BACKGROUND:Salmeterol is a long-acting beta2-adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non-bronchodilator actions of salmeterol may contribute to its efficacy. OBJECTIVE: To further evaluate the potential non-bronchodilator actions of salmeterol in vivo, using a model of nasal challenge with allergen. METHODS:Twelve asymptomatic subjects with seasonal allergic rhinitis participated in a randomized, double-blind, placebo-controlled crossover trial of the effects of a single dose of 100 microg of salmeterol on the response to allergen challenge. Sneezing and symptom scores, and levels of histamine and albumin in nasal lavages, were measured throughout the protocol. Concentrations of tryptase, prostaglandin D2 and lysozyme were measured during the acute allergic response, while levels of IL-3, IL-5 and IL-8 were measured at later time points. Numbers of eosinophils and of total white blood cells were also recorded. RESULTS:Salmeterol did not affect sneezing or symptom scores at any point. During the immediate response to allergen challenge, mast cell activation, reflected by concentrations of histamine, tryptase and prostaglandin D2, and serous glandular secretion, assessed by measurements of lysozyme, were unaffected by salmeterol treatment but vascular permeability, reflected by concentrations of albumin in nasal lavages, was significantly reduced. At later time points, salmeterol had no effect on levels of histamine or albumin and did not affect cellular infiltration. Concentrations of IL-3, IL-5 and IL-8 were not increased by allergen challenge in these subjects, so the effects of salmeterol could not be evaluated. CONCLUSIONS: Treatment with a single dose of salmeterol had no effect on activation of mast cells or cellular infiltration but inhibited vascular permeability. The ability of salmeterol to inhibit antigen-induced vascular permeability may contribute to its therapeutic efficacy in asthma.
RCT Entities:
BACKGROUND:Salmeterol is a long-acting beta2-adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non-bronchodilator actions of salmeterol may contribute to its efficacy. OBJECTIVE: To further evaluate the potential non-bronchodilator actions of salmeterol in vivo, using a model of nasal challenge with allergen. METHODS: Twelve asymptomatic subjects with seasonal allergic rhinitis participated in a randomized, double-blind, placebo-controlled crossover trial of the effects of a single dose of 100 microg of salmeterol on the response to allergen challenge. Sneezing and symptom scores, and levels of histamine and albumin in nasal lavages, were measured throughout the protocol. Concentrations of tryptase, prostaglandin D2 and lysozyme were measured during the acute allergic response, while levels of IL-3, IL-5 and IL-8 were measured at later time points. Numbers of eosinophils and of total white blood cells were also recorded. RESULTS:Salmeterol did not affect sneezing or symptom scores at any point. During the immediate response to allergen challenge, mast cell activation, reflected by concentrations of histamine, tryptase and prostaglandin D2, and serous glandular secretion, assessed by measurements of lysozyme, were unaffected by salmeterol treatment but vascular permeability, reflected by concentrations of albumin in nasal lavages, was significantly reduced. At later time points, salmeterol had no effect on levels of histamine or albumin and did not affect cellular infiltration. Concentrations of IL-3, IL-5 and IL-8 were not increased by allergen challenge in these subjects, so the effects of salmeterol could not be evaluated. CONCLUSIONS: Treatment with a single dose of salmeterol had no effect on activation of mast cells or cellular infiltration but inhibited vascular permeability. The ability of salmeterol to inhibit antigen-induced vascular permeability may contribute to its therapeutic efficacy in asthma.