The ABCD of GOLD made clear

Calverley, Peter M.A.

doi:10.1183/09031936.00117413

Cited by 8 publications

(9 citation statements)

References 23 publications

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“…However, looking at the data, there are clearly no differences in any of the pre-specified outcomes. Unfortunately, the authors were not able to subdivide their patients by the more recent Global Initiative for Chronic Obstructive Lung Disease classification, which has been reviewed previously in the ERJ [13]. However, it is clear that the chronic use of ICS in patients with a mean FEV1 .60% predicted is largely unnecessary, at least when the alternative is an effective long-acting inhaled bronchodilator.…”

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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“…The observational cohorts have impacted COPD guidance and have also provided data to determine whether the new proposed Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification [97] is clinically useful. This has been discussed in detail by the authors and it is clear that there are some limitations to the newly proposed system [98,99]. Although patients in GOLD group B are considered to be symptomatic but at low risk of events, their mortality is very similar to the less symptomatic but exacerbation-prone group C patients [100].…”

Section: Observational Studiesmentioning

confidence: 98%

Large trials, new knowledge: the changing face of COPD management

Soyza

Calverley

2015

Eur Respir J

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Large, well-designed, drug-treatment trials have allowed useful advances to be made in the treatment and diagnosis of chronic obstructive pulmonary disease (COPD). The two main clinical trial designs that provide evidence of effectiveness are randomised controlled trials (RCTs) and observational studies. RCTs are generally considered to provide more robust evidence than that obtained from observational studies and can generate informative secondary analyses in addition to the primary research query. In COPD, however, well-designed comparator-controlled RCTs, although successful, have been shown to have some limitations, such as a lack of generalisability. The findings of observational studies, whilst prone to bias, can generate valuable data and have also provided useful information relating to the efficacy of treatments in the current COPD management guidelines. This review focuses on major COPD studies published since 2007 (including UPLIFT, TIOSPIR, ECLIPSE and COPDGene), and assesses the influence such RCTs and large observational studies have had on our knowledge of COPD, and how these may impact future trial designs. @ERSpublications Findings of RCTs and large observational studies contribute significantly to our knowledge of COPD http://ow.ly/J1rp0

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“…GOLD has faced the challenge of COPD heterogeneity by evolving from an initial disease staging based only on the degree of airflow limitation (FEV 1 , forced expiratory volume during the first second) [ 15 ] to the incorporation of symptoms and frequency of severe exacerbations into the scoring system (2011 GOLD update) (see Table 1 for details) and acknowledging the negative impact of co-morbid conditions on prognosis. Evidence-based data using the 2011 GOLD classification are currently emerging, but the results are not yet consolidated [ 16 , 17 ]. Alternative available options for COPD classification or prediction of survival [ 18 - 22 ] are also insufficient for subject-specific prediction and stratification of management.…”

Section: Introductionmentioning

confidence: 99%

“… The 2011 COPD Update [ 1 ] defines four risk categories for COPD patients (A to D) depending upon: i) symptoms (modified dyspnea score from th Medical Research Council, mMRC) or CAT questionnaire; ii) spirometric classification : GOLD I: FEV 1 ≥ 80% pred; GOLD II: 50% ≤ FEV 1 < 80% pred; GOLD III: 30% ≤ FEV 1 < 50% pred; and, GOLD IV: FEV 1 < 30% and/or PaO 2 < 60 mmHg breathing F I O 2 0.21); and, iii) frequency of exacerbations per year . Recent reports have assessed the predictive value of this classification [ 16 , 17 ] …”

Section: Introductionmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

et al. 2014

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Background and hypothesisHeterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics.Objective and methodTo explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena.Results(1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering.ConclusionsThe results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

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The ABCD of GOLD made clear

Cited by 8 publications

References 23 publications

What to use INSTEAD of inhaled corticosteroids in COPD?

What to use INSTEAD of inhaled corticosteroids in COPD?

Large trials, new knowledge: the changing face of COPD management

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

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