Beclomethasone, formoterol and glycopyrronium: synergy of dual and triple combinations in an ex vivo model of COPD exacerbation

Abstract

<b>Background:</b> Beclomethasone (BDP)/formoterol (FF) and BDP/FF/glycopyrronium (GB) combinations synergistically relax human isolated bronchi [1], but no data are available on their interaction in hyperresponsive COPD airways. <b>Aims and objectives:</b> To pharmacologically characterized the interaction across BDP, FF, and GB administered as dual and triple combinations in an ex vivo model of COPD exacerbation. <b>Methods:</b> Human bronchi and small airways from COPD donors were challenged 2 h with lipopolysaccharide (LPS) 300 ng/ml. BDP, FF, and GB were administered alone and as dual and triple combinations (BDP/FF, BDP/FF/GB). The effect was tested on the sub-maximal tone induced by carbachol. The delta effect vs. the additive expected effect assessed via Bliss Independence equation was reported. <b>Results:</b> BDP, FF, and GB administered as dual (Figure 1a and c) or triple (Figure 1b and d) combinations elicited a significant (P&lt;0.05) synergistic bronchorelaxant effect when compared with the expected effect in both medium bronchi (Figure 1a and b) and small airways (Figure 1c and d). <b>Conclusion:</b> BDP/FF 100:6 and BDP/FF/GB 100:6:12.5 synergistically interact in hyperresponsive medium bronchi and small airways from COPD donors. The greater effect of triple compared to dual combination supports the clinical benefit of BDP/FF/GB in preventing COPD exacerbation. 1. Rogliani et al. Br J Pharmacol 2020, 177:1150-1163