title: Actions other than smooth muscle relaxation may play a role in the protective effects of formoterol on the allergen-induced late asthmatic reaction.
abstract: Long-acting beta(2)-adrenoceptor agonists attenuate the allergen-induced late asthmatic reaction. We evaluated whether other mechanisms in addition to airway smooth muscle relaxation may be implicated in this protective effect. The effects of formoterol (Foradil Aerolizer(TM), 24 microg dry powder) on the late asthmatic reaction were assessed by a randomised crossover factorial study in 24 patients with asthma. Four challenge/treatment combinations were tested: (A) saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D) allergen/formoterol. Formoterol and placebo were administered double blind after the last inhalation of the allergen or saline. FEV(1) was measured up to 32 h. The bronchodilator effect of formoterol was estimated as (B-A) and the overall protective effect as (D-C). The effect not due to bronchodilation was estimated as [(D-C)-(B-A)]/2. The bronchodilator effect of formoterol was statistically significant up to 5h (all P< or =0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32 h after allergen inhalation (all P< or =0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5 h and between 7 and 28 h after allergen inhalation (all P< or =0.035). Our results suggest that functional antagonism may not be the sole mechanism by which formoterol attenuates the allergen-induced late asthmatic reaction.
authors.affiliation: Department of Motor and Rehabilitative Sciences, Centre of Respiratory Phisiopathology, University of Genoa, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Brusasco
authors.forename: E
authors.initials: E
authors.lastname: Crimi
authors.forename: G
authors.initials: G
authors.lastname: Gherson
authors.forename: R
authors.initials: R
authors.lastname: Nardelli
authors.forename: V
authors.initials: V
authors.lastname: Oldani
authors.forename: B
authors.initials: B
authors.lastname: Francucci
authors.forename: G
authors.initials: G
authors.lastname: Della Cioppa
authors.forename: S
authors.initials: S
authors.lastname: Senn
authors.forename: L M
authors.initials: LM
authors.lastname: Fabbri
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000485:Allergens / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D000485:Allergens; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D004983:Ethanolamines; D016210:Methacholine Chloride; D000068759:Formoterol Fumarate