Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.

This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10-15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2high asthma (N = 4) compared to T2low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies.

BACKGROUND:Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26-/lo, CD26int and CD26hi subsets within different lymphocyte populations. METHODS:The proportion of CD26-/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4+CD26-/lo Teff cell subset by LC-MS/MS and immunofluorescence. RESULTS:Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4-CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26-/lo subsets. Specifically, CD4+CD26-/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes. CONCLUSION:There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26-/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.

Background: Paracetamol has been related to a higher prevalence of asthma. However, the relationship between paracetamol and rhinitis is still under debate. ObjectiveS: Our objective was to evaluate the relationship between the paracetamol use with the prevalence of rhinitis symptoms in children and adolescents from our region (Galicia; North-West Spain). Methods: We carried out a cross-sectional study using the ISAAC questionnaire. Based on the answers to the questionnaire, four categories of rhinitis were defined: "Rhinitis ever" (RE); "Recent rhinitis" (RR); "Recent rhinoconjunctivitis" (RRC) and "Severe rhinoconjunctivitis" (SRC). Paracetamol consumption in the past year was evaluated based on the response to a questionnaire with 3 possible responses: never, at least once a year, at least once per month. Consumption of paracetamol in the first year of life was evaluated with two response options, yes or no. The Odds ratio (OR) and Confidence interval 95% (CI) of the prevalence of rhinitis symptoms according to the paracetamol use was calculated using logistic regression, adjusted by gender, body mass index, parental smoking, maternal education level, cat, and dog at home. Results: We included 10,690 children and 10,730 adolescents. In table 1 it is shown that more frequent use of paracetamol is associated with a higher prevalence of rhinitis, both in children and adolescents. Conclusions: Higher use or paracetamol seems to be associated with higher prevalence of rhinitis ACKNOWLEDGMENTS: Maria-Jose Jove Foundation.

Background: The efficacy of mepolizumab in the treatment of patients with severe eosinophilic asthma (SEA) is already known. However, it is not yet known whether there is any relationship between the age of the patients and the response to this treatment. Objective: To analyse the impact of age on the response to mepolizumab in patients with SEA. Methods: We carried out a multicentre (8 hospitals), retrospective study, including all adult patients with SEA, in whom treatment with mepolizumab was started, who had received at least one dose of the drug, with follow-up of at least 6 months. Three groups of patients were defined according to tertiles of age (group 1: ≤53 years-old, group 2: >53 to ≤64, group 3: ≥ 65 years old) and then we analysed the control of asthma with the Asthma Control Test (ACT), number of exacerbations, number of hospital admissions, dose of inhaled (ICS) and systemic steroids (OCS) and lung function with FEV1. Results: We included 122 patients, 73% women, mean age 58 years old. ACT, number of exacerbations, and OCS dose improved similarly in the 3 age groups. The ICS dose did not change significantly in either group. Hospital admissions were significantly reduced in groups 1 and 3. FEV1 improved significantly in groups 1 and 2, the response being clearly higher in the younger group, 439 milliliters versus 174 milliliters (Figure 1). Conclusions: Age does not appear to be a limiting factor in the response to mepolizumab in patients with SEA, although the improvement in lung function is greater in younger patients.

Background: Severe eosinophilic asthma (SEA) is a T2high-endotype with recurrent exacerbations and poor disease control. Mepolizumab (anti-IL5 mAb) decreases the number of peripheral blood eosinophils, but the effect on their function is poorly understood. Our aim was to identify changes in the phenotype or activation of eosinophils in response to mepolizumab in patients with SEA. Methods: Blood samples were collected from healthy controls (HC; n=10) and SEA patients (n=12) before (T0) and after mepolizumab treatment (T4, 16, 32 weeks). Expression of proteins related to eosinophil activation (CD11b, CD44, CD48), immunomodulatory function (galectins 1/10), and eosinophil subsets, including resident (rEOS; CCR3+CD62LhiIL-3Rαlo) and inflammatory (iEOS; CCR3+CD62LloIL-3Rhi) eosinophils, were analyzed by flow cytometry. Results: Eosinophils from SEA display higher levels of Siglec-8, IL-5Rα, CD11b and CD44 (p<0.05) compared to HC, but no changes in regulatory proteins. Treatment with mepolizumab led to a decrease in eosinophil number (from 545.0 cells/μL at T0 to 133.1 cells/μL at T32; p<0.001) and a clear reduction of CD44 (p<0.01), together with a transition from rEOS to iEOS. All these changes were observed at early time point (T4) and maintained at T32. Conclusions: The number and activation status of eosinophils in peripheral blood is decreased by mepolizumab treatment and restored to HC levels. This treatment also induces a transition of iEOS to rEOS. Altogether, our results demonstrate a significant effect of mepolizumab on the function of eosinophils, which can be used as an indicator of response to this treatment. GSK provided funding for this study.

Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes.Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N = 512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A stan-dardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps. (c) 2023 SEPAR. Published by Elsevier Espan similar to a, S.L.U. All rights reserved.

Food allergies are a growing health problem that generate high costs for health systems. Food allergies have a prevalence of 6-8% in children and 2-3% in adults, which is increasing in the last 10 years due to industrialization. The wide variety of ingredients containing food allergens, in combination with the high number of product formulations and processing methods to produce food makes allergen detection a challenge. It is important to highlight that even trace amounts of allergens are able to elicit allergic reactions and the commercialization of food products with a potential health risk is forbidden (European Union Regulation (EU) 178/2002). Hence, precautionary allergen labeling must be provided in the different food products. In addition, this creates a real need for the development of highly sensitive and reliable techniques that allow the detection and quantification of multiple allergens present in trace amounts. This, together with the possibility to perform new allergen discovery studies (shotgun proteomics), makes Proteomic approaches a widely used methodology in this field. In this chapter we summarize the current knowledge regarding food allergies and the proteomic studies performed for the analysis of the different allergens. We briefly describe immunological processes underlying the different types of food allergies, the causative allergens involved in these processes, as well as the different proteomic approaches developed to identify (e.g., LC-MS/MS) and quantify (e.g., targeted proteomics such as selected/multiple reaction monitoring, SRM/MSM) these allergens in different conditions (e.g., complex mixtures, ultra-processed food, etc). Moreover, we have performed a comprehensive review of the different allergens and proteomic studies carried out in the field of plant food allergies, including gluten related disorders (GRDs), pollen-fruit allergy syndrome (PFAS), legumes allergy, and tree-nuts allergy, as well as animal food allergies, including cow´s milk, red meat, egg, fish, and shellfish allergies.

The impact of ICS on the prognosis for #COVID19 in #asthma patients requires a thorough evaluation of a range of factors that interact in this process, in order to draw solid conclusions, since at the present time the debate continues https://bit.ly/3xLNBrc.

Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6–7 and 13–14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6–7 years old group. The prevalence OR’s are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.

Introduction:Risk stratification of patients with COVID-19 can be fundamental to support clinical decision-making and optimize resources. The objective of our study is to identify among the routinely tested clinical and analytical parameters those that would allow us to determine patients with the highest risk of dying from COVID-19. Material and methods:We carried out a retrospective cohort multicentric study by consecutively, including hospitalized patients with COVID-19 admitted in any of the 11 hospitals in the healthcare network of HM Hospitals-Spain. We collected the clinical, demographic, analytical, and radiological data from the patient's medical records.To assess each of the biomarkers' predictive impact and measure the statistical significance of the variables involved in the analysis, we applied a random forest with a permutation method. We used the similarity measure induced by a previously classification model and adjusted the k-groups clustering algorithm based on the energy distance to stratify patients into a high and low-risk group. Finally, we adjusted two optimal classification trees to have a schematic representation of the cut-off points. Results:We included 1246 patients (average age of 65.36 years, 62% males). During the study one hundred sixty-eight patients (13%) died. High values of age, D-Dimer, White Blood Cell, Na, CRP, and creatinine represent the factors that identify high-risk patients who would die. Conclusions:Age seems to be the primary predictor of mortality in patients with SARS-CoV-2 infection, while the impact of acute phase reactants and blood cellularity is also highly relevant.

