Anti-inflammatory effect of anti-muscarinic antagonists

Anti-inflammatory effect of anti-muscarinic antagonists

Inhaled long-acting muscarinic antagonists (LAMA) are the cornerstone of COPD treatment. GINA guidelines also recommend tiotropium as an add-on treatment for steps 4-5 (mostly severe asthma). Importantly, new inhalers delivering simultaneously corticosteroids, long-acting beta2 agonists and LAMAs have recently received indication for both COPD and asthma (so-called triple therapy). LAMAs display a direct bronchodilatory effect through the inhibition of acethylcholine-mediated neurotransmission and the subsequent relaxation of airway smooth muscle cells. Nevertheless, accumulating evidence indicates that LAMAs also exert anti-inflammatory effects on the airway mucosa. The inhibition of acetylcholine signalling in both stromal (eg bronchial epithelial cells) and immune cells is associated with decreased expression of IL-1beta, IL-8 and other chemotactic factors for neutrophils. Moreover, some data also suggests that LAMAs inhibit the release of IL-5 and IL-13, which might counterbalance the inflammatory events of many asthma patients. Nevertheless, most data on the anti-inflammatory effect of LAMAs derive from cell lines or experimental COPD models and the majority of studies have been conducted with tiotropium. Therefore, there is a need to evaluate thoroughly the consistency and strength of their anti-inflammatory effect on asthma, and to identify research priorities on the topic (eg need to measure immune effect of the drug in humans and to investigate LAMAs other than tiotropium). In this task force we intend to conduct a systematic revision of the literature following an adequate methodology in order to clarify the effect of tiotropium and other LAMAs in asthma. Similarly, we will identify research priorities on the topic.

Chair: Ibon Eguiluz Gracia
Secretary: Ioana Agache