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asthma
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CODEINE (C) AND ALTERNARIA (A) DIFFER IN ABILITY TO ELICIT LATE CUTANEOUS RESPONSES (LCR). R. Smith and T Casale. Iowa City. IA. Since LCR are believed to be mast cell mediated, and C and other opiates have been shown to degranulate cutaneous mast cells (JACI 73:775, 1984), we investigated whether C Skin responses in 11 normal could elicit LCR. (NL) and 10 A-sensitive subjects were measured l/4, 1, 3, 5, and 7 hrs after intradermal skin tests with 0.5, 5, 50, and 500 pg C and 1,000 and 10,000 PNU A. As expected, A-sensitive subjects had significantly greater wheals (W) and erythema (E) in response to A than NLs We found no significant differ(p=0.0001). ences between A-sensitive and NL groups in W and E responses to any C dose over time (p=O.83, 2-and S-way ANOVA). Comparison of C and A skin responses in only A-sensitive subjects revealed different results over time for C and A. When doses of C and A that elicited equivalent W and E responses at l/4 hr were compared at further time points, we found that A-induced responses were larger. In general, the W and E induced by C was virtually undetectable at 7 hrs. whereas A-induced resoonses peaked at this time. For examole: ' HRS/mm 3 7 I/4 c-50 pg W 1421 I5'+I 17+2 211 4+ 2 E 4022 19;5 6+1 1;1 I+ 1 A-10,000 W 1551 23+3* 34+5* 35+11* 37+11* E 44+5 39+6* 42+7* 47+10* 47+10* (*~<0.05 vs. C response) Therefore, although C and antigen appear to elicit mast cell dearanulation and eauivalent immediate skin responses, they differ'in their ability to produce LCR.
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IMMEDIATE ADVERSE REACTIONS TO ACETAMINOPHEN. Mark Ellis, MD, Irene Haydik, MD, Sherwin Gillman, MD, Leo Cummins, MD, Mitchell Cairo, MD.Orange,CA. We searched for immune mechanisms in iannediate
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adverse reactions to acetaminophen in 3 patients. A 6 year old black male and his 9 year old sister on several occasions developed severe bronchospasm within 30 min. of ingesting Tylenol@ Elixer. A 22 year old male developed 3 episodes of acute urticaria and angioedema within 30 min. after ingesting Vanquish Caplet@. All 3 patients reproduced their symptoms after a single-blind placebo controlled oral challenge with Tylenol @ but were unreactive to oral challen e with aspirin. ingesting 32 mg of Tylenol8 Elixer the 2 chit:::: developed sneezing, rhinorrhea, pruritis, wheesing and a 250% decrease in FEVl. The 22 year old patient developed marked urticaria/angioedema and PEFR decreased from 605 to 400. Prick skin tests using purified acetaminophen mixed in HSA were negative. leukocyte histamine release --In vitro (HR) was assesed by incubating serial dilutions of acetaminophen in fresh whole blood. Blood incubated with anti-IgE was used to determine maximal histamine release utilizing competative binding radioimmuno-assay with anti-histamine antibody. There was no significant increase in HR in patients' blood incubated with acetaminophen compared to normal controls. In conclusion, we report 3 patients developing severe bronchospasm and urticaria/angioedema after a singleblind p acebo controlled oral challenge with d but purified Tylenol acetaminophen did not induce --in viva (skin test) or --in vitro histamine release.
