Skip to main content
SpringerLink
Log in

Safety Considerations of Inhaled Corticosteroids in the Elderly

  • Therapy in Practice
  • Published:
Drugs & Aging Aims and scope Submit manuscript

An Erratum to this article was published on 17 November 2015

Abstract

Inhaled corticosteroids (ICSs) are widely used in the treatment of patients with chronic obstructive pulmonary diseases. However, high-dose regimens and long-term use of ICSs have the potential to cause a variety of local and systemic side effects such as candidiasis, cataracts, glaucoma, and osteoporosis. The use of ICSs can also be associated with the risk of bone fractures, diabetes mellitus and pneumonia. These ICS-related side effects are of particular importance in elderly patients due to the presence of comorbidities and age-related behavioral, cognitive, and psychological problems, which can all interact with inhaled treatment. We reviewed the available literature on the clinically relevant side effects of ICSs in the elderly to provide practical measures to properly monitor and manage the risk of ICSs in the geriatric population. Inspection of the mouth, monitoring of ocular pressure, and use of bone-protective drugs may be necessary in patients on prolonged ICS therapy. Above all, the use of the lowest possible ICS dose and a careful re-assessment of the inhalation procedure should be recommended. Taken together, these observations suggest that physicians should use ICSs appropriately for those patients in whom the benefit will outweigh the risk, especially chronic obstructive pulmonary disease (COPD) patients with previous frequent exacerbations. Given the paucity of information on the topic and the need to extrapolate the results from studies with broader age ranges, we strongly encourage the design of specifically tailored clinical studies in the elderly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2014. http://www.ginasthma.org/.

  2. Scichilone N, Pedone C, Battaglia S, Sorino C, Bellia V. Diagnosis and management of asthma in the elderly. Eur J Intern Med. 2014;25:336–42.

    Article  PubMed  Google Scholar 

  3. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of COPD. 2014. http://www.goldcopd.org/.

  4. Louie S, Zeki AA, Schivo M, Chan AL, Yoneda KY, Avdalovic M, Morrissey BM, Albertson TE. The asthma-chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations. Expert Rev Clin Pharmacol. 2013;6:197–219.

    Article  CAS  PubMed  Google Scholar 

  5. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728–35.

    Article  CAS  PubMed  Google Scholar 

  6. Soriano JB, Davis KJ, Coleman B, Visick G, Mannino D, Pride NB. The proportional Venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom. Chest. 2003;124:474–81.

    Article  PubMed  Google Scholar 

  7. Dalby C, Polanowski T, Larsson T, Borgstrom L, Edsbacker S, Harrison TW. The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir Res. 2009;10:104.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Miller-Larsson A, Jansson P, Runstrom A, Brattsand R. Prolonged airway activity and improved selectivity of budesonide possibly due to esterification. Am J Respir Crit Care Med. 2000;162:1455–61.

    Article  CAS  PubMed  Google Scholar 

  9. Colice GL. Pharmacodynamic and pharmacokinetic considerations in choosing an inhaled corticosteroid. Treat Respir Med. 2006;5:245–53.

    Article  CAS  PubMed  Google Scholar 

  10. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J. 2006;28:1042–50.

    Article  CAS  PubMed  Google Scholar 

  11. Barnes NC. The properties of inhaled corticosteroids: similarities and differences. Prim Care Respir J. 2007;16:149–54.

    Article  PubMed  Google Scholar 

  12. Valotis A, Neukam K, Elert O, Hogger P. Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate. J Pharm Sci. 2004;93:1337–50.

    Article  CAS  PubMed  Google Scholar 

  13. Borgstrom L. The pharmacokinetics of inhaled hydrofluoroalkane formulations. J Allergy Clin Immunol. 1999;104:S246–9.

    Article  CAS  PubMed  Google Scholar 

  14. Leach CL, Bethke TD, Boudreau RJ, Hasselquist BE, Drollmann A, Davidson P, Wurst W. Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers. J Aerosol Med. 2006;19:117–26.

    Article  CAS  PubMed  Google Scholar 

  15. Richter K, Kanniess F, Biberger C, Nave R, Magnussen H. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol. 2005;45:146–52.

