Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1-4-year-old children with moderate asthma. Nebulised cromoglycate, theophylline, and placebo in preschool asthmatic children. Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial. Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice. A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma. Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. Nebulised sodium cromoglycate in recurrently wheezy preschool children. Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children. Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate. Pretreatment of exercise-induced asthma in children using disodium cromoglycate and fenoterol inhalation powder. Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma. Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up. Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children. Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life. Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma. Inhibition of exercise-induced-asthma (EIA) by nedocromil sodium and sodium cromoglycate in children. Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children. Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study). Nebulised sodium cromoglycate in the treatment of wheezy bronchitis. A multicentre double-blind placebo controlled study.
Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children. The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children. We studied the feasibility and effects of this therapy compared with placebo in children aged 1-4 years.
                218 children aged 1-4 years with moderate asthma were recruited through 151 general practitioners between March, 1995, and March, 1996. They were randomly assigned sodium cromoglycate (10 mg three times daily) or placebo, given by inhaler with spacer device and face-mask for 5 months. Rescue medication (ipratropium plus fenoterol aerosol) was available during the baseline period of 1 month and the intervention period. Parents completed a daily symptom-score list. The primary outcome measure was the proportion of symptom-free days in months 2 to 5. Analysis was by both intention to treat and on treatment.
                167 (77%) children completed the trial. 131 (78%) of these children used at least 80% of the recommended dose. Of the 51 children who stopped prematurely, 23 had difficulties with inhaled treatment. The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period (95% CI for mean difference 5.1 to 17.5 cromoglycate, 11.9 to 23.3 placebo). However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days (mean 65.7 [SD 25.3] vs 64.3 [24.5]%; 95% CI for difference -8.46 to 5.70) or in any other outcome measure.
                Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years. However, long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group. Sixteen children aged under 5 years with chronic asthma completed a double-blind crossover trial of treatment with oral choline theophyllinate (6.7 mg/kg four times daily) and nebulised sodium cromoglycate (20 mg four times daily). The trial comprised three 8-week treatment periods during which active sodium cromoglycate, active choline theophyllinate, and placebo were given in random order. Symptom scores for sleep disturbance, cough, wheeze, and daily activities were similar during the three treatment periods if results were analysed using Friedman's non-parametric analysis of variance. However the Mantel-Haenszel test showed that sodium cromoglycate was superior to placebo (P less than 0.05) in maintaining normal daily activities. Either regimen is safe and well tolerated by young children. Seventeen asthmatic children under 5 years of age took part in a double-blind controlled trial of nebulized sodium cromoglycate solution. Daily symptom scores kept by the parents showed improvement in 11 children during active treatment, and a significant improvement in scores for cough by day and night was obtained for the group as a whole. Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma.
                To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial.
                Health economics were evaluated in 138 children, ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months; budesonide 400 microg/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment.
                In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195; US $487; Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication.
                A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate. We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen. Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate, reproterol, sodium cromoglycate plus reproterol, and placebo in exercise-induced asthma. Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited exercise-induced asthma. The best protection is effected by the combination of sodium cromoglycate and reproterol. A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive. A double blind crossover study of nebulised sodium cromoglycate in 27 asthmatic preschool children was carried out over a one year period. All subjects had sufficiently severe asthma to have had at least one admission to hospital. The active treatment was sodium cromoglycate 20 mg (in 2 ml) administered by a nebuliser four times daily. Assessment was made by a diary card and clinical examination. Results were analysed in 24 subjects who completed the study. Statistical analysis allowed for order of treatment and seasonal effects. Significant results in favour of treatment with sodium cromoglycate were obtained for night cough, day activity, percentage of symptom free days, and overall severity of asthma. During active treatment there was no reduction in the rate of admissions to hospital or intravenous drugs used. The wheeze score during the week after an upper respiratory tract infection was not reduced during treatment with sodium cromoglycate. Nebulised sodium cromoglycate is a tedious prophylactic treatment for the young asthmatic