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Background: Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. Aim: To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. Methods: After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 lg daily or fluticasone propionate/ salmeterol (FP/S) 500/100 lg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Results: Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV1) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV1 in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD20FEV1 Mch improved significantly from 90.42 (±30.08) lg to 432.41 (±122.71) lg in the BDP/ F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN2 test parameters. Conclusion: The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN2 tests.

Background: Several in vitro studies demonstrate that corticosteroids and long-acting β2 agonists may have a complementary and synergistic mode of action on the inflammatory processes in asthma. Methods: Sputum was induced in 20 mild to moderate asthmatic patients and the induced sputum cells (ISC) were cultured with beclomethasone dipropionate (BDP) 10−7 M, salbutamol 10−8 M and formoterol 10−8 M either alone or in combination, BDP plus salbutamol and BDP plus formoterol, for 24 h. We measured the levels of growth macrophages-colony stimulating factor (GM-CSF), released on activation normal T cells expressed and activated (RANTES) and interleukin-8 (IL-8), in the supernatant of stimulated cells by ELISA. Furthermore, we assessed nuclear translocation of glucocorticoid receptor (GR) and the expression of β2 receptor in ISC by immunofluorescence and RT-PCR, respectively. Results: The release of GM-CSF, RANTES and IL-8 in ISC was significantly reduced by BDP plus salbutamol or formoterol as compared with either drug alone (P