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      A proposal for the withdrawal of inhaled corticosteroids in the clinical practice of chronic obstructive pulmonary disease

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          According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β 2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations. However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.

          Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations. This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.

          Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks.

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          Most cited references 63

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          Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

          To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Double blind, placebo controlled study. Eighteen UK hospitals. 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.
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            Decreased histone deacetylase activity in chronic obstructive pulmonary disease.

            Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation that is greater in patients with advanced disease. We asked whether there is a link between the severity of disease and the reduction in histone deacetylase (HDAC) activity in the peripheral lung tissue of patients with COPD of varying severity. HDAC is a key molecule in the repression of production of proinflammatory cytokines in alveolar macrophages. HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of specimens of surgically resected lung tissue from nonsmokers without COPD, patients with COPD of varying severity, and patients with pneumonia or cystic fibrosis. Alveolar macrophages from nonsmokers, smokers, and patients with COPD and bronchial-biopsy specimens from nonsmokers, healthy smokers, patients with COPD, and those with mild asthma were also examined. Total RNA extracted from lung tissue and macrophages was used for quantitative reverse-transcriptase-polymerase-chain-reaction assay of HDAC1 through HDAC8 and interleukin-8. Expression of HDAC2 protein was quantified with the use of Western blotting. Histone-4 acetylation at the interleukin-8 promoter was evaluated with the use of a chromatin immunoprecipitation assay. Specimens of lung tissue obtained from patients with increasing clinical stages of COPD had graded reductions in HDAC activity and increases in interleukin-8 messenger RNA (mRNA) and histone-4 acetylation at the interleukin-8 promoter. The mRNA expression of HDAC2, HDAC5, and HDAC8 and expression of the HDAC2 protein were also lower in patients with increasing severity of disease. HDAC activity was decreased in patients with COPD, as compared with normal subjects, in both the macrophages and biopsy specimens, with no changes in HAT activity, whereas HAT activity was increased in biopsy specimens obtained from patients with asthma. Neither HAT activity nor HDAC activity was changed in lung tissue from patients with cystic fibrosis or pneumonia. Patients with COPD have a progressive reduction in total HDAC activity that reflects the severity of the disease. Copyright 2005 Massachusetts Medical Society.
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              Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial

              Blood eosinophil counts might predict response to inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. We used data from the WISDOM trial to assess whether patients with COPD with higher blood eosinophil counts would be more likely to have exacerbations if ICS treatment was withdrawn.

                Author and article information

                +34 93 2746083 ,
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                28 November 2017
                28 November 2017
                : 18
                [1 ]ISNI 0000 0001 0675 8654, GRID grid.411083.f, Pneumology Department, , Hospital Universitari Vall d’Hebron, ; P. Vall d’Hebron 119-129, 08035 Barcelona, Spain
                [2 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, CIBER de Enfermedades Respiratorias (CIBERES), ; Barcelona, Spain
                [3 ]ISNI 0000 0004 1796 5984, GRID grid.411164.7, Department of Respiratory Medicine, , Hospital Universitario Son Espases-IdISBa, ; Palma de Mallorca, Spain
                [4 ]ISNI 0000 0004 1771 1175, GRID grid.411342.1, Pneumology, Allergy and Thoracic Surgery Department, , Hospital Universitario Puerta del Mar, ; Cádiz, Spain
                [5 ]ISNI 0000000103580096, GRID grid.7759.c, Medicine Department, , University of Cádiz, ; Cádiz, Spain
                [6 ]ISNI 0000 0001 0671 5785, GRID grid.411068.a, Pulmonary Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), , Hospital Clínico San Carlos, ; Madrid, Spain
                [7 ]ISNI 0000 0001 2157 7667, GRID grid.4795.f, Departamento de Medicina, Facultad de Medicina, , Universidad Complutense de Madrid, ; Madrid, Spain
                [8 ]Respiratory Department, AIG de Medicina, Hospital de Alta Resolución de Loja, Agencia Sanitaria Hospital de Poniente, Loja, Granada Spain
                [9 ]GRID grid.411308.f, Department of Respiratory Medicine, , Hospital Clínico Universitario and Instituto de Investigación Sanitaria (INCLIVA) Valencia, ; Valencia, Spain
                [10 ]Pneumology Department of Hospital Galdakao-Usansolo, Biscay, Spain
                [11 ]Red de Investigación en Servicios Sanitarios y Enfermedades Crónicas (REDISSEC), Bilbao, Spain
                [12 ]Health Center Menasalbas, Autonomic Health Service, Toledo, Spain
                [13 ]ISNI 0000 0004 1765 5855, GRID grid.411336.2, Pneumology Department, , Hospital Universitary “Príncipe de Asturias”, Alcalá de Henares, ; Madrid, Spain
                [14 ]Centro de Salud Lucena I, Lucena, Córdoba, Spain
                [15 ]Servicio de Neumología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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