    Article  CAS  PubMed  Google Scholar 

  16. Affrime MB, Cuss F, Padhi D, Wirth M, Pai S, Clement RP, Lim J, Kantesaria B, Alton K, Cayen MN. Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers. J Clin Pharmacol. 2000;40:1227–36.

    CAS  PubMed  Google Scholar 

  17. Kaliner MA. Pharmacologic characteristics and adrenal suppression with newer inhaled corticosteroids: A comparison of ciclesonide and fluticasone propionate. Clin Ther. 2006;28:319–31.

    Article  CAS  PubMed  Google Scholar 

  18. Harrison TW, Tattersfield AE. Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects. Thorax. 2003;58:258–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Rohatagi S, Luo Y, Shen L, Guo Z, Schemm C, Huang Y, Chen K, David M, Nave R, King SP. Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide. Am J Ther. 2005;12:201–9.

    Article  PubMed  Google Scholar 

  20. Szefler S, Rohatagi S, Williams J, Lloyd M, Kundu S, Banerji D. Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma. Chest. 2005;128:1104–14.

    Article  CAS  PubMed  Google Scholar 

  21. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest. 2004;126:213–9.

    Article  CAS  PubMed  Google Scholar 

  22. Yawn BP, Li Y, Tian H, Zhang J, Arcona S, Kahler KH. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int J Chron Obstruct Pulmon Dis. 2013;8:295–304.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Sobieraj DM, White CM, Coleman CI. Benefits and risks of adjunctive inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Clin Ther. 2008;30:1416–25.

    Article  CAS  PubMed  Google Scholar 

  24. Loke YK, Kwok CS, Singh S. Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. BMJ. 2011;342:d1309.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Mattishent K, Thavarajah M, Blanco P, Gilbert D, Wilson AM, Loke YK. Meta-review: adverse effects of inhaled corticosteroids relevant to older patients. Drugs. 2014;74:539–47.

    Article  CAS  PubMed  Google Scholar 

  26. Kennedy WA, Laurier C, Gautrin D, Ghezzo H, Pare M, Malo JL, Contandriopoulos AP. Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids. J Clin Epidemiol. 2000;53:696–701.

    Article  CAS  PubMed  Google Scholar 

  27. Black RL, Oglesby RB, Von Sallmann L, Bunim JJ. Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. JAMA. 1960;174:166–71.

    Article  CAS  PubMed  Google Scholar 

  28. Urban RC Jr, Cotlier E. Corticosteroid-induced cataracts. Surv Ophthalmol. 1986;31:102–10.

    Article  CAS  PubMed  Google Scholar 

  29. Allen MB, Ray SG, Leitch AG, Dhillon B, Cullen B. Steroid aerosols and cataract formation. BMJ. 1989;299:432–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Karim AK, Thompson GM, Jacob TJ. Steroid aerosols and cataract formation. BMJ. 1989;299:918.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Abuekteish F, Kirkpatrick JN, Russell G. Posterior subcapsular cataract and inhaled corticosteroid therapy. Thorax. 1995;50:674–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Simons FE, Persaud MP, Gillespie CA, Cheang M, Shuckett EP. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids. Lancet. 1993;342:776–8.

    Article  CAS  PubMed  Google Scholar 

  33. Nassif E, Weinberger M, Sherman B, Brown K. Extrapulmonary effects of maintenance corticosteroid therapy with alternate-day prednisone and inhaled beclomethasone in children with chronic asthma. J Allergy Clin Immunol. 1987;80:518–29.

    Article  CAS  PubMed  Google Scholar 

  34. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med. 1997;337:8–14.

    Article  CAS  PubMed  Google Scholar 

  35. Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA. 1998;280:539–43.

    Article  CAS  PubMed  Google Scholar 

  36. 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 

  37. Smeeth L, Boulis M, Hubbard R, Fletcher AE. A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol. 2003;87:1247–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Samiy N, Walton DS, Dreyer EB. Inhaled steroids: effect on intraocular pressure in patients without glaucoma. Can J Ophthalmol. 1996;31:120–3.

