Nedocromil in the outpatient management of asthma.

OBJECTIVE: To more closely approximate the use of a nonsteroidal inhaled anti-inflammatory medication for asthma, nedocromil sodium, under actual ambulatory practice conditions. DESIGN: Large, open-label trial. PATIENTS: One thousand two hundred one patients from 286 primary care and specialty centers. INTERVENTION: Four weeks of treatment with nedocromil sodium (4 mg delivered from the valve and 3.5 mg delivered from the mouthpiece of a metered inhalor [2 puffs, four times daily]). MAIN OUTCOME MEASURES: Asthma symptom scores, peak expiratory flow rate, a lifestyle assessment measures questionnaire, and mean number of days missed per month from work or school. RESULTS: Statistically significant improvements were seen after 1 and 4 weeks of treatment for cough, daytime and nighttime asthma, morning tightness, peak expiratory flow rate, and all four measured lifestyle assessment factors (P < .001). An additional clinically relevant outcome measure, mean number of days missed per month from work or school, was reduced by 75% (P < .001). No serious adverse reactions were reported. CONCLUSION: This study reproduces the high level of efficacy and safety of nedocromil that was previously reported in placebo-controlled clinical studies.

Safety of bronchodilator therapy in pediatric asthma patients.

This article reviews the drugs used in the treatment of childhood asthma (bronchodilators and anti-inflammatory agents) from the perspective of their safety and clinical tolerability. Adverse events observed in adults are likely to be seen to a greater degree in children and adolescents for many types of antiasthma drugs. It is clear that current therapy in childhood asthma is based on finding an optimal balance between efficacy and risk of side effects. In this regard, the fast-acting beta 2-adrenergic agonists, exemplified by albuterol, find a prominent place in therapy. Inhaled corticosteroids are also effective and well-tolerated first-line agents. Other bronchodilators (theophylline, ipratropium, slow-acting beta 2-agonists) and anti-inflammatory agents (cromolyn, nedocromil) should be added as required to control the condition, always keeping risk/benefit considerations in mind.

A multicenter trial of nedocromil sodium, 1% nasal solution, compared with cromolyn sodium and placebo in ragweed seasonal allergic rhinitis.

This study was a double-blind, parallel-group study to evaluate a new medication, nedocromil sodium, 1%, in comparison with placebo and cromolyn sodium, 4%, for treatment of ragweed seasonal allergic rhinitis. Two hundred thirty-three patients (aged 12 to 65 years) from eight centers were randomized to treatment, one spray per nostril, four times daily, with nedocromil sodium, cromolyn sodium, or matched placebo (80, 76, and 77 patients, respectively). All patients had at least a 2-year history of ragweed seasonal allergic rhinitis. Treatment was for 8 weeks during the ragweed season, and daily pollen counts were used to identify the peak 3-week period. Clinic examinations were made before and after the 1-week baseline and after 1, 3, 5, and 8 weeks of treatment. Rhinitis symptoms were recorded each day by the patients. Nedocromil sodium was more effective than placebo (p less than 0.05) in relieving symptoms as recorded by the patients. Cromolyn sodium was also more effective than placebo, but the difference was not usually significant. Similarly, the active treatments were both better than placebo for clinical parameters measured at visits and for global opinions of treatment, and more rescue therapy was used by the placebo-treated group. There was no significant difference between the two active treatments, but the trend throughout was in favor of nedocromil sodium. Our findings demonstrated nedocromil sodium to be at least as effective as an established therapy (cromolyn sodium) in reducing symptoms of rhinitis during the peak ragweed pollen season.

Clinical benefits of cromolyn sodium aerosol (MDI) in the treatment of asthma in children.

A double-blind, placebo-controlled study was performed to determine the efficacy and safety of cromolyn sodium (Intal) administered to children by metered dose inhaler (MDI). Prior to entry, subjects were well controlled on cromolyn sodium capsules by Spinhaler turbo-inhaler plus beta 2 agonists. An active control interval of 2 weeks on cromolyn sodium capsules was followed by a 4-week single-blind period on placebo capsules. Those subjects whose asthma worsened significantly on placebo entered a 10-week double-blind phase, randomized to receive either cromolyn sodium (2 mg per dose) or placebo by MDI. Diary data, physician evaluation, and pulmonary function tests were used to assess efficacy, and scores were compared with the baseline value at 2-week intervals. Forty children with asthma, 8 to 20 years of age, entered the study and 32 qualified for the randomized phase. No significant differences existed between the treatment groups at baseline. Most comparative data favored the cromolyn sodium group over the course of the study. Significant differences (p less than .05) were noted for diary scores of breathlessness and overall asthma severity. There was significant improvement at the final visit favoring the cromolyn sodium group in restriction on normal activity, FEV1, and PEFR. The cromolyn sodium group also experienced a decreasing need for concomitant bronchodilators. Both groups preferred pressurized aerosol by MDI over powdered capsules by Spinhaler. (Intal and Spinhaler are registered trademarks of Fisons Corporation.)

A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma.

