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

BackgroundA special regulatory role for prostaglandin E-2 (PGE(2)) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). ObjectiveTo 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). MethodsInduced 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), and leukotriene C-4, D-4, and E-4, were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA. ResultsNERD 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 HCP=0.04, ATA-CRSwNP vs HCP<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. ConclusionAspirin-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.