An update on long-acting muscarinic agents for asthma therapy

The manifestations of asthma are influenced by the dysfunction of the autonomic nervous system, which results in elevated vagal tone within the airways. Acetylcholine (ACh) plays a pivotal role in the pathophysiology of asthma through its interaction with muscarinic acetylcholine receptors (mAChRs). Consequently, using mAChR antagonists to counteract the actions of ACh is scientifically sound. This narrative review methodically examines the latest information on the mechanisms and evidence supporting the use of long-acting muscarinic antagonists (LAMAs) in asthma. Adding a LAMA to existing asthma treatments involving an ICS and a LABA, within a single inhaler triple therapy (SITT), improves lung function regulating airflow limitation, reduces exacerbations, and eosinophilic inflammation and offers a more comprehensive approach to managing inflammation and tissue remodeling, which are linked to ACh. Additionally, it disrupts the vicious cycle of ACh release that contributes to neuronal plasticity and dysfunction of small airways. Identifying treatable traits is key to using SITT in a customized way that aligns with patients' needs. The 5T (Triple Therapy Targeting Treatable Traits) approach proposes the utilization of SITT for all asthma cases, not solely severe ones, and involves using LAMAs in ICS/LABA combinations earlier than current guidelines recommend.