In a randomized double-blind multicenter clinical study, 116 children with asthma were randomly assigned to treatment with an inhaled beta-2-agonist (salbutamol 0.2 mg) plus an inhaled corticosteroid (budesonide 0.2 mg) three times a day (BA+CS) or to an inhaled beta-2-agonist (salbutamol 0.2 mg) plus a placebo three times a day (BA+PL). After a median follow-up time of 22 months, 26 patients receiving BA+PL (45%) had withdrawn from randomized treatment, mainly because of asthma symptoms, compared with three withdrawals in the patients receiving BA+CS (p less than 0.0001). The FEV1, expressed as a percentage of the predicted value for age, sex, and height, showed an absolute increase of 7.0% after 2 months of BA+CS compared with a decrease of 4.0% after 2 months of BA+PL. This 11% difference in percent predicted FEV1 (95% confidence interval, 7 to 15%; p less than 0.0001) was then maintained after a median follow-up period of 22 months. Postbronchodilator FEV1 showed an absolute increase of 3.7% predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1% predicted in children receiving BA+PL (p = 0.0005). Thereafter, this difference between the two treatment groups was maintained. Average peak expiratory flow rate (PEFR) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group (p = 0.003). This difference then remained for the median follow-up time of 22 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 micrograms 3 times/day) and inhaled beta-2-agonist (salbutamol 200 micrograms 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 micrograms daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with none in the continuous treatment group. After tapering-off, symptoms of asthma and additional bronchodilator use increased, and both FEV1% predicted and PD20 histamine (provocation dose of histamine causing a 20% fall in FEV1) decreased, whereas these all remained unchanged in the group that continued treatment with inhaled corticosteroid. We conclude that in this study long-term treatment with 600 micrograms budesonide daily suppressed underlying mechanisms of asthma, but did not cure the disease.

Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma.One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values).Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF.We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.

Hematological recovery in children with IBD-associated anemia is slow with expectant management, regardless of the type of anemia at T0. Present results underline the need for a more active approach to improve Hb.

The effects of treatment with budesonide (200 pg twice daily) and terbutaline (500 pg four times daily) has been compared with the effects of placebo and terbutaline in 27 children with mild asthma, aged 7-14 years, in a double blind, randomised placebo controlled study over eight weeks. Bronchial responsiveness (PC20 histamine), lung function, the amplitude of diurnal variation in peak expiratory flow (PEF), and symptom scores were measured. Baseline FEV, was over 70% predicted and PC20 histamine less than 8 mg/ml. Twelve children were treated with budesonide and terbutaline and 15 with placebo and terbutaline. After four and eight weeks of treatment the change in PC20 was significantly greater after budesonide and terbutaline than after terbutaline alone by 2-1 (95% CI 0-5-3 8) and 1-3 (95% CI 0-1-2-5) doubling doses respectively. Mean FEV, did not change in either group. The change in afternoon and nocturnal PEF was significantly greater after budesonide and terbutaline than after terbutaline alone. The amplitude of diurnal variation in PEF did not change significantly in either group. Peak flow reversibility decreased in the budesonide group. There were no differences between treatments for cough and dyspnoea, but wheeze improved in the budesonide group. The children with mild asthma treated with budesonide and terbutaline showed improvement in bronchial responsiveness, afternoon and nocturnal PEF, and symptoms of wheeze and a fall in peak flow reversibility by comparison with those who received terbutaline alone.

CD patients with mild disease were treated with aminosalicylate monotherapy more frequently. These patients, however, tend to have more exacerbations, shorter duration of first remission, and longer total duration of systemic steroid use. Our data support the concept that severity of disease at diagnosis does not reliably predict subsequent clinical course. This study suggests that there is no indication that children with mild CD should be treated differently compared to children with moderate-severe disease.

It is unclear whether cyclosporine A (CsA) can be withdrawn safely during follow-up after pediatric liver transplantation. In our transplant program we have been using a strict protocol to withdraw CsA. The aim of this study was to retrospectively assess the effects of CsA withdrawal after pediatric liver transplantation on the incidence of rejection and renal function. Between 1986 and 2001, 91 children received CsA for at least 2 yr after liver transplantation. Specific criteria for eligibility to withdraw CsA were set. In 53 of the 91 children CsA was withdrawn. In 35 patients (66%) withdrawal of CsA did not cause rejection. In these patients the renal function improved compared with baseline values (glomerular filtration rate (GFR) at 1 yr, ϩ16 mL/minute/1.73 m 3 , P Ͻ 0.001; at 2 yr, ϩ10 mL/minute/1.73 m 3 , P Ͻ 0.05). After CsA withdrawal, 18 patients developed rejection (34%), which could be effectively treated by methylprednisolone and restarting CsA. Failure to withdraw CsA was not associated with increased incidence of graft loss. A body weight below 10 kg at the time of transplantation correlated significantly with successful withdrawal of CsA (Ͻ10 kg, 85% vs. Ͼ 10 kg, 60%; P Ͻ 0.05). In conclusion CsA can successfully be withdrawn in a major proportion of selected pediatric liver transplantation patients during follow-up. The success rate is the highest in children with a body weight below 10 kg at the time of transplantation. Successful withdrawal improves renal function, whereas failure to withdraw is not associated with graft loss or persisting morbidity.

The effect of long-term treatment with inhaled corticosteroid on exercise-induced asthma (EIA) was studied in 55 children, aged 7-18 yrs (mean 12 yrs). We also compared the time course of stabilization of EIA to that of other indicators of airway responsiveness, such as peak expiratory flow (PEF) variation and the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1). All children participated in an ongoing multicentre study to compare the effects of long-term treatment either with the beta 2-agonist salbutamol (600 micrograms.day-1) plus the inhaled corticosteroid budesonide (600 micrograms.day-1) (BA+CS), or salbutamol plus placebo (BA+PL), on airway calibre, airway responsiveness and symptoms. After a median follow-up of 22 months, the study design had to be changed, because of the high number of drop-outs on BA+PL. At that time, the treatment regimen of all children who had not withdrawn was changed into BA+CS. At the moment of change, and after 2 and 8 months of treatment, a treadmill exercise test was performed in two centres. Eighteen of the 22 children (82%) who were treated with BA+PL from the beginning had EIA, compared to 18 of the 33 children (55%) who were treated with BA-CS (p < 0.05). After 2 and 8 months of treatment with BA+CS in the patients previously on BA+PL this percentage decreased to 59 and 55%, respectively, and was not significantly different between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)