Effects of 2 Inhaled Corticosteroids on Growth

Results of a Randomized Controlled Trial

Author Information
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#aainfo>   Fernando M. de
Benedictis, MD; Alejandro Teper, MD; Robin J. Green, MD; Attilio L. Boner,
MD; Lisa Williams, MSc; Hilary Medley, DipClinSci; for the International
Study Group
Objective  To compare the long-term effect of treatment with fluticasone
propionate or beclomethasone dipropionate on growth in asthmatic children.
Design  Prospective, multicenter, randomized, double-blind, parallel-group
study.
Setting  Children requiring regular treatment with inhaled corticosteroids
and with a sexual maturity rating of Tanner stage 1 (prepubertal).
Patients  Three hundred forty-three children aged 4 to 11 years with asthma.
The growth population (excluding patients with protocol violations likely to
affect growth measurements) included 277 patients.
Interventions  Fluticasone propionate or beclomethasone dipropionate, both
at a dosage of 200 µg administered twice daily via a dry powder inhaler
(Diskhaler) for 12 months.
Main Outcome Measures  Growth velocity, lung function, and serum and urinary
cortisol levels.
Results  The adjusted mean growth velocity in the fluticasone group was
significantly greater than that in the beclomethasone group (5.01 [SE, 0.14]
vs 4.10 [SE, 0.15] cm/y; difference, 0.91 cm; 95% confidence interval,
0.63-1.20 cm; P<.001). Both treatments improved lung function, with
significant differences in favor of fluticasone. Adverse events were similar
in both groups, and there were no significant differences in effect on serum
and urinary cortisol levels.
Conclusions  The more favorable risk-benefit ratio of fluticasone indicates
that this agent is preferable to beclomethasone for the long-term treatment
of children with asthma, especially if moderate doses are required.
Arch Pediatr Adolesc Med. 2001;155:1248-1254
POA10026
ASTHMA IS characterized by symptoms of wheeze, cough, and tightness of the
chest resulting from an inflammatory response in the airways. 1
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r1> , 2
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r2>  Anti-inflammatory
drugs such as inhaled corticosteroids are recommended in all age groups if
inhaled, short-acting beta-agonists are required more than once a week. 1
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r1>  Beclomethasone
dipropionate and budesonide have similar efficacy profiles, 3
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r3>  but fluticasone
propionate is at least as effective and as well tolerated as beclomethasone
and budesonide at half the dose. 4
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r4>
Short-term studies have indicated that inhaled beclomethasone dipropionate
and budesonide (400 µg/d) can affect lower-leg growth rates in children, 5-7
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r5>  but these data do
not accurately predict long-term growth. 8
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r8>  One year of
treatment with beclomethasone dipropionate, 400 µg/d, has been shown to
cause significant slowing of growth, compared with placebo or
noncorticosteroid control drug. 9
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r9> , 10
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r10>  In contrast, a
12-month, placebo-controlled study showed that prepubescent children treated
with fluticasone propionate, 50 or 100 µg twice daily, grew at the expected
velocity for their age. 11
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r11>  Furthermore, a
significant difference in growth rate was found during a period of 20 months
in steroid-naive asthmatic children treated with fluticasone propionate, 200
µg/d (5.75 cm/y), compared with beclomethasone dipropionate, 400 µg/d (4.94
cm/y). 12 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r12>
There are, however, limited data on the effect of fluticasone propionate at
dosages of greater than 200 µg/d on growth rates. This study was therefore
designed to compare the effects on growth of fluticasone propionate with
that of beclomethasone dipropionate, both at a dosage of 400 µg/d
administered via a dry powder inhaler (Diskhaler; GlaxoSmithKline,
Greenford, England) in children with a history of chronic asthma. Lung
function was also evaluated, to provide an indication of the risk-benefit
ratio of the treatments.



POPULATION, MATERIALS, AND METHODS



We conducted the study in Holland, Hungary, Italy, Poland, Argentina, Chile,
and South Africa under the conditions described in the Declaration of
Helsinki. Approval from the Ethics Committee of each participating center
and prior written informed consent from the appropriate child, parent,
and/or guardian were obtained.
STUDY POPULATION

Boys (aged 4-11 years) or girls (aged 4-9 years) with a sexual maturity
rating of Tanner stage 1 were eligible for entry into the study if they
required treatment with inhaled fluticasone propionate, 100 to 200 µg/d, or
beclomethasone dipropionate or budesonide, 200 to 500 µg/d, for at least the
previous 8 weeks, at a constant dosage for at least 4 weeks before the
run-in period. Patients with intermittent asthma or disorders that could
affect growth, patients receiving oral or parenteral steroids, and patients
admitted to a hospital with respiratory disease in the 4 weeks before the
run-in period were excluded from the study.
During the 2-week run-in period, patients continued to receive their
existing inhaled corticosteroid treatment and albuterol sulfate from a
metered-dose or dry-powder inhaler on an as-needed basis. Patients were
randomized to treatment if they demonstrated a mean morning peak expiratory
flow (PEF) during the last 7 days of the run-in period of no greater than
85% of their maximum achievable response after inhalation of albuterol
sulfate, 400 µg, via a metered dose inhaler. Patients also had to have an
asthma symptom score of at least 1 or require albuterol at least once daily
on at least 4 of the last 7 days of the run-in period.
Patients were permitted to continue with the following antiasthma
treatments, providing that the dose remained constant during the course of
the study: cromolyn sodium, nedocromil sodium, methylxanthines, ketotifen
fumarate, anticholinergics, and oral or long-acting beta-agonists. In
addition, the following treatments were permitted for use as needed: oral
corticosteroids for asthma exacerbations, intranasal corticosteroids,
decongestants, antihistamines, and antibiotics.
STUDY DESIGN

The study was a prospective, multicenter, randomized, double-blind,
parallel-group design. The 2-week run-in period was followed by 52 weeks of
treatment with fluticasone propionate or beclomethasone dipropionate, both
administered at a dosage of 200 µg twice daily using a dry powder inhaler
(Diskhaler). No specific instructions were given with respect to mouth
rinsing. This was left to the investigators' discretion, according to local
practice. Both formulations looked the same because of the predominance of
lactose in the formulation, and any taste associated with the products would
be attributable to the lactose. Treatment randomization was generated by
computer using a validated computer program (Patient Allocation for Clinical
Trials; GlaxoSmithKline). Each investigator was given a block of treatment
(minimum block size, 4 treatments) and provided with individually sealed
envelopes containing details of the medication that corresponded to each
patient's treatment number. Treatment was assigned in ascending order,
starting with the lowest number.
Patients visited the clinic after 2 and 4 weeks of treatment, and then at
12-week intervals for the next 48 weeks. A follow-up visit was arranged at 2
weeks after completion of treatment. No detailed assessments of compliance
were made during the study. Although compliance with inhaled corticosteroid
therapy is generally considered to be poor, the purpose of this study was to
compare 2 inhaled corticosteroids for which it was assumed that compliance
rates would be similar. However, investigators were asked to confirm whether
patients were taking their medication correctly at each clinic visit.
OUTCOME MEASURES

The primary end point was growth velocity, measured by means of stadiometry
during the 52-week treatment. Secondary end points included asthma symptom
scores, beta-agonist use, asthma exacerbation rate, and lung function
measurements.
The study was powered to detect a difference in growth of 1 cm/y between the
treatments. Based on data from a previous study, 13
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r13>  if the SD of
growth velocity was 2.7 cm/y, it would be necessary to recruit 240 patients,
ie, 120 per treatment group, to ensure a power of 80% to detect a difference
of 1 cm/y at the 5% significance level.
On a daily basis, each patient recorded their daytime and nighttime asthma
symptom score (0 indicates no symptoms; 1, mild; 2, moderate; and 3,
severe), morning and evening PEF, the number of doses of as-needed albuterol
administered, and concurrent medication on a diary card. This information
was entered throughout the run-in period and the first 4 weeks of treatment,
and on the 14 days before subsequent clinic visits.
Height and lung function were recorded at each clinic visit. Height was
measured on a standard calibrated, wall-mounted stadiometer (Harpenden;
Holtain Ltd, Crymych, Wales) that was supplied to each participating center.
Staff were trained in its use to ensure standardization of the measuring
technique. The same operator collected all height measurements in triplicate
at the same time (plusmn4 hours) for an individual subject throughout the
study. The PEF was measured using a mini–Wright peak flowmeter (Clement
Clark International Ltd, Harlow, England). Optional spirometer measurements
of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC),
and forced expiratory flow from 25% to 75% of the FVC measurement
(FEF25%-75%) were also obtained. Patients were asked to stop beta-agonist
use (4 hours for short-acting and 12 hours for long-acting agents) before
the spirometry measurements.
Adverse events, including exacerbations of asthma, were recorded at each
clinic visit. An asthma exacerbation was predefined as any worsening of
asthma symptoms requiring a change or addition to the patient's asthma
medications, other than an increased use of as-needed albuterol.
Nonfasting venous blood samples were taken at the start and the end of the
treatment period for determination of standard hematologic and biochemical
variables. Urine and blood samples were collected at the start of treatment
and after 16 and 52 weeks for the measurement of morning serum cortisol
level and overnight 12-hour urinary cortisol excretion. Samples were
analyzed using a fluorescent polarization antibody technique.
STATISTICAL ANALYSIS