The efficacy and safety of cromolyn sodium by metered-dose inhaler (MDI) (1 mg per actuation) was evaluated with a double-blind, placebo-controlled, parallel-study design. Subjects with asthma, aged 8 to 58 years, whose asthma was well controlled taking cromolyn sodium capsules by Spinhaler turboinhaler, plus beta 2-agonists, entered the study after being maintained with cromolyn sodium capsules for a minimum of 4 weeks. The investigation began with a 2-week control interval with cromolyn sodium capsules followed by a 4-week single-blind period with placebo capsules. Subjects whose asthma significantly worsened while they were receiving placebo therapy were then randomized to a 10-week double-blind phase in which they received either active cromolyn sodium or placebo by MDI. Efficacy variables included diary data, physician evaluation, and spirometry. Comparisons were made between baseline period scores and each assessment variable over time. Of 155 subjects entered, 93 qualified for the double-blind, randomized phase. Eighty-three subjects completed the study and were analyzed. At baseline there existed no significant differences between the active-treatment and placebo-treatment groups. Significant differences (p less than 0.05) in favor of the cromolyn sodium-treatment group, however, were noted at all time points for daily diary symptoms (cough, breathlessness, and overall asthma severity), physician's assessments at each clinic visit, physician's and patient's overall final assessments, FEV1 at each clinic visit, and FVC and peak expiratory flow rate at the final visit. Concomitant bronchodilator medication use was less in the cromolyn sodium-treatment group. Cromolyn sodium by MDI is highly effective for (1) controlling asthmatic symptoms, (2) improving lung functions, and (3) decreasing the need for concomitant bronchodilators.

Duration of action of oral albuterol in an asthmatic population.

In a randomized, double-blind, two-way crossover study in four centers, 124 patients received single doses of 4 or 6 mg of albuterol and placebo on two separate visits. Pulmonary function tests were performed at intervals up to ten hours. Both dosages produced peak bronchodilation responses which occurred at two hours and significant activity was maintained for at least eight hours. Adverse experiences were typical of adrenergic agents.

Routine elective penicillin allergy skin testing in children and adolescents: study of sensitization.

This study aims at evaluating the possibility in children and adolescents of (re)sensitization to penicillin that could result from skin test and challenge. Patients (240) with a history of a reaction to penicillin or one of its analogs were skin-tested with penicillin G, commerical benzlpenicilloyl polylysine, and a minor determinant mixture consisting of sodium benzylpenicilloate and sodium benzylpenilloate. The patients were tested when well, in no immediate need for penicillin, and during a routine office visit. Twenty-one (8.75%) patients had one or more positive skin tests. Three (14%) of the positive reactors reacted only to the MDM mixture, with one reacting only to the benzylpenilloate component. Of the patients with negative skin tests, 219 were given a 10-day course of oral penicillin. Three (1.4%) of the patients developed a-mild skin exanthem 7 to 10 days after starting the penicillin. All skin test-negative patients were retested 4 wk or more after completion of the oral challenge. Only two patients (less than 1%) who tolerated an oral challenge of penicillin had a positive skin test upon retesting. We believe that the described penicillin allergy testing procedure in children and adolescents with a history of allergy to penicillin or certain analogs is a safe, highly predictive, nonsensitizing office procedure in the hands of physicians experienced with skin testing. It should be considered for all such individuals labeled as allergic to penicillin when they are well and not in immediate need of penicillin.

A comparison of cromolyn and bronchodilators in patients with mild to moderately severe asthma in an office practice.

The efficacy and safety of two treatment regimens, based in the one case on cromolyn and in the other on bronchodilators, were compared in an eight week study in predominantly young, mild to moderate asthmatics in an office practice. We utilized subjective and objective measures of assessment. Cromolyn was as effective as the bronchodilator regimen except in terms of asthmatic cough, which was better controlled by cromolyn. An equal number of patients could not tolerate each regimen and were dropped from the study. Among those who continued and completed the study cromolyn was devoid of adverse effects whereas 62% of the patients maintained on theophylline with or without a concomitant beta-agonist reported side effects. The results of this preliminary study and of our subsequent broader clinical experience suggest that a re-evaluation of the current approach to managing the symptoms of chronic asthma is indicated, at least in pediatric patients.

Ancillary medical therapy: help or hindrance.

Aside from the more traditional methods of treating bronchial asthma, it has been the purpose of this review to consider some of the ancillary modes of therapy and to decide if they have a place in clinical practice. Regarding antihistamines, there is little evidence to support their therapeutic use in the management of asthma, but there is strong evidence for their safety in the treatment of allergic rhinitis or urticaria in asthmatic patients. Iodides have been used for years, but there is no good body of evidence to demonstrate their effectiveness. While they may be helpful in rare cases, one must be fully aware of their potential side effects and toxicity. Mucolytic agents induce bronchospasm and for the present should be contraindicated in asthma management. Of all ancillary modes of therapy, the anticholinergic agents seem the most promising. This is based on the theory of cholinergic mechanisms in asthma production as well as some clinical trials supporting this efficacy. Many of the problems of inhaled atropine have been eliminated with the development of atropinelike anticholinergic agents such as ipratropium bromide and oxytropium but unfortunately, none of these has been approved as yet for use in the United States.