Study objectives: To identify the characteristics of
airway inflammation in persistent asthma and to examine the role of
neutrophilic inflammation in noneosinophilic persistent asthma.
Methods: Nonsmoking adults (n = 56) with persistent
asthma and healthy control subjects (n = 8) underwent hypertonic
saline solution challenge and sputum induction. Selected sputum
portions were dispersed with dithiothreitol and assayed for total cell
count, cellular differential, supernatant eosinophil cationic protein
(ECP), myeloperoxidase, and interleukin (IL)-8.
Results: We identified two distinct inflammatory patterns.
Typical eosinophilic inflammation occurred in 41% of subjects, whereas
the remainder exhibited noneosinophilic asthma (59%). Both neutrophil
percentage and absolute neutrophil counts were increased in subjects
with noneosinophilic asthma (64%, 283 × 106/mL)
compared to eosinophilic asthma (14%, 41 × 106/mL) and
control subjects (34%, 49 × 106/mL; p = 0.0001).
Myeloperoxidase was elevated in both noneosinophilic (280 ng/mL) and
eosinophilic groups (254 ng/mL) compared with control subjects (82
ng/mL; p = 0.002). Sputum IL-8 levels were highest in subjects with
noneosinophilic asthma (45 ng/mL) compared to eosinophilic asthma (9.6
ng/mL) and control subjects (3.5 ng/mL; p = 0.0001). Neutrophils
correlated with IL-8 levels (r = 0.72). ECP was
highest in subjects with eosinophilic asthma (2,685 ng/mL) compared
with noneosinophilic asthma (1,081 ng/mL) and control subjects (110
ng/mL; p = 0.0001).
analysis in persistent asthma identifies two different inflammatory
patterns. The most common pattern is noneosinophilic, associated with a
neutrophil influx and activation, which may be mediated by IL-8
secretion. There is heterogeneity of airway inflammation in persistent
asthma, which indicates differing mechanisms and may impact on