A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler

Abstract

Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short-term lower leg and height growth. The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 μg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre-pubertal children with asthma were included in a randomized open-label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1-yr height growth suppression of budesonide 200 μg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids. Short-term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated.

Methodology and implications of knemometry in growth assessment of inhaled glucocorticoids

“…CFC+S, chlorofluorocarbon pressurized metered dose inhaler with a spacer; CFC, chlorofluorocarbon pressurized metered dose inhaler without a spacer; HFA+S, hydroflouroalkane-134a pressurized metered dose inhaler with a spacer; HFA, hydroflouroalkane-134a pressurized metered dose inhaler without a spacer; DP, dry powder inhaler. randomized, parallel group trial of inhaled budesonide 200 lg from the Pulaimax Ò dry powder inhaler reported in the present issue of the journal are very consistent with the analysis (43). The mean 2-wk lower leg growth rate was 0.17 mm/wk in the budesonide group compared with 0.39 mm/wk in the montelukast group, thus representing a 44% suppression.…”

“…So, although no specific cut‐off level can be identified in individuals from the available randomized, double‐blind short‐term knemometry and intermediate‐term height growth rate studies, good evidence have been provided that if the short‐term lower leg growth suppression in populations of children is higher than approximately 25% the risk of intermediate‐term growth suppression becomes significant with a mean height growth rate retardation in the range of approximately 0.5–1.5 cm during the first year of treatment (35). The results of the 1‐yr randomized, parallel group trial of inhaled budesonide 200 μg from the Pulaimax ® dry powder inhaler reported in the present issue of the journal are very consistent with the analysis (43). The mean 2‐wk lower leg growth rate was 0.17 mm/wk in the budesonide group compared with 0.39 mm/wk in the montelukast group, thus representing a 44% suppression.…”

Factors influencing growth effects of inhaled corticosteroids in children

“…However, once-daily morning budesonide dosing of 200 µg administered through a DPI slowed growth by 1 cm over 1 year compared with growth seen in prepubertal peers receiving montelukast, suggesting even once-daily morning dosing can impose growth suppression. E8 …”

The Effects of Inhaled Corticosteroids on Growth in Children

“…Mean 2-weeks lower leg growth rate was 0.17 mm/week in the budesonide and 0.39 mm/week in the montelukast treated children (p = 0.02). Mean 1-year height growth rate was 5.51 cm/year in the budesonide and 6.51 cm/year in the montelukast group [ 54 ]. A recent study by Zeiger et al .…”