Pathogenic Mechanisms andIn VitroDiagnosis of AERD

Abstract

Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis, nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in asthmatics following the exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway mucosa as well as blood cells. Genetic and functional metabolic studies on vital and non-vital cells pointed to the variability and the crucial role of lipid mediators in disease susceptibility and their response to medication. Eicosanoids, exemplified by prostaglandin E2 (PGE2) and peptidoleukotrienes (pLT), are potential metabolic biomarkers contributing to the AERD phenotype. Also other mediators are implicated in the progress of AERD. Considering the various pathogenic mechanisms of AERD, a multitude of metabolic and genetic markers is suggested to be implicated and were introduced as potential biomarkers for in vitro diagnosis during the past decades. Deduced from an eicosanoid-related pathogenic mechanism, functional tests balancing PGE2 and pLT as well as other eicosanoids from preferentially vital leukocytes demonstrated their applicability for in vitro diagnosis of AERD.

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

“…Serum levels of LTE 4 , PGF 2 a, and 11-dehydro TXB 2 showed no significant differences between normal healthy controls and asthmatic patients, while serum level of eoxin C 4 was significantly higher in asthmatic patients than in normal controls (P = 0.025) after adjusting for age and sex.…”

“…In group 2, serum levels of LTE 4 and LTE 4 /PGF 2 a ratios were significantly higher, but serum PGF 2 a levels were lower in patients with AERD than in patients with ATA (P = 0.049, P = 0.001, and P = 0.008, respectively) ( Fig. 5a-c).…”

“…Urine levels of LTE 4 , PGF 2 a, 11-dehydro TXB 2 , and eoxin C 4 before and after the Lys-ASA BPT in group 1…”

“…S1c and f). Among nine metabolites selected, six were identifiable based on the database and the MS/MS fragment pattern of pure analytical standards: ureidosuccinicacid, N-acetylvanilalanine, 3-ketosphingosine, PGF 2 a, LTE 4 , and sphingomyelin (d18:0/13:0) (Table S1). From the results of untargeted metabolomic analysis, we found that eicosanoid associated with arachidonic acid was related to the phenotype of AERD.…”

“…Comparison of serum metabolite levels between normal controls and asthmatic patients (aspirin-exacerbated respiratory disease and aspirin-tolerant asthma) Serum levels of LTE 4 , PGF 2 a, LTE 4 /PGF 2 a ratio, 11-dehydro TXB 2 , and eoxin C 4 in normal controls were 15.12 AE 3.22 pg/mL, 22.31 AE 13.31 pg/mL, 0.69 AE 0.18, 0.27 AE 0.14 ng/mL, and 1.27 AE 0.88 pg/mL, respectively. Serum levels of LTE 4 , PGF 2 a, and 11-dehydro TXB 2 showed no significant differences between normal healthy controls and asthmatic patients, while serum level of eoxin C 4 was significantly higher in asthmatic patients than in normal controls (P = 0.025) after adjusting for age and sex.…”