The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review

Abstract

Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.

Chronic Obstructive Pulmonary Disease: Epidemiology, Biomarkers, and Paving the Way to Lung Cancer

“…The components of non-neuronal cholinergic systems, i.e., acetylcholine and cholinergic receptors, can modulate airway inflammatory cells [171]. The anti-inflammatory and bronchodilator effects of long-acting muscarinic receptor antagonists (LAMAs), such as tiotropium, were recently reviewed [172]. Emphasizing the importance of research on the tumor microenvironment focusing on the immune system, immune checkpoint blockade has shown revolutionary therapeutic achievements.…”

Stem Cell-Based Regenerative Therapy and Derived Products in COPD: A Systematic Review and Meta-Analysis

“…Currently, available treatments are primarily directed at reducing symptoms of COPD and prevent the risk of future exacerbations [ 1 ]. Inhaled bronchodilators acting via different mechanisms of action remain the pharmacological mainstay for treating most COPD patients, either administered alone or in combination as dual therapy or as triple therapy with the addition of an inhaled corticosteroid (ICS) [ 1 , 8 , 9 ].…”

Muscarinic receptor antagonists and airway inflammation: A systematic review on pharmacological models

“…In asthma, LAMAs are indicated as alternative controller option to medium/high maintenance dose of ICS/LABA in Global Initiative for Asthma (GINA) Step 4 and as add-on therapy to high dose ICS/LABA as either a separate inhaler or a triple combination inhaler in GINA Step 5 [ 17 ]. Evidence coming from a recent systematic review supports the beneficial impact of muscarinic receptor antagonists and in particular LAMAs, against airway inflammation from bench-to-bedside, with a synthesis of results shown in Table 1 [ 18 ].…”

“…Evidence coming from a recent systematic review supports the beneficial impact of muscarinic receptor antagonists and in particular LAMAs, against airway inflammation from bench-to-bedside, with a synthesis of results shown in Table 1 [ 18 ].…”

“…Starting from our recently published systematic review [ 18 ], the aim of the present study was to systematically assess the currently employed pharmacological models used to study the impact of muscarinic receptor antagonists against airway inflammation and to give an insight on the current advances in preclinical respiratory research.…”