Partial inhibition of the early and late asthmatic response by a single dose of salmeterol.

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 µg 30 min before allergen inhalation and two weeks of 250 µg 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.PATIENTS AND 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.CONCLUSION: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 µg immediately before allergen challenge, despite increasing baseline PC20and 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.

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BECLOMETHASONE GIVEN AFTER THE EARLY ASTHMATIC RESPONSE INHIBITS THE LATE RESPONSE AND THE INCREASED METHACHOLINE RESPONSIVENESS AND CROMOLYN DOES NOT

PEDIATRICS ◽

10.1542/peds.94.2.267 ◽

1994 ◽

Vol 94 (2) ◽

pp. 267-267

Author(s):

David F. Graft

Keyword(s):

Single Dose ◽

Late Phase ◽

Allergen Challenge ◽

Allergen Exposure ◽

Phase Response ◽

Atopic Asthma ◽

Late Response ◽

Double Blind ◽

Asthmatic Response ◽

Late Asthmatic Response

Purpose of the Study. To investigate whether beclomethasone or cromolyn provides any protection from the late asthmatic response if given after the allergen exposure. Methods. Ten patients with mild, stable, atopic asthma with late asthmatic responses entered a double blind, double dummy trial comparing a single dose of inhaled beclomethasone (500 µg), cromolyn (20 mg), and placebo administered 2 hours after allergen challenge on the severity of the late asthmatic response and the change in the log of PC20 methacholine. Findings. The late asthmatic response after beclomethasone of 7.3% ± 6.1% decrease in FEV1 was significantly less than that experienced after cromolyn (20.4% ± 15.2%) or placebo (26.4% ± 8.2%); cromolyn was not different than placebo. There was a trend for the change in log PC20 methacholine to be less following beclomethasone administration than that seen with placebo or cromolyn. Reviewer's Comments. It is well known that a single dose of cromolyn given before allergen exposure inhibits both the early and late phase response, whereas beclomethasone given prior to exposure will only prevent the late phase response. However, many individuals don't plan ahead well enough and need to know what medication should be taken if they have forgotten to take any pretreatment. This study indicates that, if bedomethasone, albeit in a dose equal to 12 puffs of the U.S. concentration, is taken even as late as 2 hours after the exposure, it can significantly inhibit the development of the late phase response. Cromolyn given at that time provides only minimal benefit.

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