Thirty-two centers from 7 countries were involved in the study, and all
centers within a country constituted a single subgroup for the purposes of
statistical analysis. All analyses were performed on the intent-to-treat
population except growth velocity, which was performed on the growth
population. Treatment differences were tested using a 2-sided significance
test at the 5% level.
Growth velocity was calculated for each patient during the 52-week study
using linear regression of all the available clinic visit means of the
triplicate height measurements. Only patients with at least 2 data points,
one at randomization and the other on or after 16 weeks of treatment, were
included in the growth population. Tanner staging assessments were performed
by a physician at each visit, and patients were excluded from the growth
population if they reached a Tanner stage of 2 or more at any time during
the study. Patients were also excluded from the growth population if there
were other factors likely to affect the measurement of growth (such as poor
compliance or use of systemic corticosteroids). Growth velocity was
investigated using analysis of covariance, with the patient's height and age
at randomization, country grouping, sex, and ethnic origin taken as
covariates in the model. The difference between treatment groups was tested,
and the associated P value and 95% confidence interval (CI) were produced.
The primary end point (growth velocity) was also analyzed for the
intent-to-treat population, excluding only those patients with no height
measurements at baseline and/or during treatment.
Individual country-specific growth charts were not available for this
international multicenter study conducted in 7 countries. However, we
compared individual patients' growth velocities against the North American
growth charts 14 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r14>
to calculate the number of patients with a growth velocity below the 3rd,
10th, 25th, and 50th percentiles. Percentiles were determined using the mean
age for the time in which the patient was in the study. We compared the
proportion of patients in each treatment group below the specified
percentile using the Fisher exact test.
Clinic lung function variables (PEF, FEV1, FVC, and FEF25%-75%) were also
analyzed using an analysis of covariance with pretreatment lung function,
age, sex, and country grouping included as covariates.
Diary card lung function variables (morning and evening PEF) were
investigated using a similar method to that used for clinic lung function
variables, with baseline taken as the mean of the last 7 days of the run-in
period. Diary-card symptom data were analyzed using the van Elteren
extension to the Wilcoxon rank sum test, which allowed possible imbalances
between countries to be taken into account in the analysis.
The frequency of asthma exacerbations for each patient was also analyzed
using the van Elteren extension to the Wilcoxon rank sum test. 15
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r15>  The number of
patients with exacerbations in each treatment group were compared using the
Fisher exact test.
Logarithm-transformed serum and urinary cortisol measurements were analyzed
using an analysis of covariance similar to that used for clinic lung
function variables. The difference between treatments was expressed as a
ratio, and the corresponding P value and 95% CI for this ratio were
calculated.



