Background: The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms.Objective: To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids.Methods: A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 mu g, fluticasone propionate 88 mu g, fluticasone propionate 220 mu g, salmeterol 42 mu g plus fluticasone propionate 88 mu g, salmeterol 42 mu g plus fluticasone propionate 220 mu g, or placebo for 4 weeks.Results: Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV1 at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement.Conclusion: Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta(2)-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.

Background: This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP. Methods: In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 μg/d, 400 μg/d, or 800 μg/d of HFA-BDP or 100 μg/d, 400 μg/d, or 800 μg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled β-agonist for symptom control on diary cards were assessed over 6 weeks of treatment. Results: Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV1 percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV1 percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV1 percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 μg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma). Conclusions: Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP. (J Allergy Clin Immunol 1999;1215-22.)