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 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.

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.

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 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.

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.

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.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

Origin of the New World Plasmodium vivax: Facts and New Approaches.

Malaria is one of the most important human diseases throughout tropical and sub-tropical regions of the world. Global distribution and ample host range have contributed to the genetic diversity of the etiological agent, Plasmodium. Phylogeographical analyses demonstrated that Plasmodium falciparum and Plasmodium vivax follow an Out of Africa (OOA) expansion, having a higher genetic diversity in African populations and a low genetic diversity in South American populations. Modeling the evolutionary rate of conserved genes for both P. falciparum and P. vivax determined the approximate arrival of human malaria in South America. Bayesian computational methods suggest that P. falciparum originated in Africa and arrived in South America through multiple independent introductions by the transatlantic African slave trade; however, in South America, P. vivax could have been introduced through an alternate migratory route. Alignments of P. vivax mitogenomes have revealed low genetic variation between the South American and Southeast Asian populations suggesting introduction through either pre-Columbian human migration or post-colonization events. To confirm the findings of these phylogeographical analyses, molecular methods were used to diagnose malaria infection in archeological remains of pre-Columbian ethnic groups. Immunohistochemistry tests were used and identified P. vivax but not P. falciparum in histologically prepared tissues from pre-Columbian Peruvian mummies, whereas shotgun metagenomics sequencing of DNA isolated from pre-Columbian Caribbean coprolites revealed Plasmodium-homologous reads; current evidence suggests that only P. vivax might have been present in pre-Columbian South America.

From cyclic nanorings to single-walled carbon nanotubes: disclosing the evolution of their electronic structure with the help of theoretical methods.

We systematically investigate the relationships between structural and electronic effects of finite size zigzag or armchair carbon nanotubes of various diameters and lengths, starting from a molecular template of varying shape and diameter, i.e. cyclic oligoacene or oligophenacene molecules, and disclosing how adding layers and/or end-caps (i.e. hemifullerenes) can modify their (poly)radicaloid nature. We mostly used tight-binding and finite-temperature density-based methods, the former providing a simple but intuitive picture about their electronic structure, and the latter dealing effectively with strong correlation effects by relying on a fractional occupation number weighted electron density (ρFOD), with additional RAS-SF calculations backing up the latter results. We also explore how minor structural modifications of nanotube end-caps might influence the results, showing that topology, together with the chemical nature of the systems, is pivotal for the understanding of the electronic properties of these and other related systems.

Impact Of "eHealth" in Allergic Diseases and Allergic Patients.

The emergence of new technology enables allergists and patients to compile data and receive feedback regarding key symptoms, risk behavior, and/or management. The term "eHealth" refers to a diverse group of tools that use computerized technologies to improve both the efficacy and the efficiency of the health care industry. eHealth comprises a variety of technologies, as follows: mobile devices (mHealth) in medical care, including electronic diaries, wearable sensors, and adherence monitoring; health informatics (eg, electronic health records, computerized physician order entry, clinical decision support); telemedicine, which is the use of information and communication technologies for the management of diseases and medical education; social media platforms, and the analysis of information acquired through these platforms using "big data" technologies. In this review, we summarize the latest findings on the use of eHealth technology and the relevance of eHealth to allergic conditions.

Antimicrobial activity of broccoli (Brassica oleracea var. italica) cultivar Avenger against pathogenic bacteria, phytopathogenic filamentous fungi and yeast.

