Increased urinary excretion of the prostaglandin D"2 metabolite 9@a,11@b-prostaglandin F"2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction

Prostaglandin (PG)D"2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD"2, 9@a,11@b-PGF"2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9@a,11@b-PGF"2 in healthy volunteers. Morning baseline values of urinary 9@a,11@b-PGF"2 were measured in three groups-healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)-and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9@a,11@b-PGF"2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9@a,11@b-PGF"2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9@a,11@b-PGF"2, supporting dose-dependent release of PGD"2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9@a,11@b-PGF"2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9@a,11@b-PGF"2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo. (J ALLERGY CLIN IMMUNOL 1996;98:421-32.)