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Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis

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Abstract

Background

Recent studies have suggested a possible association between respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to ascertain the risk of upper respiratory tract infection (URTI) with long-term inhaled corticosteroid use among patients with asthma.

Methods

Through a comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google Scholar from inception to May 2018, we included randomized controlled trials of any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse event. We conducted meta-analyses by the Peto approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI.

Results

Seventeen trials (15,336 subjects) were included. Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08–1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05–2.03; I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04–1.39; I2 = 25%; p = 0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto OR, 1.18; 95% CI 1.02–1.38; p = 0.03; heterogeneity: I2 = 21%) but not budesonide, low-dose fluticasone treatment was associated with a significantly higher risk of URTI but not high dose.

Conclusions

This study raises safety concerns about the risk of URTI associated with ICS use in patients with asthma, but it should be further investigated.

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References

  1. Thomson NC, Spears M. Inhaled corticosteroids for asthma: on-demand or continuous use. Expert Rev Respir Med. 2013;7(6):687–99.

    Article  CAS  PubMed  Google Scholar 

  2. Barnes PJ, Pedersen S. Efficacy and safety of inhaled corticosteroids in asthma. Report of a workshop held in Eze, France, October 1992. Am Rev Respir Dis. 1993;148(4 Pt 2):1–26

    Article  Google Scholar 

  3. Juniper EF, Kline PA, Vanzieleghem MA, Ramsdale EH, O’Byrne PM, Hargreave FE. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. 1990;142(4):832–6.

    Article  CAS  PubMed  Google Scholar 

  4. GlaxoSmithKline. GlaxoSmithKline clinical trials register. http://ctr.gsk.co.uk/medicinelist.asp. Accessed 26 Aug 2008.

  5. 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(3):219–29.

    Article  PubMed  Google Scholar 

  6. Zhang L, Prietsch SO, Mendes AP,et al. Inhaled corticosteroids increase the risk of oropharyngeal colonization by Streptococcus pneumoniae in children with asthma. Respirology. 2013;18(2):272–7.

    Article  PubMed  Google Scholar 

  7. Calverley P, Anderson J, Celli B, TORCH Investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. New Engl J Med. 2007;356:775–89.

    Article  CAS  PubMed  Google Scholar 

  8. Yang M, Chen H, Zhang Y, Du Y, Xu Y, Jiang P, Xu Z. Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis. Inhal Toxicol. 2017;29(5):219–26.

    Article  CAS  PubMed  Google Scholar 

  9. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sheffer AL, Silverman M, Woolcock AJ, Díaz PV, Lindberg B, Lindmark B. Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study. Ann Allergy Asthma Immunol. 2005;94(1):48–54.

    Article  CAS  PubMed  Google Scholar 

  11. Corren J, Korenblat PE, Miller CJ, O’Brien CD, Mezzanotte WS. Twelve-week, randomized, placebo-controlled, multicenter study of the efficacy and tolerability of budesonide and formoterol in one metered-dose inhaler compared with budesonide alone and formoterol alone in adolescents and adults with asthma. Clin Ther. 2007;29(5):823–43.

    Article  CAS  PubMed  Google Scholar 

  12. Karpel JP, Nayak A, Lumry W, Craig TJ, Kerwin E, Fish JE, Lutsky B. Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma. Respir Med. 2007;101(3):628–37.

    Article  PubMed  Google Scholar 

  13. Woodcock A, Bateman ED, Busse WW, Lötvall J, Snowise NG, Forth R, Jacques L, Haumann B, Bleecker ER. Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial. Respir Res. 2011;12:132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Busse WW, Bleecker ER, Bateman ED, Lötvall J, Forth R, Davis AM, Jacques L, Haumann B, Woodcock A. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax. 2012;67(1):35–41.

    Article  PubMed  Google Scholar 

  15. Busse WW, Bateman ED, O’Byrne PM, Lötvall J, Woodcock A, Medley H, Forth R, Jacques L. Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial. Allergy. 2014;69(11):1522–30.

    Article  CAS  PubMed  Google Scholar 

  16. Lin J, Tang H, Chen P, Wang H, Kim MK, Crawford J, Jacques L, Stone S. Efficacy and safety evaluation of once-daily fluticasone furoate/vilanterol in Asian patients with asthma uncontrolled on a low- to mid-strength inhaled corticosteroid or low-dose inhaled corticosteroid/long-acting beta2-agonist. Allergy Asthma Proc. 2016;37(4):302–10.

    Article  CAS  PubMed  Google Scholar 

  17. Nathan RA, Rooklin A, Schoaf L, Scott C, Ellsworth A, House K, Dorinsky P. Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study. Clin Ther. 2006;28(1):73–85.

    Article  CAS  PubMed  Google Scholar 

  18. Oliver A, Bjermer L, Quinn D, Saggu P, Thomas P, Yarnall K, Lötvall J. Modulation of allergen-induced bronchoconstriction by fluticasone furoate and vilanterol alone or in combination. Allergy. 2013;68(9):1136–42.

