Drug provocation test
DPTs were performed in a single blind manner [9, 12-14, 24]: placebo capsules were given at different times on the first day; and increasing doses of NSAIDs were administered orally on the second/third days. The two/three test days were separated by at least 1 week. Drugs and placebo were given in opaque capsules prepared by the hospital pharmacy service.
DPT to ASA was performed in patients reporting less than 3 episodes induced by less than 3 different NSAIDs in order to classify them into CRs (they reacted to ASA) or SRs (they tolerated ASA) (Figure 1) [10]. For DPT, two doses of ASA were administered orally (50 and 100 mg) with an interval of 180 minutes on the 2nd day test. If negative, other two doses of ASA (250 and 500 mg) were administered on the 3rd day, also with a 180-minute interval.
In addition to ASA, DPT to the culprit AP was performed in subjects who tolerated ASA if they reported less than 2 episodes induced by APs [10, 18]. If they reacted, they were classified into SRs, whereas if they tolerated the culprit APs, they were confirmed as non-allergic (Figure 1) [10]. Drugs were given in increasing doses every 90 minutes: 5, 50,100, 200, and 250 mg for ibuprofen (accumulative dose 600 mg); 3.125, 3.125, 6.25, and 12.5 for dexketoprofen (accumulative dose 25 mg); 5, 10, and 50 mg in the second day and 50, 100, 100, 250 mg (accumulative dose 500 mg) in the third day for naproxen; and 5, 10, 10, and 25 mg for ketoprofen (accumulative dose 50 mg).
If cutaneous and/or respiratory symptoms or alterations in vital signs appeared, the procedure was stopped and the symptoms were evaluated and treated. If no symptoms appeared during DPT and the therapeutic dose was achieved, a 2-day/8-hour course of the therapeutic dose after a gap of 24 hours was performed [13].
Before beginning the DPT procedure, patients were stable and their forced expiratory volume in 1s had to be at least 80% of the predicted value, with an absolute volume of at least 1.5 L. Medications were stopped before DPT according to international guidelines [9, 12-14, 24].