Dupilumab: A new paradigm for the treatment of allergic diseases

Moderate and severe forms of allergic diseases such as atopic dermatitis and asthma are a challenge for clinicians. In these conditions, which severely affect the quality of life of the patient and frequently have associated allergic comorbidities, the therapeutic options are often very limited. Treatment with systemic corticosteroids and immunosuppressants has adverse effects in the long term, and a significant proportion of patients remain refractory to therapy. In this context, the emerging biological drugs constitute a truly innovative therapeutic approach. A leading example is dupilumab, a monoclonal antibody targeting the α chain of the interleukin (IL)-4 receptor. Dupilumab inhibits the biological effects of the cytokines IL-4 and IL-13, which are key drivers in the T H 2 response. The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. In 2017, the United States Food and Drug Administration and the European Medicines Agency approved the use of dupilumab for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with prescribed topical treatment. The results of phase III clinical studies of dupilumab in patients with persistent, uncontrolled asthma have been highly promising. The safety and tolerability profile of dupilumab has proven to be very favorable in long-term clinical trials. In this review, we focus on the mechanism of action of dupilumab, its development, and its impact on daily clinical practice in allergic diseases.Las formas clínicas moderadas y graves de enfermedades alérgicas comunes como la dermatitis atópica o el asma constituyen un reto para los clínicos. En estos casos, que afectan intensamente la calidad de vida del paciente y con frecuencia conllevan otras enfermedades alérgicas asociadas, las opciones terapéuticas son a menudo muy limitadas. El tratamiento con corticosteroides sistémicos o inmunosupresores tiene efectos adversos a largo plazo y una proporción significativa de pacientes se muestra refractaria a la terapia. En este contexto, los nuevos fármacos biológicos, dirigidos a la base inmunológica de la enfermedad, ofrecen un enfoque terapéutico verdaderamente innovador. Un ejemplo destacado de estos fármacos es dupilumab, un anticuerpo monoclonal dirigido contra la cadena alfa del receptor de la interleucina (IL)-4. Dupilumab inhibe los efectos biológicos de las citoquinas IL-4 e IL-13, unos de los principales efectores de la respuesta Th2. La efectividad y seguridad de dupilumab en el tratamiento de enfermedades alérgicas se han probado durante más de diez años en una variedad de grandes ensayos clínicos en dermatitis atópica, asma, rinosinusitis crónica con poliposis nasal y esofagitis eosinofílica. La FDA y la EMA aprobaron en 2017 el uso de dupilumab en el tratamiento de pacientes adultos con dermatitis atópica moderada o grave que no se controla adecuadamente con tratamiento tópico. Los estudios clínicos de Fase 3 de dupilumab en pacientes con asma persistente no controlada también han sido muy prometedores. En los ensayos clínicos a largo plazo la seguridad y tolerabilidad de dupilumab ha demostrado ser muy elevada. En esta revisión nos hemos centrado en el mecanismo de acción de dupilumab, su desarrollo como fármaco y su impacto en la terapia de enfermedades alérgica

Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air® real-world data

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMBackground: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. Methods: We analysed 2015–2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms (‘VAS Global Symptoms’) and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median ‘VAS Global Symptoms’ was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p <.001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1-antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. Conclusions: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severityThis study was funded by ARIA. MASK-air® has been supported by EU grants (EU Structural and Development grant, POLLAR: EIT Health and Structural and Development Funds) and educational grants from Mylan-Viatris, ALK, GSK, Novartis and Uriach. Open Access funding enabled and organized by Projekt DEA

Prevalence of severe atopic dermatitis in adults in 3 areas of Spain

The study was sponsored by Sanof

Nonallergic asthma and its severity: Biomarkers for its discrimination in peripheral samples

