Assessment of inhaled BDP-dose dependency of exhaled nitric oxide and local and serum eosinophilic markers in steroids-naive nonatopic asthmatics

ABSTRACT

The aim of the present study was to assess the dose-dependency from inhaled steroids of changes of airways inflammation [eosinophils count and eosinophil cationic protein (ECP)] measures in induced sputum and in serum, as well as that of exhaled nitric oxide. Twenty steroid-naive patients with nonatopic asthma of mild to moderate degree [forced expiratory volume in 1 s (FEV₁) = 70% of predicted] and with negative response to the standard tests for allergy were selected; after a 1-week run-in period they were randomized to receive a 12-week treatment period of inhaled beclomethasone dipropionate dry powder given with the Pulvinal® inhaler (Clenil P®, Chiesi Farmaceutici S.p.A., Parma, Italy) in two different dose regimens, 400 μg bid (high dose) or 200 μg bid (low dose), over a double blind, parallel groups design. The following outcome measures were assessed in baseline and after 1, 6 and 12 weeks of treatment: FEV₁ (l), eosinophils count in sputum (%), is ECP (μg/l), serum eosinophils count (%), serum ECP (μg/l) and exhaled NO (ppb). The results showed that all the considered parameters improved in both groups: the increase over baseline of FEV₁ and the decrease of NO were significant at any time in the high-dose group and only at week 12 in the low-dose group (NS between groups), whereas the markers of eosinophilic activity showed more consistent reductions in the high-dose than in the low-dose group when measured in induced sputum (P < 0.05 between groups after 6 and 12 weeks for eosinophils count and after 12 weeks for ECP). Decreases over baseline of markers measured in serum were more rapid in the high-dose group, without differences between groups. A marked trend towards a negative correlation was found between FEV₁ and ECP, (r = −0.72, P < 0.05), between FEV₁ and eosinophils in sputum (r = −0.31, NS) and between FEV₁ and exhaled NO (r = −0.38, NS), all of them only in the high-dose group. The results of the study demonstrate that changes of levels of eosinophilic activity in the airways are dependent from the daily dose of inhaled steroids when measured in induced sputum and that the local assessment can therefore represent a practical and noninvasive method to monitor the extent of airways inflammation.