The mode of action of anticholinergics in asthma

Abstract

Acetylcholine binds to muscarinic receptors to play a key role in the pathophysiology of asthma, leading to bronchoconstriction, increased mucus secretion, inflammation and airway remodelling. Anticholinergics are muscarinic receptor antagonists that are used in the treatment of chronic obstructive pulmonary disease and asthma. Recent in vivo and in vitro data have increased our understanding of how acetylcholine contributes to the disease manifestations of asthma, as well as elucidating the mechanism of action of anticholinergics. This review assesses the latest literature on acetylcholine in asthma pathophysiology, with a closer look at its role in airway inflammation and remodelling. New insights into the mechanism of action of anticholinergics, their effects on airway remodelling, and a review of the efficacy and safety of long-acting anticholinergics in asthma treatment will also be covered, including a summary of the latest clinical trial data.

FIGURE 1

A summary of the role of acetylcholine in asthma pathophysiology. Acetylcholine is the predominant parasympathetic neurotransmitter in the airways. It is released from airway neurons and non-neuronal cells, such as airway epithelial cells, and binds to muscarinic M₁, M₂ and M₃ receptors. These receptors are found on airway epithelial cells, smooth muscle cells and submucosal glands. Binding of acetylcholine to the muscarinic receptors triggers a host of downstream effects associated with the pathophysiology of asthma.