Maintenance therapy in COPD: time to phase out ICS and switch   to the new LAMA/LABA inhalers?

Tariq, Syed M.; Thomas, Enson

doi:10.2147/copd.s138006

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…2,20 COPD is a complex disease with progressive destruction of functional lung tissue with few effective therapies. 1,21 These highlights the need for searching new molecular targets and active pathways involved in the progression of this disease. Here, we reported that activation of Wnt pathway by LiCl and AMPK by metformin protected against lung inflammatory responses and airspace enlargement, which is mediated by Nrf2 signal.…”

Section: Discussionmentioning

confidence: 99%

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/β‐catenin and AMPK pathways

Cui

Zhang

et al. 2018

J Cellular Molecular Medi

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Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β‐catenin and AMP‐activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β‐catenin and AMPK modulate nuclear factor erythroid‐2 related factor‐2 (Nrf2)‐mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase‐induced airspace enlargement and cigarette smoke extract (CSE)‐induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2−/− mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up‐regulated, whereas Wnt3a knockdown further down‐regulated the levels of Nrf2 and its target proteins heme oxygenase‐1 (HO‐1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/β‐catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, β‐catenin, Nrf2 phosphorylation and activation but reduced the levels of IL‐6 and IL‐8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE‐induced increase in IL‐6 and IL‐8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β‐catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.

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Section: Discussionmentioning

confidence: 99%

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/β‐catenin and AMPK pathways

Cui

Zhang

et al. 2018

J Cellular Molecular Medi

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“…ICS is indicated for the treatment of patients with moderate-to-severe COPD and a history of exacerbations. Despite this, several studies have found that this does not reflect current clinical practice, and ICS is commonly prescribed in patients with less severe COPD [ 3 , 14 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B: an observational study using the Clinical Practice Research Datalink (CPRD)

et al. 2018

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BackgroundRecent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it is known that ICS is frequently prescribed for patients with less severe COPD. Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use. The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen.MethodsLinked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing. Treatment acquisition costs were not assessed.ResultsResults showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine outcomes assessed. Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 < 50% predicted), one prior exacerbation or elevated blood eosinophils.ConclusionsThese data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0767-2) contains supplementary material, which is available to authorized users.

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“… 2 However, ICS withdrawal is not represented in the algorithm, because it was agreed by the panel that there is insufficient evidence to establish clear criteria as to when and how to discontinue ICS in patients with COPD. 24 …”

Section: Algorithm Of Pharmacologic Treatmentmentioning

confidence: 99%

Russian guidelines for the management of COPD: algorithm of pharmacologic treatment

Айсанов

Avdeev

Архипов

et al. 2018

COPD

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The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A–D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.

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Maintenance therapy in COPD: time to phase out ICS and switch to the new LAMA/LABA inhalers?

Cited by 19 publications

References 28 publications

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/β‐catenin and AMPK pathways

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/β‐catenin and AMPK pathways

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B: an observational study using the Clinical Practice Research Datalink (CPRD)

Russian guidelines for the management of COPD: algorithm of pharmacologic treatment

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