child but is useful when other treatments have failed. To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG) administered by metered dose inhaler (MDI) in preventing exercise-induced asthma (EIA), 12 asthmatic children with EIA were studied in a randomized, double-blind, cross-over, placebo-controlled study. NS and SCG were given by MDI alone, and by MDI with a 700 ml spacer device (Fisonair, Fisons, UK), in order to assess the benefit of using such a device. Following a baseline exercise challenge, the protective effect of NS, SCG or placebo was evaluated in each subject. The percentage fall in forced expiratory volume in one second, and percentage protection were measured. NS and SCG provided a significant and comparable protection from EIA, and both were better than placebo. No further improvement was observed after drug administration via the spacer. Both NS and SCG are effective in preventing EIA in children, when administered at the recommended clinical dose, and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good. A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals. The effect of pretreatment with inhalation powder containing fenoterol, sodium cromoglycate, fenoterol plus sodium cromoglycate and placebo, in the prevention of exercise-induced asthma was compared in a randomized, double-blind, cross-over investigation including 17 asthmatic children with exercise-induced asthma. Six minutes of treadmill running was carried out in a climate chamber 30 minutes after pretreatment on the four test days. The post-exercise fall in PEF after pretreatment with fenoterol was 7%, with sodium cromoglycate 20%, with fenoterol plus sodium cromoglycate 6% and after placebo 27%. Both sodium cromoglycate and fenoterol provided protection against exercise-induced asthma (p less than 0.05 and p less than 0.001). Fenoterol gave significantly better protection than sodium cromoglycate (p less than 0.001), and it is concluded that the treatment of choice for the prevention of exercise-induced asthma is the inhalation of a beta 2-agonist. According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed. Children born prematurely frequently have recurrent respiratory symptoms at follow-up and benefit from bronchodilator therapy. We have assessed if regular inhaled sodium cromoglycate would reduce this respiratory morbidity and need for bronchodilator therapy. Sixteen symptomatic children (median gestational age 29 weeks, post-natal age 15 months) were entered into a randomized double-blind, placebo-controlled trial. In two 3-week periods, the patients received either placebo or sodium cromoglycate (5 mg) as one puff q.d.s. from an inhaler via a coffee cup. Parents recorded their child's symptoms and need for bronchodilator therapy throughout and lung function was assessed by measurement of functional residual capacity (FRC) at the beginning and end of each 3-week period. The symptom score was reduced by 49% in the active compared to the placebo period (P less than 0.01) and bronchodilator was taken on a mean of 2.9 days per infant in the active period compared to 7.9 days in the placebo period (P less than 0.01). There was a significant improvement in FRC in ten of 16 patients over the active period but only in two infants over the placebo period (P less than 0.01). We conclude regular inhaled sodium cromoglycate is useful prophylaxis for symptomatic pre-term children. To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG. In a double blind crossover trial, we compared sodium cromoglycate, ipratropium bromide, and water in 23 asthmatic children less than 2 years old (mean age 11.8 months). Each child received nebulised solutions containing 20 mg of sodium cromoglycate, 250 micrograms of ipratropium bromide, or 2 ml water three times a day for three two month periods. Daily symptom scores did not show significant differences between the treatments but parental preferences indicated that both sodium cromoglycate and ipratropium bromide were superior to placebo. Sodium cromoglycate was prophylactic and was more likely to help the older patients. Ipratropium bromide produced an immediate clinical benefit and the response was not age dependent. We were unable to pick responders from non-responders on the basis of lung function tests performed on a routine outpatient basis. Both ipratropium bromide and sodium cromoglycate help some but not all asthmatic children aged less than 2 years. A double-blind trial involving 20 asthmatic patients was carried out to test the effect of fenoterol and sodium cromoglycate alone and in combination on ventilatory function one hour after medication. The results show that fenoterol, whether alone or in combination with sodium cromoglycate, can increase the forced expiratory volume in one second (FEV1) by up to 25% both after rest and after exercise. No patient suffered a decrease in FEV1 using fenoterol, and at least 80% of them recorded an increase in ventilatory ability. Sodium cromoglycate was of no benefit in eliminating early reaction to exercise-induced asthma. Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma. Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children. Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy. The efficacy of nebulised sodium cromoglycate (SCG) used as a prophylactic treatment of wheezy bronchitis in children aged 1 to 4 years was evaluated in a multicentre double-blind placebo controlled, group comparative study. Fifty-four patients completed the 10-week trial (29 treated with SCG and 25 treated with placebo), preceded by 4-8 weeks baseline. Nebulised SCG did not prove significantly superior to placebo in reducing day wheezing, day coughing, or sleep disturbance due to wheezing or coughing at night. Neither was there significant difference in the use of supportive medicine (beta 2-agonist and theophylline) between the groups. Extra doctor visits, hospital admissions, and parental preference did not show significant difference either.
There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma.