Exhaled Breath Condensate Eicosanoid Levels Associate With Asthma and Its Severity

Abstract

Background The relationship between anti-inflammatory lipoxins and pro-inflammatory leukotrienes may be important in the pathobiology of asthma and its severity. Objective To investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can non-invasively characterize the asthmatic diathesis and its severity. Methods We measured lipoxin A4 (LXA4) and leukotriene B4 (LTB4) levels in EBC collected from asthmatics of different severities and from healthy controls. Results EBC LXA4 and LTB4 levels are elevated in asthmatics as compared to healthy controls (LXA4 31.40 vs. 2.41 pg/ml EBC respectively, p < 0.001; LTB4 45.62 vs. 3.82 pg/ml EBC, p < 0.001). While both eicosanoids are elevated in asthmatics, the ratio LXA4 to LTB4 decreases with increasing asthma severity. It is 41% lower in severe versus moderate asthmatics (0.52 vs. 0.88, p = 0.034). EBC LXA4 levels correlate with the degree of airflow obstruction measured by FEV1 (r = 0.28, p = 0.018). A cut-off value of 7 pg LXA4/ml EBC provides 90% sensitivity and 92% specificity for the diagnosis of asthma (AUC 0.96, p < 0.001). A cut-off value of 11 pg LTB4/ml EBC provides 100% sensitivity and 100% specificity for the diagnosis of asthma (AUC 1, p < 0.001). Conclusions Pro-resolving and pro-inflammatory eicosanoids are generated in airways of all asthmatics. The proportion of pro-resolving compounds declines with asthma severity. These findings support the role for EBC eicosanoid measurements in the non-invasive diagnosis of asthma and suggest that pro-resolving eicosanoid pathways are dys-regulated in severe asthma.