ArticleRespiratory research2016
Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review.International journal of chronic obstructive pulmonary diseasePooled it
- The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026Review
- Effects of Inhaled Corticosteroids and Long-Acting β2-Agonists on Efferocytosis and Inflammatory Cell Survival: An In Vitro Study Relevant to COPD and Lung Cancer.International journal of molecular sciences · 2026Article
- The Role of the Acetylcholine System in Common Respiratory Diseases and COVID-19.Molecules (Basel, Switzerland) · 2023Review
- The diversity of neuroimmune circuits controlling lung inflammation.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- Muscarinic receptor antagonists and airway inflammation: A systematic review on pharmacological models.Heliyon · 2022Review
- The pan-JAK inhibitor LAS194046 reduces neutrophil activation from severe asthma and COPD patients in vitro.Scientific reports · 2022Article
- Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease.Diagnostics (Basel, Switzerland) · 2021Review
- Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity.Frontiers in immunology · 2021Review
- Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Article
- The Cholinergic Pathways in Inflammation: A Potential Pharmacotherapeutic Target for COPD.Frontiers in pharmacology · 2018Review
- Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?Respiratory research · 2017Review
- Effects of Glutathione S-Transferase Gene Polymorphisms and Antioxidant Capacity per Unit Albumin on the Pathogenesis of Chronic Obstructive Pulmonary Disease.Oxidative medicine and cellular longevity · 2017Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect.
methodsHuman sputum and blood neutrophils were isolated from healthy individuals (n = 37), patients with stable COPD (n = 52) and those with exacerbated COPD (n = 16). The cells were incubated with corticosteroid fluticasone propionate (0.1 nM-1 μM), aclidinium bromide (0.1 nM-1 μM) or a combination thereof and stimulated with 1 μg of lipopolysaccharide/ml or 5 % cigarette smoke extract. Levels of the pro-inflammatory mediators interleukin-8, matrix metalloproteinase-9, CCL-5, granulocyte-macrophage colony-stimulating factor and interleukin-1β were measured and the mechanisms of corticosteroid resistance evaluated at the end of the incubation.
resultsThe non-neuronal cholinergic system was over-expressed in neutrophils from COPD patients, as evidenced by increases in the expression of muscarinic receptors (M2, M4 and M5), choline acetyltransferase and vesicular acetylcholine transporter. Aclidinium bromide demonstrated anti-inflammatory effects on neutrophils from COPD patients, reversing their resistance to corticosteroids. Additive effects of combined aclidinium bromide and fluticasone propionate in blocking M2 receptor levels, inhibiting phosphoinositide 3-kinase-δ and enhancing the glucocorticoid response element transcription factor were demonstrated and were accompanied by an increase in the corticosteroid-induced expression of anti-inflammatory-related genes.
conclusionsLAMAs potentiate the anti-inflammatory effects of corticosteroids in neutrophils from COPD patients in vitro, thus providing a scientific rationale for their use in combination with corticosteroids in the treatment of COPD.
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