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Vestbo J.,University of Manchester | Vestbo J.,University of Southern Denmark | Hurd S.S.,Global Initiative for Chronic Obstructive Lung Disease | Agusti A.G.,University of Barcelona | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents themaincontents of thesecond5-year revision of theGOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry isrequired for the clinical diagnosis ofCOPDto avoid misdiagnosis and to ensure proper evaluation of severity of airflowlimitation. Thedocumenthighlights that theassessment of thepatientwith COPDshould always includeassessment of (1)symptoms,(2)severityof airflow limitation, (3) history of exacerbations, and (4) comorbidities. Thefirst threepointscanbeusedtoevaluatelevelof symptomsandrisk of futureexacerbations, andthis isdoneinawaythatsplitspatientswith COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities aswell asCOPDin the presence of comorbidities. The revised document also contains a newsection on exacerbations of COPD. TheGOLDinitiative will continue tobringCOPDto the attention of all relevant shareholdersandwillhopefullyinspire futurenationaland local guidelines on the management of COPD. Copyright © 2013 by the American Thoracic Society.

Snell N.,UK National Heart and Lung Institute | Vestbo J.,University of Southern Denmark | Vestbo J.,University of Manchester
Respiratory Medicine | Year: 2013

Objective To evaluate the efficacy and tolerability of the selective CRTh2 (DP2) receptor antagonist AZD1981 compared with placebo in patients with moderate to severe COPD. Methods In this multicentre, randomised, double-blind, parallel-group, phase IIa study (ClinicalTrials.gov identifier: NCT00690482) patients with moderate to severe COPD received either AZD1981 1000 mg twice daily or matching placebo for 4 weeks. Inhaled terbutaline was used as-needed as reliever medication throughout. The co-primary endpoints were change from baseline to end of treatment in pre-bronchodilator forced expiratory volume in 1 s [FEV1] and the Clinical COPD Questionnaire (CCQ). Additional endpoints included other lung function measures, 6-min walk test (6-MWT), COPD symptom score, reliever medication use and tolerability. Results 118 patients were randomised to treatment (AZD1981 n = 61; placebo n = 57); 83% of patients were male and the mean age was 63 years (range 43-83). There were no significant differences in the mean difference in change from baseline to end of treatment between AZD1981 and placebo for the co-primary endpoints of pre-bronchodilator FEV1 (AZD1981-placebo: -0.015, 95% CI: -0.10 to 0.070; p = 0.72) and CCQ total score (difference: 0.042, 95% CI: -0.21 to 0.30; p = 0.75). Similarly, no differences were observed between treatments for the other outcomes of lung function, COPD symptom score, 6-MWT, BODE index, and use of reliever medication. AZD1981 was well tolerated. Conclusion There was no beneficial clinical effect of AZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified. © 2013 Elsevier Ltd. All rights reserved.

Bush A.,UK National Heart and Lung Institute | Fleming L.,Clinical Fellow Paediatric Allergy
Paediatric Respiratory Reviews | Year: 2011

The acid test of phenotyping is that it leads either to a clinically useful or mechanistically important insight. Phenotypes may change over time, but the exact definition of a phenotype shift is unclear. Methods of phenotyping are either investigator driven, in which a priori prejudices are applied to the data, or (semi) objective, in which mathematical techniques or systems biology approaches are applied to the dataset. However, the composition of the dataset is driven by investigator prejudice. Phenotyping is likely most useful in severe asthma, because mild and moderate asthma responds to simple treatments, and no great subtlety is required. Our non-evidence based approach is to define the subpopulation of genuine severe, therapy-resistant asthmatics from the generality of problematic severe asthma. We then investigate them invasively with bronchoscopy and a steroid trial using intramuscular triamcinolone to determine the nature of any inflammatory process; whether inflammation and symptoms are concordant or discordant; whether the inflammatory process is steroid resistant or sensitive; and whether the child has persistent airflow limitation. Other possibly relevant phenotypes include the child with severe exacerbations; brittle asthma; and severe asthma with fungal sensitization. Severe, therapy resistant asthma is a disparate disease, and only international uniform approaches, carefully characterising the children as a prelude to focussed clinical trials will allow progress to be made, and vindicate (or otherwise) our suggested approach. © 2011 Elsevier Ltd.

Bush A.,UK National Heart and Lung Institute | Zar H.J.,University of Cape Town
Current Opinion in Allergy and Clinical Immunology | Year: 2011

Purpose of Review: In 2009, an expert panel met to propose a WHO definition of asthma severity and control, and criteria for describing exacerbations and their severity, which would be globally applicable. This review addresses their findings in the context of recent literature, and assesses the usefulness of these definitions in children in particular. Recent Findings: Severe asthma was defined by the level of current clinical control and risks as: 'Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)'. Severe asthma includes three groups, with different public health messages and challenges: untreated severe asthma, due to undiagnosed asthma or unavailability of therapy, difficult-to-treat severe asthma (due to adherence issues, inappropriate or incorrect use of medicines, environmental triggers or co-morbidity), and treatment-resistant severe asthma, including asthma for which control is not achieved despite the highest level of recommended treatment or asthma which is controlled only with the highest level of recommended treatment. Summary: These definitions will enable more precise measurement of the burden of severe childhood asthma globally. International collaborations in epidemiological and mechanistic studies, and randomized controlled trials of treatment, will be facilitated. However, both pathophysiology and severity are influenced by a number of factors with wide global variation; international comparisons should be interpreted with caution. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Steiner M.C.,University of Leicester | Roubenoff R.,Novartis | Tal-Singer R.,Glaxosmithkline | Polkey M.I.,UK National Heart and Lung Institute
Thorax | Year: 2012

Skeletal muscle dysfunction is a prevalent and clinically important systemic manifestation of chronic obstructive pulmonary disease (COPD) that predicts morbidity and mortality. Skeletal muscle retains its plasticity in response to anabolic stimuli such as exercise in COPD and is therefore a promising target for novel pharmacological therapies aimed at reducing disability and healthcare utilisation and improving mortality. In this article, we outline the steps the academic and pharmaceutical communities need to undertake for such therapeutic advances to be realised. Copyright Article author (or their employer) 2012.

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