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Dose-Response Relationship and Reproducibility of the Fall in Exhaled Nitric Oxide After Inhaled Beclomethasone Dipropionate Therapy in Asthma Patients: ResultsA

Dose-Response Relationship and Reproducibility of the Fall in Exhaled Nitric Oxide After Inhaled Beclomethasone Dipropionate Therapy in Asthma PatientsStudy A: Dose-Response Study
Baseline Characteristics: Fifteen subjects were recruited to the study. Geometric mean (95% confidence limit [CL]) baseline measurements were as follows: Feno, 103.5 ppb (78.5 to 136.7); PC20, 0.01 mg/mL (0.00 to 0.19); mean ± SD FEV1 and FVC at baseline were 3.01 ± 0.73 L (83.5 ± 16.6% predicted) and 4.49 ± 0.97 L (103.4 ± 12.2% predicted), respectively.
The Dose Response of the Fall in Feno: The general model showed that the test for treatment differences in Feno was highly significant, indicating that at least two of the treatment means differed (p < 0.001). The summarized results are shown in Table 1 and are depicted in Figure 1. There was no significant change between Feno at baseline and after 1 week of placebo inhaler treatment. There was a progressive fall in Feno as the dose of iBDP was increased, and all doses of iBDP were associated with a significant change in Feno from baseline and placebo values, even after correcting for multiple comparisons. Feno with 100 pg of iBDP was significantly different from 800 pg, but no significant differences were seen between the 100-pg and 400-pg doses or between the 400-pg and 800-pg doses. tadanafil

The Dose Response in High- and Low-Feno Groups: A post hoc inspection separated subjects into those with baseline Feno of 60 to 100 ppb (n = 6) and > 100 ppb (n = 9), on the assumption that airway inflammation would be mild to moderate and moderate to severe in these two groups, respectively. Figure 1 shows the Feno responses of the entire cohort and the two subgroups. In descriptive terms, the Iow-Feno group showed a modest fall in Feno with 100 pg/d, but no further decline in Feno as the dose of iBDP was increased. The high-FENO group showed a progressive fall in Feno at each dose level, eventually reaching a similar level of Feno as the low-FENO group. Statistical analysis was not applied here due to small sample sizes.
The Dose Response in PC20: The general model showed that the test for treatment differences in PC20 was highly significant, indicating that at least two of the treatment means differed (p = 0.002). The summarized results are shown in Table 1 and are depicted in Figure 2. There was no significant change between PC20 at baseline and after 1 week of placebo inhaler treatment. However, all doses of iBDP were associated with a significant change in PC20 from baseline and placebo values even after correcting for multiple comparisons (Table 1). No significant differences were seen for PC20 between 100 ^g/d and 400 ^g/d (p = 0.485), between 100 ^g/d and 800 ^g/d (p = 0.451), or between 400 ^g/d and 800 ^g/d (p = 0.977) of iBDP.
The Dose Response in PC20 According to Baseline Feno: A post hoc inspection separated subjects into those with baseline Feno of 60 to 100 ppb (n = 6) and > 100 ppb (n = 9), on the assumption that airway inflammation would be mild to moderate and moderate to severe in these two groups, respectively. Figure 2 shows the PC20 responses of the entire cohort and the two subgroups. In descriptive terms, the PC20 response in the Iow-Feno group showed a progressive increase as the dose of iBDP rose. However, the PC20 response of the high-FENO group showed no change as the iBDP dose increased. Statistical analysis was not applied here due to small sample size.
The Dose Response of the Change in FEV1: The general model showed that the test for treatment differences in FEV1 was highly significant, indicating that at least two of the treatment means differed (p < 0.001). The summarized results are shown in Table 1 and Figure 3. There was no significant change between FEV1 at baseline and after 1 week of placebo inhaler treatment. However, all doses of iBDP were associated with a significant change in FEV1 from placebo and baseline values after correcting for multiple comparisons, except for the 100-^g dose compared to baseline. No significant differences were seen for FEV1 between any of the doses of iBDP. For FVC, there were no significant differences between any of the treatment levels, compared with baseline or placebo.
Fig1
Figure 1. Dose-response study: the change in Feno at each visit corresponding to baseline, placebo treatment, and then increasing doses of iBDP. The Feno trend for all the subjects (n = 15) is shown together with separate trends for high-baseline (n = 6) and low-baseline (n = 9) Feno groups. Feno at all doses of iBDP was significantly different from placebo treatment, but only Feno levels with 100 ^g/d and 800 ^g/d of iBDP were significantly different.
Fig2
Figure 2. Dose-response study: the change in PC20 at each dose level of iBDP. The PC20 trend for all the subjects (n = 15) is shown together with separate trends for high-baseline (n = 6) and low-baseline (n = 9) Feno groups. PC20 at all doses of iBDP was significantly different from placebo treatment, but PC20 values were not different among any of the three active medication doses.
Fig3
Figure 3. Dose-response study: the change in FEV1 at each dose level of iBDP for the entire cohort. FEV1 at all doses of iBDP was significantly different from placebo treatment, but FEV1 values were not different among any of the three active medication doses.
Table 1—Dose-Response Study: the Change in Feno, PC20, and Spirometry During the Study

Visit
Variables 1 2 3 4 5
iBDP, |xg/d Feno, ppb PC20, mg/mLfev1, l fvc, l 103.5 (78.5-136.7) 0.01 (0.00-0.19) 3.10 ± 0.73 4.49 ± 0.97 Placebo 96.0 (67.9-135.6) 0.02 (0.00-0.52) 3.00 ± 0.84 4.42 ± 0.93 10059.0 (41.3-84.2)t 0.09 (0.00-3.22)§ 3.29 ± 0.71| 4.61 ± 0.84 40045.2 (35.7-57.2)| 0.31 (0.00-20.2)| 3.36 ± 0.73# 4.54 ± 0.84 80037.4 (29.1-48.0)| 0.48 (0.01-28.1)** 3.41 ± 0.80J 4.60 ± 0.80