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Review article: Biomedical intelligence

Vol. 151 No. 0506 (2021)

Beware the inhaled steroids or corticophobia?

Cite this as:
Swiss Med Wkly. 2021;151:w20450
Published
06.02.2021

Summary

Inhaled corticosteroids have been the cornerstone of atopic, allergic asthma management for more than half a century. They have side effects (as does every medication), but they have transformed the control of asthma and saved many lives since their introduction. The current review revisits local and systemic side effects of inhaled corticosteroids and explores the prevalence and nature of parental fears (“corticophobia”) in different parts of the world. The empathetic physician treating asthma should bear in mind the impact of parental concerns on the management of this potentially life-threatening disease and try to dispel myths at every opportunity by emphasising the well-established benefits and excellent safety profile of inhaled corticosteroids.

References

  1. van Aalderen WM, Sprikkelman AB. Inhaled corticosteroids in childhood asthma: the story continues. Eur J Pediatr. 2011;170(6):709–18. doi:.https://doi.org/10.1007/s00431-010-1319-z
  2. Crompton G. A brief history of inhaled asthma therapy over the last fifty years. Prim Care Respir J. 2006;15(6):326–31. doi:.https://doi.org/10.1016/j.pcrj.2006.09.002
  3. Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, et al. After asthma: redefining airways diseases. Lancet. 2018;391(10118):350–400. doi:.https://doi.org/10.1016/S0140-6736(17)30879-6
  4. Heffler E, Madeira LNG, Ferrando M, Puggioni F, Racca F, Malvezzi L, et al. Inhaled Corticosteroids Safety and Adverse Effects in Patients with Asthma. J Allergy Clin Immunol Pract. 2018;6(3):776–81. doi:.https://doi.org/10.1016/j.jaip.2018.01.025
  5. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2020. Available from: https://ginasthma.org/gina-reports/
  6. Rubin BK, Zhao W, Winders TA. What do patients want from their asthma care doctors? Paediatr Respir Rev. 2018;27:86–9. doi:.https://doi.org/10.1016/j.prrv.2017.11.002
  7. Abu-Shaheen AK, Nofal A, Heena H. Parental Perceptions and Practices toward Childhood Asthma. BioMed Res Int. 2016;2016:6364194. doi:.https://doi.org/10.1155/2016/6364194
  8. Zedan MM, Ezz El Regal M, A Osman E, E Fouda A. Steroid Phobia among Parents of Asthmatic Children: Myths and Truth. Iran J Allergy Asthma Immunol. 2010;9(3):163–8.
  9. Özçeker D, Uçkun U, İslamova D, Tamay Z, Güler N. Corticosteroid phobia among parents of asthmatic children. Turk J Pediatr. 2018;60(2):142–6. doi:.https://doi.org/10.24953/turkjped.2018.02.004
  10. Hossny E, Rosario N, Lee BW, Singh M, El-Ghoneimy D, Soh JY, et al. The use of inhaled corticosteroids in pediatric asthma: update. World Allergy Organ J. 2016;9:26. doi:.https://doi.org/10.1186/s40413-016-0117-0
  11. Bazzy-Asaad A. Safety of inhaled corticosteroids in children with asthma. Curr Opin Pediatr. 2001;13(6):523–7. doi:.https://doi.org/10.1097/00008480-200112000-00005
  12. Gulliver T, Morton R, Eid N. Inhaled corticosteroids in children with asthma: pharmacologic determinants of safety and efficacy and other clinical considerations. Paediatr Drugs. 2007;9(3):185–94. doi:.https://doi.org/10.2165/00148581-200709030-00007
