Addressing unmet needs in the treatment of COPD

Patalano, Francesco; Banerji, Donald; D’Andrea, Peter; Fogel, Robert; Altman, Pablo; Colthorpe, Paul

doi:10.1183/09059180.00004014

Cited by 14 publications

(5 citation statements)

References 90 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Firstly, some of the non-frequently exacerbating patients with moderate COPD recruited in the CRYSTAL study were appropriately treated with a single long-acting bronchodilator, whereas most of the patients on LABA + ICS were inappropriately treated according to the GOLD recommendations [28], as it happens often in clinical practice. Importantly, the CRYSTAL study results show that even in these mildly symptomatic patients, the switch from a mono-bronchodilator regimen (with or without ICS) to a dual bronchodilator (IND/GLY) significantly improved their lung function, breathlessness and overall quality of life.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

et al. 2017

View full text Add to dashboard Cite

BackgroundDual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.MethodsThe CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.ResultsThe study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies.ConclusionsIND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.Trial registrationClinicalTrials.gov number: NCT01985334.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0622-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

et al. 2017

View full text Add to dashboard Cite

show abstract

“… 63 , 64 The efficacy of triple therapy (LABA/LAMA/ICS) in the reduction of exacerbations may have benefits, compared with LABA/LAMA in exacerbating patients with COPD; however, there is a need for prospective clinical trials in this specific population to explore this further. 65 Other anti-inflammatory options in exacerbating patients with COPD on effective inhaled therapies include phosphodiesterase-4 inhibitors and macrolides. The results of the Roflumilast and Exacerbations in patients receiving Appropriate Combination Therapy (REACT) study provide some evidence that, in patients with severe COPD with symptoms of chronic bronchitis and at least two exacerbations in the previous year, treatment with roflumilast may reduce exacerbations and hospital admissions, on top of ICS and LABA therapy compared with placebo.…”

Section: Principles Of Managementmentioning

confidence: 99%

The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

Κostikas

Clemens

Patalano

2016

COPD

View full text Add to dashboard Cite

The term asthma–COPD overlap syndrome (ACOS) is one of multiple terms used to describe patients with characteristics of both COPD and asthma, representing ~20% of patients with obstructive airway diseases. The recognition of both sets of morbidities in patients is important to guide practical treatment decisions. It is widely recognized that patients with COPD and coexisting asthma present with a higher disease burden, despite the conceptual expectation that the “reversible” or “treatable” component of asthma would allow for more effective management and better outcomes. However, subcategorization into terms such as ACOS is complicated by the vast spectrum of heterogeneity that is encapsulated by asthma and COPD, resulting in different clinical clusters. In this review, we discuss the possibility that these different clusters are suboptimally described by the umbrella term “ACOS”, as this additional categorization may lead to clinical confusion and potential inappropriate use of resources. We suggest that a more clinically relevant approach would be to recognize the extreme variability and the numerous phenotypes encompassed within obstructive airway diseases, with various degrees of overlapping in individual patients. In addition, we discuss some of the evidence to be considered when making practical decisions on the treatment of patients with overlapping characteristics between COPD and asthma, as well as the potential options for phenotype and biomarker-driven management of airway disease with the aim of providing more personalized treatment for patients. Finally, we highlight the need for more evidence in patients with overlapping disease characteristics and to facilitate better characterization of potential treatment responders.

show abstract

“…Development of new therapies to address unmet needs, especially those that can slow disease progression in COPD, is of utmost importance to patients and clinicians (Patalano et al, 2014). Oxidative stress plays an important role in COPD and thus has garnered attention as a potential area for new therapies.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Potent, Selective Nrf2 Activator, 3-(Pyridin-3-Ylsulfonyl)-5-(Trifluoromethyl)-2H-Chromen-2-One, in Cellular and In Vivo Models of Pulmonary Oxidative Stress

Yonchuk

Foley

Bolognese

et al. 2017

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of oxidative stress and cellular repair and can be activated through inhibition of its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (Keap1). Several small molecule disrupters of the Nrf2-Keap1 complex have recently been tested and/or approved for human therapeutic use but lack either potency or selectivity. The main goal of our work was to develop a potent, selective activator of NRF2 as protection against oxidative stress. In human bronchial epithelial cells, our Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2-chromen-2-one (PSTC), induced Nrf2 nuclear translocation, Nrf2-regulated gene expression, and downstream signaling events, including induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme activity and heme oxygenase-1 protein expression, in an Nrf2-dependent manner. As a marker of subsequent functional activity, PSTC restored oxidant (-butyl hydroperoxide)-induced glutathione depletion. The compound's engagement of the Nrf2 signaling pathway translated to an in vivo setting, with induction of Nrf2-regulated gene expression and NQO1 enzyme activity, as well as restoration of oxidant (ozone)-induced glutathione depletion, occurring in the lungs of PSTC-treated rodents. Under disease conditions, PSTC engaged its target, inducing the expression of Nrf2-regulated genes in human bronchial epithelial cells derived from patients with chronic obstructive pulmonary disease, as well as in the lungs of cigarette smoke-exposed mice. Subsequent to the latter, a dose-dependent inhibition of cigarette smoke-induced pulmonary inflammation was observed. Finally, in contrast with bardoxolone methyl and sulforaphane, PSTC did not inhibit interleukin-1-induced nuclear factor-B translocation or insulin-induced S6 phosphorylation in human cells, emphasizing the on-target activity of this compound. In summary, we characterize a potent, selective Nrf2 activator that offers protection against pulmonary oxidative stress in several cellular and in vivo models.

show abstract

Addressing unmet needs in the treatment of COPD

Cited by 14 publications

References 90 publications

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

Characterization of the Potent, Selective Nrf2 Activator, 3-(Pyridin-3-Ylsulfonyl)-5-(Trifluoromethyl)-2H-Chromen-2-One, in Cellular and In Vivo Models of Pulmonary Oxidative Stress

Contact Info

Product

Resources

About

Addressing unmet needs in the treatment of COPD

Cited by 14 publications

References 90 publications

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

The asthma&ndash;COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

Characterization of the Potent, Selective Nrf2 Activator, 3-(Pyridin-3-Ylsulfonyl)-5-(Trifluoromethyl)-2H-Chromen-2-One, in Cellular and In Vivo Models of Pulmonary Oxidative Stress

Contact Info

Product

Resources

About

The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?