Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone

Abstract

Background: The effect on linear growth of daily long-term inhaled corticosteroid therapy in preschool-aged children with recurrent wheezing is controversial.

Objective: We sought to determine the effect of daily inhaled corticosteroid given for 2 years on linear growth in preschool children with recurrent wheezing.

Methods: Children aged 2 and 3 years with recurrent wheezing and positive modified Asthma Predictive Index scores were randomized to a 2-year treatment period of chlorofluorocarbon-delivered fluticasone propionate (176 μg/d) or masked placebo delivered through a valved chamber with a mask and then followed for 2 years off study medication. Height growth determined by means of stadiometry was compared between treatment groups.

Results: In the study cohort as a whole, the fluticasone group did not have significantly less linear growth than the placebo group (change in height from baseline difference, -0.2 cm; 95% CI, -1.1 to 0.6) 2 years after discontinuation of study treatment. In post hoc analyses children 2 years old who weighed less than 15 kg at enrollment and were treated with fluticasone had less linear growth compared with those treated with placebo (change in height from baseline difference, -1.6 cm; 95% CI, -2.8 to -0.4; P = .009).

Conclusion: Linear growth was not significantly different in high-risk preschool-aged children with recurrent wheezing treated with 176 μg/d chlorofluorocarbon-delivered fluticasone compared with placebo 2 years after fluticasone is discontinued. However, post hoc subgroup analyses revealed that children who are younger in age and of lesser weight relative to the entire study cohort had significantly less linear growth, possibly because of a higher relative fluticasone exposure.

Figure 1

Post-hoc subgroup analyses: Difference in height change from baseline between treatment and placebo group [height change (left panel) and z-score change (right panel)] from baseline to 48 months for fluticasone treated group as compared to placebo treated group. Children at particular risk for less linear growth during treatment were those children who were two years of age and <15 kg at enrollment. At the end of the two-year observation period, linear growth was only reduced in the children that were two years of age at enrollment of lesser weight (relative to the cohort) versus the younger children with a higher weight (Panels C & G) or the older children with any enrollment weight (Panel D & H). Results were obtained using linear mixed-effects regression including data from all study visits while adjusting for baseline covariates. Significant differences between treatment groups denoted by: † (p<0.05) and ‡(p<0.01).

Figure 2

Scattergrams of growth from baseline (z-score) during treatment versus enrollment weight by treatment group. Top panels: overall cohort, middle panels: subjects 2 years old at enrollment, bottom panels: subjects 3 years old at enrollment. Children at particular risk for less linear growth during treatment were those that had an enrollment weight of <17 kg versus those that had a lesser exposure compared to their respective placebo counterparts (Panel A). This was more pronounced in the children who were two years of age at enrollment (Panel B). After the ICS treatment ended, these younger children of lesser weight (relative to the cohort) did not demonstrate the same catch-up in linear growth demonstrated by the younger, heavier children (Panel E) or older children of any weight (Panel F). Two years after treatment discontinuation, less linear growth was observed in only the younger children of lesser weight (Panel H). Solid lines (blue:ICS, red:Placebo) represent fitted values from non-parametric smoothing spline with 95% confidence bands (24). All data values were used for model fitting, but estimated regression lines are truncated to avoid extrapolation beyond the main part of the data.