In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS‐CoV‐2, and COVID‐19.

Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the “epithelial barrier hypothesis”. Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to dysbiotic bacteria. Here, we provide scientific evidence on the altered human exposome and its impact on epithelial barriers.

Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition with an incompletely understood immuno‐pathogenesis involving a T2 response. EoE is triggered by food allergens although, unlike IgE‐mediated allergies, it exhibits high IgG4 levels in oesophageal biopsies and in circulation. We investigated whether other antibody isotypes specific for food allergens are elevated in EoE and vary with disease activity.Methods: Plasma samples from patients with active EoE (n = 51), inactive EoE (n = 82) and non‐EoE controls (n = 14) were analysed for food‐specific IgG and IgA subclasses against casein, whey, wheat, egg and individual cow's milk allergens by ELISA. α‐lactalbumin (Bos d 4)‐ and β‐lactoglobulin (Bos d 5)‐specific B cells were measured by flow cytometry in a subset of patients.Results: Food allergen‐specific antibodies in the plasma varied across EoE subgroups and non‐EoE controls. Elevated IgG4 in EoE patients confirmed a strong antibody response to food allergens, including casein, wheat and egg. α_S1‐casein (Bos d 9)‐specific IgG, IgG2, IgG4, IgA1 and IgA2 differed between EoE and non‐EoE controls and between active and inactive EoE. β‐casein (Bos d 11, A1 variant) measurements showed higher levels of specific IgG2 and IgG4 in both EoE groups, whereas whey‐derived allergens showed opposing responses: Bos d 4 responses favoured IgG4, and Bos d 5 responses were elevated across multiple IgG and IgA subclasses in EoE. Allergen‐specific B cells could not be isolated from the circulation.Conclusion: Our findings reveal distinct antibody profiles in EoE plasma, with elevated IgG and IgA subclasses beyond IgG4, highlighting a complex immune response to food allergens. Differential antibody responses support their clinical relevance in dietary management strategies, while the absence of allergen‐specific B cells in circulation likely restricts antibody production to the inflamed oesophagus. Future research should explore whether these antibody profiles can guide personalised treatment and novel therapeutic targets in EoE.

Background/Objectives: Our study was designed to explore the potential role of allogeneic CD8⁺ T lymphocytes present in red blood cell concentrates (RBCs) in the development of transfusion-related immunomodulation (TRIM) and the effect of storage time on these cells. Methods: From six units of whole blood, donated by volunteers, RBCs were obtained and each one was divided into three equal parts to provide the samples for storage days 0, 21, and 42. On related days, mononuclear cells (MNCs) were isolated from these RBC samples. MNCs were cultured, and phytohemagglutinin was added to half of the culture wells to stimulate the cells and achieve T cell division. Supernatants and MNCs were obtained from stimulated (STI) and unstimulated (US) wells. Supernatants were used for cytokine analyses, while MNCs were used to investigate the T cells and transcription factors. Results: The frequency of CD8⁺ T lymphocytes (Tc), their subgroups (Tc1, Tc2, and Tc17), specific transcription factors, and effector cytokines decreased during the storage time, but cell viability increased. CD3⁺CD8⁺TNF-α+ cells were significantly higher in the STI group on day 0 compared to the US group. Other cells did not respond to the mitogen (phytohemagglutinin) stimulation. Conclusions: During storage, the number of Tc cells and their ability to respond to mitogens decreased over time. The unresponsiveness was not recovered in ex vivo cell culture. Our findings suggest that transfused Tc cells are unlikely to be primary mediators of TRIM.