Asthma is a complex and heterogeneous respiratory disorder characterized by chronic airway inflammation. It has generally been associated with allergic mechanisms related to type 2 airway inflammation. Nevertheless, between 10 and 33% of asthmatic individuals have nonallergic asthma (NA). Several targeted treatments are in clinical development for patients with Th2 immune response, but few biomarkers are been defined for low or non-Th2-mediated inflammation asthma. We have recently defined by gene expression a set of genes as potential biomarkers of NA, mainly associated with disease severity: IL10, MSR1, PHLDA1, SERPINB2, CHI3L1, IL8, and PI3. Here, we analyzed their protein expression and specificity using sera and isolated peripheral blood mononuclear cells (PBMCs). First, protein quantification was carried out using ELISA (in sera) or Western blot (proteins extracted from PBMCs by Trizol procedure), depending on the biomarker in 30 healthy controls (C) subjects and 30 NA patients. A receiver operating characteristic curve analysis was performed by using the R program to study the specificity and sensitivity of the candidate biomarkers at a gene- and protein expression level. Four kinds of comparisons were performed: total NA group vs C group, severe NA patients vs C, moderate-mild NA patients vs C, and severe NA patients vs moderate-mild NA patients. We found that all the single genes showed good sensitivity vs specificity for some phenotypic discrimination, with CHI3L1 and PI3 exhibiting the best results for C vs NA: CHI3L1 area under the curve (AUC) (CI 95%): 0.95 (0.84-1.00) and PI3 AUC: 0.99 (0.98-1.00); C vs severe NA: PI3 AUC: 1 (0.99-1.00); and C vs moderate-mild NA: CHI3L1 AUC: 1 (0.99-1.00) and PI3 AUC: 0.99 (0.96-1.00). However, the results for discriminating asthma disease and severity with protein expression were better when two or three biomarkers were combined. In conclusion, individual genes and combinations of proteins have been evaluated as reliable biomarkers for classifying NA subjects and their severity. These new panels could be good diagnostic tests.This work was supported in part by research grants supported in part by research grants PI13/01730 and PI17/01682, cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). SB was supported by Fundación Conchita Rábago. DC was supported by a contract from Comunidad de Madrid (PEJD-2016/BMD-2682, Sistema de Garantía Juvenil), and LC-J was supported by a contract from MINECO (PEJ-2014-A-31609, Sistema de Garantía Juvenil), both cofinanced by Fondo Social Europeo (FSE) and Iniciativa de Empleo Juvenil (IEJ)

Suppressors of Cytokine Signaling 3 Expression in Eosinophils: Regulation by PGE2 and Th2 Cytokines

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2 (PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production

Design of Virtual Hands for Natural Interaction in the Metaverse

[EN] The emergence of the Metaverse is raising important questions in the field of human-machine interaction that must be addressed for a successful implementation of the new paradigm. Therefore, the exploration and integration of both technology and human interaction within this new framework are needed. This paper describes an innovative and technically viable proposal for virtual shopping in the fashion field. Virtual hands directly scanned from the real world have been integrated, after a retopology process, in a virtual environment created for the Metaverse, and have been integrated with digital nails. Human interaction with the Metaverse has been carried out through the acquisition of the real posture of the user's hands using an infrared-based sensor and mapping it in its virtualized version, achieving natural identification. The technique has been successfully tested in an immersive shopping experience with the Meta Quest 2 headset as a pilot project, where a transactions mechanism based on the blockchain technology (non-fungible tokens, NFTs) has allowed for the development of a feasible solution for massive audiences. The consumers' reactions were extremely positive, with a total of 250 in-person participants and 120 remote accesses to the Metaverse. Very interesting technical guidelines are raised in this project, the resolution of which may be useful for future implementations.This research is part of the R+D project PID2020-118021RB-I00, funded by MICIN/AEI/10.13039/501100011033, and R+D project UJI-B2022-48 funded by University Jaume I.Cerdá Boluda, J.; Mora, MC.; Lloret Romero, MN.; Scarani, S.; Sastre, J. (2024). Design of Virtual Hands for Natural Interaction in the Metaverse. Sensors. 24(3). https://doi.org/10.3390/s2403074124

Discriminatory molecular biomarkers of allergic and nonallergic asthma and its severity

