EBC metabolomics for asthma severity.

Asthma is a heterogeneous disease with diverse severity and represents a considerable socio-economic burden. Exhaled Breath Condensate (EBC) is a biofluid directly obtained from the airway lining fluid non-invasively. We attempted to discriminate severe from mild-to-moderate asthma using EBC metabolomics based on both NMR and UHPLC-MS techniques. 36 patients were included in this study (15 patients with severe and 21 with mild-to-moderate asthma). EBC was collected and analyzed using both NMR and UHPLC-MS techniques for possible metabolites. Using PLS and oPLS analysis for the UHPLC-MS data, no metabolite was found to be sufficient for the discrimination of asthma severity. However, when another PLS-regression model was applied five metabolites were found to discriminate severe from mild-to-moderate asthma. Amino-acid lysine was the only metabolite that discriminated the two study groups using NMR data (p= 0.04, t-test with Welch's correction, AUC 0.66). EBC is an easily available biofluid which directly represents the lower airways but difficult-to-use for metabolomic analysis. Our study presents some encouraging findings for the discrimination of asthma severity subgroups using EBC metabolomics but more well-designed studies with a higher number of patients need to be conducted.

Is thromboxane a potent antinatriuretic factor and is it involved in the development of acute renal failure?

Glycerol-treated rats exhibited significantly increased urinary thromboxane B2(TXB)2, prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6kPGF1 alpha) excretion and urine volume (UV). These increases were associated with significant decreases in creatinine clearance (CCr), urinary sodium concentration (UNa), urinary sodium excretion (UNaV), and fractional excretion of sodium (FENa%), which is consistent with the development of the prerenal (reversible) phase of acute renal failure (ARF). When glycerol-treated rats were pretreated with a selective inhibitor of thromboxane A2 (TXA2) synthesis (imidazole), urinary PGE2 and 6kPGF1 alpha excretion and UV remained unchanged, whereas CCr, UNa, UNaV decreases were partially prevented. Additionally, FENa% was increased, indicating inhibition of sodium reabsorption. The findings indicate that inhibition of TXA2 synthesis increases UNaV and partially improves CCr in glycerol-treated rats. Further histologic observation and functional follow-up over longer periods of time are needed to clarify the role of TXA2 in the development of ARF.