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 (FENO) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the FENO 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 microg/d of iBDP; period 3, 400 microg/D of iBDP; and period 4, 800 microg/d of iBDP. Spirometry, FENO, 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 microg/d of iBDP for 14 days (period 2), washout on placebo treatment until the FENO was within 15% of baseline (period 3), and 200 microg/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). FENO 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 FENO from placebo treatment, but with significant separation of only the 100-microg and 800-microg doses by FENO. 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: FENO fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between FENO in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220).

CONCLUSIONS

FENO was superior to FEV(1) and PC(20) in separating doses of iBDP. The fall in FENO after two identical administrations of iBDP separated by placebo washout was highly reproducible.