title: Inhaled lysine-aspirin as a bronchoprovocation procedure in aspirin-sensitive asthma: its repeatability, absence of a late-phase reaction, and the role of histamine.
abstract: Inhalation of an aerosolized solution of lysine-aspirin has previously been described as a safer technique than oral challenge with aspirin for the diagnosis of aspirin-sensitive asthma. We describe a modification of this method that involves inhalation of serially doubling incremental concentrations of lysine-aspirin by a standardized technique and allows construction of concentration-response curves. In 11 subjects with asthma, mean (SEM) age 48.2 (2.9) years, the geometric mean (range) provocation concentrations of histamine and lysine-aspirin required to produce a 20% decrease in FEV1 from baseline were 0.6 (0.04 to 3.2) and 48.3 (15.5 to 219) mg/ml, respectively. No relationship was found between these values. In seven of nine subjects investigated on two consecutive occasions, bronchoconstriction with lysine-aspirin was repeatable to within a single doubling concentration difference. Bronchoconstriction provoked by lysine-aspirin was more rapid than with oral aspirin and was not followed by any late asthmatic reaction or increase in nonspecific airway hyperresponsiveness. In six subjects, premedication with the selective H1 histamine-receptor antagonist, terfenadine, had no significant effect on bronchoconstriction provoked by inhaled lysine-aspirin, indicating little role for release of histamine in the response. We conclude that inhalation of lysine-aspirin may be used as a bronchoprovocation procedure for the diagnosis and investigation of aspirin-sensitive asthma.
authors.affiliation: Department of Immunopharmacology, Medicine I, Southampton General Hospital, England.
authors.forename: G D
authors.initials: GD
authors.lastname: Phillips
authors.forename: R
authors.initials: R
authors.lastname: Foord
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects* / Q000031:analogs & derivatives*; D001249:Asthma / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008239:Lysine / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006632:Histamine; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate