Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion.
Allergen challenge is associated with an increased excretion of urinary leukotriene E4. The source of this increase is unknown, although the lack of effect of inhaled beta-agonists and sodium cromoglycate suggests that airway mast cells may not be involved. We investigated this further using a new and topically potent inhaled glucocorticoid, fluticasone propionate (FP). A group of 10 mild atopic asthmatic subjects (6 males; FEV1 > 60% of predicted; PC20 histamine < or = 8 mg/ml; and on inhaled beta 2-agonists only) were studied before and after a 2-wk period of FP (1,000 micrograms/day) or placebo administered by metered-dose inhalers as two puffs twice per day through a large-volume spacer. Treatments were assigned in a double-blind crossover fashion separated by a 3-wk washout period. The PC20 histamine was measured at the start and end of each treatment when subjects also received a bronchial allergen challenge. Urine was collected for 4 h after allergen challenge for determination of LTE4 using HPLC-RIA, and 2 h later the PC20 histamine measurement was repeated. The 2-wk treatment with FP significantly inhibited both early and late responses to allergen: the maximum % fall in FEV1 during the early (0 to 2 h) and late response (2 to 6 h) was 32.6 +/- 3.4 and 19.6 +/- 5.2, respectively, following placebo versus 19.5 +/- 4.5 and 3.6 +/- 2.6 following FP (both p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
K M
KM
O'Shaughnessy
R
R
Wellings
B
B
Gillies
R W
RW
Fuller
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000485:Allergens; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids; D006632:Histamine; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine; D013997:Time Factors
D000485:Allergens; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D013189:SRS-A; D017999:Leukotriene E4; D006632:Histamine; D000068298:Fluticasone