It is important to underline that the results of the different meta-analysis reported need to be taken with caution because of differences in the studied population and in the outcomes. Twice-daily LABAs are formoterol fumarate (FF) or propionate (FP) and salmeterol (SAL). The efficacy and safety of this combination was studied several randomized, double-blind, parallel-group, multicenter trials (Derom et al., 2016). 126, 105–115. Prim. As pMDIs, the formation of the aerosol is instantaneous but for a correct inhalation it’s required a higher coordination (Lavorini, 2013). Respir. The rate of moderate or severe exacerbations was significantly reduced with ACL/FF 400/12 μg compared with placebo (p < 0.05) but not monotherapies. (2016) published a review and meta-analysis on duration of treatment of LABA and LAMA combinations in COPD patients; they included 14 studies that reported results of 20 randomized controlled trials. No use, distribution or reproduction is permitted which does not comply with these terms. Respir. Once-daily LABA are currently called ultra-LABA. A single study enrolled 44 COPD subjects in a randomized, double-blind, multi-center, cross-over study. (2013). (2015). TIO/OLO 5/5 μg differed significantly from TIO 5 μg monotherapy in terms of pulmonary function [FEV1 area under curve (AUC)0–24, FEV1 AUC0–12, and FEV1 AUC12–24] and reducing symptoms of dyspnea (TDI and HRQ). 9, 1365–1375. Recently Calzetta et al. doi: 10.1164/rccm.201207-1299OC, Lavorini, F. (2013). It is generally assumed that the primary role of the LABA is to augment the anti-inflammatory actions of the CS, by the mechanisms described in the preceding sections.83 However, CS can also augment the anti-inflammatory actions of LABAs, consistent with synergistic interactions between the two components. Comparison between TIO/OLO 5/5 μg FDC OD and OLO 5 μg OD, was generally statistically but not clinically significant in favor of fixed dose association not reaching the minimal clinical important difference (MCID). Salmeterol and Formoterol Receptor. Glucocorticoids achieve this by binding to receptors in cytosol – known as glucocorticoid receptors (GR). Anticholinergics have a different mechanism of action compared with short-acting β 2-agonists (SABAs) and LABAs, which bind to airway β 2-receptors to trigger smooth muscle relaxation [69, 70]. Since none of the available LAMA/LABA FDCs have been compared in head-to-head trials, they can only be weighed against each other by indirect comparisons as meta-analysis. 19:CD001104. The administration of these two drugs simultaneously with the same device (single inhalator) should ensure a better adherence to the treatment and ad hoc dosages to produce a “synergistic effect between the two drugs respect to the administration of the two drugs separately (Tashkin and Ferguson, 2013). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Vilanterol: Long-acting selective beta2-adrenergic agonist (LABA); stimulates intracellular adenyl cyclase resulting in increased cAMP levels causing bronchial smooth muscle relaxation; also inhibits release of mediators of immediate hypersensitivity from cells, especially from mast cells . Figure 1. |, Pharmacology Mechanism of Action and Rationale for LAMA/LABA Fixed Dose Combinations in a Single Inhaler for COPD, LAMA/LABA Fixed Dose Combinations in a Single Inhaler for COPD: Evidences From Clinical Trials, The Role of LAMA/LABA Fixed Dose Combinations in a Single Inhaler for COPD Therapy in Global Initiative for Obstructive Lung Disease Recommendations, Critical Issues for LABA/LAMA Combinations in a Single Inhaler Therapy for COPD, Global initiative for chronic obstructive Lung disease [GOLD], 2018, Inhaler Error Steering Committee et al., 2013, https://clinicaltrials.gov/ct2/show/NCT03265145?term=NCT03265145&rank=1, https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf, Creative Commons Attribution License (CC BY). This allows the active portion of the molecule to continuously bind and unbind at β2 receptors in the smooth muscle in the lungs.