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      Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD

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          Abstract

          Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.

          A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case–control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23–1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.

          Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk–benefit balance is crucial for the indication of ICSs.

          Abstract

          Long-term use of inhaled corticosteroids in COPD is associated with a significantly increased risk of side-effects, especially oral candidiasis, dysphonia, pneumonia, mycobacterial disease, diabetes and fractures https://bit.ly/3t0AGfO

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          Most cited references109

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD

            The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain.
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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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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 June 2021
                24 June 2021
                : 30
                : 160
                : 210075
                Affiliations
                [1 ]Pneumology Dept, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain
                [2 ]Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
                [3 ]Primary Care University Research Institute Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
                [4 ]Medicine Dept, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
                [5 ]Dept of Physiotherapy, Bayero University, Kano, Nigeria
                [6 ]Both authors contributed equally and are considered first authors
                Author notes
                Corresponding author: Marc Miravitlles ( marcm@ 123456separ.es )
                Author information
                https://orcid.org/0000-0002-9850-9520
                Article
                ERR-0075-2021
                10.1183/16000617.0075-2021
                9488732
                34168063
                bb5f6ab0-161e-4987-9431-501e7207489a
                Copyright ©The authors 2021

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 12 January 2021
                : 26 March 2021
                Funding
                Funded by: Boehringer Ingelheim, doi 10.13039/100001003;
                Award ID: N/A
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