Asthma, Inhaled Corticosteroids and Growth

The National Asthma Education and Prevention Program (NAEPP) establishes guidelines for asthma management in children and adults.1 In order to apply these guidelines, patients with asthma are placed in one of four categories – mild intermittent, mild persistent, moderate persistent or severe persistent – based on the frequency and severity of their symptoms. According to the NAEPP guidelines, patients with moderate persistent symptoms should be treated with daily inhaled corticosteroids (ICSs).

ICSs are the drug of choice for controlling persistent asthma symptoms.1 By controlling the inflammation and mucosal edema associated with asthma, they reduce exacerbations and prevent airway remodeling. Good asthma control results in lower morbidity and mortality and decreases healthcare costs.

But steroids have many potential side effects, including growth suppression, which is a particular cause for concern in children whose asthma symptoms require daily doses of ICSs. Nevertheless, asthma itself, particularly if poorly controlled, may result in growth suppression even in the absence of ICS treatment. Hormonal, nutritional and socioeconomic factors, recurrent respiratory infections, limited access to care and chronic hypoxemia are among the possible contributors.2

Does the daily use of ICSs during childhood and adolescence suppress growth permanently? And, even as clinical evidence suggests that ICSs might affect a child’s linear growth in the short term, is this temporary growth deceleration acceptable, given the effectiveness of ICSs in managing asthma?

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Review of the Literature

To answer these questions, I searched the literature for studies investigating the effect of daily ICS use for asthma treatment on the linear growth of children and adolescents. I limited the search to human clinical trials with a study period of at least 1 year, with level 3 evidence or higher, and with publication dates within the previous 5 years. I did not include studies that weren’t published in English. Studies had to have been limited to children and adolescents, and the study group had to have been compared with nonasthmatic controls or with nationally accepted growth curves. Studies comparing multiple ICS types (e.g., fluticasone with budesonide) and studies with fewer than 50 participants were excluded.

Three studies met the search criteria: one high-quality cohort study,3 one high-quality case-control study,2 and one systematic review of five randomized controlled trials4 (see table). One other study5 investigated the effect of ICS use on target growth (anticipated adult height); however, this study was excluded because the three other studies did not include adult height as an outcomes measure.

The case-control study showed a decrease in growth velocity over a 6-month period in children receiving ICSs; the cohort study found no difference in growth over a 1-year period in children using ICSs. The systematic review found that standard pediatric doses of ICSs suppress growth slightly in the short term, although the reduction decreases as length of treatment increases.

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While the cohort study found no significant growth suppression among children treated with ICSs,3 the other two found that treatment with moderate doses of an ICS may suppress growth in the short term, but that the growth suppression is reduced as the length of treatment increases.2,4 The systematic review of randomized controlled trials found that daily ICS dosing results in mild growth suppression, with a mean difference in height of approximately 1 cm.4 Moreover, the case control study and systematic review both found that children typically recover that growth after 1 year of treatment.2,4

The risk of growth suppression appears to be dose-dependent, implying that patients with severe asthma symptoms who thus require larger doses of ICSs are more likely to experience a temporary growth suppression.2-4

Educating About Risks, Benefits

Evidence suggests that ICSs delay linear growth in the short term. This temporary growth deceleration is acceptable given the effectiveness of ICSs in controlling asthma symptoms. Nevertheless, parents are often hesitant to begin daily ICS treatment for their children because of concerns about potential side effects.

Healthcare providers treating children with asthma should educate parents thoroughly about the importance of adherence to medication regimens, of avoiding asthma triggers, and about the risk-to-benefit profile of all asthma-control medications. It is critical that parents understand that the benefits of ICS therapy outweigh the risks of short-term growth suppression, that this suppression generally occurs only at higher doses, and that growth typically is regained over the long term.

Randomized controlled trials in the setting of asthma – a potentially fatal disease if left untreated – are difficult to accomplish, given the ethics of withholding treatment to patients in a control group. Still, future research could include evaluating the maximum adult height achieved by patients who used ICSs throughout childhood and adolescence. Research also might focus on other factors suspected of suppressing growth that are unrelated to ICS use by children with asthma, such as socioeconomic factors (parents’ education level, environmental exposure to asthma triggers, etc.), nutritional factors and access to medical care. Moreover, future studies should include larger sample sizes and should extend longer than 12 months.

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References

1. National Asthma Education and Prevention Program. Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; 2007. NIH publication 07-4051.

2. Priftis KN, et al. The effect of inhaled budesonide on adrenal and growth suppression in asthmatic children. Eur Respir J. 2006;27(2):316-320.

3. Arend EE, et al. Inhaled corticosteroid treatment and growth of asthmatic children seen at outpatient clinics. J Pediatr (Rio J). 2006;82(3):197-203.

4. Rachelefsky G. Inhaled corticosteroids and asthma control in children: assessing impairment and risk. Pediatrics. 2009;123(1):353-366.

5. Larsson L, et al. Budesonide-treated asthmatic adolescents attain target height: a population-based follow-up study from Sweden. Pharmacoepidemiol Drug Saf. 2002;11(8):715-720.

Danielle L. Kempton is an assistant professor and the clinical coordinator at the Midwestern University PA program in Glendale, Ariz. She has completed a disclosure statement and reports no relationships related to this article.

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