title: Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma.
abstract: Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.
authors.affiliation: Glaxo Wellcome Research and Development, U.K.
authors.forename: J
authors.initials: J
authors.lastname: Westbroek
authors.forename: S
authors.initials: S
authors.lastname: Saarelainen
authors.forename: M
authors.initials: M
authors.lastname: Laher
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: H
authors.initials: H
authors.lastname: Barnacle
authors.forename: J
authors.initials: J
authors.lastname: Efthimiou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011239:Prednisolone; D000068298:Fluticasone