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This Article Full Text (PDF) Free All Versions of this Article: chest.06-2982v1 132/1/98    most recent Submit a response View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Maneechotesuwan, K Articles by Barnes, P. Search for Related Content PubMed PubMed Citation Articles by Maneechotesuwan, K Articles by Barnes, P.

Loss of Control of Asthma Following Inhaled Corticosteroid Withdrawal is Associated with Increased Sputum Inteleukin-8 andNeutrophils

From Airways Disease Section, National Heart and Lung Institute, Imperial College, London, UK

p.j.barnes{at}imperial.ac.uk

Abstract

BackgroundThe role of neutrophils in exacerbations of asthma is poorly understood. We examined the effect of withdrawal of inhaled corticosteroids on sputum inflammatory indices in a double-blind study in patients with moderate stable asthma.

MethodsFollowing a 2-week run in period, 24 subjects were randomized to receive either budesonide (400 µg twice a day) or placebo and the study was continued for a further 10 weeks. Results: 8/12 patients developed loss of asthma control over the 10 week period of steroid withdrawal, whereas only 1/10 with budesonide treatment exacerbated. Those with an exacerbation had increased sputum IL-8 (p<0.0001) and increased sputum neutrophil numbers (p<0.0001) compared to those without an exacerbation. The significant elevation in sputum interleukin-8 (IL-8) and neutrophil counts initially occurred 2 weeks prior to an exacerbation. Sputum neutrophilia correlated positively with changes in IL-8 levels (r² = 0.76, p=0.01).

ConclusionsRapid withdrawal of inhaled corticosteroids results in an exacerbation of asthma that is preceded by an increase in sputum neutrophils and IL-8 concentrations, in contrast to an increase in eosinophils reported in previous studies where inhaled steroids are slowly tapered.

Key Words: asthma • interleukin-8 • neutrophil • exacerbation

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