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Open Access 01-12-2019 | Bronchial Asthma | Research article

Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma

Authors: Anuradha KWDA, Prematilake GLDC, Batuwita BAUI, Kannangoda KASR, Hewagamage US, Wijeratne S, Lankatilake Kantha, de Silva KSH

Published in: BMC Pediatrics | Issue 1/2019

Abstract

Background

Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. However adverse effects of ICS on Hypothalamo Pituitary Adrenal (HPA) axis, growth and bone metabolism are a concern. Hence the primary objective of this study was to describe the effects of long term inhaled corticosteroid therapy (ICS) on adrenal function, growth and bone health in children with asthma in comparison to an age and sex matched group of children with asthma who were not on long term ICS. Describing the association between the dose of ICS and duration of therapy on the above parameters were secondary objectives.

Method

Seventy children with asthma on ICS and 70 controls were studied. Diagnosis of asthma in selected patients was reviewed according to the criteria laid down by GINA 2018 guidelines. The estimated adult heights were interpreted relative to their Mid Parental Height (MPH) range. Serum calcium, alkaline phosphatase and vitamin D levels were analyzed in both groups and cortisol value at 30 min following a low dose short synacthen test was obtained from the study group. The average daily dose of ICS (Beclamethasone) was categorized as low, medium and high (100–200, 200–400, > 400 μg /day) respectively according to published literature.

Results

Heights of all children were within the MPH range. There was no statistically significant difference in the bone profiles and vitamin D levels between the two groups (Ca: p = 0.554, vitamin D: p = 0.187) but vitamin D levels were insufficient (< 50 nmol/l) in 34% of cases and 41% of controls. Suppressed cortisol levels were seen in 24%. Doses of ICS were low, medium and high in 56, 32 and 12% of children respectively. The association between adrenal suppression with longer duration of therapy (p < 0.01) and with increasing dose of ICS (p < 0.001) were statistically significant.

Conclusion

ICS had no impact on the growth and bone profiles but its dose and duration were significantly associated with adrenal suppression.

Global Initiative For Asthma. (2017). Global strategy for asthma management and prevention. [online] available at:https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-tracked_v1.3.pdf[accessed 15 Feb 2019].

Enrico H, Lorena N, Girardi M, Matteo F, Francesca P, Luca M, Giorgio GP. Inhaled Corticosteroids Safety and Adverse Effects in Patients with Asthma. The Journal of Allergy and Clinical Immunology in Practice. 2008;6–3:776–81.

Nicola A, Kenneth RC, William CS, John PS, Steven K. Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol. 2005:571–9.

Karine IEK. CSACI position statement: systemic effect of inhaled corticosteroids on adrenal suppression in the management of pediatric asthma. Allergy Asthma, and Clinical Immunology. 2015;11:1–9.CrossRef

Ronald D. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med. 2006;100:1307–17.CrossRef

Alexandra A, Harold K, Sheldon S. Adrenal suppression :A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy. Allergy Asthma and Clinical Immunology. 2011;7:13.CrossRef

Kurahashi I, Matsunuma A, Kawane T, Abe M, Horiuchi N. Deaxamethasone enhances vitamin D-24-hydroxylase expression in osteoblastic (UMR-106) and renal (LLC-PK₁) cells treated with 1α,25-dihyroxyvitamin D₃. Endocrine. 2002;17:109–18.CrossRef

Dhawan P, Christakos S. Novel regulation of 25-hydroxyvitamin D₃ 24-hydroxylase 24(OH) ase transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBPβ, and the vitamin D receptor in 24(OH) ase transcription. J Cell Biochem. 2010;110:1314–23.CrossRef

Tanner JM, Goldstein H, Whitehouse RH. Standards for children’s height at ages 2-9 years allowing for height of parents. Archives of Disease in Childhood. 1970;45:755–62.CrossRef

10.

Park J, Mohammed D, Joanne B. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence. Arch Dis Child. 2016;101:860–5.CrossRef

11.

Craig F, Munns N, Bonny L. Global consensus recommendations on prevention and Management of Nutritional Rickets. Horm Res Paediatr. 2016;85:83–106.CrossRef

12.

