Laurie Barclay, MD

July 18, 2014

Inhaled corticosteroids may suppress growth in the first year of treatment in children with asthma, but lower doses may minimize the effects, according to findings of 2 systematic reviews published online July 17 in the Cochrane Library.

Inhaled corticosteroids are the most effective drugs for asthma control, reducing asthma mortality, hospital visits, and exacerbations while improving quality of life. Although they are generally considered first-line treatment for persistent asthma, their potential effect on childhood growth was previously undefined, and the potential for growth retardation and other systemic adverse effects continues to be a matter of concern.

Of the 7 inhaled corticosteroids currently available worldwide (beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone), ciclesonide, fluticasone, and mometasone are newer and are thought to have a better safety profile.

“The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimetre less during the first year of treatment,” lead author of the first article, Linjie Zhang, MD, PhD, from the Faculty of Medicine, Federal University of Rio Grande in Brazil, said in a Cochrane news release. “But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared to the known benefits of the drugs for controlling asthma and ensuring full lung growth.”

Dr. Zhang and colleagues searched the Cochrane Airways Group Specialised Register of trials, respiratory journals, meeting abstracts, ClinicalTrials.gov, and manufacturers’ clinical trial databases in January 2014 for pertinent parallel-group randomized controlled trials.

They included 25 trials in their review. The trials enrolled a total of 8471 participants aged 18 years or younger who had mild to moderate persistent asthma treated with any of the available inhaled corticosteroids except for triamcinolone. Fourteen of these trials, enrolling a total of 5717 children, reported on growth over the course of a year.

Compared with placebo or nonsteroidal drugs, inhaled corticosteroids as a group suppressed growth rates, with those in the treatment group growing an average of 0.5 cm less than the average for the control group.

Compared with placebo or nonsteroidal drugs, inhaled corticosteroids were associated with a statistically significant reduction in linear growth velocity (−0.48 cm/year; 95% confidence interval, −0.65 to −0.30 cm/year; P < .0001) and in the change from baseline in height (mean difference, −0.61 cm/year; 95% confidence interval, −0.83 to −0.38) during a 1-year treatment period.

However, there was no statistically significant difference in linear growth velocity between participants treated with inhaled corticosteroids and controls during the second year of treatment.

The effect size of inhaled corticosteroids on linear growth velocity appeared to be associated more strongly with the specific drug than with the device or dose.

Lower Doses May Minimize Growth Suppression

The second article, by Aniela I. Pruteanu, MD, from the Research Centre, Centre Hospitalier Universitaire Sainte-Justine, and the Department of Pediatrics, University of Montreal, Québec, Canada, and colleagues included 22 trials of low or medium doses of inhaled corticosteroids in children, with data on different doses of all drugs except triamcinolone and flunisolide. Of 3 trials reporting follow-up for at least 1 year in a total of 728 children, 1 tested 3 different dosing regimens.

“Only 14% of the trials we looked at monitored growth in a systematic way for over a year,” said senior author Francine Ducharme, MD, also from the Department of Pediatrics, in the news release. “This is a matter of major concern, given the importance of this topic.”

The 3 trials showed that reducing the inhaled corticosteroid dose by about 1 puff per day was associated with improved growth by a quarter centimeter at 1 year.

“We recommend that the minimal effective dose be used in children with asthma until further data on doses becomes available,” Dr. Ducharme said. “Growth should be carefully documented in all children treated with inhaled corticosteroids, as well in all future trials testing inhaled corticosteroids in children.”

Growth suppression varied across studies, which could in part be because of use of specific drugs and/or other factors affecting growth.

“Conclusions about the superiority of 1 drug over another should be confirmed by further trials that directly compare the drugs,” said Dr. Zhang, who was also a coauthor on the second review.

The investigators also recommend additional long-term trials and trials comparing different doses, particularly in children with more severe asthma requiring higher doses of inhaled corticosteroids.

“In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of [inhaled corticosteroids] and low to medium doses of [hydrofluoroalkane]-beclomethasone equivalent, favouring the use of low-dose ICS,” Dr. Pruteanu and colleagues conclude. “No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents’ and physicians’ concerns about the growth suppressive effect of [inhaled corticosteroids], lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern.”

These reviews received no external funding. The authors have disclosed no relevant financial relationships.

Cochrane Library. Published online July 17, 2014. Zhang abstract, Pruteanu abstract

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