CROSS SENSITIVITY WITH ACETAMINOPHEN IN ASA-SENSITIVE ASTHMATICS, RA.Settipane,MD DD.Stevenson,M.D., La Jolla, Calif. Drugs inhibiting cyclooxygenase, regularly cross-react with aspirin(ASA) Although some experiments suggest that acetamenophen (ACETAMEN) is a weak inhibitor of cyclooxygenase in certain tissues, conclusions about its effects on lung tissues cannot be made and controversy exists as to whether or not true cross-reactivity occurs with ASA. This study was designed to determine if ACETAMEN behaved like ASA and nonsteroidal anti-inflamatory drugs(NSAIDs) by inducing desensitization and crossdesensitization. Three ASA-sensitive asthmatics, who gave a history of reactions to ACETAMEN, underwent double blind placebo controlled challenges and reacted to 1Gmg ACETAMEN with a >20% & in FEVl. Two patients were desensitized to ASA and then rechallenged with 1Gmg ACETAMEN without reaction.One pt was desensitized to 1 and 1.5 Gms of ACETAMEN but attempts to achieve desensitization with 2 Gms.of ACETAMEN failed. Cross-sensitivity between ASA and ACETAMEN occurs when large doses(> 1 Gm.) of ACETAMEN are used. Furthermore, crossdesensitization suggests that similar mechanisms are responsible for reactions to ASA, ACETAMEN( high dose) and NSAIDs.
Between 1979 and 1987, 277 patients with suspected ASA asthma underwent oral ASA challenges at Scripps Clinic. A total of 292 single blinded, placebo controlled oral ASA challenges were conducted; 154 (56%) patients had a > 20% decline in FEVl post ASA. 51 patients underwent ASA desensitization (ASA-D) and continued this state while being treated with daily ASA (ASA Rx); 3 patients were lost to followup. 48 patients continued open ASATBX for l-87 months (mean 32.2); 27 of these continue ASA Bx to the present, 12 discontinued(dc) ASA due to side effects (usually GI),2 dc for surgery, 4 dc for no improvement, and 3 dc for missed ASA doses and did not reASA-D. In 34 patients who received systemic corticosteroids(CS);dose prior to ASA-D was 12.6 mg/day (range O-40 mg) and during ASA Rx dose was reduced to 5.17 mg/day, range 0 - 30 mg (-7.43 mg/day, p C 0.01 ). In 26 pts. oral topical CS usage was not significantly changed. Of the 51 patients who started ASA Rx, half continued this treatment for at least several years and were able to significantly reduce systemic CS treatment while maintaining control of their respiratory disease.
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CODEINE (C) AND ALTERNARIA (A) DIFFER IN ABILITY TO ELICIT LATE CUTANEOUS RESPONSES (LCR). R. Smith and T Casale. Iowa City. IA. Since LCR are believed to be mast cell mediated, and C and other opiates have been shown to degranulate cutaneous mast cells (JACI 73:775, 1984), we investigated whether C Skin responses in 11 normal could elicit LCR. (NL) and 10 A-sensitive subjects were measured l/4, 1, 3, 5, and 7 hrs after intradermal skin tests with 0.5, 5, 50, and 500 pg C and 1,000 and 10,000 PNU A. As expected, A-sensitive subjects had significantly greater wheals (W) and erythema (E) in response to A than NLs We found no significant differ(p=0.0001). ences between A-sensitive and NL groups in W and E responses to any C dose over time (p=O.83, 2-and S-way ANOVA). Comparison of C and A skin responses in only A-sensitive subjects revealed different results over time for C and A. When doses of C and A that elicited equivalent W and E responses at l/4 hr were compared at further time points, we found that A-induced responses were larger. In general, the W and E induced by C was virtually undetectable at 7 hrs. whereas A-induced resoonses peaked at this time. For examole: ' HRS/mm 3 7 I/4 c-50 pg W 1421 I5'+I 17+2 211 4+ 2 E 4022 19;5 6+1 1;1 I+ 1 A-10,000 W 1551 23+3* 34+5* 35+11* 37+11* E 44+5 39+6* 42+7* 47+10* 47+10* (*~<0.05 vs. C response) Therefore, although C and antigen appear to elicit mast cell dearanulation and eauivalent immediate skin responses, they differ'in their ability to produce LCR.