The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Asthma is a complex disease comprising various phenotypes and endotypes, all of which still need solid biomarkers for accurate classification. In a previous study, we defined specific genes related to asthma and respiratory allergy by studying the expression of 94 genes in a population composed of 4 groups of subjects: healthy control, nonallergic asthmatic, asthmatic allergic, and nonasthmatic allergic patients. An analysis of differential gene expression between controls and patients revealed a set of statistically relevant genes mainly associated with disease severity, i.e., CHI3L1, IL-8, IL-10, MSR1, PHLDA1, PI3, and SERPINB2. Here, we analyzed whether these genes and their proteins could be potential asthma biomarkers to distinguish between nonallergic asthmatic and asthmatic allergic subjects. Protein quantification was determined by ELISA (in serum) or Western blot (in protein extracted from peripheral blood mononuclear cells or PBMCs). Statistical analyses were performed by unpaired t-test using the Graph-Pad program. The sensitivity and specificity of the gene and protein expression of several candidate biomarkers in differentiating the two groups (and the severity subgroups) was performed by receiver operating characteristic (ROC) curve analysis using the R program. The ROC curve analysis determined single genes with good sensitivity and specificity for discriminating some of the phenotypes. However, interesting combinations of two or three protein biomarkers were found to distinguish the asthma disease and disease severity between the different phenotypes of this pathology using reproducible techniques in easy-to-obtain samples. Gene and protein panels formed by single biomarkers and biomarker combinations have been defined in easily obtainable samples and by standardized techniques. These panels could be useful for characterizing phenotypes of asthma, specifically when differentiating asthma severity.Supported in part by research grants PI13/01730 and PI17/01682, cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). SB was supported by a grant from the Fundación Conchita Rábago and PI17/01682. DC was supported by a contract from Madrid regional government (PEJD-2016/BMD-2682, Sistema de Garantía Juvenil), LC-J was supported by a contract from MINECO (PEJ-2014-A- 31609, Sistema de Garantía Juvenil), and MdP was supported by a contract from Madrid regional government (PEJ-2017- AI/SAL-5938, Sistema de Garantía Juvenil), all cofinanced by The European Social Fund (ESF) and the Youth Employment Initiative (YEI

Impact of the laser scanning strategy on the quality of 17-4PH stainless steel parts manufactured by selective laser melting

[EN] A significant correlation between scanning strategies and the quality of parts manufactured additively with Selective Laser Melting (SLM) technology is shown. Therefore, a in deep study of the influence of scanning strategy is of great value for the manufacturing process in order to promote SLM technology in applications with high service requirements. In particular, this research is carried out on 17-4PH stainless steel parts, which is an alloy widely used in sectors such as aerospace or automotive for its excellent mechanical properties. This research proposes to evaluate the properties of 17-4PH parts manufactured using three usual scanning strategies (normal, concentric and hexagonal) in order to optimize the SLM process depending on the final part application. According to the obtained results, the following general conclusions have been drawn. Hexagonal strategy can be considered the most appropriate in terms of porosity. Both hexagonal and normal strategy have good mechanical properties, as well as geometrical and dimensional quality. Regarding surface finish of top face (where the used scanning pattern is visible), normal strategy is the most appropriate. In general, concentric strategy presents different results from the others: larger and irregular pores, ductile tensile behaviour, low roughness on lateral faces, and high geometrical errors in samples with large scanning vectors. As a future work, it is proposed to manufacture SLM parts combining these strategies in order to improve their properties. In addition, it is proposed to evaluate the influence of different post-process operations on the quality of parts printed by SLM using different strategies.S

Therapeutic potential of peptides from Ole e 1 in olive-pollen allergy

Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approachesSupported by research grants PI13/01730, PI17/01682 cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). D. Calzada was supported by a contract from Comunidad de Madrid (PEJD-2016/BMD- 2682, Sistema de Garantía Juvenil), L. Cremades-Jimeno was supported by a contract from MINECO (PEJ-2014-A-31609, Sistema de Garantía Juvenil) and MA. de Pedro was supported by a contract from Comunidad de Madrid (PEJ-2017-AI/SAL-5938, Sistema de Garantía Juvenil), all cofinanced by Fondo Social Europeo (FSE) and Iniciativa de Empleo Juvenil (IEJ). S. Baos was supported by Fundación Conchita Rábago and PI17/01682

Towards Functional Parts by Binder Jetting Calcium-Sulphate with Thermal Treatment Post-Processing

[EN] The objective of our research is to improve the properties of calcium-sulphate hemihydrate parts printed by binder jetting. In this paper, we show the thermal treatment results when using temperature time ramps on binder-jetted ceramic parts without infiltrating. The results show that the mechanical properties of printed parts are improved substantially. Two different thermal cycles were investigated for their effect on the dehydration process of CaSO4·½H2O using infrared analysis. The thermal-treated samples were compared with respect to porosity, surface roughness, compression strength and dimensional and weight variation. The proposed thermal treatment significantly improves the compression strength in a short time, guaranteeing dimensional stability while providing a good surface. This improvement in mechanical properties offers a great chance for using binder-jetted parts as functional components, for example, in the casting field or the medical sector (scaffolds).SIAgencia Estatal de Investigació