  13. Carlsen KH. Inhaled steroids and local side-effects. Allergy. 2001;56(10):925–7.
  14. Dubus JC, Marguet C, Deschildre A, Mely L, Le Roux P, Brouard J, et al.; Réseau de Recherche Clinique en Pneumonologie Pédiatrique. Local side-effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age, and device. Allergy. 2001;56(10):944–8. doi:.https://doi.org/10.1034/j.1398-9995.2001.00100.x
  15. Camargos P, Zhang L, Lasmar L, Brand P. Question 2: What are the effects of inhaled corticosteroids on growth in children? Paediatr Respir Rev. 2018;28:33–40. doi:.https://doi.org/10.1016/j.prrv.2018.03.008
  16. Brook CG. Short stature never killed anybody. J Pediatr. 1998;133(5):591–2. doi:.https://doi.org/10.1016/S0022-3476(98)70095-2
  17. Bush A. Inhaled corticosteroid and children’s growth. Arch Dis Child. 2014;99(3):191–2. doi:.https://doi.org/10.1136/archdischild-2012-303105
  18. Kapadia CR, Nebesio TD, Myers SE, Willi S, Miller BS, Allen DB, et al.; Drugs and Therapeutics Committee of the Pediatric Endocrine Society. Endocrine Effects of Inhaled Corticosteroids in Children. JAMA Pediatr. 2016;170(2):163–70. doi:.https://doi.org/10.1001/jamapediatrics.2015.3526
  19. Wolfgram PM, Allen DB. Effects of Inhaled Corticosteroids on Growth, Bone Metabolism, and Adrenal Function. Adv Pediatr. 2017;64(1):331–45. doi:.https://doi.org/10.1016/j.yapd.2017.03.006
  20. Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014;7(4):CD009471. doi:.https://doi.org/10.1002/ebch.1988
  21. Pruteanu AI, Chauhan BF, Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth. Cochrane Database Syst Rev. 2014;9(4):CD009878. doi:.https://doi.org/10.1002/ebch.1989
  22. Bush A, Fleming L. 2012 and never been KISSed: we need to improve the care of children with asthma. Prim Care Respir J. 2012;21(3):242–4. doi:.https://doi.org/10.4104/pcrj.2012.00062
  23. Brand PL. Inhaled corticosteroids reduce growth. Or do they? Eur Respir J. 2001;17(2):287–94. doi:.https://doi.org/10.1183/09031936.01.17202870
  24. Lemanske RF, Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, et al.; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010;362(11):975–85. doi:.https://doi.org/10.1056/NEJMoa1001278
  25. Axelsson I, Naumburg E, Prietsch SO, Zhang L. Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth. Cochrane Database Syst Rev. 2019;6:CD010126. doi:.https://doi.org/10.1002/14651858.CD010126.pub2
  26. Kelly HW, Sternberg AL, Lescher R, Fuhlbrigge AL, Williams P, Zeiger RS, et al.; CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367(10):904–12. doi:.https://doi.org/10.1056/NEJMoa1203229
  27. Zhang L, Lasmar LB, Castro-Rodriguez JA. The impact of asthma and its treatment on growth: an evidence-based review. J Pediatr (Rio J). 2019;95(Suppl 1):10–22. doi:.https://doi.org/10.1016/j.jped.2018.10.005
  28. Cohen MB, Abram LE. Growth patterns of allergic children; a statistical study using the grid technique. J Allergy. 1948;19(3):165–71. doi:.https://doi.org/10.1016/0021-8707(48)90049-5
  29. Russell G. Childhood asthma and growth--a review of the literature. Respir Med. 1994;88(Suppl A):31–6, discussion 36–7. doi:.https://doi.org/10.1016/S0954-6111(05)80038-1
  30. Ekins-Daukes S, Simpson CR, Helms PJ, Taylor MW, McLay JS. Burden of corticosteroids in children with asthma in primary care: retrospective observational study. BMJ. 2002;324(7350):1374. doi:.https://doi.org/10.1136/bmj.324.7350.1374
  31. Allen DB. Inhaled corticosteroids and growth: still an issue after all these years. J Pediatr. 2015;166(2):463–9. doi:.https://doi.org/10.1016/j.jpeds.2014.09.055
  32. Powell SG, Frydenberg M, Thomsen PH. The effects of long-term medication on growth in children and adolescents with ADHD: an observational study of a large cohort of real-life patients. Child Adolesc Psychiatry Ment Health. 2015;9(1):50. doi:.https://doi.org/10.1186/s13034-015-0082-3
  33. Lee HS, Wang SY, Salter DM, Wang CC, Chen SJ, Fan HC. The impact of the use of antiepileptic drugs on the growth of children. BMC Pediatr. 2013;13(1):211. doi:.https://doi.org/10.1186/1471-2431-13-211
