An Increase in Tryptase on the First Day of Hymenoptera Venom Immunotherapy Might Be a Predictor of Future Systemic Reactions During Treatment.

BACKGROUND AND OBJECTIVE: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. METHODS: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. RESULTS: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 µg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. CONCLUSIONS: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety.

An increase in tryptase on the first day of hymenoptera venom immunotherapy might be a predictor of future systemic reactions during treatment

Background: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. Methods: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. Results: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 μg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. Conclusions: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety

Antecedentes: Se ha observado una disminución progresiva del nivel de triptasa sérica (TS) basal durante la inmunoterapia con veneno de himenópteros (ITVH), así como la conservación de la variación circadiana de triptasa en pacientes que han tolerado una repicadura controlada. Ambos hallazgos se han relacionado con la eficacia del tratamiento. Objetivo: Estudiar si la variación (aumento o disminución) de la TS durante el primer día de ITVH se relaciona con un mayor riesgo de presentar reacciones adversas sistémicas (RAS) con futuras dosis de ITVH. Método: Estudio prospectivo de pacientes sometidos a ITVH en pauta de inicio agrupada y que continuaron con el tratamiento durante al menos 6 meses. Se determinó la TS el primer día de ITVH, antes de la primera dosis (triptasa pre-IT) y tras la última dosis (triptasa post-IT). Se analizaron las diferencias entre los dos grupos de pacientes (con o sin RAS). Resultados: Se administraron 160 ITVH a 150 pacientes. El valor medio de TS basal fue 4,3 μg/L, siendo > 11,4 μg/L en 4 casos. Un total de 25 ITVH (15,6%) presentaron RAS. En 64% de los 25 pacientes con RAS, el valor de triptasa post-IT fue más alto que el valor de triptasa pre-IT; el incremento medio fue del 19% en estos pacientes. Encontramos una relación significativa entre este aumento de triptasa el primer día de ITVH y la aparición de RAS con futuras dosis de ITVH (risk ratio 7,6). Esta elevación fue independiente del día de aparición de la reacción, de la gravedad de la misma, así como del valor basal de triptasa. Conclusiones: Un ligero aumento de triptasa el primer día de ITVH es una variable independiente, fuertemente relacionada con un alto riesgo de presentar una futura RAS. Este sencillo biomarcador podría ser útil para mejorar la seguridad de estos pacientes

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Key issues in hymenoptera venom allergy: an update

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis (AU)

En esta revisión el Comité de Alergia a Himenópteros de la SEAIC ha analizado la literatura científica más reciente sobre los principales problemas diagnósticos de la alergia a himenópteros, así como sobre las dificultades que pueden surgir durante la inmunoterapia con venenos. Se revisan especialmente las novedades relacionadas con el diagnóstico molecular y los perfiles moleculares de riesgo. También se describe la alergia a himenópteros poco habituales y los problemas diagnósticos y terapéuticos que esta conlleva. Por último, se tratan los síndromes de activación mastocitaria clonal, íntimamente relacionados con la alergia a himenópteros, que se han convertido en un nuevo reto diagnóstico para el alergólogo (AU)

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Insect venom immunotherapy: analysis of the safety and tolerance of 3 buildup protocols frequently used in Spain

Introduction: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. Materials and Methods: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Results: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. Conclusions: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach (AU)

Introducción: La inmunoterapia con veneno de himenópteros (ITV) es un tratamiento eficaz, pero no está desprovisto de riesgo ya que pueden ocurrir reacciones adversas locales o sistémicas, especialmente en las etapas iniciales del tratamiento. Comparamos la tolerancia de tres protocolos de inicio de ITV y analizamos los factores de riesgo asociados con las reacciones adversas que se produjeron en esta fase. Métodos: Se incluyeron 165 pacientes divididos en tres grupos según el protocolo de iniciación utilizado (3, 4 o 9 semanas). Evaluamos la gravedad de las reacciones sistémicas de acuerdo con el modelo de la Organización Mundial de Alergia. Analizamos los resultados mediante estadística descriptiva exploratoria y comparamos variables mediante el análisis de la varianza. Resultados: Cincuenta y tres pacientes (32%) experimentaron algún tipo de reacción adversa; 43 eran locales y 10 sistémicas. Las reacciones locales fueron inmediatas en 27 pacientes (63%) y tardías en 16 (37%). La gravedad de la reacción local fue leve o moderada en 15 pacientes y grave en 13. Las reacciones sistémicas fueron de grado 1 o 2. No encontramos asociación significativa entre la modalidad de tratamiento y la aparición de reacciones adversas locales o sistémicas o el tipo de reacción local. Solo encontramos una asociación estadísticamente significativa de la gravedad de la reacción local con el sexo femenino. En cuanto a los factores de riesgo asociados con las reacciones sistémicas en la fase de inicio, no se encontraron diferencias significativas en estos valores en función del protocolo utilizado o el insecto responsable. Conclusiones: Los protocolos de inicio comparados demostraron ser seguros y no difirieron significativamente entre sí. En la población estudiada, el protocolo de 9-semanas no produjo reacciones sistémicas, por lo que se puede considerar el protocolo más seguro (AU)

Fluorocytometric analysis of induced sputum cells in an asthmatic population.

