Protective effects of fluticasone on allergen-induced airway responses and sputum inflammatory markers.
BACKGROUND
A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made.


OBJECTIVE
To compare the effects of pretreatment with fluticasone 250 microg 30 min before allergen inhalation and two weeks of 250 microg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h.


METHODS
Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study.


RESULTS
Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean +/- SEM maximum percentage fall in FEV1 (10.8+/-3.6 compared with single placebo 18. 8+/-3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1+/-2.5) compared with regular placebo (19.6+/-4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia.


CONCLUSIONS
Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 microg immediately before allergen challenge, despite increasing baseline PC20 and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.
Parameswaran
K
K
Department of Medicine, St Joseph's Hospital, Hamilton, Ontario, Canada.
Inman
M D
MD
Watson
R M
RM
Morris
M M
MM
Efthimiadis
A
A
Ventresca
P G
PG
Lam
R
R
O'Byrne
P M
PM
Hargreave
F E
FE
D000287:Administration, Topical; D000328:Adult; D000485:Allergens; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D013183:Sputum / Q000166:cytology / Q000276:immunology
D000485:Allergens; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D005938:Glucocorticoids; D016210:Methacholine Chloride; D000068298:Fluticasone