Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis

Bafadhel, Mona; Davies, Lisa; Calverley, Peter M.A.; Aaron, Shawn D.; Brightling, Christopher E.; Pavord, Ian D.

doi:10.1183/09031936.00062614

Cited by 158 publications

(142 citation statements)

References 9 publications

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“…I suspect not, although I do believe we are beginning to define the value of such treatment with greater precision. Data from acute trials of oral corticosteroids in COPD exacerbations suggest that patients with a baseline eosinophil count that is raised by only modest degree are more likely to get benefit from the corticosteroids, whilst those who do not show this feature do not [17]. From the database study of elderly COPD patients a history of asthma was a strong identifying factor for patients who clearly benefitted from an ICS in their treatment regime [18].…”

Section: @Erspublicationsmentioning

confidence: 99%

What to use INSTEAD of inhaled corticosteroids in COPD?

Calverley

2014

Eur Respir J

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@ERSpublicationsThe way we use ICS in #COPD should change if we are to offer the safest and most effective treatment to our patients http://ow.ly/Czukb Inhaled corticosteroids (ICS) have had an important impact on the management of chronic obstructive pulmonary disease (COPD). When combined with an inhaled long-acting b-agonist (LABA), they improve lung function more than is the case with the LABA alone, improve health status and reduce the number of exacerbations patients experience [1]. There are data to suggest that they modify the decline in lung function and improve survival but these effects remain more controversial [1,2]. There have always been concerns about the risks of developing osteoporosis or cataracts and even diabetes in COPD patients who use ICS drugs, although randomised controlled studies suggest that the impact of such changes are small in patients with more severe COPD [3]. However, there is now consistent evidence from randomised controlled trials that patients using fluticasone-based corticosteroids are more likely to develop pneumonia [4,5]. The clinical significance of these events remains less certain [6,7] as does the generalised ability of these findings to all ICS [8]. Nonetheless, concerns about the balance of the risks and benefits of ICSbased treatments has led to renewed interest in defining patients who could be managed as well with other therapies.One way to establish whether ICS treatment should be continued is to stop it and see what happens. Early observational studies and randomised control trials suggested that acute withdrawal of ICS from the treatment regimen of COPD patients precipitated an exacerbation and/or increased symptoms [9,10]. Recently, two relatively large studies have examined the effects of withdrawing ICS in rather different populations of patients who were clinically stable at the time of study entry. The larger of these, the Withdrawal of Inhaled Steroids During Optimised Management (WISDOM) trial, screened 3426 patients, of whom 2488 were randomised [11]. All the patients were given an ICS, a LABA and the long-acting antimuscarinic agent (LAMA) tiotropium for 6 weeks then randomised either to continue these drugs or to reduce slowly the dose of the ICS over 3 months, after which time they were managed on the LABA and LAMA alone. To the surprise of everyone, not least the investigators, there was no difference in the exacerbation rate during the period of ICS withdrawal, nor was there a difference in the overall exacerbation rate for moderate and severe events over the year as a whole. There was a suggestion that the number of severe exacerbations increased transiently, just after the ICS was completely withdrawn, and a difference of ,50 mL in lung function emerged between the two treatments, in keeping with the known effects if ICS on forced expiratory volume in 1 s (FEV1) [1]. Neither the prior exacerbation history nor the previous treatment used by the patient influenced these conclusions.With hindsight, it would have been better to extend the follow-...

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Section: @Erspublicationsmentioning

confidence: 99%

What to use INSTEAD of inhaled corticosteroids in COPD?

Calverley

2014

Eur Respir J

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“…Peripheral blood eosinophils were found to predict eosinophilic exacerbations of COPD [135] and oral corticosteroid responsiveness of AECOPD [136]. Expired nitric oxide is of limited usefulness in COPD because it is affected by smoking and values fall with increasing airflow limitation [137,138].…”

Section: Copd Phenotypes or How To Predict Which Patients Benefit Fromentioning

confidence: 99%

Inhaled corticosteroids in COPD: the clinical evidence

2014

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In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn.The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths.Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured. @ERSpublicationsThe benefits of ICS in COPD are limited. Better tools are needed to identify which patients might benefit.

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“…The blood eosinophil count also has utility as a marker of the response to oral corticosteroid therapy given to hasten recovery at the time of an exacerbation. All of the benefits of treatment occurs in subjects with a blood eosinophil count ⩾2% [25] and there is evidence of net harm in patients with a count <2% [26].…”

Section: @Erspublicationsmentioning

confidence: 99%

Blood eosinophil count: a biomarker of an important treatable trait in patients with airway disease

Pavord

Agustí

2016

Eur Respir J

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@ERSpublicationsBlood eosinophil count can identify eosinophilic airway inflammation, a "treatable trait" of COPD http://ow.ly/Xn098Inhaled corticosteroids (ICS) are widely used to treat patients with chronic obstructive pulmonary disease (COPD). Their main impact is to reduce the risk of exacerbations; in contrast to long-acting bronchodilators their effects on symptoms and lung function are small and insufficient to use as a guide of treatment efficacy. As a result, ICS are applied in a "risk-directed" fashion, with treatment directed at patients deemed to be at risk of exacerbations because of a past history of events, and/or poor lung function [1]. A better, more precise strategy would be to apply treatment in a targeted fashion according to a biomarker indicating the likelihood that corticosteroid treatment will have a positive effect on the outcome of interest (i.e. reduction in exacerbations or decline in lung function).Interest in better targeting of ICS treatment has increased recently for three reasons [2]. First, there has been increasing recognition of the potentially adverse effects of ICS treatment. Pneumonia risk increases as a function of ICS dose and treatment duration [3] and there are many other potential adverse effects, including increased risk of tuberculosis and nontuberculosis mycobacterial infection [4]. Second, ICS use, particular high dose potent ICS use, has increased substantially in the last 10 years and much of this use is outside current guidelines [5]. Withdrawing ICS may be difficult to do in a condition when the primary goal of treatment is to reduce future events, and trials of ICS withdrawal have had a limited impact [6]. And, finally, we have other potentially attractive treatment options for patients with symptomatic COPD, notably the combination of long-acting β 2 -agonists (LABA) and long acting anti-muscarinic agents (LAMA). These agents have generally greater effects on symptoms and lung function than ICS/LABA and might have a similar effect on exacerbation frequency [7]. However, their use has been limited by the lack of satisfactory information on whom should we switch from ICS/LABA to LABA/LAMA and how we should do this.In order to move from a risk directed to a biomarker directed ICS treatment strategy, the biomarker should indicate a corticosteroid responsive element on the causal pathway of the aspect of the condition we are attempting to modify. The induced sputum eosinophil count, a biomarker of eosinophilic airway inflammation, is an established candidate biomarker. Proof-of-concept studies have shown a consistent and compelling relationship between a raised induced sputum eosinophil count and the short-term response to oral [8,9] and inhaled [10] corticosteroids. This is also the case for long-term management, since management guided by the sputum eosinophil count results in better outcomes than guideline-based management [11,12]. However, there are other requirements for a biomarkers to be clinically useful, including being readily accessible in ordinary clin...

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Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis

Cited by 158 publications

References 9 publications

What to use INSTEAD of inhaled corticosteroids in COPD?

What to use INSTEAD of inhaled corticosteroids in COPD?

Inhaled corticosteroids in COPD: the clinical evidence

Blood eosinophil count: a biomarker of an important treatable trait in patients with airway disease

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