Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs

Background Multiple NSAID-induced urticaria/angioedema (MNSAID-UA) is an entity well differentiated from aspirin-exacerbated respiratory disease (AERD), although no detailed phenotype analysis has yet been performed. The objective was to evaluate the functional characteristics of MNSAID-UA subjects by analyzing the response to nasal lysine-aspirin challenge and measurement of nasal inflammatory mediator release compared with AERD subjects and controls. Methods The study included 85 subjects with confirmed hypersensitivity to NSAIDs (3 episodes with >2 different NSAIDs or positive drug provocation) with either cutaneous (MNSAID-UA, n=25) or respiratory manifestations (AERD, n=60) and 30 tolerant controls (15 aspirin-tolerant asthmatic patients and 15 healthy controls). Nasal lavages at 0, 15, 60, and 120min after lysine-aspirin challenge were analyzed for ECP, tryptase, PGE(2), PGD(2), LTD4, and LTE4. Results Lysine nasal challenge was positive in 80% of the AERD cases but positive only in 12% of the MNSAID-UA group. MNSAID-UA subjects showed no changes in nasal ECP, whereas subjects with AERD had increased levels of ECP, with the highest peak at 15min after challenge (P<0.05). Tryptase levels were higher in AERD compared with MNSAID-UA and controls with the highest release of tryptase at 60min (P<0.05). Significant increases in PGD(2), LTD4, and LTE4 were observed in AERD (at 60min for PGD(2), LTD4, and LTE4) but not in MNSAID-UA or control subjects (P<0.05). Conclusions Data support the observation that MNSAID-UA, although sharing a common response with AERD to COX inhibitors, seems to have a distinctive phenotype, based on the response to nasal challenge and the release of inflammatory mediators.