Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma?

Overview

Journal Drugs

Specialty Pharmacology

Date 2023 Jun 11

PMID 37303017

Authors

Mario Cazzola

Paola Rogliani

Maria Gabriella Matera

Affiliations

Soon will be listed here.

Abstract

A growing number of clinical trials are documenting that adding a long-acting muscarinic antagonist (LAMA) to established asthma treatment with an inhaled corticosteroid (ICS) and a long-acting β-agonist (LABA) is a treatment option that improves the health of patients with uncontrolled severe asthma even when therapy is optimized. These favorable results are the reason why the leading guidelines recommend triple therapy with ICS + LABA + LAMA in patients with asthma uncontrolled by medium- to high-dose ICS-LABA. However, we suggest adding LAMAs to ICS-LABAs at an earlier clinical stage. Such action could positively influence airflow limitation, exacerbations, and eosinophilic inflammation, conditions that are associated with acetylcholine (ACh) activity. It could also interrupt the vicious cycle related to a continuous release of ACh leading to the progressive expansion of neuronal plasticity resulting in small airway dysfunction. The utility of an earlier use of triple therapy in asthma should, in any case, be confirmed by statistically powered trials.

Citing Articles

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro.

Matera M, Rinaldi B, Calabrese C, Belardo C, Calzetta L, Cazzola M Respir Res. 2024; 25(1):104.

PMID: 38419021 PMC: 10902985. DOI: 10.1186/s12931-024-02710-8.

References

Cazzola M, Page C, Calzetta L, Matera M . Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012; 64(3):450-504. DOI: 10.1124/pr.111.004580. View

Matera M, Page C, Calzetta L, Rogliani P, Cazzola M . Pharmacology and Therapeutics of Bronchodilators Revisited. Pharmacol Rev. 2019; 72(1):218-252. DOI: 10.1124/pr.119.018150. View

Cazzola M, Rogliani P, Matera M . The latest on the role of LAMAs in asthma. J Allergy Clin Immunol. 2020; 146(6):1288-1291. DOI: 10.1016/j.jaci.2020.06.014. View

Cazzola M, Centanni S, Donner C . Anticholinergic agents. Pulm Pharmacol Ther. 1999; 11(5-6):381-92. View

Barnes P . Airway inflammation and autonomic control. Eur J Respir Dis Suppl. 1986; 147:80-7. View

Westby M, Benson M, Gibson P . Anticholinergic agents for chronic asthma in adults. Cochrane Database Syst Rev. 2004; (3):CD003269. PMC: 6483359. DOI: 10.1002/14651858.CD003269.pub2. View

Gross N . Anticholinergic agents in asthma and COPD. Eur J Pharmacol. 2006; 533(1-3):36-9. DOI: 10.1016/j.ejphar.2005.12.072. View

Kageyama N, Igarashi A, Ichinose M, Miura M, Yamauchi H, Tomaki M . Chronic allergen exposure enhances cholinergic neurotransmission in sensitized guinea-pigs. Eur Respir J. 1995; 8(5):752-4. View

Pieper M . The non-neuronal cholinergic system as novel drug target in the airways. Life Sci. 2012; 91(21-22):1113-8. DOI: 10.1016/j.lfs.2012.08.030. View

10.

Verbout N, Lorton J, Jacoby D, Fryer A . Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2007; 292(5):L1126-35. DOI: 10.1152/ajplung.00455.2006. View

11.

Kistemaker L, Prakash Y . Airway Innervation and Plasticity in Asthma. Physiology (Bethesda). 2019; 34(4):283-298. PMC: 6863372. DOI: 10.1152/physiol.00050.2018. View

12.

Coulson F, Fryer A . Muscarinic acetylcholine receptors and airway diseases. Pharmacol Ther. 2003; 98(1):59-69. DOI: 10.1016/s0163-7258(03)00004-4. View

13.

Kistemaker L, Gosens R . Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci. 2014; 36(3):164-71. DOI: 10.1016/j.tips.2014.11.005. View

14.

Gosens R, Gross N . The mode of action of anticholinergics in asthma. Eur Respir J. 2018; 52(4). PMC: 6340638. DOI: 10.1183/13993003.01247-2017. View

15.

Cazzola M, Ora J, Rogliani P, Matera M . Role of muscarinic antagonists in asthma therapy. Expert Rev Respir Med. 2017; 11(3):239-253. DOI: 10.1080/17476348.2017.1289844. View

17.

Cazzola M, Calzetta L, Matera M . Long-acting muscarinic antagonists and small airways in asthma: Which link?. Allergy. 2021; 76(7):1990-2001. DOI: 10.1111/all.14766. View

18.

Haag S, Matthiesen S, Juergens U, Racke K . Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J. 2008; 32(3):555-62. DOI: 10.1183/09031936.00129307. View

19.

Milara J, Serrano A, Peiro T, Artigues E, Gavalda A, Miralpeix M . Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition. Eur Respir J. 2012; 41(6):1264-74. DOI: 10.1183/09031936.00017712. View

20.

Matera M, Rinaldi B, Berardo C, Rinaldi M, Cazzola M . A review of the pharmacokinetics of M muscarinic receptor antagonists used for the treatment of asthma. Expert Opin Drug Metab Toxicol. 2020; 16(2):143-148. DOI: 10.1080/17425255.2020.1716730. View

21.

Cazzola M, Calzetta L, Rogliani P, Puxeddu E, Facciolo F, Matera M . Interaction between corticosteroids and muscarinic antagonists in human airways. Pulm Pharmacol Ther. 2015; 36:1-9. DOI: 10.1016/j.pupt.2015.11.004. View