Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Systemic activity of inhaled topical steroid in toddlers studied by knemometry. Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone. Comparison of salmeterol with beclomethasone in adult patients with mild persistent asthma who are already on low-dose inhaled steroids. Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide. Growth of asthmatic children during treatment with budesonide: a double blind trial. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function. Steroid-sparing effects of fluticasone propionate 100 microg and salmeterol 50 microg administered twice daily in a single product in patients previously controlled with fluticasone propionate 250 microg administered twice daily. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group.
Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis. The short-term linear growth rate of the lower leg in toddlers was measured and evaluated in order to study the possible effect of inhaled budesonide on this factor in toddlers with mild recurrent wheezing. The short-term linear growth rate of the lower leg was measured weekly using a hand-held knemometer. Eighteen toddlers aged 13-36 months (mean 27 months) with a history of recurrent wheezing requiring inhaled topical steroids, but without need of regular medication during the months prior to the study, were studied. The children were randomized blindly through three consecutive treatment periods of four weeks with placebo or budesonide in daily doses of 200 micrograms and 800 micrograms administered as a pressurized aerosol inhaled via a spacer with a face mask. Twenty-nine percent (median) of the nominal dose was delivered at the mouth of the children. Three children were withdrawn because of exacerbations and one because of non-compliance. The precision of the measurement procedure was 51 microns/day. The mean growth rate during placebo, low-dose and high-dose steroid treatment was 92 microns/day, 114 microns/day and 46 microns/day respectively. The growth rate during the high-dose treatment was suppressed significantly compared to placebo treatment (95% CI -76 microns/day to -17 microns/day), whereas the growth rate during low-dose steroid treatment was indistinguishable from placebo treatment (95% CI -7 to +52 microns/day). In conclusion, measurement of short-term linear growth rate by knemometry in toddlers is a fast and gentle method with a high level of precision.(ABSTRACT TRUNCATED AT 250 WORDS) Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate. Current guidelines on asthma management recommend the early use of inhaled corticosteroids. Recent studies of patients with moderate to severe asthma show that the addition of salmeterol is superior to a further increase of the steroids. In this study with adult, mild persistent asthma patients, we compared the effects of adding salmeterol 50 microg b.i.d. versus beclomethasone dipropionate (BDP) 200 microg b.i.d. (both via Diskhaler dry powder inhaler) to the low-dose inhaled steroids. A double-blind, randomized, parallel-group study was conducted with a run-in period of 2 weeks and a treatment period of 12 weeks. Patients (n = 233) were randomized with a peak expiratory flow (PEF) reversibility of 22 +/- 10% (mean +/- SD) in the run-in period. The morning PEF was 84 +/- 17% predicted and the age was 42 +/- 14 years (45% males). The average prestudy inhaled steroid dose was 361 microg daily. Within a week of salmeterol treatment the daily PEF recordings reached maximal levels. At the end of the treatment period the evening PEF remained significantly better in the salmeterol group than in the BDP group (p = 0.036). The PEFs, measured at the general practitioners' (GPs') office, were at least 95% of the predicted values and the post-salbutamol values at the end of both treatments. However, the salmeterol group had already obtained this level after 2 weeks and differed significantly from the beclomethasone group (p = 0.003 for percent predicted and p = 0.0007 for post-salbutamol PEF values). The symptom scores and the use of rescue medication showed a similar profile. Quality of life improved with both treatments, but without significant statistical differences between the groups. The frequency of adverse events, typical for beta2-agonists, was low and showed no differences between the groups. These results showed that the addition of salmeterol is at least as effective as adding beclomethasone in normalizing peak flows and improving asthma control in mild persistent asthma patients. Furthermore, salmeterol has a much faster onset of action. In asthmatic children inhaled corticosteroids are widely used. However, there are some concerns about the systemic adverse effects of these drugs, especially in the growing child. We performed this prospective study in order to compare the effects of 400 microg/day of budesonide (BUD) and 250 microg/day of fluticasone propionate (FP) on growth in prepubertal (aged 4-11.5 years), moderate persisting asthmatic children. One hundred patients (51 boys and 49 girls), who were randomized into two groups, were recruited for the study. The first group was treated with BUD, 2X 200 microg/day, and the second group was treated with FP, 2X 125 microg/day, by using a medium-size volume-spacer metered-dose inhaler. Growth in children with asthma who were treated by inhaled corticosteroids was calculated by growth velocity over a 12-month period. Comparisons between treatment groups were calculated by t-test and chi-square test. There were no significant differences between BUD and FP groups for sex, age, first height, and growth velocity. Moderate persisting, prepubertal asthmatic children treated with 250 microg/day of FP appeared to have no different linear growth than those children who received 400 microg/day of BUD. To determine whether the inhaled glucocorticosteroid budesonide has any adverse effect on short term linear growth in children with mild asthma.