BACKGROUND: Bronchial mucosal inflammation is the major pathogenic process in asthma. In the latest years, induced sputum (IS) examination has become an important non-invasive method of assessing airway inflammation. Flow cytometry has been recently applied to the study of IS though it is not exempt of methodological difficulties. The aim of the present study was to further study if the fluorocytometric analysis of IS could represent a reliable tool to assess the presence of bronchial activated lymphocytes in stable mild asthmatic patients. METHODS: Induced sputa from controls and asthmatic patients were processed in isotonic 3mM dithiothreitol (DTT), a mucolytic agent required for cell dispersion. The individualized cells were then stained with monoclonal antibodies for three-colour flow-cytometric analysis. Total IgE and ECP were measured in serum and in the sputum fluid phase. RESULTS: The cellularity of asthmatic sputa is enriched in eosinophils (mean, 26.63%) with respect to controls, but not in lymphocytes. However, lymphocytes from asthmatics show increased surface expression of activation markers (CD25 in T cells, CD23 in B cells). Surprisingly, no differences were observed in the detected levels of CD54 on IS lymphocytes and eosinophils between asthmatics and non-asthmatics. Furthermore, there was a significantly higher concentration of ECP and total IgE in the sputum from the asthmatic group. CONCLUSION: Fluorocytometric analysis of induced sputum is a reliable non-invasive method for the study of bronchial immune cells. It could provide complementary information on activated cells in the bronchial mucosa even in non-smokers, mild and stable asthmatics and it is reasonable to speculate that it will be useful in monitoring the effect of the treatment in these patients.

Measurement of serum levels of eosinophil cationic protein in the diagnosis of acute gastrointestinal anisakiasis.

Thirty-two patients with abdominal pain and/or intestinal pseudo-obstruction who had consumed raw or undercooked fish in the previous 72 h, were included in a study of anisakiasis, a parasitation of the human gastrointestinal tract by third stage Anisakis simplex larvae. Skin prick test (SPT) against A. simplex were positive in all the patients. High median eosinophil cationic protein (ECP) serum concentrations (> 15 mg/L) at day 0 with normal serum levels at day 30 and a rise of median total and specific IgE against A. simplex at day 30, were observed. We conclude that a raised serum level of ECP in the first 72 h from the onset of symptoms coinciding with a positive SPT against A. simplex and high total and specific immunoglobulin (IgE) in the first month after the parasitation, could be a useful tool in the diagnosis of gastrointestinal anisakiasis, even if the parasite cannot be isolated.

The effect of dithiothreitol on VLA-4 detection in peripheral blood and induced sputum cells.

BACKGROUND: Induced sputum has been shown to be a reliable technique for investigating airway inflammation non-invasively. Flow cytometry could provide useful information in this area. However, the viscosity of the sample entails the use of a mucolytic agent. Dithiothreitol (DDT) is the most frequently used agent although it could affect detection of different inflammatory markers. METHODS: To measure the effect of DDT on the detection of certain adhesion molecules in eosinophils and lymphocytes, sputum was induced from seven non-smoking asthmatic and non-asthmatic subjects treated with 0.1 M DDT. The samples were analyzed by flow cytometry. Whole blood samples from the same subjects were also processed with DTT and analyzed by flow cytometry. RESULTS: Very late activated antigen-4 (VLA-4) levels on eosinophils in intracellular and surface staining were much lower than expected. VLA-4 on lymphocytes was also altered but less so than on eosinophils. VLA-4 levels were also decreased on blood cells after DTT treatment. No abnormalities were found in the detection of CD29 on eosinophils and the beta7-chain in lymphocytes. CONCLUSIONS: Flow cytometry could be used as a complementary method to induced sputum in the investigation of airway inflammation. However, DTT could interfere with the detection of some inflammatory markers, as is the case with VLA-4.

Nasal provocation test (NPT) with aspirin: a sensitive and safe method to diagnose aspirin-induced asthma (AIA).

BACKGROUND: We have aimed to determine the sensitivity and specificity of a simpler technique with less risk than oral provocation to diagnose aspirin-induced asthma (AIA). METHODS: We studied a group of 20 AIA patients compared to a control group with 40 aspirin-tolerant patients (confirmed by oral provocation test): 10 asthmatic patients and 30 healthy subjects. A nasal provocation test (NPT) with lysine acetylsalicylic acid (L-ASA) was carried out. Nasal and pulmonary functions were monitored with anterior active rhinomanometry (AAR) and spirometry. An L-ASA solution (900 mg/ml L-ASA, equivalent to 500 mg/ml acetylsalicylic acid) was diluted with saline solution. We administered four increasing doses: 5, 25, 50 and 100 mg/ml acetylsalicylic acid (ASA) with saline solution control. Nasal and pulmonary functions were monitored with rhinomanometry and spirometry. The patients were controlled for nasal inspiratory peak flow and expiratory peak flow. RESULTS: The results showed high sensitivity and specificity: 80% and 92.5%, respectively, with an 84.2% positive predictive value and an 89.2% negative predictive value. The patients had no bronchial or systemic symptoms, and no decreases over 20% were recorded in the FEV1. CONCLUSION: NPT has a high sensitivity and specificity in the diagnosis of AIA. An oral provocation should be performed to confirm the result whenever the clinical situation of the patient permits it.

The effect of dithiothreitol on VLA-4 detection in peripheral blood and induced sputum cells

Background: Induced sputum has been shown to be a reliable technique for investigating airway inflammation non-invasively. Flow cytometry could provide useful information in this area. However, the viscosity of the sample entails the use of a mucolytic agent. Dithiothreitol (DDT) is the most frequently used agent although it could affect detection of different inflammatory markers. Methods: To measure the effect of DDT on the detection of certain adhesion molecules in eosinophils and lymphocytes, sputum was induced from seven non-smoking asthmatic and non-asthmatic subjects treated with 0.1 M DDT. The samples were analyzed by flow cytometry. Whole blood samples from the same subjects were also processed with DTT and analyzed by flow cytometry. Results: Very late activated antigen-4 (VLA-4) levels on eosinophils in intracellular and surface staining were much lower than expected. VLA-4 on lymphocytes was also altered but less so than on eosinophils. VLA-4 levels were also decreased on blood cells after DTT treatment. No abnormalities were found in the detection of CD29 on eosinophils and the β7-chain in lymphocytes. Conclusions: Flow cytometry could be used as a complementary method to induced sputum in the investigation of airway inflammation. However, DTT could interfere with the detection of some inflammatory markers, as is the case with VLA-4 (AU)

Antecedentes: El esputo inducido se ha mostrado como una técnica fiable para estudiar de un modo no invasivo, la inflamación de la vía respiratoria en el asma bronquial. La citometría de flujo puede aportar información útil en este campo. No obstante, la viscosidad de la muestra implica la utilización de una gente mucolítico, siendo el Ditiotreitol (DTT) uno de los más usados, a pesar de que puede alterar la expresión de diferentes mediadores inflamatorios. Métodos: Se indujo esputo de 7 sujetos asmáticos y no asmáticos, todos no fumadores. Se trataron las muestras con DTT 0.1M y se analizaron concitometría de flujo. Muestras de sangre de los mismos sujetos igualmente fueron procesadas con DTT 0.1M y analizadas. Resultados: Los niveles de detección de VLA-4 en la superficie y a nivel intracelular en los eosinófilos, fue más baja de lo esperado. La alteración de los niveles de VLA-4 en linfocitos fue menor que en los eosinófilos. En sangre, la detección de VLA-4 disminuyó en las muestras tratadas con DTT. No se observaron anormalidades en la detección de CD29 en eosinófilos ni en la cadena 7 en linfocitos. Conclusiones: La citometría de flujo puede ser usada en el estudio de la inflamación en la vía aérea aunque se debe tener en cuenta que el DTT altera la detección de algunos marcadores, como así se comprueba para el VLA-4 (AU)

[Analysis of 83 bronchospasm episodes seen at urgent care during one spring night]. / Análisis de 83 episodios de broncoespasmo atendidos una noche de primavera en urgencias.

BACKGROUND: The new treatments for the bronchial inflammation in asthma, have contributed to decrease the mortality rate. However, there is still a group of population with no diagnosis fo asthma, who requires urgent medical attention in situations such as air pollution or risen pollen levels. On 2nd June 2000, 83 subjects with an acute crisis of asthma, came to the Emergency Room in our Hospital in just 6 hours, coinciding with the highest annual pollen measurement and a strong storm. METHODS AND RESULTS: Personal data from those 83 patients, medical behaviour at the Casualty and post-attention recommendations were considered for analysis. 21 % never had previous diagnosis of asthma and 93 % followed no regular medical control. 61.45 % did no treatment. A chest radiography was taken in 53.76 % of the patients. Salbutamol was administrated in most of them (92.18 %) and parentally administration of steroids in 23.47 %. 21 % were referred to an specialist. CONCLUSIONS: A significant rate of asthmatics is under-diagnosed, under-controlled and under-treated. Public Health authorities should consider the creation of new Allergy Units, a fluid communication between general practitioners and specialists, and the monitorization of pollen recounts with special plans of emergency situations to contribute to solve this problem.

Adverse reaction to tetrazepam.

Adverse reactions caused by benzodiazepines rarely occur. We present a case of a 70-year-old man who developed a maculopapular exanthema after the ingestion of tetrazepam. For his diagnosis, skin tests were performed, including prick and patch tests, not only with the benzodiazepine implicated in the reaction, but also with benzodiazepines of other groups. Single-blind oral challenge tests were also performed in the patient, in order to assess his tolerance to other benzodiazepines.