The current non-randomized study compared the efficacy of three LABA/LAMA fixed-dose combination therapies in patients with COPD from Far Eastern Memorial Hospital in Taiwan over a period of 12 months. CAT score, FEV1, FVC improved after treatment with UME/VIL, IND/GLY, and TIO/OLO. Results revealed that clinical outcomes after 12 months of treatment (CAT, FEV1 and FVC differences) were significantly affected by the type of COPD medication used. All lung function measurements and symptoms were significantly improved for users of TIO/OLO compared to users of IND/GLY and UME/VIL. The differences between the effects of UME/VIL and IND/GLY were not as pronounced. Besides, there was an also statistical significance for decreased exacerbation rate in patients with TIO/OLO treatment.
Previously published studies have demonstrated the efficacy and safety of fixed dual long-acting bronchodilators for COPD patients, specifically TIO/OLO. TIO/OLO is indicated for the maintenance treatment of airflow obstruction in adults with COPD.  This indication is supported by results from multiple randomized phase III studies of varying duration (6–52 weeks).[11, 13-14] TIO/OLO maintenance therapy improved lung function to a greater extent than the individual components or placebo and provided clinically meaningful improvements in health-related quality of life and dyspnoea in 12- and 52-week studies. Tiotropium/olodaterol consistently improved 24-h lung function in 6-week studies, providing greater benefits than the monotherapies, placebo or twice-daily fixed-dose fluticasone propionate/salmeterol. Worth noting, in the subgroup analysis from Tonado  and DYNAGITO study , combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations in Japanese population compared with other races. Taken together including our results, TIO+OLO combination therapy may have a superior treatment efficacy in Asian population.
Current therapeutic policies for COPD management focus on improvement of symptoms, reduction of the risk for acute exacerbations, and reduced prognosis or mortality. Based on the treatment benefits evidenced, dual LAMA/LABA combinations play an essential role in stable COPD therapy. Long-acting inhaled bronchodilators have been demonstrated for their potential to reduce COPD exacerbations in several studies. [16–20] Among of these studies have showed that the LAMA tiotropium (TIO) has greater efficacy against exacerbations than LABAs (POET-COPD  INVIGORATE studies ). In addition, the efficacy of TIO in reducing exacerbations was shown to be non-inferior to that of fixed-dose combination therapy with inhaled corticosteroids (ICS) and LABA salmeterol (INSPIRE study).  In the SPARK study, fixed-dose combination therapy with IND/GLY was not superior to TIO monotherapy in reducing moderate and severe exacerbations.  Moreover, there was no significant differences in symptoms, health status, or risk of exacerbation between UMEC plus VIL and TIO.  Therefore, TIO have the treatment superiority for symptoms relief and reduced exacerbation compared with ICS/LABA or IND/GLY and UME/VIL.
Olodaterol (OLO) is a novel once-daily LABA bronchodilator that was effective in lung function improvement. [24-26] The combination of TIO and OLO provides additional advantages in lung function and improves health-related quality of life. [27-29] The DYNAGITO study was performed to compare the safety and efficacy of TIO/OLO dual therapy versus TIO monotherapy in reducing exacerbations in COPD patients with a history of at least one exacerbation in the previous 12 months and TIO+OLO combination therapy provided a numerically greater reduction in moderate-to-severe exacerbations than TIO monotherapy.  Besides, anti-inflammatory effects were the central role for reducing AE and combined with TIO plus OLO had the synergistic effect for reducing neutrophils inflammation in vitro study.  In fact, ideal dual bronchodilator agents should have these efficacy including: the decrease in hyperinflation and mechanical stress, the modulation of mucus production and mucociliary clearance, the improvement of symptoms fluctuation and severity, and some potential direct and indirect anti- inflammatory properties.  Based on previous studies, therefore, only TIO plus OLO combined bronchodilator agents have the overwhelming efficacy for COPD than other two dual bronchodilator agents from bench research, clinical trials and real-world practice.
Another treatment efficacy reason is the inhaled device. Several inhaled devices available in the treatment COPD patients using dual bronchodilator agents including Breezhaler device for IND/GLY, Ellipta device for UME/VIL and Respimat device for TIO/OLO. Ciciliani and their colleagues had compared these devices using combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD) simulations and Respimat showed the lowest amount of particles depositing in the mouth–throat model and the highest amount reaching all regions of the simulation lung model.  Therefore, TIO/OLO via Respimat with greater pharmacodynamic efficacy and inhaled device benefits achieved the treatment superiority for COPD compared with other two bronchodilator agents.
Several limitation were noted in this study. First, this is not a prospective randomized study to compare these treatment efficacy. Validating the current results in terms of their clinical relevance will require further well-designed randomized controlled trials. Second, there was relative small population to enroll the study. It should include large population to confirm these results. Third, the study period was only 12 months. It needed to long time to follow these treatment effectiveness. Fourth, the study performance was only one center and it may have potential bias. The study was the first time, head-to head comparison the efficacy in these different kinds LABA/LAMA fixed combination agents, though there was some limitations and bias.