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Dose-Response Relationship and Reproducibility of the Fall in Exhaled Nitric Oxide After Inhaled Beclomethasone Dipropionate Therapy in Asthma Patients: Discussion2

There are few studies examining the dose response of inhaled corticosteroids on bronchial reactivity. In a three-parallel-dose group, double-blind, placebo-controlled, randomized, crossover study, with a washout period of 3 to 8 weeks, Taylor et al used adenosine-5′-monophosphate (AMP) to study the effect of 14 days of treatment with 100 mg/d, 400 mg/d, and 1,600 mg/d of the inhaled corticosteroid ciclesonide on airway responsiveness to AMP and inflammatory parameters in induced sputum. Compared with placebo, 100 mg/d, 400 ^g/d, and 1,600 ^g/d of ciclesonide reduced airway responsiveness to AMP by 1.6 (95% confidence interval [CI], — 0.1 to 3.4; not significant), 2.0 (95% CI, 0.4 to 3.6; p < 0.05), and 3.4 (95% CI, 2.3 to 4. 4; p < 0.05) doubling doses, respectively, and this was dose dependent (p = 0.039). A significant reduction in the percentage of eosinophils in induced sputum was observed after 400 ^g/d and 1,600 ^g of ciclesonide (p < 0. 05) but was not dose dependent. canadian health care mall

The short-term reproducibility of the depressant effect of 200 mg/d of iBDP on Feno shows that the effect is predictable and that in most subjects, cessation of inhaled steroid therapy results in return of Feno levels to baseline values within 1 week to 2 weeks. This also indicates that subjects tend to return to a certain level of Feno. Indeed, we have observed that subjects who return for different studies tend to have similar Feno levels each time, Three subjects, however, were withdrawn from the study as Feno remained depressed for up to 6 weeks, The factors determining this prolonged effect are unknown, Perhaps these subjects were not reexposed to an environmental allergen. Of great interest is the contrast between the changes in FEV1 and Feno. Feno reacted rapidly to the administration and withdrawal of medication, whereas FEV1 improved progressively throughout the study, Thus, these two parameters are temporally discordant and may be assessing different components of the asthmatic state.
In summary, Feno was superior to both FEV1 and PC20 in establishing a dose response for 100 mg/d and 800 g/d of iBDP, but was unable to separate 100 mg/d from 400 mg/d, and 400 mg/d from 800 mg/d. perhaps related to sample size, The effect of iBDP on Feno is highly reproducible in the short term, Exhaled NO monitoring may be useful in determining the minimal effective dose of inhaled steroids, perhaps only in those subjects who have a raised baseline Feno, and could also be used to compare the potencies of anti-inflammatory medications.