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  Position Statement

Academy Position Statement: Inhaled Corticosteroids and Systemic Infections

This position statement was originally released in 1993 under the same title. It was updated, reviewed by the membership and the Board of Directors, and published on the Academy Web site in 2002 under the title: "Inhaled Corticosteroids and Systemic Infections."

The statement below is not to be construed as dictating an exclusive course of action nor is it intended to replace the medical judgment of healthcare professionals. The unique circumstances of individual patients and environments are to be taken into account in any diagnosis and treatment plan. The above statement reflects clinical and scientific advances as of the date of publication and is subject to change.

Corticosteroids play an important role in the control and management of asthma and allergic rhinitis. Systemically administered corticosteroids may place patients at risk of life threatening infections, particularly viral infections (e.g. varicella), presumably because of T-cell suppression.1,2 Pharmacological systemic doses of corticosteroids are also associated with decreased immunoglobulin levels in some individuals,3,4,5,6 although the ability to respond with a proper antibody response to antigen appears to remain intact.5,7

The actual extent to which oral and parenteral corticosteroid treatment predisposes patients who are not immunocompromised to severe or increased infections has actually not been clearly established. The most frequently studied type of infection in this regard is varicella. Although single case reports of fatal varicella infection in normal children with asthma receiving systemic corticosteroids suggest a potential danger,8,9,10 there are other studies that conclude systemic corticosteroids do not contribute to the morbidity or mortality rates associated with varicella in patients with asthma.11,12,13 Use of systemic corticosteroids for acute asthma or when given in the preoperative period has not been found to result in an increased risk of bacterial infections needing antibiotics.14,15

Systemic effects of inhaled corticosteroids can occur, especially when high doses are used for long periods. Minor but definite alterations of adrenal-hypothalmic-pituitary axis function have been noted in patients receiving inhaled corticosteroids,16 but these changes are rarely clinically significant. Because of the different degrees of end organ sensitivity to corticosteroids,17 it is not possible to extrapolate from these endocrine effects to a concern that inhaled corticosteroids also have significant effects on the immune system. In fact, usual doses of inhaled corticosteroids for asthma and allergic rhinitis have been found to have minimal to no measurable effects on the immune system.18,19,20,21,22,23,24

Furthermore, to date, there has been no link established between inhaled corticosteroids and pulmonary or systemic infections. A review of the extensive medical literature on beclomethasone dipropionate (BDP), an inhaled corticosteroid steroid available for clinical use since the 1970s, failed to identify any association between severe viral infections (e.g., varicella, measles) and inhaled BDP.25 Considerable clinical experience has also accumulated with the other inhaled corticosteroids (triamcinolone acetonide, flunisolide, budesonide, fluticasone propionate) and as with BDP, an increased tendency toward infections other than occasional oral candidiasis has not been noted.16, 26-31

In support of this is the fact that the 2000 Red Book (report of the Committee on Infectious Diseases, American Academy of Pediatrics) has not deemed it necessary to warn against the administration of live virus vaccines in patients who are receiving inhaled corticosteroids.32 A large survey of allergists conducted in 1993 to assess if there was a perception of increased infections being seen in their patients on inhaled corticosteroids did not reveal a concern for this being a complication of inhaled corticosteroid treatment.33, 34

In summary, treatment of asthma and allergic rhinitis with inhaled corticosteroids at usual and customary doses does not appear to predispose individuals to increased numbers of systemic infections, or more serious infections.