Asthma is a respiratory disease traditionally classified according to different phenotypes (e.g., allergic/non allergic) and endotypes (T2high/T2low) and with a strong influence of environmental triggers that vary seasonally, such as allergens, tobacco smoke, weather, contaminants, or respiratory viral infections. Exosomes are extracellular vesicles that carry potential biomarkers, like microRNAs (miRNAs). Some miRNAs have been related to asthma (e.g., miR21, miR146a), allergic diseases (e.g., miR16, miR21, miR126), or Th phenotypes (e.g., miR215, miR126, miR146a). Thus, miR215 is present in Th2 cells and could identify T2high asthma, while miR126 is more abundant in Th17 cells and could be a biomarker for T2low asthma. Therefore, we selected 12 miRNAs related in the literature to Th cells (Th1, Th2, Th17) as well as asthma/allergic diseases. We studied their levels (RTqPCR) in serum exosomes from healthy controls (n=30) and asthma patients (n= 119) classified by the allergic/non allergic phenotype, the T2high/T2low endotype, or the severity degree. We have also collected anthropometric, demographic, haematological, biochemical, and spirometric variables. We detected 5 out of 12 miRNAs with high confidence (miR16 and miR21, asthma/allergic disease; miR215, Th2; miR126, Th17; miR146a, Treg). After miRNA levels normalization, we found no differences between allergic/no allergic or T2high/T2low asthma. In contrast, when asthma severity was considered, we detected miR21, miR215, and especially miR126 and miR146a upregulated in severe patients compared to mild-intermittent asthmatics, with a clear seasonal influence (higher during fall). In conclusion, miRNAs could be biomarkers for asthma severity.

Introduction and Background Mediterranean diet (MD) seems to be related with less prevalence of asthma symptoms. However, the relationship between MD and rhinitis is still under debate. Aims and Objectives: The objective of our study was to evaluate the relationship of the MD with the prevalence of rhinitis symptoms in the child and adolescent population in our region Methods: We carried out a cross-sectional study using a questionnaire on rhinitis by the ISAAC study, for children (6-7 years) and adolescents (13-14 years) from Galicia (North-West Spain). Based on the answers to the questionnaire, the following categories of rhinitis were defined: “Rhinitis ever” (RE); “Recent rhinitis” (RR); “Recent rhinoconjunctivitis” (RRC) and “Severe rhinoconjunctivitis” (SRC). The Mediterranean Diet Score (MDS) was calculated according to the method developed by Garcia-Marcos (Thorax 2007: 62: 503–8). The Odds ratio (OR) and Confidence interval 95% (CI) of the prevalence of rhinitis symptoms according to adherence to MDS in quartiles was calculated using logistic regression. Results: In our study 10,690 children and 10,730 adolescents were included. Higher adherence to the MD is associated with a higher prevalence of RR in children (OR: 1.205, CI: 1.035-1.402) and of RRC in adolescents (OR: 1.306, CI: 1.042-1.637) (Table 1) Conclusions: Higher adherence to MD seems to be associated with higher prevalence of rhinitis

BACKGROUND:Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients.METHODS:Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2high -Atopic/T2high -Non-atopic/T2low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR.RESULTS:We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p.CONCLUSION:Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.

Background Frequent and highly prevalent as comorbidities in Chronic Obstructive Pulmonary Disease (COPD) patients, both depression and anxiety seem to have an impact on COPD prognosis. However, they are underdiagnosed and rarely treated properly. Aim To establish the prevalence of depression and anxiety in patients admitted for Acute Exacerbation of COPD (AECOPD) and determine their influence on COPD prognosis. Methods Prospective observational study conducted from October 1, 2016 to October 1, 2018 at the following centers in Galicia, Spain: Salnés County Hospital, Arquitecto Marcide, and Clinic Hospital Complex of Santiago de Compostela. Patients admitted for AECOPD who agreed to participate and completed the anxiety and depression scale (HADS) were included in the study. Results 288 patients (46.8%) were included, mean age was 73.7 years (SD 10.9), 84.7% were male. 67.7% patients were diagnosed with probable depression, and depression was established in 41.7%; anxiety was probable in 68.2% and established in 35.4%. 60.4% of all patients showed symptoms of both anxiety and depression. Multivariate analysis relates established depression with a higher risk of late readmission (OR 2.06, 95% CI 1.28; 3.31) and a lower risk of mortality at 18 months (OR 0.57, 95% CI 0.37; 0.90). Conclusion The prevalence of anxiety and depression in COPD patients is high. Depression seems to be an independent factor for AECOPD, so early detection and a multidisciplinary approach could improve the prognosis of both entities. The study was approved by the Ethical Committee of Galicia (code 2016/460).