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. 2022 May 4;31(164):210196.
doi: 10.1183/16000617.0196-2021. Print 2022 Jun 30.

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

Luigino Calzetta  1 , Beatrice Ludovica Ritondo  2 , Maria Cristina Zappa  3 , Gian Marco Manzetti  2 , Andrea Perduno  2 , Janis Shute  4 , Paola Rogliani  2
Affiliations

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

Luigino Calzetta et al. Eur Respir Rev. .

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.

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Conflict of interest statement

Conflict of interest: L. Calzetta reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, non-financial support from AstraZeneca, grants from Chiesi Farmaceutici, grants from Almirall, personal fees from ABC Farmaceutici, personal fees from Edmond Pharma, grants and personal fees from Zambon, personal fees from Verona Pharma, and personal fees from Ockham Biotech. Conflict of interest: B.L. Ritondo declares no conflict of interest. Conflict of interest: M.C. Zappa declares no conflict of interest. Conflict of interest: G.M. Manzetti. declares no conflict of interest. Conflict of interest: A. Perduno declares no conflict of interest. Conflict of interest: J. Shute is the Scientific Director of Ockham Biotech Ltd. Conflict of interest: P. Rogliani reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, personal fees from AstraZeneca, grants and personal fees from Chiesi Farmaceutici, grants and personal fees from Almirall, grants from Zambon, personal fees from Biofutura, personal fees from GlaxoSmithKline, personal fees from Menarini, and personal fees from Mundipharma.

Figures

FIGURE 1
FIGURE 1
Flow diagram for the identification of the clinical studies included in the systematic review.
FIGURE 2
FIGURE 2
a) Traffic light plot for assessment of the risk of bias of each included randomised controlled trial and b) weighted plot for the assessment of the overall risk of bias via the Cochrane Risk of Bias 2 tool (n=16 studies, from 16 records).
FIGURE 3
FIGURE 3
The beneficial effect of long-acting muscarinic antagonists (LAMAs) against mucus hypersecretion in large and medium bronchi, and in small airways when using inhaler devices effective at delivering the drug into the small airway compartment. ACh: acetylcholine; LAMA: long-acting muscarinic antagonist; mAChRs: M3 muscarinic ACh receptors.
See this image and copyright information in PMC

References

    1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) . Global Strategy for the Diagnosis, Management and Prevention of COPD. 2021. Available from: http://goldcopd.org/
    1. World Health Organization . COPD predicted to be third leading cause of death in 2030. 2008. Available from: www.who.int/gard/news_events/World_Health_Statistics_2008/en/
    1. Blanco I, Diego I, Bueno P, et al. . Geographic distribution of COPD prevalence in the world displayed by Geographic Information System maps. Eur Respir J 2019; 54: 1900610. doi:10.1183/13993003.00610-2019 - DOI - PubMed
    1. Shen Y, Huang S, Kang J, et al. . Management of airway mucus hypersecretion in chronic airway inflammatory disease: Chinese expert consensus (English edition). Int J COPD 2018; 13: 399–407. doi:10.2147/COPD.S144312 - DOI - PMC - PubMed
    1. Mijošek V, Lasitschka F, Warth A, et al. . Endoplasmic reticulum stress is a danger signal promoting innate inflammatory responses in bronchial epithelial cells. J Innate Immun 2016; 8: 464–478. doi:10.1159/000447668 - DOI - PMC - PubMed

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