RESULTS



Of the 403 enrolled patients, 343 were randomized to treatment (170 to
fluticasone and 173 to beclomethasone) (intent-to-treat population). The
treatment groups were generally balanced with respect to age, sex, race,
duration and severity of asthma, and use of corticosteroids before the study
( Table 1
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_t1.html> ).
For the analyses of growth velocity, the intent-to-treat population excluded
3 patients treated with fluticasone and 4 patients treated with
beclomethasone for whom there were insufficient height measurements.
Sixty-six patients were excluded from the growth population, which therefore
consisted of 277 patients (137 in the fluticasone group and 140 in the
beclomethasone group) ( Figure 1
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_f1.html> ).
Eight patients (3 receiving fluticasone and 5 receiving beclomethasone)
required oral corticosteroid treatment and were excluded from the growth
population.
The mean (SD) baseline height in both treatment groups for the growth
population was comparable (fluticasone group, 123.8 [9.7] cm; beclomethasone
group, 124.3 [10.8] cm), and there was a gradual increase in height over
time in both groups ( Figure 2
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_f2.html> ).
Adjusted mean (SE) growth velocity was significantly greater in the
fluticasone than in the beclomethasone group (5.01 [0.14] vs 4.10 [0.15]
cm/y; difference, 0.91 cm; 95% CI, 0.63-1.20 cm; P<.001). The growth
velocity frequency distribution for both treatment groups is displayed in
Figure 3
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_f3.html> . The
results of the analyses for the intent-to-treat population were similar. The
adjusted mean growth velocity was greater in the fluticasone group than in
the beclomethasone group (4.76 [0.28] vs 4.06 [0.29] cm/y; difference, 0.70
cm; 95% CI, 0.13-1.26 cm; P<.02). The SEs for the intent-to-treat population
analyses (0.28 and 0.29), however, were nearly twice those for the growth
population analyses (0.14 and 0.15), indicating that the patients removed
from the analyses were contributing to a large proportion of the variation.
The difference in growth velocity between the fluticasone group (n = 127;
adjusted mean, 5.04 [SE, 0.15] cm/y) and the beclomethasone group (n = 135;
adjusted mean, 4.05 [SE, 0.16] cm/y) remained significant (P<.001) when
excluding those patients who received intranasal corticosteroids during the
study.
Table 2
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_t2.html>
shows the number of patients with a growth velocity below the specified
North American standard percentiles. As expected from the study population,
most patients in each treatment group were below the 50th percentile.
However, there was a significant difference between treatment groups,
whereby patients treated with beclomethasone were more likely to be below a
specific percentile than patients treated with fluticasone (P<.001).
The mean change from baseline in morning percentage of predicted PEF was
higher at all weekly time points for patients receiving fluticasone than
those receiving beclomethasone ( Figure 4
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_f4.html> ).
During the 52-week treatment, the adjusted mean morning PEF was
significantly higher in the fluticasone group (percentage of predicted,
105.6% vs 102.0%; difference, 3.6%; 95% CI, 1.2%-6.0%; P = .003) (mean PEF,
251.3 vs 242.8 L/min; difference, 8.5 L/min; 95% CI, 2.8-14.2 L/min; P =
.004). Results for evening PEF were similar, with a higher mean value in the
fluticasone group during the entire treatment period (255.1 vs 246.5 L/min;
difference, 8.6 L/min; 95% CI, 3.0-14.1 L/min; P = .003). Both treatments
produced significant improvements from baseline in clinic lung function
assessments, with a significantly greater benefit in the fluticasone group
compared with the beclomethasone group for all measured variables at week 52
(adjusted mean PEF, 282.5 vs 267.3 L/min [P<.001]; FEV1, 1.8 vs 1.6 L
[P<.001]; FVC, 2.0 vs 1.9 L [P = .008]; FEF25%-75%, 2.2 vs 2.0 L/s [P =
.02]).
There were no significant differences between treatment groups for any
assessment period with respect to diary-card symptoms or the as-needed use
of albuterol. There was no significant difference between treatments in the
total number of exacerbations (47 in the fluticasone group vs 52 in the
beclomethasone group) and the percentage of patients who experienced at
least 1 exacerbation (16% of patients in the fluticasone group vs 19% of
patients in the beclomethasone group). The incidence of exacerbations was
similar in the small group of patients (n = 55) who were previously
receiving a daily dose of inhaled corticosteroids greater than 400 µg/d (11%
of the fluticasone group vs 18% of the beclomethasone group).
Both treatments were well tolerated, and the numbers and types of adverse
events were similar in both treatment groups ( Table 3
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_t3.html> ).
During the treatment period, there were no significant changes from baseline
in morning serum cortisol levels in either treatment group, despite a trend
toward reduced levels in both groups. A significant reduction from baseline
in overnight urinary cortisol levels was found in the beclomethasone group;
however, the differences between treatments were not statistically
significant ( Table 4
<http://archpedi.ama-assn.org/issues/v155n11/fig_tab/poa10026_t4.html> ).



COMMENT



The primary purpose of this study was to compare the effect of fluticasone
and beclomethasone on the growth of children with a history of chronic
asthma requiring treatment with inhaled corticosteroids. To overcome any
influence of the pubertal growth spurt, the analysis of growth velocity
excluded patients with a sexual maturity rating of greater than Tanner stage
1 at any time during the study. The growth rate of children treated with
fluticasone was significantly greater than that of children treated with
beclomethasone.
Analysis of growth velocity using SD scores was considered, to compare the
results with the equivalent healthy population. However, this comparison
would not have been conclusive for 2 main reasons. First, children with
moderate to severe asthma have been shown to have slower growth rates and
later onset of puberty than nonasthmatic children. 16
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r16>  Thus, the
differences between the growth rates measured in this study from reference
values could be attributable to the treatment used or to the patients'
asthma. Second, reference growth values are not available for all the
countries where this study was conducted, and comparison with data from
England or the United States could be confounded by factors such as
nutritional or ethnic differences. 14
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r14> , 17
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r17>  This problem might
have been avoided if a control group had been included in the study, but the
use of placebo would not be ethical in a population with asthma requiring
long-term therapy. Inclusion of a control group taking active, nonsteroidal
therapy would have caused problems with multinational approval and would
also have led to difficulties with treatment blinding.
The comparison of the data against North American percentiles clearly
illustrates these problems. Most patients in both treatment groups had a
growth velocity below the 50th percentile. This could be attributable to the
influence of asthma, the influence of treatment, and/or the inapplicability
of the North American standards. 14
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r14>  Nevertheless, in
the comparison of both treatment groups, which was the objective of the
study, the results of this analysis were entirely consistent with primary
outcome data. Patients treated with beclomethasone were significantly more
likely to have a growth velocity below a specified percentile than were
patients treated with fluticasone.
A potential criticism of this study design is that intranasal
corticosteroids were permitted for use as required. There is evidence that
intranasal beclomethasone can affect growth in children, 18
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r18>  but other
intranasal corticosteroids have lower systemic bioavailabilities and so may
not have the same effect on growth. There was, however, no change in the
outcome of this study when excluding those patients who received treatment
with an intranasal corticosteroid during the course of the study.
To our knowledge, this is the first large, prospective, long-term study on
the comparative effects of 2 inhaled corticosteroids on growth of asthmatic
children. In a recent study of 333 children with moderate to severe asthma,
Ferguson et al 19 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r19>
demonstrated a significant difference in growth rate in favor of fluticasone
propionate (400 µg/d) compared with budesonide (800 µg/d) during a 20-week
period. However, that study was not specifically designed to critically
assess growth as an outcome factor, and height was measured by means of
stadiometry only in a subgroup of patients.
The finding that children treated with fluticasone propionate, 200 µg twice
daily, grew at a faster rate than those treated with beclomethasone
dipropionate, 200 µg twice daily, was unexpected. The dose of fluticasone
was twice the therapeutic equivalent dose of beclomethasone, 4
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r4>  and it could
therefore be predicted that the systemic effects of the drugs would be
similar.
Although the mean growth velocity in the fluticasone group was significantly
greater than that in the beclomethasone group, an effect on growth velocity
with fluticasone cannot be excluded. Although the growth velocity of
prepubertal children treated with fluticasone propionate at doses of 100 and
200 µg/d for 1 year was not different from that of children treated with
placebo, 11 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r11>  a
trend for slower growth velocity compared with children treated with placebo
was evident. Furthermore, an effect of budesonide on growth velocity in
children has been observed. 20
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r20> , 21
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r21>  However, it has
been demonstrated recently that these initial reductions in growth velocity
are not correlated with attained adult height. 22
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r22>  Indeed, the
difference between attained adult height and target adult height after
treatment with budesonide (mean dose, 412 µg/d for a mean of 9.2 years) was
not different from that of children with asthma not receiving inhaled
corticosteroids or that of healthy siblings of the budesonide-treated
children.
Fluticasone and beclomethasone improved lung function, but there was a
significantly greater improvement with fluticasone in all efficacy
assessments, both in morning and evening PEF and in results of clinic visit
spirometry. This finding is not surprising considering the at least 2-fold
greater clinical potency of fluticasone compared with beclomethasone, and is
in keeping with other studies of inhaled corticosteroids in asthmatic
children 4 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r4> , 23
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r23>  and adults. 4
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r4> , 24
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r24>
There was no difference between treatment groups for morning serum and
overnight urinary cortisol levels, although there were trends toward greater
reductions in the beclomethasone group. This does not contradict the results
of previous studies, which showed that fluticasone is much less likely to
produce endogenous cortisol suppression than is beclomethasone at equipotent
doses. 4 <http://archpedi.ama-assn.org/issues/v155n11/rfull/#r4> , 23
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r23> , 25-27
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r25>  Finally, both
drugs were well tolerated. The incidence of rhinitis was lower in the
beclomethasone group than in the fluticasone group. This may reflect a
beneficial effect on rhinitis through the more systemically active
beclomethasone.
The results of this study are not necessarily transferable to all
formulations of fluticasone and beclomethasone. The systemic bioavailability
of inhaled corticosteroids in adults is known to depend on the inhalation
device. For fluticasone, the systemic bioavailability via the Diskus
(GlaxoSmithKline) and Diskhaler dry powder inhalers is 16.6% and 11.9%,
respectively, in healthy volunteers, 28
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r28>  and for the
metered-dose inhaler containing a chlorofluorocarbon or hydrofluoroalkane
propellant, the corresponding values are 26.4% and 28.6%, respectively. 29
<http://archpedi.ama-assn.org/issues/v155n11/rfull/#r29>  Together with the
elimination of the traditional coordination problems associated with
metered-dose inhalers, this finding provides further evidence that a powder
inhaler may be more appropriate for use in children with asthma than a
metered-dose inhaler.



