@article {Calzetta210196, author = {Luigino Calzetta and Beatrice Ludovica Ritondo and Maria Cristina Zappa and Gian Marco Manzetti and Andrea Perduno and Janis Shute and Paola Rogliani}, title = {The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review}, volume = {31}, number = {164}, elocation-id = {210196}, year = {2022}, doi = {10.1183/16000617.0196-2021}, publisher = {European Respiratory Society}, abstract = {Patients suffering from chronic obstructive pulmonary disease (COPD) clinically manifest airway mucus hypersecretion as sputum expectoration and cough. Evidence accumulated in the past decade has shown that the cholinergic system not only regulates airway smooth muscle contraction but also the activity of inflammatory and airway epithelial cells, including goblet cells, and submucosal gland activity. Long-acting muscarinic antagonists (LAMAs) with the most favourable M3/M2 muscarinic acetylcholine (ACh) receptors residency properties are not only excellent bronchodilators but potentially also mucus-modifying agents, able to positively impact on mucus hypersecretion and cough. The aim of this systematic review was to investigate the impact of LAMAs on mucus hypersecretion and cough in COPD patients. The evidence confirmed that LAMAs, mainly tiotropium and aclidinium, improved sputum production and cough in moderate to severe COPD. Thus, LAMAs not only antagonise the ACh-induced bronchoconstriction of the airways but also appear to limit the production of mucus secreted in response to ACh by airway goblet cells and/or submucosal glands. Further clinical studies are necessary to evaluate the impact of LAMAs exclusively on sputum symptoms and cough as primary end-points and to investigate whether LAMAs have a modulatory action on the rheological properties of mucus.This systematic review provides evidence that LAMAs, mainly tiotropium and aclidinium, have a beneficial impact on mucus hypersecretion and mucociliary clearance, with consequent improvement of sputum production and cough in moderate to severe COPD. https://bit.ly/3wHXZiZ}, issn = {0905-9180}, URL = {https://err.ersjournals.com/content/31/164/210196}, eprint = {https://err.ersjournals.com/content/31/164/210196.full.pdf}, journal = {European Respiratory Review} }