Allen DB. Sense and sensitivity: assessing inhaled corticosteroid effects on the hypothalamic- pituitary-adrenal axis. Ann Allergy Asthma Immunology. 2002;89:537–9.CrossRef

13.

Santiago AH, Ratzan S. Acute adrenal crisis in an asthmatic child treated with inhaled fluticasone proprionate. Int J Pediatr Endocrinol. 2010;749239. https://doi.org/10.1155/2010/749239.CrossRef

14.

Drake AJ, Howells RJ, Shield JPH, Prendiville A, Ward PS, Crowne EC. Symptomatic adrenal insufficiency presenting with hypoglycaemia in asthmatic children with asthma receiving high dose inhaled fluticasone propionate. Br Med J. 2002;324(7345):1081–2.CrossRef

15.

Kannisto S, Korppi M, Remes K, Voutilainen R. Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab. 2000;85(2):652–7.PubMed

16.

Zollner EW, Lombard CJ, Galal U, Hough S, Irusen EM, Weinberg E. Hypothalamic-pituitary-adrenal axis suppression in asthmatic school children. Pediatrics. 2012;130:e1512.CrossRef

17.

Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. New England Journel Medicine. 2000;343:1064–9.CrossRef

18.

Pedersen S. Do Inhaled Corticosteroids Inhibit Growth in Children? American Journal of Respiratory and Critical Care Medicine. 164(4):521–35.CrossRef

19.

EfthimiouJ BPJ. Effect of inhaled corticosteroids on bones and growth. European Respiratory Journal. 1998;11:1167–77.CrossRef

20.

Pruteanu AI, Chauhan BF, Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Systemic Review. 2014;7. https://doi.org/10.1002/14651858.

21.

Thomas BC, Stanhope R, Grant DB. Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids. Acta Paediatr. 1994;83(2):196–9.CrossRef

22.

Wright CM, Cheetham CD. The strengths and limitations of parental heights as a predictor of attained height. Arch Dis Child. 1999;81(3):257–60.CrossRef

23.

Axelsson I, Naumburg E, Prietsch SOM, Zhang L. Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD010126.

24.

Fatma D, Ozlem KARA, Derya TEPE, ESEN I. Bone Mineral density and vitamin D status in children and adolescents with congenital adrenal hyperplasi Turkish. J Med Sci. 2014:109–14.

25.

Tse SM, Kelly HW, Litonjua AA, Van Natta ML, Weiss ST, Tantisira KG. Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D. J Allergy Clinical Immunology. 2012:53–60.

26.

Arend EE, Fischer GB, Debiasi M, Schmid H. Inhaled corticosteroid treatment and growth of asthmatic children seen at outpatient clinics. J Pediatr. 2006;82(3):197–203.CrossRef

27.

Skoner DP. Inhaled corticosteroids Effects on growth and bone health. Alergy Asthma Immunology. 2016;117:595.CrossRef

28.

Allen HD, Thong IG, Clifton-Bligh P, Holmes S, Nery L, Wilson KB. Effects ofhigh-dose inhaled corticosteroids on bone metabolism in prepubertal childrenwith asthma. Pediatr Pulmonol. 2000;29:188e193.CrossRef

29.

Hopp RJ, Degan JA, Phelan J, Lappe J, Gallagher GC. Cross-sectional study of bone density in asthmatic children. Pediatr Pulmonol. 1995;20:189e192.CrossRef

30.

The Childhood Asthma Management Program Research Group. Long-termeffects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343:1054–63.CrossRef

31.

Della Giustina A, Landi M, Bellini F, et al. Vitamin D, allergies and asthma: focus on pediatric patients. World Allergy Organ J. 2014;7(1):27.CrossRef

Title: Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma
Authors: Anuradha KWDA
Prematilake GLDC
Batuwita BAUI
Kannangoda KASR
Hewagamage US
Wijeratne S
Lankatilake Kantha
de Silva KSH
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Bronchial Asthma
Published in: BMC Pediatrics / Issue 1/2019
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-019-1760-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma

Abstract

Background

Method

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Results

Conclusion

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