Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: A pilot study

Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but ther e are few studies evaluating their safety in young children. We, therefore, prospectively administered beclomethasone diproprionate (BDP) to 12 clinic ally stable young children with CF to examine the safety of this therapy wi th respect to adrenal suppression and airway infection. To determine potent ial mechanisms of corticosteroid action in CF, we also examined airway mark ers of inflammation before and after inhaled steroid treatment. BDP 210 mug twice a day was given via spacer for 2 months. Twelve-hour serum and urine cortisols and response to low-dose synthetic ACTH cortisol stimulation wer e assessed. Bronchoalveolar lavage fluid (BALF) was examined pre- and postt reatment with BDP by quantitative bacteriology and indices of airway inflam mation, including levels of total neutrophils, neutrophil elastase-alpha -1 antiprotease complexes (NEAP), CA 19-9 mucin-associated antigen, interleuk in-8 (IL-8), and macrophage IL-8 mRNA. Following 2 months of treatment, serum and urine cortisol levels were uncha nged. Response to low-dose ACTH cortisol stimulation was not significantly decreased at 30 min. Posttreatment BALF bacteria[ density was not statistic ally different from pretreatment; however, one patient who was initially cu lture negative became culture-positive with Hemophilus influenzae. BALF tot al neutrophil counts, corrected for epithelial lining fluid dilution, were decreased to approximately one third of pretreatment values (P=0.03). NEAP and CA 19-9 mucin-associated antigen demonstrated similar decreases. BALF I L-8 levels and macrophage IL-8 mRNA levels were not statistically changed. These findings suggest that treatment with BDP 420 mug per day for 2 months in young children with CF does not affect urine and blood cortisol, causes no decrease in adrenal reserve, and does not result in a clinically signif icant increase in airway infection. In addition, the fall in bronchoalveola r lavage fluid inflammatory markers following BDP suggests possible modulat ion of neutrophil influx into the CF airway and provides justification for further studies of inhaled corticosteroids in CF. (C) 2001 Wiley-Liss, Inc.