Effectiveness and tolerability of zafirlukast for the treatment of asthma in children.

OBJECTIVE: This study was undertaken to examine the dose-response relationship of zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the 10-mg BID dose in school-aged children with mild to moderate asthma. BACKGROUND: The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor antagonist, has been demonstrated in adolescents and adults aged > or = 12 years. METHODS: Data from 2 placebo-controlled, parallel-group, multicenter trials (trial 1, 4-week double-blind; trial 2, 6-week double-blind) were integrated. Children aged 5 to 11 years were randomly assigned to receive zafirlukast 5 mg BID (n = 99), 10 mg BID (n = 205), 20 mg BID (n = 105), 40 mg BID (n = 99), or placebo (n = 206). The primary outcome was change from baseline in forced expiratory volume in 1 second (FEV1) expressed as percent of predicted normal. Secondary outcomes were FEV1 (L), morning and evening peak expiratory flow, peak flow variability, short-acting beta2-agonist use, asthma episode score, and nights awakened by asthma. RESULTS: Mean baseline FEV1 was 76.5% of predicted. The greatest improvements were generally seen with zafirlukast 5 mg BID or 10 mg BID, with no additional clinically significant benefits seen at higher doses. The pooled data analysis showed that 10 mg BID compared with placebo significantly improved (P < 0.045) all efficacy outcomes except asthma-episode score and nights awakened with asthma. However, in the subset of children who had > or = 1 night awakened per week at baseline (zafirlukast 10 mg BID = 78; placebo = 86), 10 mg BID significantly reduced nights awakened (P = 0.009) (mean difference from placebo at end point = -0.81 night/wk). All zafirlukast doses were well tolerated and had tolerability profiles that were clinically indistinguishable from placebo. CONCLUSION: These results support the effectiveness and tolerability of the 10-mg BID dose of zafirlukast for the prophylaxis and chronic treatment of mild to moderate asthma in children.

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

EMLA cream for painless skin testing: a preliminary report.

The purposes of this open study were to evaluate the anesthetic properties of eutectic mixture of local anesthetics (EMLA) prior to intradermal skin testing and to evaluate the possible effect of EMLA on the extent of wheal and flare reaction. Subjects included 40 patients, ranging from 1 to 9 years of age. The eutectic mixture of local anesthetics was applied in a 2-mm thickness to the upper outer arm, covered with a dressing, and allowed to remain in place for one hour. Complete anesthesia was obtained in 36 of the 40 cases (90%), and partial anesthesia occurred in two additional patients. There were no significant differences in wheal or flare reactions between treated and untreated skin. Side effects were minimal. This preliminary report indicates that EMLA cream appears to be a safe and effective means of achieving local anesthesia prior to intradermal skin injection. It does not jeopardize the validity of test results.

In vitro resistance to dexamethasone of basophils from patients receiving long-term steroid therapy.

Previous studies have shown that in vitro culture of human basophils for 24 h with physiologic concentrations of glucocorticoids leads to a pronounced inhibition of the subsequent release of histamine or leukotrienes when the cells are challenged with anti-IgE. However, both acute and chronic therapy in vivo with steroids fails to lead to an impairment of subsequent histamine release in vitro. To test whether the failure of in vivo steroid therapy to inhibit subsequent in vitro histamine release was due to the selection of a subpopulation of basophils that responded normally to anti-IgE but were resistant to steroids, the in vitro sensitivity to inhibition of mediator release by steroids in basophils obtained from normal patients as well as patients receiving chronic steroid therapy was studied. Basophils from steroid-dependent asthmatics (SDA) who had been receiving steroid doses orally of 7.5 to 50 mg equivalents of prednisone per day (mean, 19 mg), patients with collagen vascular disease (CVD) who had been receiving steroids orally of 4 to 80 mg equivalents (mean, 25 mg), non-steroid-dependent asthmatics (NSDA), and normal subjects were prepared, and their in vitro response to the potent glucocorticoid, dexamethasone, was determined. Dexamethasone was considerably more effective as an inhibitor of histamine release from basophils of normal subjects and NSDA than from basophils of SDA and patients with CVD. Because this was true in both SDA and patients with CVD, it seems most likely to be the result of the treatment with steroids rather than the underlying disease processes. Such a finding may be the result of a steroid-induced selection process by which sensitive cells are removed from the bloodstream in steroid-treated persons.