Exhaled 15-HETE and thromboxin-B2 are associated with therapeutic
outcome in childhood asthma
Abstract
Background: Dysregulation of eicosanoids is associated with asthma and a
composite of oxylipins, including exhaled LTB4, but their potential
utility in monitoring the therapeutic outcomes has not been
comprehensively assessed. Objectives: We aimed to examine the levels of
major eicosanoids representing different metabolic pathways in exhaled
breath condensates (EBCs) of children with asthma during exacerbation
and after treatment. Methods: Levels of 6 exhaled eicosanoid species in
asthmatic children and healthy subjects were evaluated using ELISA.
Results: In addition to those previously reported, including LTB4, LTE4,
LXA4 and PGE2, the levels of exhaled 15-HETE, but not TXB2, showed
significant difference between asthmatics (N=318) and healthy controls
(N=97). When the asthmatic population was stratified into different
severity groups, the severe group was characterized by significantly
lower levels of 15-HETE and 15-HETE/LTB4 ratio, as compared to the mild
and control groups. Receiver Operating Characteristic (ROC) analyses
revealed similar distinguishing power for the level of exhaled 15-HETE
and those of FEV1 and FeNO. Analysis of asthmatics (N=75) during
exacerbation and convalescence showed significant improvement in lung
function (FEV1; p<0.001), but not FeNO, concomitant with
significantly increased levels of 15-HETE (p<0.001) and
reduced levels of TXB2 (p<0.05) after therapy, particularly
for those who at the top 30% level during exacerbation. Further,
decreased LTB4 and LXA4 at convalescence were noted only in those at the
top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE
was found to discriminate childhood asthma while decreased levels of
exhaled TXB2 and increased levels of 15-HETE were prominent after
treatment.