Prostaglandin E₂ decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin.

Abstract

A special regulatory role for prostaglandin E₂ (PGE₂ ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE₂ 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). 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, PGE₂ , 8-iso-PGE₂ , tetranor-PGE-M, 8-iso-PGF₂ α, and leukotriene C₄ , D₄ , and E₄ , were determined using mass spectrometry. Urinary excretion of LTE₄ was measured by ELISA. 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 PGE₂ 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 PGE₂ 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 PGE₂ as in HC resulted from 2.8 times lower dose of aspirin. Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE₂ biosynthesis. These results support the mechanism of PGE₂ biosynthesis inhibition as a trigger for bronchoconstriction in NERD.