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Original Research: COPD |

Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and InfluenzaTB/Influenza and Inhaled Corticosteroids in COPD: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Yaa-Hui Dong, PhD; Chia-Hsuin Chang, MD, ScD; Fe-Lin Lin Wu, PhD; Li-Jiuan Shen, PhD; Peter M. A. Calverley, MD; Claes-Göran Löfdahl, MD, FCCP; Mei-Shu Lai, MD, PhD; Donald A. Mahler, MD, FCCP
Author and Funding Information

From the National Taiwan University Health Data Research Center (Dr Dong), Taipei, Taiwan; Graduate Institute of Clinical Pharmacy (Drs Dong, Wu, and Shen) and Department of Pharmacy (Drs Wu and Shen), College of Medicine, National Taiwan University, Taipei, Taiwan; Center of Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research (Drs Dong and Lai), Department of Internal Medicine (Dr Chang), and Department of Pharmacy (Drs Wu and Shen), National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Epidemiology and Preventive Medicine (Drs Chang and Lai), College of Public Health, National Taiwan University, Taipei, Taiwan; Clinical Science Center (Dr Calverley), University Hospital Aintree, Liverpool, England; Department of Respiratory Medicine and Allergology (Dr Löfdahl), Lund University Hospital, Lund, Sweden; Section of Pulmonary and Critical Care Medicine (Dr Mahler), Geisel School of Medicine at Dartmouth, Hanover, NH; and Dartmouth-Hitchcock Medical Center (Dr Mahler), Lebanon, NH.

Correspondence to: Mei-Shu Lai, MD, PhD, Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 17 Xuzhou Rd, Taipei 10055, Taiwan; e-mail: mslai@ntu.edu.tw


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.

References 8, 9, 21, 26, 27, 30, 33-36, 38-40, 42, 44, 46.

†References 8, 9, 20, 21, 26, 27, 29-31, 33-35, 38-41, 44, 46.

‡References 8, 9, 20, 21, 26, 27, 29, 33-35, 38-40, 43-45.

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.


Chest. 2014;145(6):1286-1297. doi:10.1378/chest.13-2137
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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.

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