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Inhaled budesonide decreases airway inflammatory response to allergen.

Abstract：

:To define the mechanisms by which inhaled glucocorticosteroid regulates allergen-induced airway inflammation, a double-blind, placebo-controlled, cross-over study with inhaled budesonide was conducted in 14 subjects with allergic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were randomized to budesonide (400 microgram, twice daily) or placebo treatment for 4 wk. At the end of each treatment phase, whole-lung allergen inhalation challenge was performed, followed by BAL 48 h later. Budesonide treatment improved the FEV(1), attenuated both the immediate- and late-phase response to allergen, and prevented the increase in bronchial hyperresponsiveness after allergen challenge. Budesonide treatment also decreased allergen-induced airway eosinophilia. To determine the effects of budesonide on airway cell function, BAL cells were stimulated ex vivo with the T cell mitogen PHA, and cytokine generation was measured by ELISA. Budesonide decreased ex vivo generation of IL-5 and IFN-gamma by BAL cells. Ex vivo IL-5 production was significantly correlated with the number of airway eosinophils (r(s) = 0.61), and levels of eosinophil-derived neurotoxin (EDN) (r(s) = 0.57) and IL-5 (r(s) = 0.52) in BAL fluid. Moreover, PHA-induced IL-5 generation correlated with FEV(1) fall during the late-phase response to allergen (r(s) = 0.60). Budesonide decreased circulating eosinophils and serum levels of IL-5, but did not reduce IL-5 generation by peripheral blood mononuclear cells. The reduction in circulating eosinophils correlated with the decrease in levels of EDN (r(s) = 0.61) in BAL fluid and late response to inhaled allergen (r(s) = 0.51). These findings suggest that long-term treatment with inhaled budesonide reduces airway cell generation of cytokines, specifically IL-5, which then decreases circulating eosinophils and their availability for recruitment to the airway after allergen exposure.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Kelly EA,Busse WW,Jarjour NN

doi

10.1164/ajrccm.162.3.9910077

keywords:

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

883-90

issue

3 Pt 1

eissn

1073-449X

issn

1535-4970

journal_volume

162

pub_type

临床试验,杂志文章,随机对照试验

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Inhaled budesonide decreases airway inflammatory response to allergen.