Means of increasing sensitivity of an in vitro diagnostic test for aspirin intolerance

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Abstract
Pseudo-allergic reactions caused by aspirin (acetyl salicylic acid; ASA) often resemble immediate-type hypersensitivity reactions consisting of urticaria and angioedema or rhinoconjunctivitis, asthma and nasal polyps. In the last few years, a new in vitro assay based on determination of sulfidoleucotrienes from isolated leucocytes (cellular allergen stimulation test — CAST) has been introduced for type I allergies and pseudoallergic reactions. In ASA intolerance, there is only limited experience using this assay with — in some studies — only moderate sensitivity. Furthermore, the necessity to use freshly isolated leucocytes from untreated patients is inconvenient for routine settings. The purpose of our study was to search for possibilities of increasing the sensitivity of the test and to use stored blood samples which would permit shipping, two requirements for the clinical suitability of this test. Leucotriene release in response to ASA and other non-steroidal anti-inflammatory drugs (NSAIDs) was analysed in 38 ASA-intolerant patients (predominantly airway-related symptoms n = 22; predominantly cutaneous symptoms n = 16) and 50 controls. The diagnosis of ASA intolerance was established by history and placebo-controlled oral challenge tests. Using 24 h-stored leucocytes obtained from 10 ASA-intolerant patients and 10 healthy controls there were no significant differences of leucotriene release by resting, ionomycin-, and anti FcεRIα-stimulated leucocytes compared with freshly isolated leucocytes. Analysis of ASA + C5a-mediated leucotriene release by stored blood samples in combination with indomethacin- and diclofenac-mediated leucotriene release in ASA-intolerant patients (n = 38) resulted in an increased sensitivity (from 50 to 72.7% in ASA-intolerant patients with predominantly airway-related symptoms and from 81 to 100% in ASA-intolerant patients with predominantly skin symptoms) compared with assays in which only ASA + C5a-mediated leucotriene release has been determined. Moreover, the specificity of the assay remained high (96.7% when analysing different NSAIDs compared with > 99% when analysing only ASA + C5a-mediated leucotriene release). In vitro stimulation with ASA + C5a leucocyte stimulation with other NSAIDs should be performed to achieve a higher sensitivity. This finding can be explained by the clinical observation of a high ratio of cross-reactivities between the mentioned NSAIDs.