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 microg 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 (r(2) = 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.
RCT Entities:
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 microg 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 (r(2) = 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.
Authors: A T Hastie; C Steele; C W Dunaway; W C Moore; B M Rector; E Ampleford; H Li; L C Denlinger; N Jarjour; D A Meyers; E R Bleecker Journal: Clin Exp Allergy Date: 2018-04-15 Impact factor: 5.018
Authors: Annette T Hastie; Wendy C Moore; Huashi Li; Brian M Rector; Victor E Ortega; Rodolfo M Pascual; Stephen P Peters; Deborah A Meyers; Eugene R Bleecker Journal: J Allergy Clin Immunol Date: 2013-05-21 Impact factor: 10.793
Authors: Neil E Alexis; John C Lay; Angela Haczku; Henry Gong; William Linn; Milan J Hazucha; Brad Harris; Ruth Tal-Singer; David B Peden Journal: Environ Health Perspect Date: 2008-06 Impact factor: 9.031