Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment

Abstract

Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks. Methods: Twenty six asthmatic patients aged 21-59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV 1 ) by 15% (PD 15 FEV 1 ) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD 15 FEV 1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves. Results: The increase in PD 15 FEV 1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD 15 FEV 1 was 1.85-2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment. Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.

Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐moderate persistent asthma

“…The present results showed no significant difference between once daily CIC and twice daily FP in mild-tomoderate persistent asthmatics for the primary outcome of methacholine hyper-responsiveness, amounting to a mean difference of 0.4 dd in PC 20 . This was also the case, when comparing the two treatments according to the sequence in which they were given.…”

“…The lack of difference between treatments was also evident when inspecting the individual data for the primary outcome, as seen in Figure 2. Our study was powered to detect a 1 dd difference in methacholine PC 20 , as this is the magnitude of shift which was considered as being clinically relevant. There were also no significant differences between the two drugs for any of the secondary outcomes as change from baseline, irrespective or respective of sequence.…”

“…Mean values for PC 20 as change from baseline, irrespective of sequence, showed a significant within treatment response for FP but not CIC, as indicated by the within treatment CI which excluded the zero value (Table 4). For mean PC 20 as change from baseline according to sequence, CIC given first showed a significant within treatment response, as indicated by the CI which excluded the zero value, while for CIC given second, or FP given first or second, the CIs included the zero value, indicating a nonsignificant within treatment response ( Table 5).…”

“…Mean There were no significant differences for comparisons between baselines in sequence irrespective of randomized treatments. Data for methacholine PC 20 are given in geometric means. There were no significant differences for comparisons between randomized treatments.…”

“…For mean PC 20 as change from baseline according to sequence, CIC given first showed a significant within treatment response, as indicated by the CI which excluded the zero value, while for CIC given second, or FP given first or second, the CIs included the zero value, indicating a nonsignificant within treatment response ( Table 5). Inspection of individual data for PC 20 …”