Introduction
Asthma is a chronic inflammatory disorder of the airways and is
characterized by airway hyperresponsiveness and reversible airflow
obstruction that fluctuates over time. It is also recognized as a
heterogeneous disease with varying severity, responsiveness to therapy,
and long-term outcome1. Eicosanoids are a family of
bioactive lipid mediators that regulate a wide variety of inflammatory
processes2. Eicosanoid species are generated from
polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA). AA
can be converted into prostaglandins (PGs), leukotrienes (LTs) and
hydroxyeicosatetraenoic acids (HETEs)3 by
cyclooxygenases (COXs), lipoxygenases (LOXs) and cytochrome P450
epoxygenases (CYP450). 5-LOX-derived LTA4 can be
converted to lipoxins in the presence of 15-LOX, while 15-LOX generates
15-HETE3. Lipoxins and 15-HETE have been reported to
exert anti-inflammatory activity; for example, LXA4 and
15-HETE inhibit LTB4-induced chemotaxis of
neutrophils4-6. Thromboxane B2(TXB2) is non-enzymatically hydrolyzed from COX-derived
TXA2, a potent bronchial smooth muscle
spasmogen7, is known to reduce T cell secretion of the
Th1 cytokine and favor T cell differentiation toward a Th2 cytokine
profile8.
Together, these functionally diverse classes of eicosanoids are thought
to play a critical role in maintaining homeostasis and have been an
active area of investigation in assessing the mechanism underlying
asthma and their potential utility in monitoring disease progression and
treatment outcome. Indeed, several studies have suggested their roles as
the biomarkers for screening, diagnosis, and, to a limited extent,
monitoring the treatment outcome. For example, several independent
studies have shown elevated levels of eicosanoids in the EBC of patients
with asthma9,10, but due, perhaps in part, to the
limited sample sizes and the heterogeneity of the study patient
populations, unified evidence is currently lacking. As the result,
knowledge about eicosanoids in disease progression and therapeutic
outcome remains incomplete, and their relationship with the disease
status has yet to be comprehensively explored and their clinical utility
as biomarkers remains to be determined. We have previously reported that
in a pediatric study population in Taiwan, the levels of exhaled
LTB4, LTE4, LXA4, and
PGE2 in asthmatic children were significantly different
from those of healthy controls, and the combination of exhaled
LTB4 and LXA4, together with FeNO and
FEV1, best characterized childhood
asthma11. We described herein an analysis of the
levels of exhaled eicosanoids differed at the time of acute exacerbation
and convalescence and reported that the levels of TXB2and 15-HETE were the most responsive to therapy.