Effect of triple therapy in patients with asthma-COPD overlap

Abstract

Objective: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is of increasing interest because ACO patients have significantly worse outcomes, leading to greater social and economic burdens compared with asthma or COPD alone. Some guidelines for ACO recommend triple therapy with inhaled corticosteroids, long-acting β2 agonists, and long-acting muscarinic antagonists. However, this approach is based on extrapolating data from patients with asthma or COPD alone. Therapeutic studies for ACO have not previously been conducted. Materials and methods: A 12-week, randomized, open-label cross-over pilot study was conducted in 17 ACO patients to evaluate the effect of umeclidinium (UMEC) 62.5 µg once-daily added to fluticasone furoate/vilanterol (FF/VI) 200/25 µg once-daily. A 4-week run-in, a first and a second 4-week treatment period were included. Respiratory function, respiratory impedance, fractional exhaled nitric oxide, COPD assessment test, and asthma control test scores were evaluated 0, 4, and 8 weeks after randomization. Results: Mean values of post-bronchodilator forced expiratory volume in 1 second as a percentage of the predicted value (%FEV 1 ), after UMEC was added to FF/VI, were significantly higher than after the run-in (p < 0.01). Mean values of resonant frequency during inspiration (Fres), after UMEC was added to FF/VI, were significantly lower than after the run-in (p < 0.01). Conclusion: Adding UMEC to FF/VI provides greater improvement in lung function, indicating that triple therapy is a suitable regular treatment for ACO.

<p>Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate Improves Inspiratory Capacity in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap</p>

“…7 We conducted the present study based on physiological lung function criteria described in previous studies. 6,7,10,15,19,33 In contrast, concordance with the proportion of ACO patients in several different studies indicates the validity of the physiological lung function criteria. 5,7,14,19 Further studies are required to establish better diagnostic criteria for ACO.…”

“…We previously reported the usefulness of dual therapy with ICS/LABA as a maintenance therapy for ACO, 9 and subsequently conducted a study to investigate the effect of triple therapy with ICS/LAMA/LABA. 10 We have also demonstrated the advantage of triple therapy in patients with ACO but did not focus on the IC, an index of inspiratory restraint resulting from hyperinflation of the lung. 28,29 Hyperinflation of the lung is an important finding that causes exertional dyspnea and reduced exercise in patients with COPD.…”

“…[6][7][8][9][10] ACO also has become a recent focus of interest, 6-10 because patients with ACO have worse health-related quality of life, more rapid disease progression, 11 frequent and abrupt respiratory exacerbation, 12 increased co-morbidities, and greater health-care utilization, leading to a greater socioeconomic burden than for patients with asthma or COPD alone. 9,10,13,14 Previous studies showed that 53-55% of COPD patients present with an asthma-predominant phenotype. 5,15 In the UPLIFT trial, nearly 66% of COPD patients improved their respiratory functions by more than 15% after receiving bronchodilator therapy.…”

“…8,26,27 Unfortunately, this treatment approach is based on the extrapolation of data derived from studies of patients with asthma or COPD alone, as few therapeutic studies for ACO have previously been conducted. 10 Moreover, previous reports have not considered inspiratory capacity (IC), an index of hyperinflation of the lung that causes exertional dyspnea and reduced exercise in chronic obstructive airway diseases. [28][29][30] We therefore conducted the present study to compare the efficacy of ICS/LAMA/ LABA triple therapy with that of ICS/LABA dual therapy in terms of hyperinflation of the lung to confirm the clinical benefit of triple therapy for ACO.…”

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

“…Finally, it seems fair to point out that, although we believe that the term asthma-COPD overlap (ACO) should be abandoned because it does not identify a clearly independent disease entity and rather indicates asthmatic patients who have smoked or still smoke [39], the view of many specialists is that it is correct to treat patients with ACO who remain symptomatic or suffer from frequent exacerbations with triple therapy despite initial inhaler therapy [40]. A recent pilot study, which compared the efficacy of LAMA/ICS/LABA triple therapy with ICS/LABA dual therapy, showed that 4-week once-daily treatment of ACO patients with umeclidinium 62.5 lg added to fluticasone furoate/vilanterol 200/25 lg produced significant improvements from baseline in lung function compared with once-daily treatment with fluticasone furoate/vilanterol lg alone [41]. It is obvious that more and larger studies are needed to validate such an approach, also possibly using a meta-analytical approach.…”