In an intention-to-treat analysis of the growth-suppressive effect of long-term inhaled glucocorticoid therapy for asthma initiated in children between the ages of 5 and 13 years, we found that the height deficit observed at 1 to 2 years after treatment initiation persisted into adulthood, although the deficit was neither progressive nor cumulative. Our conclusion is based on a randomized comparison of adult height, with height data available for 91% of the CAMP cohort, with the use of recognized definitions of adult height,18–21
and with consistent findings in sensitivity analyses using imputation strategies for missing data and alternative definitions of adult height (). We found little evidence that the 98 participants for whom data regarding adult height were missing differed at trial entry from the 943 participants with available data (Table S2 in the Supplementary Appendix
In contrast, the only other prospective longitudinal cohort study that followed patients into adulthood11
was an open-label study, and by the time the patients reached adulthood, only 15 of the original controls were available, so the investigators recruited 51 healthy siblings of the patients with asthma to be controls. The investigators in that study based their conclusion of a lack of long-term effect on height on the finding that both controls and participants receiving budesonide attained predicted adult height rather than on a randomized comparison of the adult heights reached by the two groups.
The growth-velocity deficit that we observed in the budesonide group, as compared with the placebo group, during the first 2 years of treatment was primarily among prepubertal children (Fig. S2 in the Supplementary Appendix
). Our ability to further disentangle the effects of duration of treatment, age at treatment, and puberty status during treatment on growth velocity was limited because of confounding. Nevertheless, the effect on adult height of budesonide as compared with placebo was clearly demonstrated in the CAMP population.
Two previous 1-year studies of beclomethasone dipropionate also showed a greater reduction in growth in prepubertal children than in pubertal children.26,27
Like other studies in which prepubertal children received different doses of the same inhaled glucocorticoids that have shown a dose–response effect on growth,28,29
our study showed a weight-based, dose-dependent effect in the CAMP participants (Table S3 in the Supplementary Appendix
We found that a longer time since asthma diagnosis at trial entry and atopy (any positive skin test) were independent risk factors for shorter adult height (Table S3 in the Supplementary Appendix
). Other investigators have reported an increased incidence of short stature in children with atopy and asthma.30–32
One of these studies31
showed that short stature was associated with an early onset of asthma (before the age of 3 years), a finding that is consistent with our data. However, atopy-induced growth retardation has been associated with a delay in bone maturation and thus was thought to be unlikely to affect adult height.32,33
Our results suggest that when asthma and atopy impair growth, the deficit may persist into adulthood.
We selected a daily dose of 400 μ
g of budesonide for the CAMP trial to ensure a therapeutic effect in both children with mild asthma and those with moderate asthma.2
Since then it has been shown that daily administration of 200 μ
g of budesonide by means of a dry-powder inhaler effectively controls asthma symptoms and reduces exacerbations in children 5 to 11 years of age.3
Even at this lower dose, there was a reported mean reduction of 1.0 cm in height during the first 2 years of therapy.3
Although the systemic effects of inhaled glucocorticoids are dose-dependent, they are also dependent on the therapeutic index of the specific inhaled glucocorticoid and the delivery device used.4–9
Thus, it seems prudent to select inhaled glucocorticoids and devices with higher therapeutic indexes and to use them in the lowest effective doses in children with persistent asthma.1,9
In conclusion, the reduction in growth seen in the first few years of administration of inhaled glucocorticoids in prepubertal children persists as lowered adult height. However, in the information about inhaled glucocorticoids and their side effects that is provided to parents, the potential effect on adult height must be balanced against the large and well-established benefit of these drugs in controlling persistent asthma. It is appropriate to use the lowest effective dose for symptom control in order to minimize concern about the effects of inhaled glucocorticoids on adult height.