Chest
Volume 145, Issue 6, June 2014, Pages 1286-1297
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Original Research
Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and Influenza: A Systematic Review and Meta-analysis of Randomized Controlled Trials

https://doi.org/10.1378/chest.13-2137Get rights and content

Background

The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.

Methods

Through a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza.

Results

Twenty-five trials (22, 898 subjects) for TB and 26 trials (23, 616 subjects) for influenza were included. Compared with non-ICS treatment, ICS treatment was associated with a significantly higher risk of TB (Peto OR, 2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24; 95% CI, 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore, the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1, 667, respectively).

Conclusions

This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD, which deserve further investigation.

Section snippets

Data Sources and Searches

We searched the databases of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013. Full-text terms and specific thesaurus terms (eg, Medical Subject Headings for MEDLINE and EMTREE for EMBASE), including “COPD” and “ICS,” were used for the search strategy (see e-Appendix 1 for details). We examined the bibliographies of relevant articles for eligible trials. To identify complete trial information and unpublished trials, we searched the clinical study

Eligible Trials

We identified 32 studies that fulfilled the eligibility criteria8, 9, 20, 21, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 and contacted 21 authors for outcome ascertainment.27, 30, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52 Nine authors (42.9%) provided outcome information; five (23.8%) did not respond, but information was confirmed by the clinical study registers of drug manufacturers. Seven

Discussion

This meta-analysis of data from randomized controlled trials demonstrated that patients with COPD receiving ICSs had an approximately twofold increased risk of TB, particularly in endemic areas such as Asia and Africa. Meanwhile, a marginally, but nonsignificantly increased risk of influenza associated with ICSs was observed. This study highlights the potential harm of ICSs in increasing respiratory infections. These findings should be weighed against benefits and risks of ICS in the management

Acknowledgments

Author contributions: Dr Lai had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Dong: contributed to the study conception and design; study selection; assessment of risk of bias; extraction, analysis, and interpretation of the data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; and final approval of the manuscript.

Dr Chang: contributed to the study

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    Part of this article was presented in abstract form at the 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, August 25-28, 2013, Montréal, QC, Canada.

    Drs Dong and Chang contributed equally to the manuscript.

    Funding/Support: This study was supported in part by the Taiwan Department of Health [Grant DOH101-TD-B-111-01].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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