Beclomethasone dipropionate and formoterol fumarate synergistically interact in hyperresponsive medium bronchi and small airways

Respiratory Research

Francesco Facciolo¹  Maria Gabriella Matera²  Mario Cazzola³  Paola Rogliani³  Luigino Calzetta³ 

[1] Thoracic Surgery Unit, “Regina Elena” National Cancer Institute;Unit of Pharmacology, Department of Experimental Medicine, University of Campania Luigi Vanvitelli;Unit of Respiratory Medicine, Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”;

关键词: ICS/LABA FDC;    Asthma;    Interaction;    Medium bronchi;    Small airways;   

DOI  :  10.1186/s12931-018-0770-7

来源: DOAJ

【 摘 要 】

Abstract Background Corticosteroids increase the expression of β2-adrenoceptors (β2-ARs) and protect them against down-regulation. Conversely, β2-AR agonists improve the anti-inflammatory action of corticosteroids. Nevertheless, it is still uncertain whether adding a long-acting β2-AR agonist (LABA) to an inhaled corticosteroid (ICS) results in an additive effect, or there is true synergy. Therefore, the aim of this study was to pharmacologically characterize the interaction between the ICS beclomethasone diproprionate (BDP) and the LABA formoterol fumarate (FF) in a validated human ex vivo model of bronchial asthma. Methods Human medium and small airways were stimulated by histamine and treated with different concentrations of BDP and FF, administered alone and in combination at concentration-ratio reproducing ex vivo that of the currently available fixed-dose combination (FDC; BDP/FF 100:6 combination-ratio). Experiments were performed in non-sensitized (NS) and passively sensitized (PS) airways. The pharmacological interaction was assessed by using Bliss Independence and Unified Theory equations. Results BDP/FF synergistically increased the overall bronchorelaxation in NS and PS airways (+ 15.15% ± 4.02%; P < 0.05 vs. additive effect). At low-to-medium concentrations the synergistic interaction was greater in PS than in NS bronchioles (+ 16.68% ± 3.02% and + 7.27% ± 3.05%, respectively). In PS small airways a very strong synergistic interaction (Combination Index: 0.08; + 20.04% ± 2.18% vs. additive effect) was detected for the total concentrations of BDP/FF combination corresponding to 10.6 ng/ml. Conclusion BDP/FF combination synergistically relaxed human bronchi; the extent of such an interaction was very strong at low-to-medium concentrations in PS small airways. Trial registration Not applicable.

【 授权许可】

Unknown