Increased levels of airway neutrophils reduces the inhibitory effects of inhaled glucocorticosteroids on allergen-induced airway eosinophils
GM Gauvreau | MD Inman | M Kelly | RM Watson | SC Dorman | PM O'Byrne
with inhaled glucocorticosteroids attenuates allergen-induced
airway inflammation but is less effective in people
with asthma who have noneosinophilic airway inflammation.
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
AND 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.
Inhaled gluticocorticosteroids 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.
Baseline airway neutrophils, not eosinophils, can
be used to predict the efficacy of inhaled steroids
on allergen-induced sputum eosinophils.