Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization.

BACKGROUND AND OBJECTIVE: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients. METHODS: Patients sensitized to Lipid transfer protein (LTP) were classified as anaphylaxis or sensitized depending on the symptoms elicited by LTP-containing food. CD34+-derived MCs from patients and controls were obtained, sensitized with pooled sera, and challenged with Pru p 3 (peach LTP). Degranulation, PGD2, and cytokine/chemokine release were measured. The TFH13 population was examined by flow cytometry in the peripheral blood of all groups. In parallel, LAD2 cells were activated similarly to patients' MCs. RESULTS: A distinguishable pattern of mast cell activation was found in anaphylaxis compared to sensitized patients. Robust degranulation, PGD2, and IL-8 and GM-CSF secretion were higher in anaphylaxis, whereas TFG- and CCL2 secretion increased in sensitized patients. Concomitantly, anaphylaxis patients had a larger TFH13 population. MC activation profile was dependent on the sera rather than the MC source. In agreement with that, LAD2 cells reproduce the same pattern as MCs from anaphylactic and sensitized patients. CONCLUSION: The distinct profile of mast cell activation allows to discriminate between anaphylaxis and sensitized patients. Pooled sera may determine mast cell activation independently of mast cell origin. Besides, the presence of TFH13 cells in anaphylaxis patients points to an essential role of IgE affinity.

Prevalence of asthma in Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVE: Asthma epidemiology reports an estimated global prevalence of about 4.3-8.6% in adults, with last differences among geographical regions. This study analyses a more significant population of asthma patients (473,737 individuals).To study the prevalence of medical diagnosis of asthma, overall and by age, gender, and disease severity, as well as comorbidities and type 2 biomarkers, and undergo medical treatments of a retrospective population-based asthma cohort from Catalonia (Spain). METHODS: Individuals with a diagnosis of asthma established by medical records at different healthcare levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, comorbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment. RESULTS: The overall diagnosed asthma prevalence in the population of Catalonia was 6.3%, where patients mainly had mild asthma (5.3%) and were significantly higher in females (6.8%) than males (5.7%). By age groups, asthma was more prevalent in boys and young men adults; however, being more prevalent in females above the age of 30y. The prevalence of severe asthma was 0.4%, 42.6% had uncontrolled asthma, and a high proportion (84.2%) were under systemic corticosteroid prescription. As expected, SABAs were the most prescribed drug (62.6%), followed by systemic corticosteroids (43.3%). More than half (53.8%) of patients showed type 2 inflammation. CONCLUSION: Asthma prevalence in Catalonia is similar to other areas studied in Spain, with a high prevalence in women and of T2 asthma.

Prevalence of Atopic Dermatitis in the adult population of Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVES: Studies on the prevalence of Atopic Dermatitis (AD) for the adult cohort in general-based populations are scarce worldwide. We performed a retrospective population-based observational cohort study of 537,098 adult patients diagnosed with AD in Catalonia (Spain), a larger population than in previous studies. To study the prevalence of AD generally by age, gender, disease severity, multi-morbidities, and serum total Immunoglobin E (tIgE) and undergo appropriate medical treatment (AMT) for the Catalan population. METHODS: Adult individuals (≥18 years old) diagnosed with AD by medical records at different health care levels (primary, hospital, emergency) from the Catalan Health System (CHS) were included. Statistical analyses were conducted to evaluate socio-demographic characteristics, prevalence, multi-morbidities, serum tIgE and AMT. RESULTS: The overall diagnosed AD prevalence in the adult Catalan population was 8.7%, being higher for the non-severe (8.5%) than for the severe (0.2%) populations and females (10.1%) than males (7.3%). Topical corticosteroids were the most prescribed drug (66.5%), and the use of all prescribed treatments was higher in severe AD patients, especially systemic corticosteroids (63.8%) and immunosuppressant agents (60.7%). More than half (52.2%) of severe AD patients reported serum tIgE ≥ 100 KU/L, and higher values were observed for those with multi-morbidities. Acute bronchitis (13.7%), allergic rhinitis (12.1%), and asthma (8.6%) were the most frequent comorbid respiratory diseases. CONCLUSIONS: Our study provides new and robust evidence of AD´s prevalence and related characteristics in adults using a large-scale population-based study and a more significant cohort of individuals.

