1. Drug hypersensitivity reactions (DHR) in asthmatic patients Authors: Edgardo JARES, Carlos E. BAENA-CAGNANI, Mario SÁNCHEZ BORGES, Luis ENSINA, Alfredo ARIAS CRUZ, Maximilano GÓMEZ, Blanca MORFIN MACIEL, Silvana MONSELL, Susana DIEZ-ZULUAGA, Sandra GONZÁLEZ DÍAZ, Galie MIMESSI, Alejandra MACIAS WEINMANN, Dirceu SOLE, Carlos SERRANO, Susana BARAYAZARRA, Iván CHERREZ, Mabel CUELLO, Paola TOCHE PINAUD, Viviana Andrea ZANACCHI, Ricardo CARDONA VILLA Affiliations: Fundación LIBRA (LIBRA Foundation) Slaai Drug allergy Committee

2. Adverse reactions to drugs are a frequent reason for consultation. There are few studies featuring these reactions in asthmatic patients. Tolerability to etoricoxib in patients with aspirin- exacerbated respiratory disease.  AERD (Aspirin-exacerbated respiratory disease)  248 aspirin challenges, 49.2%+, 97% tolerated etoricoxib (only 3 positive challenges) Background Koschel D, Weber CN, Höffken G. J Investig Allergol Clin Immunol. 2013;23(4):275-80.)

3. Adverse reactions to drugs are a frequent reason for consultation. There are few studies featuring these reactions in asthmatic patients. Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs.  25 MNSAID-UA, 60 AERD.  Lysine nasal challenge + 12% vs 80%  ECP, PGD2, LTD4, LTE4 and triptase levels after challenge in AERD but not in MNSAID‐UA  MNSAID-UA and AERD have a distinctive phenotype Background Campo P et al. Allergy. 2013 Aug;68(8):1001-7.

4. Objectives:  Identify peculiarities of drug hypersensitivity reactions in asthmatic patients.

5. Methods:  A descriptive cross-sectional study using ENDA questionnaire was carried out, reporting those patients seen in the last 2 years due to DHR.  Causal relationship was categorized into certain, probable, possible, unlikely, and conditional, according to WHO-UMC Causality Categories (1).  Severity was graded as mild, moderate and severe (2).  Patients with asthma diagnosis (clinical and functional) were selected. 1) http://who-umc.org/Graphics/24734.pdf 2) http://www.anmat.gov.ar/farmacovigilancia/docs/Guia_BPF.pdf

6. Methods:  Anaphylaxis was defined as a moderate or severe reaction occurring less than 24 hours after the administration of the drug, with urticaria and/or angioedema (U/A), and respiratory (cough, dysphonia, dyspnea, wheezing/bronchospasm, rhinitis, rhinorrhea, sneezing, nasal obstruction), and/or gastrointestinal (nausea/emesis, diarrhea, gastrointestinal cramps) (R-GI) and/or cardiovascular (tachycardia, hypotension, collapse, arrhythmia) symptoms (CV) (3,4)  Causal drugs, clinical features and severity were compared with patients without asthma.  OpenEpi software was used. All reported P values were based on 2- tailed tests; values lower than.05 were considered statistically significant. 3) Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 2006;117:391-7. 4) Simons FER, et al, for the World Allergy Organization: WAO guidelines for the assessment and management of anaphylaxis. J Allergy Clin Immunol. 2011;127:587-93.

7. Results  868 DHR in 862 patients were evaluated. 143 DHR occurred in 135 asthma patients.  Female gender was predominant.

8. Results: Clinical picture of the reactions Being asthmatic implied a 60% increased risk of having anaphylaxis because of DHR, but a duplicated risk of respiratory symptoms.

9. Respiratory Symptoms Symptoms Asthma n (%) No Asthma n (%) pOR Respiratory Symptoms 61 (42.7)191 (26.3)<0.00012.08 Disnea46 (32.1)155 (21.3)<0.011.74 Cougth36 (25.1)81 (11.1)<0.00012.67 Disphonia11 (7.6)70 (9.7)NS0.7 Wheezing- bronchospasm 24 (16.7)50 (6.9)<0.0012.72

10. There was no significant difference in severity between groups. No Asthmatic Patients Asthmatic Patients

11. Results: Main drug group responsible of DHR (certain and probable causal relationship)

12. Conclusions  we identify that asthmatic patients have a significant higher risk of having anaphylactic reactions and respiratory symptoms during DHR. Caution should be taken to prevent these reactions, and provide the patients with an effective action plan.