New perspectives on the role of muscarinic antagonists in asthma therapy

ABSTRACT

Introduction

There is increasing evidence that tiotropium, a long-acting muscarinic agent (LAMA), is useful in the presence of severe-uncontrolled asthma despite the optimization of therapy with inhaled corticosteroids (ICSs) and long-acting β₂ agonists (LABAs) as recommended by the current guidelines. Furthermore, in recent years there have been several  preclinical and clinical studies on the pharmacological and therapeutic impact of other LAMAs in asthma.

Areas covered

We have conducted an extensive search on muscarinic antagonists in asthma therapy throughout several sources and discuss what has emerged in the last 3 years (January 2017-March 2020).

Expert opinion

New evidence indicates that the effectiveness of adding a LAMA, at least tiotropium, is independent of the degree of the type 2 inflammation and age of patient. Therefore, tiotropium can be administered without the need for patient phenotyping. Umeclidinium and glycopyrronium also appear effective in asthma. Initial treatment with LAMA+ICS for those with mild asthma may be an equally effective therapeutic option as LABA+ICS but this hypothesis should be confirmed by statistically powered trials.

KEYWORDS:

• Asthma
• glycopyrronium
• tiotropium
• umeclidinium
• triple therapy

Article highlights

• Cholinergic tone is increased in asthma. An increased cholinergic tone could play a prevalent role in triggering bronchospasm in comparison to other well-known factors such as inhalation of allergens/air pollutants, virus infections, exercise, etc.

• The increased vagal activity brought on by increased acetylcholine signaling, and consequent occurrence of neuronal plasticity may be an essential reason why chronic therapy with muscarinic antagonists may play a critical role in treating asthma. By targeting muscarinic receptors, LAMAs may block, or at least reduce, the development of neuronal plasticity, in addition to their fundamental bronchodilator activity.

• There is solid documentation showing that in children, adolescents and adults the addition of tiotropium is useful in the treatment of severe asthma that remains uncontrolled despite the optimal therapy with ICSs and LABAs as recommended by the current guidelines.

• Emerging evidence suggests that the effectiveness of adding a LAMA, at least tiotropium, is independent of the degree of the type 2 inflammation.

• Information on the effects of umeclidinium and glycopyrronium in asthma is increasing, although several studies are more focused on evaluating the presence of these LAMAs in triple-fixed dose combinations that also include a LABA and an ICS. There are no clinical trials currently investigating the effect of aclidinium, another LAMA approved for COPD, in patients with asthma.

• Initial treatment with LAMA+ICS for those with mild asthma may be an equally effective therapeutic option as LABA+ICS but this hypothesis should be confirmed by statistically powered trials.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has received fees for conferences, research grants, as a consultant and to support attendance at conferences of various pharmaceutical companies, such as GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Mundipharma, Menarini, Pfizer, Novartis, Esteve, Teva Pharmaceutical, Ferrer, Rovi, Roche, Astra Zeneca, Bial, Actelion, Alter, CSL Behring, Faes Farma and Gebro Pharma. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

The paper was not funded.