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Long-acting muscarinic antagonists and small airways: which link?
  • Mario Cazzola,
  • Luigino Calzetta,
  • Maria Gabriella Matera
Mario Cazzola
University of Rome Tor Vergata
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Luigino Calzetta
Università degli Studi di Parma
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Maria Gabriella Matera
Università degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia
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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.

Peer review status:ACCEPTED

18 Dec 2020Submitted to Allergy
21 Dec 2020Submission Checks Completed
21 Dec 2020Assigned to Editor
23 Dec 2020Reviewer(s) Assigned
10 Jan 2021Review(s) Completed, Editorial Evaluation Pending
10 Jan 2021Editorial Decision: Revise Minor
16 Jan 20211st Revision Received
19 Jan 2021Submission Checks Completed
19 Jan 2021Assigned to Editor
20 Jan 2021Reviewer(s) Assigned
25 Jan 2021Review(s) Completed, Editorial Evaluation Pending
26 Jan 20212nd Revision Received
01 Feb 2021Submission Checks Completed
01 Feb 2021Assigned to Editor
03 Feb 2021Review(s) Completed, Editorial Evaluation Pending
03 Feb 2021Editorial Decision: Accept