Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma.
OBJECTIVE
To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.


METHODS
Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 microg/d, alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks; (2) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.


RESULTS
The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV(1) (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 microg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 microg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 microg alone (0.4 doubling dose), but not compared to beclomethasone, 400 microg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 microg, plus zafirlukast (but not BDP, 100 microg, plus theophylline) vs beclomethasone, 100 microg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 microg.


CONCLUSIONS
A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.
Asthma and Allergy Research Group, Section of Vascular Medicine & Biology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
Owen J
OJ
Dempsey
Stephen J
SJ
Fowler
Andrew
A
Wilson
Gwen
G
Kennedy
Brian J
BJ
Lipworth
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D002648:Child; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D012129:Respiratory Function Tests; D013449:Sulfonamides; D013806:Theophylline / Q000008:administration & dosage / Q000627:therapeutic use*; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D013806:Theophylline; D001507:Beclomethasone; C062735:zafirlukast