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

Study objectives: The fractional concentration of exhaled nitric oxide (F eno ) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the F eno fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients. Study design: Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 μg/d of iBDP; period 3, 400 μg/D of iBDP; and period 4, 800 μg/d of iBDP. Spirometry, F eno , and provocative concentration of methacholine resulting in a 20% fall in FEV 1 (PC 20 ) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 μg/d of iBDP for 14 days (period 2), washout on placebo treatment until the F eno was within 15% of baseline (period 3), and 200 μg/d of iBDP for 14 days (period 4). Results: Study A: Mean FEV 1 rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV 1 rise compared to placebo treatment, but with no significant separation of doses using FEV 1 . F eno geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in F eno from placebo treatment, but with significant separation of only the 100-μg and 800-μg doses by F eno . Geometric mean (95% confidence limits) PC 20 rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC 20 from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC 20 . Study B: F eno fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p eno in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220). Conclusions: F eno was superior to FEV 1 and PC 20 in separating doses of iBDP. The fall in F eno after two identical administrations of iBDP separated by placebo washout was highly reproducible.