Summarized design and outcomes of type 4 growth studies (i.e. ‘real life’ studies)
| First author [ref. no.] | Treatment groups and number of patients | Duration of growth assessment | Severity of asthma | Age and sexual maturity of patients at baseline | Permitted therapy (other than study treatment) | Frequency and specified protocol for stadiometry | Statistical analysis for growth | Main study outcome |
| Agertoft 5 | BUD 110–877 µg·day−1 (n=142); no steroids (n=18); healthy controls (n=51) | 3–13 yrs (prospective, until attainment of final height) (run in period of 1–2 yrs) | No requirement for continuous inhaled CS | 3–13 yrs | As-needed β-agonists, oral CS≤2 weeks·yr−1 (BUD group only) | Every 6 months, same three observers throughout | Measured adult height minus calculated target height; paired t-test | Final height. Actual minus target final heights: BUD, +0.3 cm, 95% CL −0.6, 1.2; no steroids, −0.2 cm, 95% CL −2.4, 2.1; healthy controls +0.9 cm, 95% CL −0.4, 2.2. significant reductions in GV (1.0 and 0.6 cm·yr−1) with BUD during 1st and 2nd years compared with run-in |
| Inoue 24 | BDP 100–800 µg·day−1 initiated either before pubertal growth (n=32) or after (n=29); nonsteroidal therapy (n=36) | 8–10 yrs (retrospective) | Moderate-severe | 10–12 yrs | Oral CS | Annual | Yearly mean height SDS values at ages 10–20 (final height); unpaired t-test | Final height. No significant intergroup differences in height SDS (boys or girls). Evidence of delayed pubertal growth in all three groups |
| Larsson 25 | Inhaled or oral CS (n=113); no steroids (n=82); healthy controls (n=151) | Adult height measurement only (duration of asthma therapy ≤12 yrs) | Not specified | Not applicable; height measured at age 23 (mean) | Not specified | Not specified | Measured adult height (men and women analysed separately) | Final height. No significant intergroup differences in final height (men or women) |
| Silverstein 23 | Inhaled and/or oral CS (n=58); no CS (n=95); healthy controls (n=153) | Adult height measurement only (mean time from first to last CS exposure=7.3 yrs) | Not specified | Not applicable (height measured at mean age of 25.7 yrs) | Oral CS | Not specified | Relationship between final height (adjusted for midparental height) and CS exposure; ANCOVA. | Final height. CS group=1.2 cm shorter than no CS (95% CL −3.1 0.6). No significant difference between patients with asthma and controls |
| Van Bever 26 | Inhaled CS (n=42); Nonsteroidal therapy (n=43) | Adult height measurement only (mean age at first CS exposure=13.3 yrs) | Not specified | Not applicable (height measured at mean ages of 23.6 yrs (inhaled CS) and 22.1 yrs (nonsteroid) | Oral CS | One observer throughout | Final height minus calculated target height; nonpaired t-test and ANOVA | Final height. Adult minus target height: inhaled CS −0.003±5.9 cm; no CS, 2.54±4.8 cm; p-0.0 No significant intergroup difference in adult height SDS |
| Agertoft 27 | BUD ≤800 µg·day−1 (n=216); no steroids (n=62) | 2–6 yrs (prospective) (run-in period) or 1–3 yrs) | Mild-moderate | 3–11 yrs | As-needed β-agonists, oral CS≤2 weeks·yr−1 (BUD group only) | Every 6 months, same two observers throughout | GV calculated by linear regression. Measured height converted to SDS for intergroup comparison | No significant difference in GV between BUD (5.48 cm·yr−1; 95 CL: 5.31, 5.65) and control (5.62 cm·yr−1; 95% CL: 5.07, 6.17). |
| Childhood Asthma Management Program Research Group 29 | BUD 400 µg·day−1 (n=280); nedocromil 16 mg·day−1 (n=271); PBO (n=379) (all doses reduced to zero if asthma well controlled) | 4.3 yrs (prospective) | Mild-moderate | 5–12 yrs | Oral CS; addition of BDP 336 µg·day−1 as needed | Every 2 months for the first 4 months, and every 4 months thereafter | Multiple regression, with covariates for age, sex, race, clinic, duration of asthma and skin-test reactivity | Change in height from baseline Significantly smaller increase in height with BUD versus PBO (22.7 versus 23.8 cm, p=0.005), due to lower GV during the first yr (GVs were similar thereafter) |
| Skoner 28 | TAA 600 µg·day−1 mean (n=119); nonsteroidal therapy (n=12) | 12 months (prospective) | Moderate | 6–11 yrs | Not specified | Not specified | Not specified | GV significantly lower with TAA versus no CS therapy (5.3 versus 6.1 cm·yr−1, p<0.001) |
| Skoner 30# | BUD 500–1000 µg·day−1 (n=371); “Conventional asthma therapy: (n=156) (all doses reduced to zero if asthma well controlled) | 12 months (3 studies) (prospective) | Mild | 1–9 yrs | As-needed β-agonists, oral CS | Week 4 and every 8 weeks thereafter | Changes in height SDS (general linear model); GV (linear regression); inter-group differences (general linear model) | No significant intergroup differences for pooled data. In of the three studies, GV was significantly reduced in the BUD group (−0.8 cm·yr−1, p=0.002) |
BUD: budesonide
BDP: beclomethasome dipropionate
CS: corticosteroid
PBO: placebo
TAA: triamcinolone acetonide
SDS: standard deviation score
ANCOVA: analysis of covariance
ANOVA: analysis of variance
GV: growth velocity
CL: confidence limits
Inclusion criteria for height and growth velocity were not specified for any of the studies. The population used for the growth analysis was unspecified in all but 2 studies (Agertoft et al. 5 and Skoner et al. 29; per protocol for both)
#: also published as a full paper on 1999 31