Effect of salmeterol compared with beclomethasone on allergen-induced asthmatic and inflammatory responses.
Salmeterol is a selective long-acting beta 2-agonist bronchodilator considered to have added anti-inflammatory effects, but this is controversial. We investigated the effects of a single dose of salmeterol, 100 micrograms, on the physiological and inflammatory responses to inhaled allergen and compared these with the effects of a single dose of beclomethasone, 500 micrograms, and of placebo. Eight atopic adults with mild stable asthma, treated only with inhaled short-acting beta 2-agonist when needed, attended the laboratory sequentially for screening tests, two single-blind control inhalation tests preceded 30 min by placebo or salmeterol and three allergen inhalation tests preceded by placebo, salmeterol or beclomethasone double-blind in random order. Airway responsiveness to methacholine (assessed as the provocative concentration of methacholine producing 20% fall in forced expiratory volume in one second (PC20)), induced sputum eosinophils, blood eosinophils and serum eosinophil cationic protein (ECP) were examined before and 7-48 h after treatment. The statistical power to detect twofold changes in blood and sputum parameters was > or = 90%. Salmeterol inhaled before allergen challenge completely prevented the early asthmatic response, late asthmatic response and fall in methacholine PC20 at 24 h, and produced additional bronchodilatation. These effects were similar to those obtained by the inhalation of a single dose of salmeterol before the control inhalation test, and significantly better than those observed after a single dose of beclomethasone inhaled before the allergen test. Beclomethasone had no effect on the early asthmatic response or on the fall in methacholine PC20 at 24 h but partially inhibited the late asthmatic response. Neither salmeterol nor beclomethasone had any significant effect on sputum or blood inflammatory changes 7-48 h after allergen inhalation. In conclusion, whilst salmeterol had no demonstrable anti-inflammatory action in sputum after allergen challenge in asthma, neither did a single dose of the positive anti-inflammatory control, beclomethasone. The latter result excludes a more positive judgement on the possible anti-inflammatory action of salmeterol. However, the results do indicate that potent functional effects of a single dose of salmeterol can mask the airway inflammatory cell influx caused by inhaled allergen.
Pizzichini
M M
MM
Dept of Medicine, St Joseph's Hospital, Hamilton, Ontario, Canada.
Kidney
J C
JC
Wong
B J
BJ
Morris
M M
MM
Efthimiadis
A
A
Dolovich
J
J
Hargreave
F E
FE
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000485:Allergens; 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; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068299:Salmeterol Xinafoate; D013147:Spirometry; D013183:Sputum / Q000166:cytology; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000485:Allergens; D018927:Anti-Asthmatic Agents; D000068299:Salmeterol Xinafoate; D001507:Beclomethasone; D000420:Albuterol