Chest
Volume 124, Issue 6, December 2003, Pages 2329-2340
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Reviews
Systematic Review of the Evidence Regarding Potential Complications of Inhaled Corticosteroid Use in Asthma: Collaboration of American College of Chest Physicians, American Academy of Allergy, Asthma, and Immunology, and American College of Allergy, Asthma, and Immunology

https://doi.org/10.1378/chest.124.6.2329Get rights and content

Introduction

The available clinical guidelines have been successful in improving awareness of the inflammatory nature of asthma and have promoted the use of inhaled corticosteroids (ICSs) to achieve long-term control of symptoms. Because of lingering concerns over the possible adverse consequences of ICS use, an expert panel was convened with a mandate to identify the critical questions that impact decisions regarding the use of ICSs and to evaluate the available evidence with respect to risk

Methods

A university librarian retrieved citations and abstracts from the MEDLINE and EMBASE databases using a list of National Library of Medicine search terms and key words. Reviewers were asked to systematically abstract relevant information from each of their assigned articles and to list their own clinical or scientific conclusions based on the study results. A predefined grading algorithm was used to calculate a summary quality rating score for the relevant evidence

Results

The results are presented as a series of key questions followed by a summary of the relevant evidence. An evidence grade is assigned, followed by a summary statement reflecting the panel's consensus opinion following review.

Conclusions

The preponderance of evidence supports a conclusion that the proven clinical effectiveness of ICS treatment decidedly outweighs the proven risks.

Section snippets

Identification of Evidence

A university librarian retrieved citations and abstracts from the MEDLINE and EMBASE databases using a list of National Library of Medicine search terms and key words that had been developed in conjunction with panel members. The databases included articles entered from inception through week 4 of December 2000. The recovery of articles was limited to five clinically relevant complications, including glaucoma, cataracts, skin thinning or ease of bruising, bone density or osteoporosis, and

Results

The MEDLINE and EMBASE searches initially yielded a total of 375 candidate articles. Following dual title and abstract reviews, 267 (71%) met the exclusion criteria, and 108 references remained to be evaluated.

Is There an Elevated Risk of Glaucoma Associated With ICS Use?

None of the studies identified dealing specifically with the association between glaucoma and ICS therapy used an experimental design. Samiy et al23 reported on a series of cases with patients who received variable doses of any number of medications. With this study design, no stratification based on ICS formulation or dose was possible, and the authors stated only that “90% of patients received beclomethasone dipropionate (BDP).” No control for potential confounders such as family history of

Does ICS Therapy Affect the Rate of Growth in Asthmatic Children?

Several carefully performed RCTs have been performed looking at the effect of ICS use on growth rates in children at various stages of development. The CAMP trial8 was designed to evaluate the long-term growth effects of therapy with BUD or nedocromil on children with mild-to-moderate asthma. Three equivalent groups of children were treated with inhaled BUD, 200 μg bid, inhaled nedocromil, 8 mg bid, or placebo. After 4 to 6 years of treatment, the side effects of BUD were limited to a small

Is the Risk of Skin Thinning and Easy Bruising Elevated in Patients Receiving ICS Therapy?

Several well-done observational studies confirm the association between ICS therapy and skin thinning. Mak et al37 studied 406 asthmatic outpatients from a respiratory clinic and compared the incidence of bruising to appropriately matched subjects not receiving ICSs. Therapy with ICSs increased the risk of easy bruising, especially with increased dose and prolonged duration of use. Similarly, a report of 76 asthmatic subjects by Capewell and colleagues38 in Wales revealed a positive correlation

Discussion

The established efficacy of ICS therapy generally has placed this class of medications at the center of current asthma treatment recommendations. However, despite the general acceptance of ICSs over the past several decades, substantial concerns about their undesirable effects linger, particularly in “special” populations such as children, women, and the elderly. As alternative controller medications become increasingly available, these nagging concerns have taken on new significance. Our

Expert Panel Members

James E. Fish, MD, FCCP (Co-Chair), Thomas Jefferson University, Philadelphia, PA; Stanley J. Szefler, MD (Co-Chair), National Jewish Medical and Research Center, Denver, CO; Marianne Frieri, MD, Nassau Medical Center, East Meadow, NY; David Lang, MD, Thomas Jefferson University, Philadelphia, PA; Stephen C. Lazarus, MD, University of California at San Francisco, San Francisco, CA; Dennis Ledford, MD, University of South Florida, College of Medicine, Tampa, FL; Frank T. Leone, MD, MS, FCCP,

ACKNOWLEDGMENT

We are indebted to Drs. Ann Koopman and Rodney Murray of the Scott Memorial Library at Thomas Jefferson University. Without Dr. Koopman's flexibility, talent, and diligence during the evidence collection phase, and without Dr. Murray's patience during the Internet data-collection phase, this project surely would not have been possible. The panel thanks the American College of Chest Physicians staff, Sydney Parker, PhD, Arlene Karavich, and former staff member Beth Welch, for their assistance in

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    This work was supported by The American College of Chest Physicians, The American Academy of Allergy, Asthma and Immunology, and The American College of Allergy, Asthma and Immunology.

    Online data summaries are available at http://www.chestjournal.org/cgi/content/full/124/6/2329/DC1.

    This work was performed while Dr. Fish was on the faculty of Thomas Jefferson University.

    See Appendix for list of members of the Expert Panel on Inhaled Corticosteroid Use.

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