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IMMEDIATE ADVERSE REACTIONS TO ACETAMINOPHEN. Mark Ellis, MD, Irene Haydik, MD, Sherwin Gillman, MD, Leo Cummins, MD, Mitchell Cairo, MD.Orange,CA. We searched for immune mechanisms in iannediate
48
adverse reactions to acetaminophen in 3 patients. A 6 year old black male and his 9 year old sister on several occasions developed severe bronchospasm within 30 min. of ingesting Tylenol@ Elixer. A 22 year old male developed 3 episodes of acute urticaria and angioedema within 30 min. after ingesting Vanquish Caplet@. All 3 patients reproduced their symptoms after a single-blind placebo controlled oral challenge with Tylenol @ but were unreactive to oral challen e with aspirin. ingesting 32 mg of Tylenol8 Elixer the 2 chit:::: developed sneezing, rhinorrhea, pruritis, wheesing and a 250% decrease in FEVl. The 22 year old patient developed marked urticaria/angioedema and PEFR decreased from 605 to 400. Prick skin tests using purified acetaminophen mixed in HSA were negative. leukocyte histamine release --In vitro (HR) was assesed by incubating serial dilutions of acetaminophen in fresh whole blood. Blood incubated with anti-IgE was used to determine maximal histamine release utilizing competative binding radioimmuno-assay with anti-histamine antibody. There was no significant increase in HR in patients' blood incubated with acetaminophen compared to normal controls. In conclusion, we report 3 patients developing severe bronchospasm and urticaria/angioedema after a singleblind p acebo controlled oral challenge with d but purified Tylenol acetaminophen did not induce --in viva (skin test) or --in vitro histamine release.
CROSS SENSITIVITY WITH ACETAMINOPHEN IN ASA-SENSITIVE ASTHMATICS, RA.Settipane,MD DD.Stevenson,M.D., La Jolla, Calif. Drugs inhibiting cyclooxygenase, regularly cross-react with aspirin(ASA) Although some experiments suggest that acetamenophen (ACETAMEN) is a weak inhibitor of cyclooxygenase in certain tissues, conclusions about its effects on lung tissues cannot be made and controversy exists as to whether or not true cross-reactivity occurs with ASA. This study was designed to determine if ACETAMEN behaved like ASA and nonsteroidal anti-inflamatory drugs(NSAIDs) by inducing desensitization and crossdesensitization. Three ASA-sensitive asthmatics, who gave a history of reactions to ACETAMEN, underwent double blind placebo controlled challenges and reacted to 1Gmg ACETAMEN with a >20% & in FEVl. Two patients were desensitized to ASA and then rechallenged with 1Gmg ACETAMEN without reaction.One pt was desensitized to 1 and 1.5 Gms of ACETAMEN but attempts to achieve desensitization with 2 Gms.of ACETAMEN failed. Cross-sensitivity between ASA and ACETAMEN occurs when large doses(> 1 Gm.) of ACETAMEN are used. Furthermore, crossdesensitization suggests that similar mechanisms are responsible for reactions to ASA, ACETAMEN( high dose) and NSAIDs.
Between 1979 and 1987, 277 patients with suspected ASA asthma underwent oral ASA challenges at Scripps Clinic. A total of 292 single blinded, placebo controlled oral ASA challenges were conducted; 154 (56%) patients had a > 20% decline in FEVl post ASA. 51 patients underwent ASA desensitization (ASA-D) and continued this state while being treated with daily ASA (ASA Rx); 3 patients were lost to followup. 48 patients continued open ASATBX for l-87 months (mean 32.2); 27 of these continue ASA Bx to the present, 12 discontinued(dc) ASA due to side effects (usually GI),2 dc for surgery, 4 dc for no improvement, and 3 dc for missed ASA doses and did not reASA-D. In 34 patients who received systemic corticosteroids(CS);dose prior to ASA-D was 12.6 mg/day (range O-40 mg) and during ASA Rx dose was reduced to 5.17 mg/day, range 0 - 30 mg (-7.43 mg/day, p C 0.01 ). In 26 pts. oral topical CS usage was not significantly changed. Of the 51 patients who started ASA Rx, half continued this treatment for at least several years and were able to significantly reduce systemic CS treatment while maintaining control of their respiratory disease.
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