  34. Bayman E, Drake AJ. Adrenal suppression with glucocorticoid therapy: still a problem after all these years? Arch Dis Child. 2017;102(4):338–9. doi:.https://doi.org/10.1136/archdischild-2016-311601
  35. Todd GR, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002;87(6):457–61. doi:.https://doi.org/10.1136/adc.87.6.457
  36. Anurhada KWDA, Prematilake GLDC, Batuwita BAUI, Kannangoda KASR, Hewagamage US, Wijeratne S, et al. Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma. BMC Pediatr. 2019;19(1):411. doi:.https://doi.org/10.1186/s12887-019-1760-8
  37. Ahmet A, Mokashi A, Goldbloom EB, Huot C, Jurencak R, Krishnamoorthy P, et al. Adrenal suppression from glucocorticoids: preventing an iatrogenic cause of morbidity and mortality in children. BMJ Paediatr Open. 2019;3(1):e000569. doi:.https://doi.org/10.1136/bmjpo-2019-000569
  38. Ahmet A, Kim H, Spier S. Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy. Allergy Asthma Clin Immunol. 2011;7(1):13. doi:.https://doi.org/10.1186/1710-1492-7-13
  39. Zöllner EW, Lombard CJ, Galal U, Hough S, Irusen EM, Weinberg E. Screening for hypothalamic-pituitary-adrenal axis suppression in asthmatic children remains problematic: a cross-sectional study. BMJ Open. 2013;3(8):e002935. doi:.https://doi.org/10.1136/bmjopen-2013-002935
  40. Tse SM, Kelly HW, Litonjua AA, Van Natta ML, Weiss ST, Tantisira KG ; Childhood Asthma Management Program Research Group. Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D. J Allergy Clin Immunol. 2012;130(1):53–60.e4. doi:.https://doi.org/10.1016/j.jaci.2012.04.005
  41. Loke YK, Gilbert D, Thavarajah M, Blanco P, Wilson AM. Bone mineral density and fracture risk with long-term use of inhaled corticosteroids in patients with asthma: systematic review and meta-analysis. BMJ Open. 2015;5(11):e008554. doi:.https://doi.org/10.1136/bmjopen-2015-008554
  42. Gray N, Howard A, Zhu J, Feldman LY, To T. Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma. JAMA Pediatr. 2018;172(1):57–64. doi:.https://doi.org/10.1001/jamapediatrics.2017.3579
  43. Fuhlbrigge AL, Kelly HW. Inhaled corticosteroids in children: effects on bone mineral density and growth. Lancet Respir Med. 2014;2(6):487–96. doi:.https://doi.org/10.1016/S2213-2600(14)70024-4
  44. Chalitsios CV, Shaw DE, McKeever TM. Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies. Thorax. 2021;76(1):21–8. doi:.https://doi.org/10.1136/thoraxjnl-2020-215664
  45. Hall SC, Agrawal DK. Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years. Clin Ther. 2017;39(5):917–29. doi:.https://doi.org/10.1016/j.clinthera.2017.04.002
  46. Liu J, Dong YQ, Yin J, Yao J, Shen J, Sheng GJ, et al. Meta-analysis of vitamin D and lung function in patients with asthma. Respir Res. 2019;20(1):161. doi:.https://doi.org/10.1186/s12931-019-1072-4
  47. Kim MH, Rhee CK, Shim JS, Park SY, Yoo KH, Kim BY, et al. Inhaled Corticosteroids in Asthma and the Risk of Pneumonia. Allergy Asthma Immunol Res. 2019;11(6):795–805. doi:.https://doi.org/10.4168/aair.2019.11.6.795
  48. Castellana G, Castellana M, Castellana C, Castellana G, Resta E, Carone M, et al. Inhaled Corticosteroids And Risk Of Tuberculosis In Patients With Obstructive Lung Diseases: A Systematic Review And Meta-Analysis Of Non-randomized Studies. Int J Chron Obstruct Pulmon Dis. 2019;14:2219–27. doi:.https://doi.org/10.2147/COPD.S209273
  49. Liu VX, Winthrop KL, Lu Y, Sharifi H, Nasiri HU, Ruoss SJ. Association between Inhaled Corticosteroid Use and Pulmonary Nontuberculous Mycobacterial Infection. Ann Am Thorac Soc. 2018;15(10):1169–76. doi:.https://doi.org/10.1513/AnnalsATS.201804-245OC
  50. Levy J, Zalkinder I, Kuperman O, Skibin A, Apte R, Bearman JE, et al. Effect of prolonged use of inhaled steroids on the cellular immunity of children with asthma. J Allergy Clin Immunol. 1995;95(4):806–12. doi:.https://doi.org/10.1016/S0091-6749(95)70122-2
  51. Behbehani AH, Owayed AF, Hijazi ZM, Eslah EA, Al-Jazzaf AM. Cataract and ocular hypertension in children on inhaled corticosteroid therapy. J Pediatr Ophthalmol Strabismus. 2005;42(1):23–7. doi:.https://doi.org/10.3928/01913913-20050101-03
  52. Nootheti S, Bielory L. Risk of cataracts and glaucoma with inhaled steroid use in children. Compr Ophthalmol Update. 2006;7(1):31–9.
