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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\u2010synaptically on airway smooth muscle (ASM). In small airways, M<jats:sub>3<\/jats:sub> mAChRs are expressed, but there is no vagal innervation. Non\u2010neuronal ACh released from the epithelial cells that may express choline acetyltransferase in response to inflammatory stimuli, as well as from other structural cells in the airways, including fibroblasts and mast cells, can activate mAChRs. By antagonizing M<jats:sub>3<\/jats:sub> mAChR, the contraction of the ASM is prevented and, potentially, local inflammation can be reduced and the progression of remodeling may be averted. 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\u2010acting 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. Further studies are needed to differentiate broncholytic and anti\u2010inflammatory effects of LAMAs and to better understand the interaction between LAMAs and corticosteroids, also in the context of a triple therapy that includes a \u03b2<jats:sub>2<\/jats:sub>\u2010AR agonist, at different levels of the bronchial tree.<\/jats:p>","DOI":"10.1111\/all.14766","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T04:14:59Z","timestamp":1612930499000},"page":"1990-2001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Long\u2010acting muscarinic antagonists and small airways in asthma: Which link?"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-9707","authenticated-orcid":false,"given":"Mario","family":"Cazzola","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d Rome 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