Indacaterol, glycopyrronium, and mometasone: Pharmacological interaction and anti-inflammatory profile in hyperresponsive airways

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

“…The regulation of airway inflammation by muscarinic receptors is further corroborated by findings reporting that in human bronchi, especially at the level of small airways, non-neuronal ACh is extensively released by resident cells such as epithelial cells in response to inflammatory stimulation [ 12 , 13 , 14 ]. Interestingly, the activation of muscarinic receptors expressed on epithelium in small airways induces the release of chemotactic factors and the consequent migration of eosinophils, monocytes and neutrophils into the bronchial tissue [ 10 ].…”

Clinical Interpretation of Efficacy Outcomes in Pharmacological Studies on Triple Fixed-Dose Combination Therapy for Uncontrolled Asthma: Assessment of IRIDIUM and ARGON Studies

“…Finally, but not less important, a balanced triple MF/IND/GLY FDC with MD ICS resulted as effective as HD-MF/IND in preventing moderate or severe exacerbations, 5,8 a phenomenon that was detected also against the increased contractile tone of human hyperresponsive bronchi and airway inflammation. 17 Thus, triple ICS/LABA/LAMA FDCs with moderate ICS dose should be considered for the treatment not only of uncontrolled asthma but also for those patients suffering from less severe forms of disease with airflow limitation as well as a possible as-needed therapeutic option.…”

Potential Drawbacks of ICS/LABA/LAMA Triple Fixed-Dose Combination Therapy in the Treatment of Asthma: A Quantitative Synthesis of Safety Profile

“…We should consider the opportunity of shifting from high-dose ICS/LABA to medium-dose ICS/LABA/LAMA in patients with airflow obstruction and few exacerbations, as well as the option of de-escalating the ICS dose in the triple FDC according to the patient’s clinical response to therapy. 2 …”

“…The current Global Initiative for Asthma (GINA, 2021) 1 recommendations suggest to administer as-needed low dose inhaled corticosteroid (ICS)/formoterol fixed-dose combination (FDC) as preferred controller treatment at asthma Step 1 and 2, and low dose maintenance ICS/formoterol FDC as preferred controller treatment at asthma Step 3 in adults and adolescents. 2 The GINA document also recommends to administer ICS/long-acting β 2 -adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) FDC as controller option at asthma Step 4 and as preferred treatment at add on asthma Step 5 in adults and adolescents. 2 Effectively, the co-primary endpoints of a large quantitative synthesis of data from randomized controlled trials (RCTs) indicated that triple FDC was significantly effective in preventing the risk of moderate to severe exacerbation and improving lung function.…”

“… 2 The GINA document also recommends to administer ICS/long-acting β 2 -adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) FDC as controller option at asthma Step 4 and as preferred treatment at add on asthma Step 5 in adults and adolescents. 2 Effectively, the co-primary endpoints of a large quantitative synthesis of data from randomized controlled trials (RCTs) indicated that triple FDC was significantly effective in preventing the risk of moderate to severe exacerbation and improving lung function. 3 These data were confirmed also by the clinical interpretation of efficacy outcomes in pharmacological studies on triple FDC for uncontrolled asthma, reporting that ICS/LABA/LAMA FDC reached the minimal clinically important difference for the risk of exacerbation, lung function, asthma control, and quality of life not only when compared to ICS/LABA FDC, but often also vs the free triple combination of fluticasone/salmeterol plus tiotropium where the ICS was administered at high dose.…”