  53. 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(8874):776–8. doi:.https://doi.org/10.1016/0140-6736(93)91541-S
  54. Szefler S, Weiss S, Tonascia J, Adkinson NF, Bender B, Cherniack R, et al., Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343(15):1054–63. doi:.https://doi.org/10.1056/NEJM200010123431501
  55. Chang LS, Lee HC, Tsai YC, Shen LS, Li CL, Liu SF, et al. Decreased incidence of glaucoma in children with asthma using inhaled corticosteroid: a cohort study. Oncotarget. 2017;8(62):105463–71. doi:.https://doi.org/10.18632/oncotarget.22252
  56. Yucel O, Eker Y, Nuhoglu C, Ceran O. Hemoglobin a1c levels in children with asthma using low dose inhaled corticosteroids. Indian Pediatr. 2009;46(4):300–3.
  57. Lim SH, Goh DY, Tan AY, Lee BW. Parents’ perceptions towards their child’s use of inhaled medications for asthma therapy. J Paediatr Child Health. 1996;32(4):306–9. doi:.https://doi.org/10.1111/j.1440-1754.1996.tb02559.x
  58. Chan PW, DeBruyne JA. Parental concern towards the use of inhaled therapy in children with chronic asthma. Pediatr Int. 2000;42(5):547–51. doi:.https://doi.org/10.1046/j.1442-200x.2000.01278.x
  59. Yoos HL, Kitzman H, McMullen A. Barriers to anti-inflammatory medication use in childhood asthma. Ambul Pediatr. 2003;3(4):181–90. doi:.https://doi.org/10.1367/1539-4409(2003)003<0181:BTAMUI>2.0.CO;2
  60. Gazala E, Sadka R, Bilenko N. Parents’ Fears and Concerns Toward Inhaled Corticosteroid Treatment for Their Asthmatic Children. Pediatr Asthma Allergy Immunol. 2005;18(2):82–7. doi:.https://doi.org/10.1089/pai.2005.18.82
  61. Zhao J, Shen K, Xiang L, Zhang G, Xie M, Bai J, et al. The knowledge, attitudes and practices of parents of children with asthma in 29 cities of China: a multi-center study. BMC Pediatr. 2013;13(1):20. doi:.https://doi.org/10.1186/1471-2431-13-20
  62. Ip KI, Hon KL, Tsang KYC, Leung TNH. Steroid phobia, Chinese medicine and asthma control. Clin Respir J. 2018;12(4):1559–64. doi:.https://doi.org/10.1111/crj.12705
  63. Conn KM, Halterman JS, Fisher SG, Yoos HL, Chin NP, Szilagyi PG. Parental beliefs about medications and medication adherence among urban children with asthma. Ambul Pediatr. 2005;5(5):306–10. doi:.https://doi.org/10.1367/A05-004R1.1
  64. Conn KM, Halterman JS, Lynch K, Cabana MD. The impact of parents’ medication beliefs on asthma management. Pediatrics. 2007;120(3):e521–6. doi:.https://doi.org/10.1542/peds.2006-3023
  65. Koster ES, Raaijmakers JA, Vijverberg SJ, Maitland-van der Zee AH. Inhaled corticosteroid adherence in paediatric patients: the PACMAN cohort study. Pharmacoepidemiol Drug Saf. 2011;20(10):1064–72. doi:.https://doi.org/10.1002/pds.2228
  66. Koster ES, Wijga AH, Koppelman GH, Postma DS, Brunekreef B, De Jongste JC, et al. Uncontrolled asthma at age 8: the importance of parental perception towards medication. Pediatr Allergy Immunol. 2011;22(5):462–8. doi:.https://doi.org/10.1111/j.1399-3038.2011.01150.x
  67. Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health. 1999;14(1):1–24. doi:.https://doi.org/10.1080/08870449908407311
  68. Lenney W, Bush A, Fitzgerald DA, Fletcher M, Ostrem A, Pedersen S, et al. Improving the global diagnosis and management of asthma in children. Thorax. 2018;73(7):662–9. doi:.https://doi.org/10.1136/thoraxjnl-2018-211626
