Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

Abstract

SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/QToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE 4 and LTE 4 /PGF 2 a ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE 4 and LTE 4 /PGF 2 a ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE 4 levels were significantly correlated with the fall in FEV 1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE 4 and LTE 4 /PGF 2 a ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/QToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

Plasma LTE4/PGF2α Ratio and Blood Eosinophil Count Are Increased in Elderly Asthmatics With Previous Asthma Exacerbation

“…The study subjects were divided into group 1 (asthmatics who experienced AE during the study period) and group 2 (those who did not). The LTE 4 and PGF 2α levels were quantified as previously reported 8. In brief, Mass Hunter Quantitative Analysis B.07.00 (Agilent Technologies, Santa Clara, CA, USA) was used to quantify the LTE 4 and PGF 2 levels in plasma samples.…”

A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

“…The serum and urinary levels of S1P and five eicosanoid metabolites, LTE4, prostaglandin F2 α (PGF2 α ), thromboxane B2 (TXB2), 15-hydroxyeicosatetraenoic acid (15-HETE), and eoxin C4, were determined using the Agilent 6530 quadrupole time-of-flight (Q-TOF) mass spectrometer. The device settings have been described in detail in a previous study [18]. …”

Potential Biomarkers for NSAID-Exacerbated Respiratory Disease

“…This phenomenon is present in both random urine and 24 h urine; recent studies on 24 h urine have reported an area under the curve (AUC) of 0.87 [ 35 ]. In addition, it was confirmed that the metabolites of urinary LTE4 were significantly different in NERD and ATA, even in studies that used metabolomics [ 37 ]. Urinary LTE4 can be used not only to distinguish between NERD and ATA but also to indicate the prognosis and treatment response.…”