Levels of 15-HETE and TXB2 in exhaled breath condensates as markers for diagnosis of childhood asthma and its therapeutic outcome

Abstract

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B₄ (LTB₄ ), characterizes childhood asthma. While fractional exhaled nitric oxide (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-hydroxyeicosatetraenoic acid (15-HETE), but not thromboxane B₂ (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) curve analyses revealed similar distinguishing power for the levels of 15-HETE, FEV₁ (forced expiratory volume in the first second), and FeNO, while the 15-HETE/LTB₄ ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p < 0.0001). Analysis of asthmatics (N = 75) during exacerbation and convalescence showed significant improvement in lung function (FEV₁ , p < .001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p < .001) and reduced levels of TXB₂ (p < .05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB₄ and lipoxin A₄ (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 at convalescence.

Keywords: 15-HETE; TXB2; childhood asthma; exhaled breath condensates.