    CAS  PubMed  Google Scholar 

  19. O’Byrne PM, Woodcock A, Bleecker ER, Bateman ED, Lötvall J, Forth R, Medley H, Jacques L, Busse WW. Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial. Respir Res. 2014;15:88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lumry WR, Conway MM, LaForce CF, Pearlman DS, Scott CA, Herje NE, Wu WW, Crim C. Fluticasone propionate hydrofluoroalkane inhalation aerosol in patients receiving inhaled corticosteroids. Ann Allergy Asthma Immunol. 2006;96(1):51–9.

    Article  CAS  PubMed  Google Scholar 

  21. D’Urzo A, Karpel JP, Busse WW, Boulet LP, Monahan ME, Lutsky B, Staudinger H. Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids. Curr Med Res Opin. 2005;21(8):1281–9.

    Article  CAS  PubMed  Google Scholar 

  22. Chapman KR, Patel P, D’Urzo AD, Alexander M, Mehra S, Oedekoven C, Engelstätter R, Boulet LP. Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma. Allergy. 2005;60(3):330–7.

    Article  CAS  PubMed  Google Scholar 

  23. Noonan M, Rosenwasser LJ, Martin P, O’Brien CD, O’Dowd L. Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial. Drugs. 2006;66(17):2235–54.

    Article  CAS  PubMed  Google Scholar 

  24. Chuchalin A, Jacques L, Frith L. Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids. Clin Drug Investig. 2008;28(3):169–81.

    Article  CAS  PubMed  Google Scholar 

  25. Woodcock A, Bleecker ER, Busse WW, Lötvall J, Snowise NG, Frith L, Jacques L, Haumann B, Bateman ED. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma. Respir Res. 2011;12:160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lötvall J, Bleecker ER, Busse WW, O’Byrne PM, Woodcock A, Kerwin EM, Stone S, Forth R, Jacques L, Bateman ED. Efficacy and safety of fluticasone furoate 100 µg once-daily in patients with persistent asthma: a 24-week placebo and active-controlled randomised trial. Respir Med. 2014;108(1):41–9.

    Article  PubMed  Google Scholar 

  27. Uchida A, Sakaue K, Inoue H. Epidemiology of asthma-chronic obstructive pulmonary disease overlap (ACO). Allergol Int. 2018;67(2):165–71.

    Article  PubMed  Google Scholar 

  28. Zervas E, Samitas K, Papaioannou AI, Bakakos P, Loukides S, Gaga M. An algorithmic approach for the treatment of severe uncontrolled asthma. ERJ Open Res. 2018;4(1):00125–2017.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Global Strategy for Asthma Management and Prevention. http://ginasthma.org/gina-reports/. Accessed May 2016.

  30. Brassard P, Lowe AM, Bernatsky S, Kezouh A, Suissa S. Rheumatoid arthritis, its treatments, and the risk of tuberculosis in Quebec, Canada. Arthritis Rheum. 2009;61:300–4.

    Article  PubMed  Google Scholar 

  31. Singh S, Amin A, Loke Y. 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 

  32. Bansal V, Mangi MA, Johnson MM, Festic E. Inhaled corticosteroids and incident pneumonia in patients with asthma: systematic review and meta-analysis. Acta Med Acad. 2015;44(2):135–58.

    PubMed  Google Scholar 

  33. Cazeiro C, Silva C, Mayer S, Mariany V, Wainwright CE. Inhaled corticosteroids and respiratory infections in children with asthma: a meta-analysis. Pediatrics. 2017;139(3):e20163271.

    Article  PubMed  Google Scholar 

  34. Bleecker ER, Lotvall J, O’Byrne PM, Woodcock A, Busse WW, Kerwin EM, et al. Fluticasone furoatevilanterol 100–25 mcg compared with fluticasone furoate 100 mcg in asthma: a randomized trial. J Allergy Clin Immunol Pract. 2014;2(5):553–61.

    Article  PubMed  Google Scholar 

  35. Suissa S, McGhan R, Niewoehner D, Make B. Inhaled corticosteroids in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2007;4(7):535–42.

    Article  CAS  PubMed  Google Scholar 

  36. Singh A, Aman AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease. Arch Intern Med. 2009;169(3):219–29.

    Article  PubMed  Google Scholar 

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Acknowledgements

All authors contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript. The authors are indebted to all members of the Respiratory Diseases Laboratory of Chengdu Second People’s Hospital. Financial Support: Natural Science Foundation of China, Project Grant Numbers: 81650003. Chengdu Health Bureau Science and Technology Research Fund, Project Number: 20140735. Chengdu Science and Technology Project, Project Application Numbers: 2015-HM0100621-SF. The funding bodies had no role in the study design, manuscript writing, or decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Respiratory Diseases Laboratory, Chengdu Second People’s Hospital, No. 10, Qingyun South Street, Chengdu, 610017, China

    Mingjin Yang, Hong Chen, Jiachen Lin, Jiatao Zeng & Zhibo Xu

  2. Digestive System Department, Chengdu Second People’s Hospital, Chengdu, China

    Yan Zhang

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  1. Mingjin Yang
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Correspondence to Zhibo Xu.

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Yang, M., Zhang, Y., Chen, H. et al. Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis. Infection 47, 377–385 (2019). https://doi.org/10.1007/s15010-018-1229-y

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