['Inhaled 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.', 'Human sputum and blood neutrophils were isolated from healthy individuals (n\u2009=\u200937), patients with stable COPD (n\u2009=\u200952) and those with exacerbated COPD (n\u2009=\u200916). The cells were incubated with corticosteroid fluticasone propionate (0.1 nM-1\xa0μM), aclidinium bromide (0.1 nM-1\xa0μM) or a combination thereof and stimulated with 1\xa0μg of lipopolysaccharide/ml or 5\xa0% 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.', 'The 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.'] Does non-neuronal cholinergic system contribute to corticosteroid resistance in chronic obstructive pulmonary disease patients?