The LCA revealed four distinct asthma classes differing in eicosanoid pathways.

No abstract

Background:A special regulatory role for prostaglandin E 2 (PGE 2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD).Objective: To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE 2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC). Methods:Induced sputum (IS) was collected from patients with NERD (n = 26), ATA-CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE 2 , 8-iso-PGE 2 , tetranor-PGE-M, 8-iso-PGF 2 α, and leukotriene C 4 , D 4 , and E 4 , were determined using mass spectrometry. Urinary excretion of LTE 4 was measured by ELISA.Results: NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE 2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA-CRSwNP vs HC P < 0.05). Post-challenge ISS levels of PGE 2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE 2 as in HC resulted from 2.8 times lower dose of aspirin. Conclusion:Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE 2 biosynthesis. These results support the mechanism of PGE 2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD. K E Y W O R D Seicosanoids, induced sputum, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, oral aspirin challenge, prostaglandins Abbreviations: ATA-CRSwNP, aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis; COX, cyclooxygenase; Cys-LTs, cysteinyl leukotrienes; HC, healthy control; LTC4, leukotriene C4; LTD4, leukotriene D4; LTE4, leukotriene E4; NERD, nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease; NSAIDs, nonsteroidal anti-inflammatory drugs; PGE2, prostaglandin E2; Tetranor-PGE-M, 9,15-dixo-11α-hydroxy-2,3,4,5-tetranor-prostan-1,20-dioic acid.

Abbreviations: ANN, artificial neural network; ATA, aspirin-tolerant asthma; CRSwNP, chronic rhinosinusitis with nasal polyposis; IS, induced sputum; ISS, induced sputum supernatant; LTE 4 , leukotriene E 4 ; N-ERD, nonsteroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease; PGD 2 , prostaglandin D 2 ; PGE 2 , prostaglandin E 2 ; SVM, support vector machine.