Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group. A controlled study of education for improving compliance with cromolyn sodium (Intal): the importance of physician-patient communication. Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up. Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children. The Effect of Cromolyn Sodium and Nedocromil Sodium Administered by A pressurized Aerosol with A spacer Device on Exercise-Induced Asthma in Children. Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma. Nebulised sodium cromoglycate in recurrently wheezy preschool children. Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial. Effect of cromolyn sodium on childhood asthma.
This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn. The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age. Patients were randomly assigned to an education or noneducation group. A standard education program regarding asthma and asthma medications was provided to the education group during four monthly visits. At each visit, all patients were assessed in terms of knowledge of asthma and medications, asthma-related symptoms, and pulmonary function. Patients were also asked to self-rate their compliance. The education program increased the patients' knowledge of cromolyn, and appeared to result in increased cromolyn compliance. Post-hoc analyses, however, suggested that increased compliance did not correspond to improved medical status unless the quality of management (by physician and parents) of the child's asthma was taken into account. These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance. 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. 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. To compare the effectiveness of cromolyn sodium (CS) (10 mg) and nedocromil sodium (NS) (4 mg) administered by a metered dose inhaler (MDI) with a spacer device in preventing exercise-induced asthma (EIA), eight asthmatic children with EIA were studied in a randomized double-blind, cross-over, placebo-controlled study, CS and NS provided significant, comparable protection from EIA and both were better than placebo. We conclude that CS and NS administered by a pressurized aerosol with a spacer device provide equal protection against EIA in children. 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. 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. 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. nan
There is currently no evidence from randomised trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants.