Prostaglandin E 2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin

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 ‐ CRS w NP ), as well as healthy controls ( HC ). Methods Induced sputum ( IS ) was collected from patients with NERD (n = 26), ATA ‐ CRS w NP (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 ‐ CRS w NP and HC (median NERD 9.1%, ATA ‐ CRS w NP 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 ‐ CRS w NP 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 ‐ CRS w NP . 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 .