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

Background: A special regulatory role for prostaglandin E (PGE ) 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 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 , 8-iso-PGE , tetranor-PGE-M, 8-iso-PGF α, and leukotriene C , D , and E , were determined using mass spectrometry. Urinary excretion of LTE 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 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 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 as in HC resulted from 2.8 times lower dose of aspirin.

Conclusion: Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE biosynthesis. These results support the mechanism of PGE biosynthesis inhibition as a trigger for bronchoconstriction in NERD.