Background
Beclometasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) fixed-dose combination (FDC) is suggested by GINA 2022 to treat persistently uncontrolled asthma despite medium-dose (MD) or high-dose (HD) inhaled corticosteroid (ICS)/long-acting ?2-adrenoceptor agonist (LABA) FDC, but no recommendations on the level of ICS dose have been provided.
Aim
To assess whether the dose of BDP may modulate the efficacy of triple BDP/FF/GB FDC in reducing airway inflammation in an human ex vivo model of severe eosinophilic asthma.
Methods
Human isolated airways were passively sensitized overnight and then challenged 45 min with the platelet-activating factor (100 nM) to reproduce ex vivo the condition of airways of subjects suffering from severe eosinophilic asthma. Airways were pre-treated with MD-BDP/FF/GB 3/0.18/0.38 ng/ml and HD-BDP/FF/GB 6/0.18/0.38 ng/ml. Cytokines and neurokinins were quantified via ELISA kits.
Results
When compared to MD-BDP/FF/GB, HD-BDP/FF/GB reduced the release of IL-4 (-26.07±0.73%, P<0.001), IL-5 (-37.98±1.92%, P<0.001), IL-6 (-27.02±1.14%, P<0.01), IL-13 (-24.08±1.30%, P<0.01), IL-33 (-26.69±1.66%, P<0.01), TSLP (-28.16±3.04%, P<0.05), TNF-? (-19.22±0.06%, P<0.001), and NKA (-11.88±0.40%, P<0.05).
Conclusions
Higher BDP concentrations significantly improved the anti-inflammatory profile of BDP/FF/GB FDC, when compared to the FDC in which BDP was combined at lower concentrations. HD-BDP/FF/GP was more effective also against neurogenic inflammation. The possibility of modulating the dose of the ICS may help to reduce inflammation in human hyperresponsive bronchi and, thus, optimize the therapeutic profile of BDP/FF/GB FDC.