    CAS  PubMed  Google Scholar 

  39. Garbe E, LeLorier J, Boivin JF, Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA. 1997;277:722–7.

    Article  CAS  PubMed  Google Scholar 

  40. Chapman KR, Mannino DM, Soriano JB, Vermeire PA, Buist AS, Thun MJ, Connell C, Jemal A, Lee TA, Miravitlles M, Aldington S, Beasley R. Epidemiology and costs of chronic obstructive pulmonary disease. Eur Respir J. 2006;27:188–207.

    Article  CAS  PubMed  Google Scholar 

  41. Yach D, Hawkes C, Gould CL, Hofman KJ. The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA. 2004;291:2616–22.

    Article  CAS  PubMed  Google Scholar 

  42. Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32:962–9.

    Article  CAS  PubMed  Google Scholar 

  43. Rana JS, Mittleman MA, Sheikh J, Hu FB, Manson JE, Colditz GA, Speizer FE, Barr RG, Camargo CA Jr. Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. Diabetes Care. 2004;27:2478–84.

    Article  PubMed  Google Scholar 

  44. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J, TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–89.

    Article  CAS  PubMed  Google Scholar 

  45. Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA, Investigators I. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177:19–26.

    Article  CAS  PubMed  Google Scholar 

  46. Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression. Am J Med. 2010;123:1001–6.

    Article  CAS  PubMed  Google Scholar 

  47. Slatore CG, Bryson CL, Au DH. The association of inhaled corticosteroid use with serum glucose concentration in a large cohort. Am J Med. 2009;122:472–8.

    Article  CAS  PubMed  Google Scholar 

  48. O’Byrne PM, Rennard S, Gerstein H, Radner F, Peterson S, Lindberg B, Carlsson LG, Sin DD. 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 

  49. Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med. 1995;98:196–208.

    Article  CAS  PubMed  Google Scholar 

  50. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777–87.

    Article  PubMed  Google Scholar 

  51. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102:274–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Manolagas SC. Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res. 2000;15:1001–5.

    Article  CAS  PubMed  Google Scholar 

  53. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112:352–64.

    Article  CAS  PubMed  Google Scholar 

  54. Pouw EM, Prummel MF, Oosting H, Roos CM, Endert E. Beclomethasone inhalation decreases serum osteocalcin concentrations. BMJ. 1991;302:627–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Reid DM, Nicoll JJ, Smith MA, Higgins B, Tothill P, Nuki G. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. Br Med J (Clin Res Ed). 1986;293:1463–6.

    Article  CAS  Google Scholar 

  56. Suissa S, Baltzan M, Kremer R, Ernst P. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med. 2004;169:83–8.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  58. 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 

  59. Singh S, Loke YK. Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update. Curr Opin Pulm Med. 2010;16:118–22.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Crim C, Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Willits LR, Yates JC, Vestbo J. Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results. Eur Respir J. 2009;34:641–7.

    Article  CAS  PubMed  Google Scholar 

  61. 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 

  62. Janson C, Larsson K, Lisspers KH, Stallberg B, Stratelis G, Goike H, Jorgensen L, Johansson G. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ. 2013;346:f3306.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Daveluy A, Raignoux C, Miremont-Salame G, Girodet PO, Moore N, Haramburu F, Molimard M. Drug interactions between inhaled corticosteroids and enzymatic inhibitors. Eur J Clin Pharmacol. 2009;65:743–5.

    Article  CAS  PubMed  Google Scholar 

  64. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN. Cushing’s syndrome due to interaction between inhaled corticosteroids and itraconazole. Ann Pharmacother. 2004;38:46–9.

    Article  PubMed  Google Scholar 

  65. Dormuth CR, Maclure M, Glynn RJ, Neumann P, Brookhart AM, Schneeweiss S. Emergency hospital admissions after income-based deductibles and prescription copayments in older users of inhaled medications. Clin Ther. 2008;30 Spec No:1038-50.

  66. Bynum JP, Rabins PV, Weller W, Niefeld M, Anderson GF, Wu AW. The relationship between a dementia diagnosis, chronic illness, medicare expenditures, and hospital use. J Am Geriatr Soc. 2004;52:187–94.

    Article  PubMed  Google Scholar 

  67. Thakur N, Blanc PD, Julian LJ, Yelin EH, Katz PP, Sidney S, Iribarren C, Eisner MD. COPD and cognitive impairment: the role of hypoxemia and oxygen therapy. Int J Chron Obstruct Pulmon Dis. 2010;5:263–9.

