Correspondence
Comparison of Beclomethasone, Salmeterol, and Placebo in Children with Asthma
N Engl J Med 1998; 339:704-705September 3, 1998
- Article
To the Editor:
Simons et al. (Dec. 4 issue)1 report that inhaled beclomethasone is somewhat more effective than salmeterol in controlling symptoms of asthma in children and that beclomethasone retards children's growth, whereas salmeterol does not. Additional analyses of the data are needed to clarify the growth-impairing effects of beclomethasone.
Despite randomization at base line, the groups were not well balanced with respect to height. The mean height was 138.5 cm in the placebo group, 140.0 cm in the beclomethasone group, and 134.6 cm in the salmeterol group, and these differences were significant (P=0.04 for the overall comparison among groups by the F test, P=0.01 for the comparison of salmeterol with beclomethasone, and P=0.07 for the comparison of salmeterol with placebo). This imbalance may convey a misleading visual message in Figure 2 of the article, which shows mean heights at base line and during the study in a way that could lead some readers to see only that the children assigned to salmeterol were shorter than the others throughout the study, despite the finding that patients in both the placebo group and the salmeterol group were growing at significantly faster rates than patients in the beclomethasone group.
Simons et al. report heights only as means in the three groups. What were the changes in height according to sex and pubertal status in each group over the course of the study? Such information would help determine whether the growth-impairing effects of beclomethasone are more pronounced in some children than in others. If the degree of growth impairment was not uniform, guidelines could be developed for the early identification and appropriate treatment of children with more pronounced growth impairment.
Simons et al. found that children in the placebo group grew faster than those treated with beclomethasone despite the fact that their asthma was poorly controlled. However, no differences in growth rates between the salmeterol and placebo groups were found. The growth rates of children treated with beclomethasone should be assessed at regular intervals so that the dose can be adjusted in those whose growth falls behind. In addition, the efficacy of lower doses and alternative dosing schedules of beclomethasone should be studied.
1 ReferencesSaul Malozowski, M.D., Ph.D.
Bruce V. Stadel, M.D., Ph.D.
Lee-Ping Pian, Ph.D.
Food and Drug Administration, Rockville, MD 208571
Simons FER, Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group
Full Text | Web of Science | Medline
Author/Editor Response
Dr. Simons replies:
To the Editor: The mean (±SD) heights of the salmeterol-treated children and the beclomethasone-treated children were significantly different at base-line visit 1 but not at randomization visit 2 (135.3±11.8 and 140.3±14.8 cm, respectively). The possible interactions of base-line height, sex, age, and center with treatment were all assessed, and none were significant. Pubertal status was not assessed. The results of analysis of the growth rate as a regression slope and as a simple growth rate calculated as the change in height divided by the number of months in the study were similar. Table 1Table 1
Spectrum of Growth Rates within Each Group. shows the spectrum of growth rates within each group.Figure 2 of our article was intended to show that the effect of beclomethasone on growth occurred early in treatment and was not progressive; the slopes of the lines were parallel for the three treatment groups from 3 to 12 months. We agree that the visual message of the figure could be misinterpreted.
Delays in growth can be found in children with asthma regardless of the severity of the disorder and regardless of the medications used in treatment.1 Although the children in the placebo group in our study did not have optimally controlled asthma, they did not have poorly controlled asthma; the forced expiratory volume in one second was 92±13 percent of the predicted value at base line, with an adjusted overall mean increase of 5 percent during the year.
The beneficial antiinflammatory effects of beclomethasone on persistent asthma were significant and clinically important. We agree that additional information about the long-term risk–benefit ratio of this medication is needed in children, especially with regard to the minimal effective dose, the dose response, and the optimal dosing schedule. Intermittent dosing may not be advisable, since adverse effects on growth may occur within six weeks after the initiation of inhaled beclomethasone treatment.2 Long-term, randomized, placebo-controlled studies of the potential effect on growth of newer inhaled glucocorticoids and of the different dry-powder inhaler devices, metered-dose–inhaler propellants, and add-on spacer devices used for the administration of inhaled glucocorticoids are also needed. Ideally, these studies should be performed in children who have not received glucocorticoids previously. In addition, since intranasal beclomethasone may delay growth,3 it will be important to study the long-term growth of children with asthma and concurrent allergic rhinitis who are treated with both an inhaled glucocorticoid and an intranasal glucocorticoid.
3 ReferencesF. Estelle R. Simons, M.D.
University of Manitoba, Winnipeg, MB R3A 1R9, Canada1
Ferguson AC ,Murray AB ,Tze W-J . Short stature and delayed skeletal maturation in children with allergic disease. J Allergy Clin Immunol 1982;69:461-466
CrossRef | Web of Science | Medline2
Doull IJ ,Campbell MJ ,Holgate ST . Duration of growth suppressive effects of regular inhaled corticosteroids. Arch Dis Child 1998;78:172-173
CrossRef | Web of Science | Medline3
Rachelefsky GS ,Chervinsky P ,Meltzer EO , et al. An evaluation of the effects of beclomethasone dipropionate aqueous nasal spray [Vancenase AQ (VNS)] on long-term growth in children. J Allergy Clin Immunol 1998;101:S236-S236 abstract.
CrossRef | Web of Science
- Citing Articles (3)
Citing Articles
1
Amy C. Plint, Kelly Russell, Candice L. Bjornson, Brian H. Rowe. (2008) The Cochrane Library and Long-Acting Beta-agonist Treatment for Childhood Asthma: An Overview of Reviews. Evidence-Based Child Health: A Cochrane Review Journal 3:4, 909-919
CrossRef2
Christopher J Cates, Matthew J Cates, Christopher J Cates. 2008. Regular treatment with salmeterol for chronic asthma: serious adverse events. .
CrossRef3
E. Haydn Walters, Julia AE Walters, Peter G Gibson, E. Haydn Walters. 2002. Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma. .
CrossRef
