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Side Effects With Inhaled Corticosteroids: Systemic Side Effects in Children

Published in Asthma

Side Effects With Inhaled Corticosteroids: Systemic Side Effects in ChildrenOral corticosteroids are a known risk factor for the development of subcapsular cataracts, with risk influenced by daily cumulative dose, age, and ethnic origin. The systematic review described above concluded that the risk of cataracts due to ICS was small and may only be relevant in elderly patients. Two studies not included in the systematic review generally support these findings. A study from 1993 found that the prevalence of subcapsular cataracts in 48 patients treated with long-term BUD or BDP (750 to 1,500 ^g/d) was 27%. However, the development of cataracts was correlated to prednisone but not ICS use. A study published in 2001, after the systematic review was compiled, suggested that the risk of cataracts with ICS may be related to age. An analysis of 103,289 subjects exposed to ICS vs 98,527 subjects in a control cohort found slightly higher incidence rates for cataracts in the ICS group compared with the nonexposed cohort (RR, 1.3; 95%, CI 1.1 to 1.5) after adjusting for age and gender. However, a relationship between heavy use of ICS and cataract risk that was most pronounced in subjects > 70 years old was also seen in subjects aged 40 to 49 years, but was absent in subjects aged < 40 years. add comment

The evidence for an effect of ICS on glaucoma was poor in the systematic review. However, a more recent study of 3,654 patients found a strong association between ICS use and the presence of either glaucoma or elevated intraocular pressure (odds ratio, 2.6; 95% CI, 1.2 to 5.8), but only in those patients with a family history of glaucoma. The risk increased with higher ICS doses (odds ratio, 6.3; 95% CI, 1.0 to 38.6, for more than four puffs per day). These findings were not explained by concurrent use of oral or ocular corticosteroids.
ICS safety in children was reviewed in 2002 by the NAEPP guidelines update on selected topics. The report examined four outcomes: vertical growth, bone mineral density, ocular toxicity (including posterior subcapsular cataract and glaucoma), and suppression of hypothalamic-pituitary-adrenal axis function. The conclusions of this review are outlined in Table 3. There was evidence to support a reduction in linear growth and suppression of the hypothalamic-pituitary-adrenal axis with ICS. Although ICS have the potential to decrease growth velocity, there was no evidence that ICS therapy affected final adult height. However, the authors drew attention to the need for further study regarding the long-term effects of ICS on bone mineral density and cataract formation, and whether the effects of ICS on growth velocity were more pronounced for certain developmental periods.

Table 3—Systemic Side Effects With ICS Therapy in Children

EvidenceGradej Effect on: Conclusion
A, B, C Growth Low-to-medium doses of ICS may have the potential to decrease growth velocity, although the effects are small, nonprogressive, and maybe reversible.
A Bone mineral density Low-to-medium doses of ICS appear to have no serious adverse effects on bone mineral density.
A, C Cataracts/ glaucoma Low-to-medium doses of ICS have no significant effects on the incidence of subcapsular cataracts or glaucoma.
A, C Hypothalamic-pituitary-adrenal axis function On average, children may experience only clinically insignificant, if any, effects on the hypothalamic-pituitary-adrenal axis. Rare individuals, however, maybe susceptible to ICS effects on hypothalamic-pituitary-adrenal axis even at conventional doses.