    PubMed Central  PubMed  Google Scholar 

  68. Chang SS, Chen S, McAvay GJ, Tinetti ME. Effect of coexisting chronic obstructive pulmonary disease and cognitive impairment on health outcomes in older adults. J Am Geriatr Soc. 2012;60:1839–46.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Bozek A, Jarzab J. Improved activity and mental function related to proper antiasthmatic treatment in elderly patients with Alzheimer’s disease. Allergy Asthma Proc. 2011;32:341–5.

    Article  CAS  PubMed  Google Scholar 

  70. Allen SC, Ragab S. Ability to learn inhaler technique in relation to cognitive scores and tests of praxis in old age. Postgrad Med J. 2002;78:37–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Allen SC, Jain M, Ragab S, Malik N. Acquisition and short-term retention of inhaler techniques require intact executive function in elderly subjects. Age Ageing. 2003;32:299–302.

    Article  PubMed  Google Scholar 

  72. Huang TT, Li YT, Wang CH. Individualized programme to promote self-care among older adults with asthma: randomized controlled trial. J Adv Nurs. 2009;65:348–58.

    Article  PubMed  Google Scholar 

  73. Matsunaga K, Yamagata T, Minakata Y, Ichinose M. Importance of assistance by caregivers for inhaled corticosteroid therapy in elderly patients with asthma. J Am Geriatr Soc. 2006;54:1626–7.

    Article  PubMed  Google Scholar 

  74. Jarvis S, Ind PW, Shiner RJ. Inhaled therapy in elderly COPD patients; time for re-evaluation? Age Ageing. 2007;36:213–8.

    Article  PubMed  Google Scholar 

  75. Melani AS, Zanchetta D, Barbato N, Sestini P, Cinti C, Canessa PA, Aiolfi S, Neri M. Inhalation technique and variables associated with misuse of conventional metered-dose inhalers and newer dry powder inhalers in experienced adults. Ann Allergy Asthma Immunol. 2004;93:439–46.

    Article  PubMed  Google Scholar 

  76. Allen SC. Competence thresholds for the use of inhalers in people with dementia. Age Ageing. 1997;26:83–6.

    Article  CAS  PubMed  Google Scholar 

  77. Connolly MJ. Inhaler technique of elderly patients: comparison of metered-dose inhalers and large volume spacer devices. Age Ageing. 1995;24:190–2.

    Article  CAS  PubMed  Google Scholar 

  78. Jones V, Fernandez C, Diggory P. A comparison of large volume spacer, breath-activated and dry powder inhalers in older people. Age Ageing. 1999;28:481–4.

    Article  CAS  PubMed  Google Scholar 

  79. Ho SF, OMahony MS, Steward JA, Breay P, Burr ML. Inhaler technique in older people in the community. Age Ageing. 2004;33:185–8.

    Article  PubMed  Google Scholar 

  80. Ohbayashi H, Adachi M. Influence of dentures on residual inhaled corticosteroids in the mouths of elderly asthma patients. Respir Investig. 2012;50:54–61.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

S Battaglia, I Cardillo, F Lavorini, M Spatafora, and N Scichilone declare no conflicts of interest related to this article.

Funding

No sources of funding were used to support the writing of this manuscript.

Author information

Authors and Affiliations

  1. Sezione di Pneumologia, Dipartimento di Biomedicina e Medicina Specialistica, University of Palermo, via Trabucco 180, 90146, Palermo, Italy

    Salvatore Battaglia, Irene Cardillo, Mario Spatafora & Nicola Scichilone

  2. S.O.D. Pneumologia e Fisiopatologia, Azienda Ospedaliero Universitaria Careggi, Florence, Italy

    Federico Lavorini

Authors
  1. Salvatore Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irene Cardillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Federico Lavorini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario Spatafora
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicola Scichilone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola Scichilone.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Battaglia, S., Cardillo, I., Lavorini, F. et al. Safety Considerations of Inhaled Corticosteroids in the Elderly. Drugs Aging 31, 787–796 (2014). https://doi.org/10.1007/s40266-014-0213-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-014-0213-1

Keywords

Search

Navigation