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Loss of Control of Asthma Following Inhaled Corticosteroid Withdrawal Is Associated With Increased Sputum Interleukin-8 and Neutrophils^*

Kittipong Maneechotesuwan, MD, PhD; Sarah Essilfie-Quaye, BSc; Sergei A. Kharitonov, MD, PhD; Ian M. Adcock, PhD and Peter J. Barnes, DM, DSc, FCCP

^* From Airways Disease Section, National Heart and Lung Institute, Imperial College, London, UK. Currently at the Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Siriraj Hospital, Mahidol University, Thailand.

Correspondence to: Peter J. Barnes, DM, DSc, FCCP, Airways Disease Section, Dovehouse St, London, SW3 6LY, UK; e-mail: p.j.barnes{at}imperial.ac.uk

Abstract

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

Methods: Following a 2-week run in period, 24 subjects were randomized to receive either budesonide (400 µg bid) or placebo, and the study was continued for another 10 weeks.

Results: Loss of asthma control developed in 8 of 12 patients over the 10-week period of steroid withdrawal, whereas only 1 of 10 patients with budesonide treatment had exacerbations. Those with an exacerbation had increased sputum interleukin (IL)-8 (p < 0.0001) and increased sputum neutrophil numbers (p < 0.0001) compared to those without an exacerbation. The significant elevation in sputum 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).

Conclusions: Rapid 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 in which inhaled steroids are slowly tapered.

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

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