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      Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials

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          Abstract

          Background

          We aimed to assess the association between inhaled corticosteroids (ICSs) and the risk of upper respiratory tract infection (URTI) in patients with chronic obstructive pulmonary disease (COPD).

          Methods

          PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception to October 2019. Randomized controlled trials (RCTs) of any ICSs vs control for COPD with reporting of URTI as an adverse event were included. The study was registered with PROSPERO prospectively (#CRD42020153134).

          Results

          Seventeen RCTs (20,478 patients) were included. ICSs significantly increased the risk of URTI in COPD patients (RR, 1.13; 95% CI 1.03–1.24; P = 0.01; heterogeneity: I 2  = 7%). Futher subgroup analyses suggested that short-term use of ICSs increased the risk of URTI (RR, 1.29; 95% CI 1.06–1.56; P = 0.01; heterogeneity: I 2  = 14%) but not for long-term use (RR, 1.08; 95% CI 0.97–1.2; P = 0.14; heterogeneity: I 2  = 0%). Short-term use of high-dose fluticasone increased the risk of URTI (RR, 1.33; 95% CI 1.03–1.71; P = 0.03; heterogeneity: I 2  = 0%) but not for long-term use (RR, 1.12; 95% CI 0.97–1.29; P = 0.13; heterogeneity: I 2  = 50%). Medium-dose (RR, 0.97; 95% CI 0.71–1.32; P = 0.84; heterogeneity: I 2  = 0%) and low-dose (RR, 1.39; 95% CI 0.92–2.1; P = 0.12; heterogeneity: I 2  = 30%) fluticasone did not increase the risk of URTI regardless of duration. Neither mometasone (RR, 1.05; 95% CI 0.87–1.26; P = 0.61; heterogeneity: I 2  = 0%) nor budesonide (RR, 1.08; 95% CI 0.77–1.5; P = 0.67; heterogeneity: I 2  = 46%) increased the risk of URTI, regardless of dosage or duration.

          Conclusions

          Long-term use of ICSs does not increase the risk of URTI in patients with COPD. Short-term use of high-dose fluticasone increases the risk of URTI in patients with COPD, but not mometasone or budesonide.

          Supplementary information

          Supplementary information accompanies this paper at 10.1186/s12890-020-01315-3.

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          Most cited references37

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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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            Quantifying heterogeneity in a meta-analysis.

            The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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              Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation

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                Author and article information

                Contributors
                apple0831@126.com
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                28 October 2020
                28 October 2020
                2020
                : 20
                : 282
                Affiliations
                [1 ]GRID grid.440164.3, ISNI 0000 0004 1757 8829, Department of Infectious Disease, , Chengdu Second People’s Hospital, ; No. 10 Qingyun South Street, Chengdu, 610017 China
                [2 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, Department of Respiratory Medicine and Critical Care Medicine, , West China Hospital, Sichuan University, ; No. 37 Guo Xue Xiang, Chengdu, 610041 China
                Author information
                http://orcid.org/0000-0002-0716-7546
                Article
                1315
                10.1186/s12890-020-01315-3
                7594481
                33115481
                fffe0dd2-721a-4141-9198-a476c997ea39
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 17 January 2020
                : 15 October 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                inhaled corticosteroids (ics),chronic obstructive pulmonary disease (copd),upper respiratory tract infection (urti),risk,meta-analysis

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