Prostaglandin D2: A dominant mediator of aspirin-exacerbated respiratory disease

Abstract

Background-Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy.

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

“…In the present study, urine baseline LTE 4 levels were correlated with decreases in FEV 1 % after the Lys-ASA BPT in line with previous studies [26,30]. However, baseline LTE 4 levels were not correlated with baseline FEV 1 % or asthma severity, which is inconsistent with results of previous studies [27,31].…”

Aspirin Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway

“…High-dose aspirin, which produces substantial symptomatic improvements and reduces recurrence rates for nasal polyps in AERD, does not decrease systemic levels of cysLTs (57), but eliminates the selective hyperresponsiveness to LTE 4 (7). The latter effect could reflect the capacity of high-dose aspirin to deplete TP-active PGs (58). Our study also suggests that AERD, in which eosinophilic inflammation and MC activation are prominent despite a clear association with atopy, is largely driven by innate type 2 immunity.…”

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

“…PGD 2 and its metabolites are higher at baseline in AERD subjects in comparison to aspirin tolerant individuals 30,31 . Within the AERD patients, there exists a subgroup that has particularly enhanced overproduction and release of PGD 2 during aspirin challenges that correlates with the severity of AERD and predicts failure of aspirin desensitization 6 . In addition to defining a more severe subgroup, PGD 2 likely contributes to the severity of AERD through its myriad of biological activities that include inducing vasodilation and vascular leakage as well as bronchoconstriction.…”

“…In AERD, baseline levels of PGD 2 and its metabolites are higher in the blood than in subjects who are aspirin tolerant and following ingestion of aspirin these levels further increase in AERD subjects 5,6 . Aspirin desensitization followed by continual high-dose aspirin therapy is a treatment option for AERD 7 and if the subjects tolerate the desensitization they benefit from improved disease control.…”

“…Aspirin desensitization followed by continual high-dose aspirin therapy is a treatment option for AERD 7 and if the subjects tolerate the desensitization they benefit from improved disease control. However, not all patients with AERD can be desensitized, and this group that fails desensitization is distinguished by their constitutive overproduction and aspirin-stimulated release of PGD 2 that correlates with the severity of airflow obstruction 6 . In addition to defining a more severe subgroup that fails aspirin desensitization, PGD 2 likely contributes to the severity through its myriad of biological activities that includes inducing vasodilation and vascular leakage, bronchoconstriction, and the recruitment and activation of basophils, eosinophils, dendritic cells, and both Th2-like lymphocytes and type 2 innate lymphoid cells [8][9][10][11] .…”