Correspondence

Inhaled Corticosteroids, Growth, and Compliance

N Engl J Med 2002; 347:1210-1211October 10, 2002

Article

To the Editor:

Inhaled corticosteroids are increasingly being used for the prophylactic treatment of asthma in children. The benefits have been well documented; however, the potential risk of growth suppression has not been fully investigated. Recent follow-up evaluations have found that final height is within the genetic target-height range in children in whom inhaled corticosteroids were prescribed for up to nine years.1,2 Many methodologic flaws, however, may limit the utility of follow-up growth data in children receiving inhaled corticosteroids. Most important, no measures of compliance were reported in one of these studies.1 In the other, compliance was checked at each visit by questioning patients and by recording the frequency of renewal of prescriptions.2 On the basis of these data, compliance was estimated to be 68 percent.

Simply asking patients with asthma whether they are taking their drugs, however, is a notoriously unreliable approach, overestimating true compliance.3 Such historical estimates contrast significantly with direct observations, such as those made in a double-blind study involving children treated with inhaled budesonide for 27 months in whom compliance was measured by electronic chips in the delivery device.4 After an initial 3-month period of relatively high compliance (76.9 percent), compliance rates fell to 54.2 percent at 9 months and continued to fall, to 48.8 percent at 27 months. No growth data were reported. However, in a recent placebo-controlled study of inhaled dry-powder budesonide (200 μg given twice daily), in which compliance data were not reported, there was a transient suppression in growth (in height) of approximately 20 percent during the first year of treatment; growth in most of the children recovered during the following three years.5 On the other hand, tightly controlled prospective studies involving prepubertal children treated with inhaled corticosteroids have shown consistent and cumulative growth effects of varying degrees over year-long study periods.1

A likely explanation for these observations is that during the first months of treatment, compliance is high enough to result in drug bioactivity sufficient to have an effect on growth. After that period, compliance gradually decreases to a level that leaves growth unaffected (Figure 1Figure 1Schematic Diagram of the Relation between Long-Term Growth Rate and Compliance with Treatment among Children Treated with Inhaled Dry-Powder Budesonide (200 μg Twice Daily) for Asthma.). Consequently, lack of reliable data on compliance seriously confounds the study of long-term growth effects of inhaled corticosteroids. Given the current recommendations supporting long-term and consistent use of inhaled corticosteroids to control the inflammation associated with asthma, it is crucial that future long-term evaluations of height apply sound, prospectively planned designs and include sensitive and reliable measures of compliance.

Ole D. Wolthers, M.D., D.M.Sci.
Children's Clinic Randers, DK-8900 Randers, Denmark
o.d.wolthers@dadlnet.dk

David B. Allen, M.D.
University of Wisconsin Children's Hospital, Madison, WI 53792

5 References

1. 1

   Wolthers OD. Impact of inhaled and intranasal corticosteroids on the growth of children. Biodrugs 2000;13:347-357
   CrossRef | Web of Science | Medline

2. 2

   Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-1069
   Full Text | Web of Science | Medline

3. 3

   Gordis L. Conceptual and methodologic problems in measuring patient compliance. In: Haynes RB, Taylor DW, Sackett DL, eds. Compliance in health care. Baltimore: Johns Hopkins University Press, 1979:23-45.
   

4. 4

   Jonasson G, Carlsen KH, Mowinckel P. Asthma drug adherence in a long term clinical trial. Arch Dis Child 2000;83:330-333
   CrossRef | Web of Science | Medline

5. 5

   The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-1063
   Full Text | Web of Science | Medline

Citing Articles (6)

Citing Articles

1. 1

   L. B. Bacharier, A. Boner, K.-H. Carlsen, P. A. Eigenmann, T. Frischer, M. Götz, P. J. Helms, J. Hunt, A. Liu, N. Papadopoulos, T. Platts-Mills, P. Pohunek, F. E. R. Simons, E. Valovirta, U. Wahn, J. Wildhaber, . (2008) Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy 63:1, 5-34
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   Leonard Bielory, Michael Blaiss, Stanley M. Fineman, Dennis K. Ledford, Phil Lieberman, F. Estelle R. Simons, David P. Skoner, William W. Storms. (2006) Concerns about intranasal corticosteroids for over-the-counter use: position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Annals of Allergy, Asthma & Immunology 96:4, 514-525
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3. 3

   2006. Corticosteroids—glucocorticoids, inhaled. , 958-977.
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4. 4

   O. D. Wolthers, C. Heuck. (2004) Assessment of the relation between short and intermediate term growth in children with asthma treated with inhaled glucocorticoids. Allergy 59:11, 1193-1197
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5. 5

   David B. Allen, Leonard Bielory, Hartmut Derendorf, Robert Dluhy, Gene L. Colice, Stanley J. Szefler. (2003) Inhaled Corticosteroids. Journal of Allergy and Clinical Immunology 112:3, S1-S40
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6. 6

   Tabitha L Randell, Kim C Donaghue, Geoffrey R Ambler, Christopher T Cowell, Dominic A Fitzgerald, Peter P Van Asperen. (2003) Safety of the Newer Inhaled Corticosteroids in Childhood Asthma. Pediatric Drugs 5:7, 481-504
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