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Meta-Review: Adverse Effects of Inhaled Corticosteroids Relevant to Older Patients

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Abstract

Background

In recent years, clinical trials and observational studies have raised concerns about the potential adverse effects of inhaled corticosteroids (ICS) such as pneumonia, cataract, fractures and hyperglycaemia, which are of particular concern for older patients.

Methods

We conducted a meta-review by searching electronic databases (MEDLINE, EMBASE, PubMed) for systematic reviews and meta-analyses of ICS use and the adverse effects of interest. We also evaluated new primary studies that reported information beyond that available from previously published meta-analyses. Two reviewers independently extracted data on measures of associated harm with ICS use.

Results

We identified five relevant meta-analyses for inclusion in this meta-review, and also three new studies of ICS and pneumonia. We found consistent evidence of a dose–response relationship between ICS use and serious adverse effects such as fractures and pneumonia. The estimated number needed to treat for harm due to fracture with ICS was 83 with 3-years use, and 60 per year for pneumonia. Both asthma and chronic obstructive pulmonary disease (COPD) users of ICS were at risk of pneumonia, with fluticasone appearing to confer higher risk than budesonide. There is also some suggestion that ICS use is associated with cataracts in a dose–response manner but the evidence is less robust here. Equally, the influence of ICS on diabetes mellitus remains uncertain.

Conclusions

In view of the dose–response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.

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References

  1. National Clinical Guideline Centre. Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care, 2010. London; 2010. p. 1–637.

  2. White P, Thornton H, Pinnock H, Georgopoulou S, Booth HP. Overtreatment of COPD with inhaled corticosteroids—implications for safety and costs: cross-sectional observational study. PLoS One. 2013;8:e75221.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM. 2007;356:775–89.

    Article  CAS  PubMed  Google Scholar 

  4. Singh S, Amin AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis. Arch Intern Med. 2009;169:219–29.

    Article  PubMed  Google Scholar 

  5. Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax. 2011;66:699–708.

    Article  PubMed  Google Scholar 

  6. Faverio P, Aliberti S, Bellelli G, Suigo G, Lonni S, Pesci A, et al. The management of community-acquired pneumonia in the elderly. Eur J Intern Med. 2013. doi:10.1016/j.ejim.2013.12.001.

  7. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301:513–21.

    Article  CAS  PubMed  Google Scholar 

  8. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013;187:798–803.

    Article  CAS  PubMed  Google Scholar 

  9. O’Byrne PM, Rennard S, Gerstein H, Radner F, Peterson S, Lindberg B, et al. Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids. Respir Med. 2012;106:1487–93.

    Article  PubMed  Google Scholar 

  10. Singh S, Loke YK. An overview of the benefits and drawbacks of inhaled corticosteroids in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:189–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Weatherall M, Clay J, James K, Perrin K, Shirtcliffe P, Beasley R. Dose-response relationship of inhaled corticosteroids and cataracts: a systematic review and meta-analysis. Respirology. 2009;14:983–90.

    Article  PubMed  Google Scholar 

  12. Weatherall M, James K, Clay J, Perrin K, Masoli M, Wijesinghe M, et al. Dose–response relationship for risk of non-vertebral fracture with inhaled corticosteroids. Clin Exp Allergy. 2008;38:1451–8.

    Article  CAS  PubMed  Google Scholar 

  13. Eurich DT, Lee C, Marrie TJ, Majumdar SR. Inhaled corticosteroids and risk of recurrent pneumonia: a population-based, nested case–control study. Clin Infect Dis. 2013;57:1138–44.

    Article  CAS  PubMed  Google Scholar 

  14. McKeever T, Harrison TW, Hubbard R, Shaw D. Inhaled corticosteroids and the risk of pneumonia in people with asthma: a case–control study. Chest. 2013;144:1788–94.

    Article  CAS  PubMed  Google Scholar 

  15. Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68:1029–36.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Johnstone J, Eurich DT, Majumdar SR, Jin Y, Marrie TJ. Long-term morbidity and mortality after hospitalization with community-acquired pneumonia: a population-based cohort study. Medicine (Baltimore). 2008;87:329–34.

    Article  PubMed  Google Scholar 

  17. Kwok CS, Loke YK, Woo K, Myint PK. Risk prediction models for mortality in community-acquired pneumonia: a systematic review. Biomed Res Int. 2013;2013:504136. doi:10.1155/2013/504136.

  18. Mortensen EM, Kapoor WN, Chang CC, Fine MJ. Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia. Clin Infect Dis. 2003;37:1617–24.

    Article  PubMed  Google Scholar 

  19. Kaplan V, Clermont G, Griffin MF, Kasal J, Watson RS, Linde-Zwirble WT, et al. Pneumonia: still the old man’s friend? Arch Intern Med. 2003;163:317–23.

    Article  PubMed  Google Scholar 

  20. Davydow DS, Hough CL, Levine DA, Langa KM, Iwashyna TJ. Functional disability, cognitive impairment, and depression after hospitalization for pneumonia. Am J Med. 2013;126(615–24):e5.

    PubMed  Google Scholar 

  21. Loke YK, Kwok CS, Singh S. Risk of myocardial infarction and cardiovascular death associated with inhaled corticosteroids in COPD. Eur Respir J. 2010;35:1003–21.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

YK Loke and AM Wilson were awarded a grant of £30,000 from Asthma UK charity (AUK-PG-2012-181). K. Mattishent, M. Thavarajah, P. Blanco and D. Gilbert declare no relevant conflicts of interest. The authors designed this study, collected and analysed data, and wrote the manuscript independently of Asthma UK.

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Authors and Affiliations

  1. Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK

    Katharina Mattishent, Menaka Thavarajah, Patricia Blanco, Daniel Gilbert, Andrew M. Wilson & Yoon K. Loke

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  1. Katharina Mattishent
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  2. Menaka Thavarajah
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  3. Patricia Blanco
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  4. Daniel Gilbert
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  5. Andrew M. Wilson
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  6. Yoon K. Loke
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Correspondence to Yoon K. Loke.

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Mattishent, K., Thavarajah, M., Blanco, P. et al. Meta-Review: Adverse Effects of Inhaled Corticosteroids Relevant to Older Patients. Drugs 74, 539–547 (2014). https://doi.org/10.1007/s40265-014-0202-z

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