Increased levels of airway neutrophils reduce the inhibitory effects of inhaled glucocorticosteroids on allergen-induced airway eosinophils.
BACKGROUND
Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation.


OBJECTIVE
Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells.


METHODS
Twenty-eight nonsmoking subjects with atopic asthma controlled by beta2-agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergen-induced airway responses by glucocorticosteroids was calculated.


RESULTS
Inhaled glucocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergen-induced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses.


CONCLUSIONS
Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergen-induced sputum eosinophils.
Gauvreau
Gail M
GM
St Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, Canada.
Inman
Mark D
MD
Kelly
Margaret
M
Watson
Richard M
RM
Dorman
Sandra C
SC
O'Byrne
Paul M
PM
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D019819:Budesonide / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology*; D007958:Leukocyte Count; D008875:Middle Aged; D000068656:Mometasone Furoate; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011244:Pregnadienediols / Q000008:administration & dosage; D013183:Sputum / Q000166:cytology*; D016896:Treatment Outcome
D005938:Glucocorticoids; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D019819:Budesonide