Do different inhaled corticosteroids have different impacts on growth in children with asthma?
Inhaled fluticasone (Flovent; 200 mcg per day) is associated with a greater linear growth velocity (mean difference [MD] = 0.81 cm per year; 95% CI, 0.46 to 1.16; one study, 23 participants) when compared with beclomethasone (400 mcg per day; an equivalent dose). (Strength of Recommendation: C, based on consensus, disease-oriented evidence, usual practice, expert opinion, or case series.)
Fluticasone via Diskus inhaler (200 mcg per day) is associated with a greater increase in height (MD = 0.97 cm; 95% CI, 0.62 to 1.32; two trials, 359 participants) over 20 weeks to 12 months compared with budesonide (Rhinocort) via turbuhaler (400 mcg per day). (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Budesonide via Easyhaler is associated with a greater increase in height over six months (MD = 0.37 cm; 95% CI, 0.12 to 0.62; one trial, 229 participants) when compared with budesonide via turbuhaler.1 (Strength of Recommendation: C, based on consensus, disease-oriented evidence, usual practice, expert opinion, or case series.)
Asthma affects 19 million adults and 6.2 million children in the United States.2 Between 2008 and 2013, asthma contributed to $50 billion in direct medical costs and $3 billion in indirect costs from missed school and work.3 The Global Initiative for Asthma (GINA) recommends the use of inhaled corticosteroids for all children with asthma, except for those with the mildest form (when inhaled corticosteroid use is optional).4 Inhaled corticosteroids are associated with growth delays. A randomized controlled trial found that four years of budesonide use was associated with a 1.2-cm loss in final adult height, and a meta-analysis of two observational studies showed that inhaled corticosteroid use was associated with a 0.85-cm loss in height.5 Poorly controlled asthma also slows growth velocity; a 2019 review shows that more severe asthma tends to correlate with slower growth.6
The authors of this Cochrane review studied whether different inhaled corticosteroids and delivery systems had different effects on growth in children with asthma.1 The review included six randomized trials of children four to 12 years of age with persistent asthma who were using an inhaled corticosteroid; 1,008 of the children completed their respective studies without major protocol deviations. The per-protocol population was used instead of the intention-to-treat population because the authors were trying to assess the impact of inhaled corticosteroid therapy on growth. With the small number of trials, subgroup analyses, meta-regression analysis, and sensitivity analyses were not performed. Ties to the pharmaceutical industry in two-thirds of the included studies, lack of blinding in two studies, concerns about allocation concealment in five studies, and incomplete outcomes data in two studies limited author confidence in the study results.
Compared with 400 mcg of beclomethasone per day, 200 mcg of fluticasone per day (an equivalent dose) was associated with a greater linear growth velocity (MD = 0.81 cm per year; 95% CI, 0.46 to 1.16; one study, 23 participants). When compared with a similarly equivalent dose of budesonide, fluticasone did not significantly impact linear growth velocity (two trials, 236 participants), but fluticasone via Diskus (200 mcg per day) was associated with a greater increase in height (MD = 0.97 cm; 95% CI, 0.62 to 1.32; two trials, 359 participants) over 20 weeks to 12 months when compared with budesonide via turbuhaler (400 mcg per day). With respect to delivery vehicles, budesonide via Easyhaler was associated with a greater increase in height over six months (MD = 0.37 cm; 95% CI, 0.12 to 0.62; one trial, 229 participants) than budesonide via turbuhaler.
The 2007 National Heart, Lung, and Blood Institute's Expert Panel Report 3 recommends the use of inhaled corticosteroids in all patients with persistent asthma.7 The more recent GINA guidelines echo this recommendation but also provide that a low-dose inhaled corticosteroid may be taken as a daily controller medication in those with intermittent symptoms or as an on-demand addition whenever a short-acting beta agonist is used.4 There is a slowing of growth with inhaled corticosteroid use, but the magnitude of slowing is small and the harms of uncontrolled asthma are worse (and include a slowing of growth). Family physicians should review the risks and benefits of inhaled corticosteroids with patients and their families, noting that although there may be, on average, a 1.2-cm loss in final adult height, uncontrolled severe asthma can be associated with profound morbidity, hospitalization, and even death. Among the medications studied, fluticasone seems to be associated with the best growth outcomes.
The practice recommendations in this activity are available at http://www.cochrane.org/CD010126.
Editor's Note: Dr. Saguil is a contributing editor for AFP.
The views expressed in this article are the author's and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. government.