Exhaled 15-HETE and thromboxin-B2 are associated with the therapeutic outcome in childhood asthma

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. 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, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). 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.