Abstract
Involvement of small airways, those of less than 2 mm in internal
diameter, is present in all stages of asthma and contributes
substantially to the pathophysiologic expression of asthma. Therefore,
small airways are increasingly viewed as a potential target in optimal
asthma control. Airway tone, which is increased in asthma, is mainly
controlled by the vagus nerve that releases acetylcholine (ACh) and
activates muscarinic ACh receptors (mAChRs) post-synaptically on airway
smooth muscle (ASM). In small airways, M3 mAChRs are expressed, but
there is no vagal innervation. Non-neuronal ACh released from the
epithelial cells that may express choline acetyltransferase (ChAT) in
response to inflammatory stimuli, as well as from other structural cells
in the airways, including fibroblasts and mast cells, can activate these
receptors. By antagonizing M3 mAChR, the contraction of the ASM is
prevented and, potentially, local inflammation can be reduced and the
progression of remodeling may be affected. In fact, ACh also contributes
to inflammation and remodeling of the airways and regulates the growth
of ASM. Several experimental studies have demonstrated the potential
benefit derived from the use of mAChR antagonists, mainly long-acting
mAChR antagonists (LAMAs), on small airways in asthma. However, there
are several confounding factors that may cause a wrong estimation of the
relationship between LAMAs and small airways in asthma.