Skip to main content
PMC home page
Journal of the National Medical Association logoLink to Journal of the National Medical Association
. 2006 Jun;98(6):851–861.

Safety of inhaled corticosteroids in the treatment of persistent asthma.

Stephen P Peters 1
PMCID: PMC2569377  PMID: 16775906

Abstract

OBJECTIVE: Inhaled corticosteroids (ICSs) are the most effective medications available for patients with persistent asthma of all severities and currently are recommended as the preferred asthma controller therapy by the National Heart, Lung and Blood Institute. Nevertheless, lingering concerns about potential adverse systemic effects of ICSs contribute to their underuse. This review discusses the safety of ICSs with respect to potential systemic effects of most concern to physicians and patients. METHODS: Articles reporting on the safety of ICSs in children and adults with persistent asthma were identified from the Medline database from January 1966 through December 2003, reference lists of review articles and international respiratory meetings. RESULTS: Ocular effects of ICSs and ICS effects on bone mineral density and adrenal function are minimal in patients maintained on recommended ICS doses. One-year growth studies in children have shown decreased growth velocity with ICSs, but long-term studies with inhaled budesonide and beclomethasone show no effect on final adult height, suggesting that these effects are transient. In addition, extensive data from the Swedish Medical Birth Registry show no increased risk of adverse perinatal outcomes when inhaled budesonide is administered to pregnant women with asthma. CONCLUSIONS: ICSs have minimal systemic effects in most patients when taken at recommended doses. The benefits of ICS therapy clearly outweigh the risks of uncontrolled asthma, and ICSs should be prescribed routinely as first-line therapy for children and adults with persistent disease.