                Outpatient clinic in secondary referral centre.
                15 children aged 6-13 years with normal statural growth velocity during the previous year, no signs of puberty, and no use of systemic or topical steroids in the two months before the study. DESIGN OF INTERVENTIONS: Double blind, randomised crossover trial with two active periods in which budesonide was given in divided daily doses of 200 micrograms and 800 micrograms. During run in and two washout periods placebo was given. After the second washout period the children received open treatment with 400 micrograms budesonide daily. All periods were of 18 days' duration.
                Growth of the lower leg as measured twice a week by knemometry.
                Mean growth velocity of the lower leg was 0.63 mm/week during run in and during washout 0.64 mm/week. Budesonide treatment was associated with a significant dose related reduction of growth velocity: the mean reduction in growth velocity during treatment was 0.11 (95% confidence interval -0.15 0.36 (0.13 to 0.59) mm/week with 800 micrograms budesonide (p less than 0.05; Page's test). During treatment with 400 micrograms budesonide a reduction of 0.17 (-0.10 to 0.45) mm/week was found.
                Treatment with inhaled budesonide is associated with a dose related suppression of short term linear growth in children with mild asthma. The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study. Concurrent use of an inhaled corticosteroid (ICS) and an inhaled long-acting beta2-agonist provides better overall asthma control than the use of higher doses of ICS alone.
                The purpose of this investigation was to determine whether fluticasone propionate (FP) combined with salmeterol in the Diskus device can be used to reduce the dose of ICS in patients currently stable on medium-dose ICS while maintaining asthma control.
                This was a randomized, double-blind, parallel-group, 12- to 24-week trial consisting of a 3-part run-in period. The run-in period was designed to first establish FP 250 microg administered twice a day (bid) via Diskus as the minimum effective dose. During run-in period 1, patients received FP 220 microg bid or the equivalent for 10 to 14 days. Controlled patients moved to run-in period 2 (5-28 days), which assessed asthma stability on FP 100 microg bid administered via Diskus. Only patients who became unstable on FP 100 microg bid were eligible to enter run-in period 3 (26-30 days), during which they were placed on FP 250 microg bid and those regaining asthma control were eligible for randomization. The primary efficacy endpoint was the proportion of patients who remained in the study with no evidence of worsening asthma. Secondary efficacy measures included FEV1, morning peak expiratory flow, percent of symptom-free days, and daily albuterol use.
                Only 5% of patients treated with FP100/salmeterol withdrew because of worsening asthma in the first 12 weeks; this compared with 7% in the FP250 group. All patients from a subset of sites continued in the study for an additional 12 weeks; only an additional 1% of patients treated with either FP100/salmeterol or FP250 withdrew because of worsening asthma. Secondary efficacy measures confirmed primary efficacy results.
                In patients requiring FP250 bid for asthma stability, FP100/salmeterol bid was steroid-sparing, allowing a 60% reduction in the FP dose while maintaining overall asthma control. Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 microg twice daily (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 microg twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication.
In children with mild-moderate asthma, beclomethasone 200 mcg twice daily caused a decrease in linear growth of -1.54 cm per year. These studies lasted a maximum of 54 weeks, so it remains unclear whether the decrease in growth is sustained or whether it reverses with 'catch up' after therapy is discontinued. We are unable to comment on growth effects of other inhaled steroids that have potentially less systemic effects. If inhaled steroids are required to control a child's asthma, we recommend using the minimum dose that effectively controls the child's asthma and closely following growth.