References

  1. Sloman JC, Bell PA. Cell cycle-specific effects of glucocorticoids on phytohemagglutinin-stimulated lymphocytes. Clin Exp Immunol 1980; 39:503-9.
  2. Hahn BH, MacDermott RP, Jacobs SB, et al. Immunosupressive effects of low doses of glucocorticoids: effects on autologous and allogeneic mixed leukocyte reactions. J Immunol 1980; 125:2812-7.
  3. Butler WT, Rossen RD. Effects of corticosteroids on immunity in man. J Clin Invest 1973; 52:2629-40.
  4. Katz Y, Harbeck RJ, DeMichelle D, Mitchell B, Strunk RC. Steroid-treated asthmatic patients with low levels of IgG have a normal capacity to produce specific antibodies. Pediatr Asthma Allergy Immunol 1988; 2:309-16.
  5. Berger W, Pollock J, Kiechel F, Danning M, Pearlman DS. Immunogloubilin levels in children with chronic severe asthma. Ann Allergy 1978; 41:67-74.
  6. Lack G, Ochs HD, Gelfand EW. Humoral immunity in steroid-dependent children with asthma and hypogammaglobulinemia. J Pediatr 1996; 129: 898-903.
  7. Silk HJ, Guay-Woodford L, Perez-Atayde AR, Geha RS, Broff MD. Fatal varicella in steroid-dependent asthma. J Allergy Clin Immunol 1988; 81:47-51.
  8. Lantner R, Rockoff JB, Demasi J, Boran-Ragotzy R, Middleton E. Fatal disseminated varicella in a patient with corticosteroid-dependent asthma receiving troleandomycin. Allergy Proc 1990; 11:83-7.
  9. Kasper WJ, Howe PM. Fatal varicella after a single course of corticosteroids. Pediatr Infect Dis J 1990; 9:729-32.
  10. Falliers CJ, Ellis EF. Corticosteroids and varicella. Arch Dis Child 1965; 40:593-9.
  11. Girsh LS, Yu M, Jones J, Schulaner FA. A study of the risk of mortality of varicella in patients with bronchial asthma or other allergic disease receiving corticosteroid therapy. Ann Allergy 1966; 24:690-3.
  12. Weinberg EG, Tuchinda M. Varicella in asthma children receiving alternate-day corticosteroid therapy. J Med Assoc Thailand 1973; 56:140-3.
  13. Davis H, Gergen PJ, Graham DJ. J Asthma 1998; 35(5): 419-25.
  14. Kabalin CS, Yarnold PR, Grammer LC. Low complication rate of corticosteroid-treated asthmatics undergoing surgical procedures. Arch Intern Med 1995; 155(13): 1379-84.
  15. Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. American Jl of Medicine 1995; 98:196-208.
  16. Morris HG. Factors that influence clinical responses to administered corticosteroids. J Allergy Clin Immunol 1980; 66:343-6.
  17. Businco L, Galli E, Rossi P, et al. Immune system evaluation in chronic asthmatic children receiving long-term treatment with beclomethasone. Prog Respir Res 1981; 17:290-8.
  18. Chiang J, Patterson R, McGillen J, et al. The evaluation of selected parameters of immune function in asthmatics after long-term corticosteroid therapy. Clin Allergy 1979; 9:397-410.
  19. Puddu M, Galli E, Rossi P, et al. Evaluation of the immune system in children with bronchial asthma treated with beclomethasone dipropionate. Minerva Pediatr 1981; 33:593-6.
  20. Knight A, Kolin A. Long term efficacy and safety of beclomethasone dipropionate aerosol in perennial rhinitis. Ann Allergy 1983; 50:81-4.
  21. Bunnag C, Chorranintra B, Supiyaphua P, et al. Beclomethasone dipropionate and flunisolide: an open-crossover comparative trial in perennial allergic rhinitis. Asian Pac J Allergy Immunol 1984; 2:202-6.
  22. Welsh PW, Stricker WE, Chu C-P, et al. Efficacy of beclomethasone nasal solution, flunisolide and cromolyn in relieving symptoms of ragweed allergy. Mayo Clin Proc 1987;62:125-34.
  23. Freed DLJ, Sinclaire T, Topper R, et al. IgA levels in rhinitis nasal secretions during short-term therapy with sodium cromoglycate, beclomethasone and antihistamine. In: Pepys J, Edwards AM, eds. The mast cell: its role in health and disease. Kent, England: Pitman Medical 1979; 895-804.
  24. Brogden RN, Heel RC, Spight TM, Avery GS. Beclomethasone dipropionate - a reappraisal of its pharmacodynamic properties and therapeutic efficacy. Drugs 1984; 28:99-126.
  25. Golub JR. Long-term triamcinolone acetonide aerosol treatment in adult patients with chronic bronchial asthma. Ann Allergy 1980; 44:131-7.
  26. Davis KC, Small RE. Budesonide inhalation powder: a review of its pharmacological properties and role in the treatment of asthma. Pharmacotherapy 1998; 18(4):720-8.
  27. Brogden RN, McTavish D. Budesonide. An update review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis. Drugs 1992; 44(3):375-4 07.
  28. Szefler SJ. A review of budesonide inhalation suspension in the tratment of pediatric asthma. Pharmacotherapy 2001; 21(2):195-206.
  29. Fuller R, Johnson M, Bye A. Fluticasone propionate - an update on preclinical and clinical experience. Respir Med 1995; 89 (Supplement A):3-18.
  30. Passalacqua G, Albano M, Canonica GW, Bachert C, et al. Inhaled and nasal corticosteroids: safety aspects. Allergy 2000; 55(1);16-33.
  31. Committee on Infectious Disease, American Academy of Pediatrics. Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, Illinois: American Academy of Pediatrics, 2000: 636.
  32. Welch, MJ. Inhaled steroids and severe viral infections. J Asthma 1994;31(1): 43-50.
  33. Welch MJ, Segal A, Tobey R, Szefler S, Simons FE. Inhaled corticosteroids and viral infections. J Allergy Clin Immunology 1994; 93:18.
2002 revision was drafted by:
Richard A. Nicklas, MD, FAAAAI
Michael J. Welch, MD, FAAAAI

And reviewed by the membership and the 2002 Board of Directors.

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