title: Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs.
abstract: 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 120 min after lysine-aspirin challenge were analyzed for ECP, tryptase, PGE2 , PGD2 , 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 15 min after challenge (P < 0.05). Tryptase levels were higher in AERD compared with MNSAID-UA and controls with the highest release of tryptase at 60 min (P < 0.05). Significant increases in PGD2 , LTD4 , and LTE4 were observed in AERD (at 60 min for PGD2 , 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.
authors.affiliation: Allergy Service, Carlos Haya Hospital, Málaga, Málaga, Spain. campomozo@yahoo.com
authors.forename: P
authors.initials: P
authors.lastname: Campo
authors.forename: P
authors.initials: P
authors.lastname: Ayuso
authors.forename: M
authors.initials: M
authors.lastname: Salas
authors.forename: M C
authors.initials: MC
authors.lastname: Plaza
authors.forename: J A
authors.initials: JA
authors.lastname: Cornejo-García
authors.forename: I
authors.initials: I
authors.lastname: Doña
authors.forename: M J
authors.initials: MJ
authors.lastname: Torres
authors.forename: N
authors.initials: N
authors.lastname: Blanca-López
authors.forename: G
authors.initials: G
authors.lastname: Canto
authors.forename: J-L
authors.initials: JL
authors.lastname: Guéant
authors.forename: M
authors.initials: M
authors.lastname: Sanak
authors.forename: M
authors.initials: M
authors.lastname: Blanca
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000799:Angioedema / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D014581:Urticaria / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D001241:Aspirin
keywords: aspirin-exacerbated cutaneous disease; inflammatory mediators; lysine nasal challenge; multiple nonsteroidal anti-inflammatory drug-induced urticaria/angioedema; nonsteroidal anti-inflammatory drugs