A Cochrane review [Abstract] 1 included 25 studies with a total of 8471 children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) given at low or medium daily doses were used during a period of 3 months to 4 to 6 years. Compared with placebo or non-steroidal drugs, inhaled corticosteroids (ICS) produced a statistically significant reduction in linear growth velocity (MD -0.48 cm/y, 95% CI -0.65 to -0.30; 14 studies, n=5 717) and in the change from baseline in height (MD -0.61 cm/y, 95% CI -0.83 to -0.38; 15 studies, n=3 275) during a one-year treatment period. Subgroup analysis showed a statistically significant group difference between 6 molecules in the mean reduction of linear growth velocity during one-year treatment (P value < 0.0001). Results for different molecules are shown in table T1. The subgroup analysis of daily ICS doses showed that medium doses produced a statistically significantly greater reduction in mean change from baseline in height (P value 0.05) but not in linear growth velocity (P value 0.11) during a one-year treatment period compared with low doses. Among 4 studies reporting data on linear growth after treatment cessation, 3 did not describe statistically significant catch-up growth in the ICS group 2 to 4 months after treatment cessation. One trial showed accelerated linear growth velocity in the fluticasone group at 12 months after treatment cessation, but there remained a statistically significant difference of 0.7 cm in height between the fluticasone and placebo groups at the end of the 3-year trial. One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 μg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with those treated with placebo.
| Inhaled corticosteroid | MD (95% CI) | Participants (studies) |
|---|---|---|
| CFC = chlorofluorocarbon DPI = dry powder inhaler HFA = hydrofluoroalkane | ||
| CFC-beclomethasone 400 μg/d | -0.91 cm/y (-1.26 to -0.55) | 439 (3 studies) |
| Budesonide via DPI | -0.59 cm/y (-0.73 to -0.45) | 2 790 (3 studies) |
| HFA-ciclesonide 50 to 200 μg/d | -0.08 cm/y (-0.27 to 0.11) | 609 (1 study) |
| HFA-flunisolide 400 μg/d | -0.22 cm/y (-0.63 to 0.18) | 314 (2 studies) |
| Fluticasone propionate 100 to 200 μg/d | -0.39 cm/y (-0.63 to -0.15) | 1 405 (5 sudies) |
| Mometasone via DPI 100 to 200 μg/d | -0.47 cm/y (-0.97 to 0.03) | 184 (1 study) |
Another Cochrane review [Abstract] 2 included 22 eligible studies of which 10 studies and 17 group comparisons (3 394 children with mild to moderate asthma) measured growth and contributed data to the meta-analysis. Studies used inhaled corticosteroids (ICS) (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (MD 0.20 cm/y, 95% CI 0.02 to 0.39; 4 studies, n=728 school-aged children). The ICS molecules (ciclesonide, fluticasone, mometasone) used in these comparisons did not significantly influence the magnitude of effect. Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed.
Third Cochrane review [Abstract] 3 included 6 studies with a total of 1 199 children aged from 4 to 12 years with mild-to-moderate persistent asthma. Study duration varied from 6 to 20 months.One study (n=23) showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity compared to beclomethasone (MD 0.81 cm/year, 95% CI 0.46 to 1.16). Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 studies, n=359), but no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses was observed (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 studies, n=236).Two studies compared inhalation devices, and 1 study (n=212) found a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon-metered dose inhaler (CFC-MDI) at an equivalent dose (MD -0.44 cm/year, 95% CI -1.00 to 0.12). Another study (n=229) showed a small but statistically significant greater increase in height over a period of 6 months in favour of budesonide via Easyhaler compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62).
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