Resultados de la Neumonectomía en el Cáncer de Pulmón no Microcítico: Estudio Unicéntrico de Morbi-Mortalidad / Results of Pneumonectomy in Non-Small Cell Lung Cancer: Single Center Study of Morbi-Mortality

Resumen abreviado: Estudio de la morbi-mortalidad de la neumonectomía por Cáncer de pulmón en nuestro centro durante 2012-2017. La morbilidad <90días y mortalidad <90días global fue 38,4% y 17%. La morbilidad y mortalidad son mayores en lado derecho. Durante último trienio disminuyó la morbi-mortalidad y el número de neumonectomías por año (5,3%).Introducción: Presentamos este trabajo para analizar la morbi-mortalidad de la neumonectomía en nuestro centro, así como los factores que influyen en la misma, mostrando nuestros resultados en el tiempo en dos períodos: 2012-2014 y 2015-2017.Material y métodos: Se trata de un estudio analítico y observacional retrospectivo de todas las neumonectomías por Cáncer de pulmón no células pequeñas (CPNCP) intervenidas durante 2012-2017. Se ha analizado la morbi-mortalidad de toda la muestra según lateralidad, FEV1, estadio, edad y sistema de sutura. También se ha estudiado la morbi-mortalidad durante: 2012-2014 y 2015-2017. El análisis estadístico se realizó con el software SPSS versión 26.Resultados: Se realizaron 65 neumonectomías (izquierdas: 39 y derechas: 26) en pacientes con el diagnóstico de CPNCP. La morbilidad <90días fue del 38,4% (25/65). El porcentaje de complicaciones en el lado derecho y en los pacientes con FEV1 <80% fue 46%, en estadio avanzado 50%, pacientes >75años 77% y neumonectomías con sistema de sutura TA-roticulator 50%. La mortalidad <90días global fue un 17% (11/65). La mortalidad de las neumonectomías en los pacientes con FEV1 <80% fue 18%, el lado derecho 30,7%, en estadio avanzado 22,2%, pacientes >75años 22% y neumonectomías con sistema de sutura TA-roticulator 28%. El análisis por períodos reveló una morbilidad (27,5%) y mortalidad (6,8%) más baja en último trienio y menor número de neumonectomías por año (5,3%). (AU)

Resumen abreviado: Study of the morbidity and mortality of pneumonectomy for lung cancer in our center during 2012-2017. Overall morbidity <90 days and mortality <90 days were 38.4% and 17%. Morbidity and mortality are higher on the right side. During the last triennium, morbidity and mortality and the number of pneumonectomies per year decreased (5.3%).Introduction: We present this work to analyze the morbidity and mortality of pneumonectomy in our center, as well as the factors that influence it, showing our results over time in two periods: 2012-2014 and 2015-2017.Material and methods: This is a retrospective analytical and observational study of all pneumonectomies for non-small cell lung cancer (NSCLC) operated during 2012-2017. The morbi-mortality of the entire sample was analyzed according to laterality, FEV1, stage, age and suture system. Morbi-mortality has also been studied during: 2012-2014 and 2015-2017. Statistical analysis was performed with SPSS version 26 software.Results: 65 pneumonectomies were performed (left: 39 and right: 26) in patients diagnosed with NSCLC. Morbidity <90 days was 38.4% (25/65). The percentage of complications on the right side and in patients with FEV1 <80% was 46%, in advanced stage 50%, patients >75 years old 77% and pneumonectomies with TA-roticulator suture system 50%. Overall <90-day mortality was 17% (11/65). Mortality of pneumonectomies in patients with FEV1 <80% was 18%, right side 30.7%, advanced stage 22.2%, patients >75 years old 22%, and pneumonectomies with TA-roticulator suture system 28%. The analysis by periods revealed a lower morbidity (27.5%) and mortality (6.8%) in the last triennium and a lower number of pneumonectomies per year (5.3%). (AU)