CONCLUSIONS



The 12-month growth rate of children treated with fluticasone propionate,
200 µg twice daily, was greater compared with that for children treated with
beclomethasone dipropionate, 200 µg twice daily. Lung function was improved
to a significantly greater extent with fluticasone than with beclomethasone.
On the grounds of this study, fluticasone should be chosen in preference to
beclomethasone for children with asthma, especially if moderate doses are
required.



Author/Article Information


From the Pediatric Division, University of Perugia, Perugia, Italy (Dr de
Benedictis); Hospital de Niños "R. Gutiérrez," Buenos Aires, Argentina (Dr
Teper); Sunninghill Hospital, Johannesburg, South Africa (Dr Green); the
Pediatric Division, University of Verona, Verona, Italy (Dr Boner); and
GlaxoSmithKline, Uxbridge, England (Mss Williams and Medley).

Corresponding author and reprints: Fernando M. de Benedictis, MD, Clinica
Pediatrica, Policlinico Monteluce, 06100 Perugia, Italy (e-mail:
[log in to unmask] <mailto:[log in to unmask]> ).
Accepted for publication May 25, 2001.
This study was funded by grant FLTB 3015 from GlaxoSmithKline, Uxbridge,
England.
The results of this study were presented at the European Respiratory Society
8th Annual Congress, Geneva, Switzerland, September 19-23, 1998.
The International Study Group includes the following participants: J. L.
Lanoel, MD, and A. M. Teper, MD (Argentina); E. Ceruti, MD, and G. Giraldi,
MD (Chile); A. C. H. van Kessel, MD, G. H. van Leeuwen, MD, J. C. M. Hoekx,
MD, J. H. Scheewe, MD, M. C. Kuthe, MD, N. Sorgedrager, MD, and R.
Schornagel, MD (Holland); B. Nagy, MD, I. Bittera, MD, L. Kosa, MD, and M.
Adonyi, MD (Hungary); A. Battistini, MD, A. L. Boner, MD, E. Baraldi, MD, F.
M. de Benedictis, MD, M. Giovannini, MD, M. La Rosa, MD, and M. Miraglia del
Giudice, MD (Italy); D. Chmielewska, MD, J. Alkiewicz, MD, and M. Migdat, MD
(Poland); and C. Bester, MD, G. Brereton-Stiles, MD, J. Vermeulen, MD, K. H.
E. von Delft, MD, N. J. T. de Villiers, MD, and R. J. Green, MD (South
Africa).


What This Study Adds
Inhaled corticosteroids are recommended for the treatment of asthma in all
age groups if inhaled, short-acting beta-agonists are required more than
once a week, but little is known about the comparative effects of inhaled
corticosteroids on growth rates. This 12-month study was therefore designed
to compare the effects on growth and comparative risk-benefit ratio of 2
inhaled corticosteroids, fluticasone propionate, 400 µg/d, and
beclomethasone dipropionate, 400 µg/d, in children with a history of chronic
asthma.
The adjusted mean growth velocity in the fluticasone group was significantly
greater than that in the beclomethasone group. Both treatments improved lung
function, with significant differences in favor of fluticasone. The more
favorable risk-benefit ratio of fluticasone indicates that this agent is
preferable to beclomethasone for the long-term treatment of children with
asthma, especially if moderate doses are required.






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Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.