change in RDR values are expressed as log RDR during treatment minus log RDR at baseline. PD15 values are mainly used in descriptive results due to their familiarity to clinicians; however, RDR values were used for comparisons between the challenges and correlation analysis since these values could always be exactly calculated even when a 15% fall in FEV1 could not be reached during the challenge. To be able to compare cold air challenge with mannitol and histamine challenges, a fixed-dose response was calculated for the latter two challenges. This was determined as the percentage fall in FEV1 after the highest common dose of mannitol and histamine challenges used on all three occasions. Repeated-measures analysis of variance was used to assess the effect of treatment on various indexes. The Student paired t test and analysis of variance were used to compare changes in responsiveness between the challenges at each time point. Pearson correlation values were used to investigate the relationship between the changes in the responsiveness to the challenges and the changes in other indexes of asthma severity. All analyses were carried out using SPSS for Windows 9.0 (SPSS; Chicago, IL).
Results
Inhaled budesonide decreased the sum symptom score, the frequency of each symptom, daily use of bronchodilating drugs (Fig 1), and diurnal PEF variation but did not change FEV1 percentage of predicted significantly. Figure 2 shows the superior sensitivity of diurnal PEF variation over single measurements of FEV1 in demonstrating the effect of budesonide in asthma. Table 2 describes the responsiveness of the patients to the bronchial challenges at various stages of the study. Fourteen of the 17 patients (82%) who were mannitol responsive initially became unresponsive at some stage of the study; these figures were 8 of 17 patients (47%) for histamine and 6 of 7 patients (86%) for cold air challenges. Budesonide significantly decreased mannitol (p = 0.005) and histamine (p = 0.002) RDR values (Fig 3). Budesonide-induced change in RDR values did not differ significantly between mannitol and budesonide challenges. In addition, budesonide significantly decreased the fixed-dose responses to mannitol (p = 0.035) and histamine (p = 0.009), but its effect on cold air responses did not reach statistical significance (p = 0.064; Fig 4).
After 3 months of treatment with budesonide, the correlations between changes in responsiveness to the provocation tests were weak (Table 3); after 6 months of treatment, the changes in responsiveness to all tests correlated significantly. The correlation was especially close between the changes in mannitol RDR and histamine RDR values at 6 months of treatment.