Indacaterol acetate, glycopyrronium bromide, and mometasone furoate: effect on neuronal inflammation and acetylcholine release

Background: The effect on neuronal inflammation and acetylcholine (ACh) release of LABA/ICS and LABA/LAMA/ICS combinations have been never investigated in asthma. Aims: To characterize the effect of combining indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF), the components in 2 recently approved asthma treatments, against neuronal inflammation and ACh release in an ex vivo model of asthma. Methods: Human isolated airways passively sensitized with serum of asthmatics donors were treated with either IND/MF, IND/GLY/MF, or placebo (positive control, C+). Tetanus toxin was used to block the neuronal release of ACh. The level of neurokinin A (NKA), substance P (SP) and ACh was assessed. Results: IND/MF (10/4.5 nM, 10/9 nM) and IND/GLY/MF (10/3.7/4.5 nM, 10/3.7/9 nM) reduced the levels of NKA (P<0.001 vs. C+). IND/MF (10/9 nM) and IND/GLY/MF (10/3.7/9 nM) inhibited the release of SP (P<0.05 vs. C+). All treatments prevented the release of ACh, only IND/GLY/MF (10/3.7/4.5 nM, 10/3.7/9 nM) inhibited the release of non-neuronal ACh (P<0.01 vs. C+). Results are shown in Figure 1 A-D. Conclusions: IND/MF and IND/GLY/MF combinations modulated neuronal inflammation in a synergistic manner, but only IND/GLY/MF combination reduced the release of non-neuronal ACh. These observations may explain the efficacy of IND/MF and IND/GLY/MF observed in clinical studies.