The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper

Abstract

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti-inflammatory and anti-fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype-driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real-life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients. © 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.