  69. Asthma UK. Paying to breathe: why unfair asthma prescription charges must be stopped. 2019.
  70. Hui RWH. Inhaled corticosteroid-phobia and childhood asthma: Current understanding and management implications. Paediatr Respir Rev. 2020;33:62–6. doi:.https://doi.org/10.1016/j.prrv.2019.03.009
  71. Gillissen A, Lecheler J. Kortikophobie beim Asthma bronchiale [Corticophobia in asthma]. Med Klin (Munich). 2003;98(8):417–22. Article in German. doi:.https://doi.org/10.1007/s00063-003-1262-0
  72. De Simoni A, Horne R, Fleming L, Bush A, Griffiths C. What do adolescents with asthma really think about adherence to inhalers? Insights from a qualitative analysis of a UK online forum. BMJ Open. 2017;7(6):e015245. doi:.https://doi.org/10.1136/bmjopen-2016-015245
  73. Desager K, Vermeulen F, Bodart E. Adherence to asthma treatment in childhood and adolescence - a narrative literature review. Acta Clin Belg. 2018;73(5):348–55. doi:.https://doi.org/10.1080/17843286.2017.1409684
  74. Carroll WD, Wildhaber J, Brand PLP. Parent misperception of control in childhood/adolescent asthma: the Room to Breathe survey. Eur Respir J. 2012;39(1):90–6. doi:.https://doi.org/10.1183/09031936.00048911
  75. Klok T, Kaptein AA, Duiverman EJ, Brand PL. Long-term adherence to inhaled corticosteroids in children with asthma: Observational study. Respir Med. 2015;109(9):1114–9. doi:.https://doi.org/10.1016/j.rmed.2015.07.016
  76. Engelkes M, Janssens HM, de Jongste JC, Sturkenboom MCJM, Verhamme KMC. Medication adherence and the risk of severe asthma exacerbations: a systematic review. Eur Respir J. 2015;45(2):396–407. doi:.https://doi.org/10.1183/09031936.00075614
  77. Vasbinder EC, Belitser SV, Souverein PC, van Dijk L, Vulto AG, van den Bemt PM. Non-adherence to inhaled corticosteroids and the risk of asthma exacerbations in children. Patient Prefer Adherence. 2016;10:531–8. doi:.https://doi.org/10.2147/PPA.S92824
  78. Fleming L. Asthma exacerbation prediction: recent insights. Curr Opin Allergy Clin Immunol. 2018;18(2):117–23. doi:.https://doi.org/10.1097/ACI.0000000000000428
  79. Chongmelaxme B, Chaiyakunapruk N, Dilokthornsakul P. Association between adherence and severe asthma exacerbation: A systematic review and meta-analysis. J Am Pharm Assoc (2003). 2020;60(5):669–685.e2. doi:.https://doi.org/10.1016/j.japh.2020.02.010
  80. Cambridge Dictionary. Phobia [17/03/2020]. Available from: https://dictionary.cambridge.org/dictionary/english/phobia.
  81. Rubin BK. Asthma myths, controversies, and dogma. Paediatr Respir Rev. 2015;16(2):83–7. doi:.https://doi.org/10.1016/j.prrv.2014.09.001