Prevalence of Chronic Rhinosinusitis with Nasal Polyps in Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND: Studies on the prevalence of chronic rhinosinusitis (CRS) with nasal polyps (NP) in general-based populations are scarce in Europe and worldwide. We performed a retrospective population-based observational cohort study of 30,189 adult patients diagnosed with NP in Catalonia (Spain). METHODOLOGY: Adult individuals (≤18 years old) with a diagnosis of NP established by medical records at different health care levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, multi-morbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment (AMT) and Endoscopic Sinus Surgery (ESS). RESULTS: In general population and severity sub-populations, the overall diagnosed NP prevalence was 0.49% and higher for males than females (0.60% vs 0.39%, p less than 0.0016). The prevalence for the severe NP population was 0.12%. The NP prevalence increased with age, the highest being at ≤60 years old for both gender and severity groups. Asthma (40.1%), acute rhinosinusitis (41.1%), and allergic rhinitis (32.1%) were among the most frequent comorbid respiratory diseases. ESS was performed in 15.4% of NP patients. Type 2 inflammation was present in 83.8% of the NP population and was more frequent in severe than non-severe (87.1% vs 82.7%, p less than 0.0001) patients and in those with respiratory multi-morbidities (91%). CONCLUSIONS: This is the first large-scale population-based NP epidemiology study conducted in Spain, including severity based on undergoing medical and surgical treatment and type 2 inflammation. Although the prevalence data are lower than in previous European studies, the large NP cohort studied represents an essential strength of the results.

Consensus on the management of complications of cirrhosis of the liver in pediatrics.

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers.

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products.

Risk Factors in Severe Anaphylaxis: Which Matters the Most, Food or Cofactors?

BACKGROUND AND OBJECTIVE: The prevalence of anaphylactic shock, the most severe manifestation of anaphylaxis, remains unknown. Risk factors and biomarkers have not been fully identified. Objective: To identify risk factors in patients who experience anaphylactic shock. METHODS: Using lipid transfer protein (LTP) allergy as a model, we compared the characteristics of patients who developed anaphylaxis and anaphylactic shock. We recorded demographics, pollen sensitization, foods ingested up to 2 hours before onset of the reaction, and the presence of cofactors. Culprit foods were identified through a compatible clinical history and positive allergology work-up (skin prick test and/or sIgE). RESULTS: We evaluated 150 reactions in 55 patients with anaphylaxis (134 reactions) and 12 with anaphylactic shock (16 reactions). Patients in the anaphylaxis group experienced twice as many reactions (mean [SD], 2.4 [2.5] for anaphylaxis vs 1.3 [1.5] for anaphylactic shock; P<.02). No relationship was found between any food group and severity of the reaction. The most frequent food involved in both groups of patients was the combination of several plant-derived foods (plant food mix), followed by peach and nuts. Indeed, in the reactions caused by plant food mix, the presence of a cofactor was observed more often than in other food groups. On the other hand, cofactors were not present in peach- and nut-related reactions. Exercise was the most frequent cofactor in all groups. CONCLUSION: In our series, the severity of the reactions was not determined by the kind of food or presence of a cofactor. Anaphylactic shock seems to be an infrequent presentation that may be associated with other individual-related factors requiring further evaluation.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic.At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidenceof its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However,several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures acrossmanufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. Thisarticle discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison ofproducts from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapyproducts is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes,allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that thecomparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating theinformation given for a specific product, it is necessary to take into account further inherent characteristics of products and their applicationin clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data canserve as the basis for product-specific evaluation and cross-product comparability of individual products. (AU)

La prevalencia de las enfermedades alérgicas se ha incrementado drásticamente en los últimos 50 años y hoy pueden considerarse unaepidemia. Actualmente, la inmunoterapia específica con alérgenos (ITA) es el único tratamiento dirigido a la causa subyacente de lasenfermedades alérgicas y su superioridad se basa en resultados de ensayos clínicos/estudios observacionales que demuestran su eficaciay seguridad. Pero quedan aspectos sin resolver, como la armonización y estandarización de los procesos de fabricación y cuantificaciónentre fabricantes, la declaración homogénea de la potencia y el establecimiento de estándares internacionales de referencia. En este artículo se discuten aspectos relacionados con la medida del contenido de alérgenos mayores en los extractos de ITA, cuestionandosi, como base para elegir entre productos, es apropiada la comparación entre diferentes fabricantes. La estandarización alergénica escrucial para asegurar la calidad y, por tanto, la seguridad y eficacia de la ITA. Sin embargo, la falta de armonización en los procesos defabricación, la cuantificación alergénica, las diferencias regulatorias, la práctica clínica y el etiquetado, demuestran que comparar productosbasándose únicamente en la cantidad de alérgeno mayor no está justificado y es imposible. Además, cuando se evalúa la informaciónpara un determinado producto, deben tenerse en cuenta las características propias de cada producto y su uso clínico, como el estado dela modificación del extracto, la adición de adyuvantes, la vía de administración y la dosis acumulada. Solo datos clínicos convincentesdeben servir para la evaluación específica de cada producto o como base para la comparación entre productos. (AU)