AIMS: The objective of this study was to show whether the edible part of broccoli has antibacterial and antifungal activity against micro-organism of importance in human health and vegetable spoilage, and to test if this effect was partially due to antimicrobial peptides (AMPs). METHODS AND RESULTS: Crude extracts were obtained from florets and stems of broccoli cultivar Avenger and the inhibitory effect was demonstrated against pathogenic bacteria (Bacillus cereus, Staphylococcus xylosus, Staphylococcus aureus, Shigella flexneri, Shigella sonnei, Proteus vulgaris), phytopathogenic fungi (Colletotrichum gloeosporioides, Asperigillus niger) and yeasts (Candida albicans and Rhodotorula sp.). It was shown that samples treated with proteolytic enzymes had a reduction of approximately 60% in antibacterial activity against Staph. xylosus, suggesting that proteinaceous compounds might play a role in the inhibitory effect. Antimicrobial components in crude extracts were thermoresistant and the highest activity was observed under acidic conditions. It was shown that antifungal activity of broccoli's crude extracts might not be attributed to chitinases. CONCLUSIONS: Organic broccoli cultivar Avenger has antimicrobial activity against pathogenic bacteria, yeast and phytophatogenic fungi. Data suggest that this effect is partially due to AMPs. SIGNIFICANCE AND IMPACT OF THE STUDY: Broccoli's crude extracts have activity not only against pathogenic bacteria but also against phytophatogenic fungi of importance in agriculture. We suggest for first time that the inhibitory effect is probably due to AMPs.

Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study).

BACKGROUND AND OBJECTIVE: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine. METHODS: The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs. RESULTS: CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not. CONCLUSIONS: This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

Hepatitis C hospitalizations in Spain, 2004-2013: a retrospective epidemiological study.

BACKGROUND: Hepatitis C is an important public health problem about which there is currently scarce epidemiological information. The objective of this study is to describe and analyse the demographic and epidemiological characteristics of hospitalized cases of hepatitis C in the Spanish population between 2004 and 2013. METHODS: The study uses the Hospital Discharge Records Database of the Spanish National Health System. It is a retrospective descriptive epidemiological study. The variables analysed were year of infection, age, sex, diagnostic category, days admitted and co-morbidity. RESULTS: There have been a total of 351,996 hospitalizations; 225,138 men (64%) and 126,858 women (36%). They are divided between acute hepatitis 8161 (2.3%); chronic hepatitis 325,185 (92.4%) and unspecified hepatitis 18,650 (5.3%). The mean age for men is 53.7 (+/-15.2) and for women 62.3 (+/-17.3). 22.8% also present with an Human immunodeficiency virus (HIV) disease coinfection, and 14.7% with opioid dependencies. The trend is for a gradual increase in cases without statistical significance. CONCLUSIONS: The Hepatitis C cases hospitalized had high levels of chronicity, which entails two distinct patterns of illness in men and women - who are affected in different age ranges.

Nonsteroidal anti-inflammatory drugs enhance IgE-mediated activation of human basophils in patients with food anaphylaxis dependent on and independent of nonsteroidal anti-inflammatory drugs.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cofactors worsening the allergic reactions induced by food allergens. AIM: The aim of this study was to evaluate the effect of both lysine acetylsalicylate (L-ASA) (non-selective cyclooxygenase (COX) inhibitor) and valdecoxib (selective COX-2 inhibitor) in basophils activated by peach lipid transfer protein (Pru p 3) in patients with food-dependent NSAID-induced anaphylaxis (FDNIA). METHODS: Twenty Pru p 3-allergic patients with FDNIA group, eleven peach anaphylaxis not exacerbated by NSAIDs (no-NSAID group) and 5 healthy volunteers were recruited. Basophil activation (BA) was measured as expression of CD63 (Flow(2) CAST(™) ; Bühlmann(®) ), after stimulation with Pru p 3, both alone and in combination with L-ASA (1.13, 3.38 and 6.78 mm) or valdecoxib (0.87, 7.8 and 31.25 µm). RESULTS: Basophils from no-NSAID group were significantly more reactive and sensitive to Pru p 3 than those from the FDNIA group. In both groups, an increase in BA was observed when basophils were exposed to Pru p 3 and L-ASA. In the FDNIA group, valdecoxib partially terminates the BA induced by Pru p 3, whereas in the no-NSAID group, a dual effect was observed depending on the concentration tested. CONCLUSIONS: This study indicates that subjects with food-induced anaphylaxis differ from FDNIA subjects in the higher reactivity and sensitivity of their basophils to allergen challenge. We have shown a direct effect of NSAIDs on basophils using a human model of FDNIA. Our results also suggest that selective COX2 inhibitors might be a safe alternative. BA test may be a useful tool in the study of the pathogenic mechanism of the cofactor phenomenon.