Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma. The effect of nedocromil sodium on histamine responsiveness in clinically stable asthmatic children. Effect of nedocromil sodium on bronchial hyperreactivity in children with nonatopic asthma. A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise-induced bronchoconstriction. The effect of nedocromil sodium on childhood asthma during the viral season. A double-blind, placebo-controlled study to assess the efficacy of nedocromil sodium in the management of childhood grass-pollen asthma. Early use of inhaled nedocromil sodium in children following an acute episode of asthma. Effect of nedocromil sodium on exercise-induced bronchoconstriction in children. Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study.
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, randomized, placebo-controlled, parallel-group study was undertaken in 120 clinically stable asthmatic children (aged 6-19 years) to determine the ability of 8 weeks of treatment with nedocromil sodium (4 mg, three times a day) to reduce the level of histamine responsiveness. Despite the subjects being clinically stable and reporting few asthma symptoms, approximately one-third had abnormal pulmonary function on enrollment into the study. Statistically significant increases in pulmonary function were seen in the group treated with nedocromil sodium but not in the control group (p = 0.01). Furthermore, 52% of the individuals with abnormal pulmonary function returned to normal following treatment with nedocromil sodium compared to 11% of those with abnormal pulmonary function who received placebo. However, there were no differences in the level of histamine responsiveness between the two treatment groups at baseline or after 4 or 8 weeks of treatment with nedocromil sodium or placebo. These data suggest that the level of histamine responsiveness is not intimately related to the level of asthma control in children. Although cromones inhibit immediate bronchial responses to both allergen and nonspecific challenge, their effectiveness in treating nonatopic childhood asthma is unknown. We therefore investigated a possible effect of nedocromil sodium on bronchial hyperreactivity and asthmatic symptoms in a group of children receiving this drug for nonatopic asthma.
                A double-blind, placebo-controlled, randomized trial of two parallel groups was carried out in our pediatric respiratory disease clinic. Twenty children with mild, nonatopic asthma hyperreactive to fog-induced challenge were treated with inhaled nedocromil sodium 16 mg each day for 6 weeks (group N) or with a placebo (group P). Five girls and five boys (7 to 13 years of age) were randomly assigned to group N, and three girls and seven boys (aged 6 to 16 years) to group P. Symptoms and bronchodilator use were reported on diary cards. Ultrasonic nebulized distilled water PD10 was measured administering increasing doses of nebulized distilled water (2.5, 5, 10, 20, and 40 L).
                Symptom scores were significantly affected by the active treatment. Baseline lung function was normal and remained unaltered after treatment with nedocromil sodium. Nonspecific reactivity was significantly reduced over time only in the active treatment group.
                Nedocromil sodium can reduce the severity of asthmatic symptoms and nonspecific bronchial hyperreactivity at fog-induced challenge in children with stable, nonatopic asthma. Fourteen adult subjects with stable asthma were treated using a double-blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24-53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise-induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient. Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this double-blind placebo-controlled trial was to assess the efficacy and tolerance of nedocromil sodium at a dose of 4 mg four times daily, in the management of children suffering from grass-pollen asthma. Thirty-one children suffering from seasonal asthma (24 boys and seven girls, aged 4-21 yr, mean 11 yr) were enrolled in the study during the 1988 pollen season. Only one child was aged 4 yr, and she was a cooperative girl able to use the metered dose inhaler properly. In addition, in each group there was a patient aged 20 and 21 years, respectively, who had been followed up by us since childhood. Treatments were delivered by pressurized aerosol over a period of 4 weeks following a 1-week baseline, during which patients were required to show active disease by obtaining a minimum symptom score (almost 2 points of severity score on at least 3 days of the baseline period). The patients were randomly assigned to both treatment groups, all were taking inhaled or oral bronchodilators, when necessary. Twenty-nine patients completed the trial, 16 in the nedocromil sodium treatment group and 13 in the placebo group. One child of each group was withdrawn due to treatment failure. Statistically significant differences in favour of nedocromil sodium were found regarding morning tightness and mean morning PEFR values on diary cards (P less than 0.01 and P less than 0.05, respectively), bronchodilator usage (P less than 0.05), pulmonary function tests (PFT) at clinic visits (P less than 0.05), and in parents' opinion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma.
                A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment).
                One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group.
                Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber. A double-blind, placebo-controlled, crossover study investigated the efficacy of nedocromil sodium in reducing bronchoconstriction subsequent to exercise challenge in asthmatic children. Twelve children aged 7-14 years (mean 10.8 years) were pretreated with nedocromil sodium aerosol (2 inhalations; 2 mg/inhalation) or matching placebo, 30 min prior to treadmill running. Lung function was measured at regular intervals postexercise and the mean maximum percentage decrease in PEF and FEV1 compared following nedocromil sodium or placebo pretreatment. Nedocromil sodium significantly reduced the fall in PEF (P less than 0.001) and FEV1 (P less than 0.001) and provided significantly greater protection (P less than 0.001) than placebo. No adverse reactions or unusual symptoms were observed. Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.
A limited number of small studies have shown that nedocromil is of benefit in improving lung function and some measures of symptoms, but the evidence with regard to the primary outcome of the review was conflicting. Two long-term trials did not show consistent effects on lung function outcomes, whereas several small short-term trials have shown benefit in these outcomes. Differing severities at baseline may explain this difference with milder participants experiencing less benefit, although the discrepancy between study findings may also reflect publication bias. Nedocromil sodium is associated with a very good safety profile with no significant short term or long- term adverse side effects. Although nedocromil may have advantages over inhaled corticosteroids in terms of side effects, there is a need for head to head trials of nedocromil and inhaled corticosteroids to establish whether asthma control is similar, especially in mild asthma. It is not yet clear where nedocromil should sit in relation to other therapies in the treatment of asthma in children.