Risk Factors in Severe Anaphylaxis: Which Matters the Most, Food or Cofactors?

Background: The prevalence of anaphylactic shock, the most severe manifestation of anaphylaxis, remains unknown. Risk factors and biomarkers have not been fully identified. Objective: To identify risk factors in patients who experience anaphylactic shock. Methods: Using lipid transfer protein (LTP) allergy as a model, we compared the characteristics of patients who developed anaphylaxis and anaphylactic shock. We recorded demographics, pollen sensitization, foods ingested up to 2 hours before onset of the reaction, and the presence of cofactors. Culprit foods were identified through a compatible clinical history and positive allergology work-up (skin prick test and/or sIgE). Results: We evaluated 150 reactions in 55 patients with anaphylaxis (134 reactions) and 12 with anaphylactic shock (16 reactions). Patients in the anaphylaxis group experienced twice as many reactions (mean [SD], 2.4 [2.5] for anaphylaxis vs 1.3 [1.5] for anaphylactic shock; P<.02). No relationship was found between any food group and severity of the reaction. The most frequent food involved in both groups of patients was the combination of several plant-derived foods (plant food mix), followed by peach and nuts. Indeed, in the reactions caused by plant food mix, the presence of a cofactor was observed more often than in other food groups. On the other hand, cofactors were not present in peach- and nut-related reactions. Exercise was the most frequent cofactor in all groups. Conclusion: In our series, the severity of the reactions was not determined by the kind of food or presence of a cofactor. Anaphylactic shock seems to be an infrequent presentation that may be associated with other individual-related factors requiring further evaluation (AU)

Antecedentes: La prevalencia del shock anafiláctico sigue siendo desconocida. Aún no se han identificado completamente factores de riesgo ni biomarcadores. Objetivo: Identificar factores de riesgo de shock anafiláctico. Método: Utilizando la alergia a proteína de transferencia de lípidos (LTP) como modelo, se han comparado características de pacientes que han presentado una anafilaxia (An) y pacientes que han desarrollado un shock anafiláctico (SAn). Se recopilaron datos demográficos, sensibilización a pólenes, alimentos ingeridos hasta 2 horas antes del inicio de la reacción y la presencia o no de cofactores. El alimento implicado se identificó mediante historia clínica compatible y estudio alergológico positivo (prick test y/o IgE). Resultados: Se evaluaron un total de 150 reacciones; 55 pacientes del grupo An sufrieron 134 reacciones, y 12 pacientes del grupo SAn sufrieron 16 reacciones. El grupo An experimentó el doble de reacciones por paciente (media [DS] 2,4 [2,5] en An vs 1,3 [1,5] en SAn, p<0,02). No se observó relación entre el tipo de alimento y la gravedad de la reacción. El alimento implicado con más frecuencia en ambos grupos fue la combinación de varios vegetales (“mix de vegetales”), seguido por el melocotón y frutos secos. No hubo cofactores implicados en las reacciones con melocotón ni con frutos secos. En ambos grupos el eje rcicio fue el cofactor involucrado con más frecuencia.Conclusión: En nuestra serie, el alimento y la presencia de cofactor no determinan la gravedad de una reacción. Los shocks anafilácticos parecen ser una presentación infrecuente y podrían estar relacionados con factores individuales que precisarán una evaluación más extensa (AU)

Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity. OBJECTIVES: To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA. METHODS: Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction. RESULTS: The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002). CONCLUSIONS: Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.