Full text

PDF
861

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abuekteish F., Kirkpatrick J. N., Russell G. Posterior subcapsular cataract and inhaled corticosteroid therapy. Thorax. 1995 Jun;50(6):674–676. doi: 10.1136/thx.50.6.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Acquavella John, Doe John, Tomenson John, Chester Graham, Cowell John, Bloemen Louis. Epidemiologic studies of occupational pesticide exposure and cancer: regulatory risk assessments and biologic plausibility. Ann Epidemiol. 2003 Jan;13(1):1–7. doi: 10.1016/s1047-2797(02)00423-4. [DOI] [PubMed] [Google Scholar]
  3. Agertoft L., Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000 Oct 12;343(15):1064–1069. doi: 10.1056/NEJM200010123431502. [DOI] [PubMed] [Google Scholar]
  4. Allen D. B., Bronsky E. A., LaForce C. F., Nathan R. A., Tinkelman D. G., Vandewalker M. L., Konig P. Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group. J Pediatr. 1998 Mar;132(3 Pt 1):472–477. doi: 10.1016/s0022-3476(98)70023-x. [DOI] [PubMed] [Google Scholar]
  5. Allen David B. Safety of inhaled corticosteroids in children. Pediatr Pulmonol. 2002 Mar;33(3):208–220. doi: 10.1002/ppul.10040. [DOI] [PubMed] [Google Scholar]
  6. Amin Shreyasee, Lavalley Michael P., Simms Robert W., Felson David T. The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res. 2002 Aug;17(8):1512–1526. doi: 10.1359/jbmr.2002.17.8.1512. [DOI] [PubMed] [Google Scholar]
  7. Bahceciler Nerin N., Sezgin Gülay, Nursoy Mustafa A., Barlan Isil B., Basaran Mujdat M. Inhaled corticosteroids and bone density of children with asthma. J Asthma. 2002 Apr;39(2):151–157. doi: 10.1081/jas-120002196. [DOI] [PubMed] [Google Scholar]
  8. Baker J. W., Mellon M., Wald J., Welch M., Cruz-Rivera M., Walton-Bowen K. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics. 1999 Feb;103(2):414–421. doi: 10.1542/peds.103.2.414. [DOI] [PubMed] [Google Scholar]
  9. Balkrishnan R., Norwood G. J., Anderson A. Outcomes and cost benefits associated with the introduction of inhaled corticosteroid therapy in a medicaid population of asthmatic patients. Clin Ther. 1998 May-Jun;20(3):567–580. doi: 10.1016/s0149-2918(98)80066-0. [DOI] [PubMed] [Google Scholar]
  10. Boorsma M., Andersson N., Larsson P., Ullman A. Assessment of the relative systemic potency of inhaled fluticasone and budesonide. Eur Respir J. 1996 Jul;9(7):1427–1432. doi: 10.1183/09031936.96.09071427. [DOI] [PubMed] [Google Scholar]
  11. Boothby L. A., Doering P. L. FDA labeling system for drugs in pregnancy. Ann Pharmacother. 2001 Nov;35(11):1485–1489. doi: 10.1345/aph.1A034. [DOI] [PubMed] [Google Scholar]
  12. Boulet L. P., Milot J., Gagnon L., Poubelle P. E., Brown J. Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss? Am J Respir Crit Care Med. 1999 Mar;159(3):838–844. doi: 10.1164/ajrccm.159.3.9802096. [DOI] [PubMed] [Google Scholar]
  13. Cumming R. G., Mitchell P., Leeder S. R. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med. 1997 Jul 3;337(1):8–14. doi: 10.1056/NEJM199707033370102. [DOI] [PubMed] [Google Scholar]
  14. Doull I. J., Freezer N. J., Holgate S. T. Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Am J Respir Crit Care Med. 1995 Jun;151(6):1715–1719. doi: 10.1164/ajrccm.151.6.7767512. [DOI] [PubMed] [Google Scholar]
  15. Elmståhl Sölve, Ekström Henrik, Galvard Herbert, Johnell Olof, Gerhardsson de Verdier Maria, Norjavaara Ensio. Is there an association between inhaled corticosteroids and bone density in postmenopausal women? J Allergy Clin Immunol. 2003 Jan;111(1):91–96. doi: 10.1067/mai.2003.4. [DOI] [PubMed] [Google Scholar]
  16. Garbe E., LeLorier J., Boivin J. F., Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA. 1997 Mar 5;277(9):722–727. [PubMed] [Google Scholar]
  17. Garbe E., Suissa S., LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA. 1998 Aug 12;280(6):539–543. doi: 10.1001/jama.280.6.539. [DOI] [PubMed] [Google Scholar]
  18. Greenberger P. A., Patterson R. Beclomethasone diproprionate for severe asthma during pregnancy. Ann Intern Med. 1983 Apr;98(4):478–480. doi: 10.7326/0003-4819-98-4-478. [DOI] [PubMed] [Google Scholar]
  19. Hanania N. A., Chapman K. R., Sturtridge W. C., Szalai J. P., Kesten S. Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol. 1995 Nov;96(5 Pt 1):571–579. doi: 10.1016/s0091-6749(95)70254-7. [DOI] [PubMed] [Google Scholar]
  20. Heuck C., Wolthers O. D., Kollerup G., Hansen M., Teisner B. Adverse effects of inhaled budesonide (800 micrograms) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration. J Pediatr. 1998 Nov;133(5):608–612. doi: 10.1016/s0022-3476(98)70098-8. [DOI] [PubMed] [Google Scholar]
  21. Hubbard Richard B., Smith Chris J. P., Smeeth Liam, Harrison Tim W., Tattersfield Anne E. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med. 2002 Sep 25;166(12 Pt 1):1563–1566. doi: 10.1164/rccm.200206-606OC. [DOI] [PubMed] [Google Scholar]
  22. Hughes J. A., Conry B. G., Male S. M., Eastell R. One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density. Thorax. 1999 Mar;54(3):223–229. doi: 10.1136/thx.54.3.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ip M., Lam K., Yam L., Kung A., Ng M. Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids. Chest. 1994 Jun;105(6):1722–1727. doi: 10.1378/chest.105.6.1722. [DOI] [PubMed] [Google Scholar]
  24. Israel E., Banerjee T. R., Fitzmaurice G. M., Kotlov T. V., LaHive K., LeBoff M. S. Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med. 2001 Sep 27;345(13):941–947. doi: 10.1056/NEJMoa002304. [DOI] [PubMed] [Google Scholar]
  25. Kemp J. P., Skoner D. P., Szefler S. J., Walton-Bowen K., Cruz-Rivera M., Smith J. A. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol. 1999 Sep;83(3):231–239. doi: 10.1016/S1081-1206(10)62646-4. [DOI] [PubMed] [Google Scholar]
  26. Lipworth B. J. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med. 1999 May 10;159(9):941–955. doi: 10.1001/archinte.159.9.941. [DOI] [PubMed] [Google Scholar]
  27. Lung Health Study Research Group Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med. 2000 Dec 28;343(26):1902–1909. doi: 10.1056/NEJM200012283432601. [DOI] [PubMed] [Google Scholar]
  28. Martin Richard J., Szefler Stanley J., Chinchilli Vernon M., Kraft Monica, Dolovich Myrna, Boushey Homer A., Cherniack Reuben M., Craig Timothy J., Drazen Jeffrey M., Fagan Joanne K. Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med. 2002 May 15;165(10):1377–1383. doi: 10.1164/rccm.2105013. [DOI] [PubMed] [Google Scholar]
  29. Martinati L. C., Bertoldo F., Gasperi E., Micelli S., Boner A. L. Effect on cortical and trabecular bone mass of different anti-inflammatory treatments in preadolescent children with chronic asthma. Am J Respir Crit Care Med. 1996 Jan;153(1):232–236. doi: 10.1164/ajrccm.153.1.8542121. [DOI] [PubMed] [Google Scholar]
  30. Medici T. C., Grebski E., Häcki M., Rüegsegger P., Maden C., Efthimiou J. Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects. Thorax. 2000 May;55(5):375–382. doi: 10.1136/thorax.55.5.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Norjavaara Ensio, de Verdier Maria Gerhardsson. Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide. J Allergy Clin Immunol. 2003 Apr;111(4):736–742. doi: 10.1067/mai.2003.1340. [DOI] [PubMed] [Google Scholar]
  32. Packe G. E., Robb O., Robins S. P., Reid D. M., Douglas J. G. Bone density in asthmatic patients taking inhaled corticosteroids: comparison of budesonide and beclomethasone dipropionate. J R Coll Physicians Lond. 1996 Mar-Apr;30(2):128–132. [PMC free article] [PubMed] [Google Scholar]
  33. Passalacqua G., Albano M., Canonica G. W., Bachert C., Van Cauwenberge P., Davies R. J., Durham S. R., Kontou-Fili K., Horak F., Malling H. J. Inhaled and nasal corticosteroids: safety aspects. Allergy. 2000 Jan;55(1):16–33. doi: 10.1034/j.1398-9995.2000.00370.x. [DOI] [PubMed] [Google Scholar]
  34. Pauwels Romain A., Pedersen Søren, Busse William W., Tan Wan C., Chen Yu-Zhi, Ohlsson Stefan V., Ullman Anders, Lamm Carl Johan, O'Byrne Paul M., START Investigators Group Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet. 2003 Mar 29;361(9363):1071–1076. doi: 10.1016/S0140-6736(03)12891-7. [DOI] [PubMed] [Google Scholar]
  35. Reed C. E., Offord K. P., Nelson H. S., Li J. T., Tinkelman D. G. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. J Allergy Clin Immunol. 1998 Jan;101(1 Pt 1):14–23. doi: 10.1016/s0091-6749(98)70187-3. [DOI] [PubMed] [Google Scholar]
  36. Richy Florent, Bousquet Jean, Ehrlich George E., Meunier Pierre J., Israel Elliot, Morii Hirotoshi, Devogelaer Jean-Pierre, Peel Nicola, Haim Muriel, Bruyere Olivier. Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int. 2003 Apr 23;14(3):179–190. doi: 10.1007/s00198-003-1398-z. [DOI] [PubMed] [Google Scholar]
  37. Roux Christian, Kolta Sami, Desfougères Jean-Luc, Minini Pascal, Bidat Etienne. Long-term safety of fluticasone propionate and nedocromil sodium on bone in children with asthma. Pediatrics. 2003 Jun;111(6 Pt 1):e706–e713. doi: 10.1542/peds.111.6.e706. [DOI] [PubMed] [Google Scholar]
  38. Schatz M. The efficacy and safety of asthma medications during pregnancy. Semin Perinatol. 2001 Jun;25(3):145–152. doi: 10.1053/sper.2001.24569. [DOI] [PubMed] [Google Scholar]
  39. Schatz M., Zeiger R. S., Harden K., Hoffman C. C., Chilingar L., Petitti D. The safety of asthma and allergy medications during pregnancy. J Allergy Clin Immunol. 1997 Sep;100(3):301–306. doi: 10.1016/s0091-6749(97)70241-0. [DOI] [PubMed] [Google Scholar]
  40. Simons F. E. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. N Engl J Med. 1997 Dec 4;337(23):1659–1665. doi: 10.1056/NEJM199712043372304. [DOI] [PubMed] [Google Scholar]
  41. Simons F. E., Persaud M. P., Gillespie C. A., Cheang M., Shuckett E. P. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids. Lancet. 1993 Sep 25;342(8874):776–778. doi: 10.1016/0140-6736(93)91541-s. [DOI] [PubMed] [Google Scholar]
  42. Smeeth L., Boulis M., Hubbard R., Fletcher A. E. A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol. 2003 Oct;87(10):1247–1251. doi: 10.1136/bjo.87.10.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Suissa S., Ernst P., Benayoun S., Baltzan M., Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000 Aug 3;343(5):332–336. doi: 10.1056/NEJM200008033430504. [DOI] [PubMed] [Google Scholar]
  44. Suissa S., Ernst P., Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002 Oct;57(10):880–884. doi: 10.1136/thorax.57.10.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Szefler Stanley J., Lyzell Ewa, Fitzpatrick Sherahe, Cruz-Rivera Mario. Safety profile of budesonide inhalation suspension in the pediatric population: worldwide experience. Ann Allergy Asthma Immunol. 2004 Jul;93(1):83–90. doi: 10.1016/S1081-1206(10)61451-2. [DOI] [PubMed] [Google Scholar]
  46. Szefler Stanley J., Martin Richard J., King Tonya Sharp, Boushey Homer A., Cherniack Reuben M., Chinchilli Vernon M., Craig Timothy J., Dolovich Myrna, Drazen Jeffrey M., Fagan Joanne K. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002 Mar;109(3):410–418. doi: 10.1067/mai.2002.122635. [DOI] [PubMed] [Google Scholar]
  47. Tattersfield A. E., Town G. I., Johnell O., Picado C., Aubier M., Braillon P., Karlström R. Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax. 2001 Apr;56(4):272–278. doi: 10.1136/thorax.56.4.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tinkelman D. G., Reed C. E., Nelson H. S., Offord K. P. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatrics. 1993 Jul;92(1):64–77. [PubMed] [Google Scholar]
  49. Tinkelman David G., Bronsky Edwin A., Gross Gary, Schoenwetter William F., Spector Sheldon L. Efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler) during 52 weeks of treatment in adults and children with persistent asthma. J Asthma. 2003 May;40(3):225–236. doi: 10.1081/jas-120020186. [DOI] [PubMed] [Google Scholar]
  50. Todd G. R. G., Acerini C. L., Ross-Russell R., Zahra S., Warner J. T., McCance D. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002 Dec;87(6):457–461. doi: 10.1136/adc.87.6.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Todd G., Dunlop K., McNaboe J., Ryan M. F., Carson D., Shields M. D. Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate. Lancet. 1996 Jul 6;348(9019):27–29. doi: 10.1016/s0140-6736(96)03339-9. [DOI] [PubMed] [Google Scholar]
  52. Toogood J. H., Markov A. E., Baskerville J., Dyson C. Association of ocular cataracts with inhaled and oral steroid therapy during long-term treatment of asthma. J Allergy Clin Immunol. 1993 Feb;91(2):571–579. doi: 10.1016/0091-6749(93)90263-f. [DOI] [PubMed] [Google Scholar]
  53. Wang W. Q., Ip M. S., Tsang K. W., Lam K. S. Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: a prospective study for 18 months. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 1):445–450. doi: 10.1016/S0091-6749(98)70351-3. [DOI] [PubMed] [Google Scholar]
  54. Wilson A. M., Dempsey O. J., Coutie W. J., Sims E. J., Lipworth B. J. Importance of drug-device interaction in determining systemic effects of inhaled corticosteroids. Lancet. 1999 Jun 19;353(9170):2128–2128. doi: 10.1016/S0140-6736(99)01443-9. [DOI] [PubMed] [Google Scholar]
  55. van Staa T. P., Cooper C., Leufkens H. G. M., Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. 2003 May;18(5):913–918. doi: 10.1359/jbmr.2003.18.5.913. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the National Medical Association are provided here courtesy of National Medical Association

RESOURCES